v6 symposium: the 6th international vanadium symposium” july 17 to 19th, 2008 lisbon, portugal

17-19 JulyLisbon2008

Portugal

The Chemistry and Biological

Book of AbstractsBook of Abstracts

InternationalVanadium Symposium

6th

Chemistry of Vanadium

Coordination by: João da Costa Pessoa Cover designed by: Isabel Correia and Hugo Tomás Organized and compiled by: Isabel Tomaz, Gisela Gonçalves and Sofia Gama The assistance of Pedro Adão and Amit Tyagi is acknowledged.

This book was prepared from text supplied by the authors. No additional English corrections of the included articles were made.

General Information

V6 Symposium ∷ Lisbon 2008

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Organizing Committee João Costa Pessoa (Chair), IST-TU Lisbon, Portugal Hitoshi Michibata (Co-chair), Hiroshima University, Japan Kan Kanamori (Co-chair), Toyama University, Japan Isabel Correia (secretariat), CQE/IST-TU Lisbon, Portugal Ana Isabel Tomaz (secretariat), CCMM/FC-UL, Portugal Gisela Gonçalves (secretariat), IST-TU Lisbon, Portugal Pedro Adão (secretariat), IST-TU Lisbon, Portugal Sofia Gama (secretariat), ITN, Sacavém, Portugal Amit Tyagi (secretariat), CQE/IST-TU Lisbon, Portugal National Organizing Committee João Costa Pessoa, IST-TU Lisbon, Portugal Armando Pombeiro, IST-TU Lisbon, Portugal J.J.R. Fraústo da Silva, IST-TU Lisbon, Portugal Carlos C. F. Geraldes, CNC, Coimbra University, Portugal M. Margarida C. A. Castro, CNC, Coimbra University, Portugal Manuel Aureliano Alves, FCT - Algarve University, Portugal Isabel Cavaco, FCT - Algarve University, Portugal Isabel Correia, CQE/IST-TU Lisbon, Portugal Ana Isabel Tomaz, CCMM/FC-UL, Portugal Gisela Gonçalves (secretariat), IST-TU Lisbon, Portugal Pedro Adão, IST-TU Lisbon, Portugal Sofia Gama, ITN, Sacavém, Portugal Amit Tyagi, CQE/IST-TU Lisbon, Portugal International Advisory Board Valeria Conte, Rome, Italy João Costa Pessoa, Lisbon, Portugal Debbie C. Crans, Forth Collins, USA Toshikazu Hirao, Osaka, Japan Kan Kanamori, Toyama, Japan Tamas Kiss, Szeged, Hungary Kenneth Kustin, San Diego, USA Hitoshi Michibata, Higashi-Hiroshima, Japan Lage Pettersson, Umeå, Sweden Dieter Rehder, Hamburg, Germany Alan S. Tracey, British Columbia, Canada

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Acknowledgements We would like to thank the following organizations for making this event possible.

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The Calouste Gulbenkian Foundation gardens

Entr

ance

Venuebu

ilding

Entr

ance

Venuebu

ilding

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The V6 Symposium Venue at Calouste Gulbenkian Foundation

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V6 Symposium Program

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Scientific Program – Oral Sessions Thursday, 17th July

9:10 - Introductory Remarks

9 :30 - O1 - Conte, V. (Italy) – “V-catalysed, MW assisted, oxidations with H2O2”

9.50 - O2 - Chen, C.T. (Taiwan) – ”Directed Evolution of C4-Symmetric Metal Vanadate-centered Quadruplexes: Synergistic Metal-specific Ion Transport and Asymmetric Catalysis”

10:10 - O3 - Correia, I. (Portugal) – “Vanadium-salen and salan complexes as catalysts for oxidation reactions”

10:30 - O4 - Rosenthal, E. (Germany) – “From Vanadium(V) to Vanadium(IV) – and backwards?”

10:50 - O5 - Sasai, H. (Japan) – “Chiral dinuclear vanadium(V) catalyst for dual activation of 2-naphthols in oxidative couplings”

11:10 Coffee Break

11:40 - O6 - Lorber, C. France) – “[ONNO]-type Amine Bis(phenolate)-Based Vanadium Catalysts for Ethylene Homo- and Co-polymerization”

12:00 - O7 - Hartung, J. (Germany) – “On the Reactivity of Bromoperoxidase I (Ascophyllum nodosum) in Buffered Organic Media – Formation of Carbon Bromine Bonds”

12:20 - O8 - Maurya, M. (India) – “ Synthesis, characterisation, reactivity and catalytic potential of oxovanadium(IV), oxovanadium(V) and dioxovandium(V) complexes of monobasic tridentate ligand derived from pyridoxal and 2 aminoethylbenzimidazole”

12:40 - O9 – Rangel, M. C. (Portugal) – “Insulin enhancing complexes derived from 3-hydroxy-4-pyridinones”

13:00 Lunch

14.30 - O10 -Pecoraro, V. (USA) – “Computationally Assisted Design of Asymmetric Sulfoxidation Catalysts based on Functional Models for Vanadium Dependent Haloperoxidases”

14:50 - O11 - Pettersson, L. (Sweden) – “Aqueous Vanadium(V) Speciation - The Umeå Perspective”

15:10 - O12 - Hashimoto, M. (Japan) – “Simple peroxovanadate-amino acid complexes”

15:30 - O13 - Tomaz, I. (Portugal) – “The Vanadium-MHCPE system: an evaluation towards bioavailability”

15:50 - O14 - Kiss, T. (Hungary) & IUPAC Presentation – “Comparative studies on the biospeciation of antidiabetic vanadium and zinc compounds”

16:20 Poster Session

16:50 Poster Session / Coffee Break


17:50 - O15 - Gambino, D. (Uruguay) – “Vanadium complexes with polipyridyl ligands as potential antiprotozoa agents”

18:10 - O16 - Kanamori, K. (Japan) – “Oscillating reaction of a vanadium compound. II What triggers the chaotic reaction?”

18:30 - O17 - Salifoglou, A. (Greece) – “New ternary and binary species in the structural speciation of insulin mimetic vanadium(V) in the presence of the physiological citrate and hydrogen peroxide”

18:50 -19:10

O18 – Schwendt, P. (Slovak Republic) – “Stereospecific formation of dinuclear vanadium(V) tartrato complexes”

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Friday, 18th July

9:10 - O19 - Castro, M. (Portugal) – “Chemical and Biochemical Studies of a 5-hydroxy-4-pyrimidinone V(V) Complex”

9:30 - O20 - Crans, D. C. (USA) – “How Lipids Interfaces Affect the Coordination Chemistry of Vanadium Compounds”

9 :50 - O21 - Sakurai, H. (Japan) – “Development of Anti-diabetic Vanadium Complexes and Analysis of their Molecular Mechanism”

10:10 - O22 - Willsky, G. (USA) – “Chemical and Biological Variability in Anti-diabetic and Anti-apoptotic Effects of Vanadium Complexes”

10:30 - O23 - Orvig, C. (Canada) – “Coordination of oxovanadium(IV) to human serum apo-transferrin: a calorimetric comparison study”

10:50 - O24 - Thompson, K. (Canada) – “VO(IV) complexes of maltol and ethylmaltol for oral treatment of type 2 diabetes mellitus: lessons from speciation studies and phase I and II clinical trials”

11:10 Coffee Break

11:40 - O25 - Katoh, A. (Japan) – ”Evaluation of Insulin-Mimetic Activities of Vanadyl Complexes from the Viewpoint of Heterocyclic Bidentate Ligands”

12:00 - O26 - Ding, W. (China) – “The insulin-mimetic properties of vanadium with its effects on the gene expression profiling of the insulin signaling pathway in diabetic mellitus”

12:20 - O27 - Zorzano, A. (Spain) – “Arylalkylamine vanadium salts as a new generation of antidiabetic compounds.”

12:40 - O28 - Makinen, M.W. (USA) – “Can Vanadyl Chelates Help To Detect Cancer?”

13:00 Lunch

14.30 - O29 - Zonta, C. (Italy) – “Lewis Bases in Vanadium(V) Catalyzed Oxygen Transfer Catalysis”

14:50 - O30 - Garriba, E. (Italy) – “Octahedral-square pyramidal equilibrium in bis-chelated VIVO species: spectroscopic and DFT characterization”

15:10 - O31 - Rehder, D. (Germany) – “Vanadium in Life”

15:30 - O32 - Etcheverry, S. (Argentina) – “Biological Effects and Cytotoxicity of a complex of Vanadium(V) with salicylaldehyde semicarbazone in osteoblasts in cult”

15:50 - O33A – Majlesi, K. (Iran) – “Interaction of Dioxovanadium(V) with Iminodiacetic Acid and Phenylalanine Using SIT” O33B – Rezaienejad, S. (Iran) – “Complexation of Dioxovanadium(V) with Nitrilotriacetic Acid in Different Sodium Perchlorate Aqueous Solutions Using SIT”


16:50 Poster Session / Coffee Break


17:50 - O34 - Aureliano, M. (Portugal) – “Recent advances in decameric vanadate biochemistry”

18:10 - O35 - Michibata, H. (Japan) – “A novel function of Vanabin2 and the relationship among proteins involved in the accumulation and reduction of vanadium by ascidians”

18:30 - O36 - Cohen, M. (USA) – “Vanadium Induces AIH: Implications for the Pulmonary Immune System”

18:50 - O37 - Cavaco, I. (Portugal) – “DNA cleavage activity of VO(acac)2 and derivatives”

19:10

20.30 Symposium dinner

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Saturday, 19th July

9:10 - O38 - Plass, W. (Germany) – “Vanadium haloperoxidases as versatile biological matrix:

Mechanistic aspects towards cofactor and substrate specificity” 9 :30 - O39 - Almeida, M. (Portugal) – “Vanadium haloperoxidases – a biocatalyst for iodination

reactions” 9.50 - O40 - Wever, R. (Netherlands) – “Directed evolution of vanadium chloroperoxidase: a

mutant with high bactericidal activity at alkaline pH” 10:10 - O41 - Littlechild, J. (UK) – “Vanadium containing Bromoperoxidase – Insights into the

enzymatic mechanism using X-ray crystallography” 10:30 - O42 -Butler, A. (USA) – No title available

10:50 - O46 - Ghermani, N. E. (France) – “Structural and Electrostatic properties of a decavanadate-cytosine co-crystallized complex”

11:10 Coffee Break

11:40 - O44 - Avecilla, F. (Spain) – “Influence of polydentate ligands in the structure of dinuclear V(V) compounds”

12:00 - O45 - Hayashi, Y. (Japan) – “Hexavanadate core and discovery of double stranded octadecavanadate”

12:20 - O43 - Spasojevic, A. (France) – “Crystallographic statistical studies of the decavanadate anion: toward a prediction of the non-covalent interactions”

12:40 - O47 - Antunes, O. (Brasil) – “A New Oxo-Vanadium complex employing an imidazole rich tripodal ligand”

13:00 Lunch

14.30 - O48 - Kabanos, T. (Greece) – “Oxovanadium(V) compounds with bis(hydroxyamino)-triazines: Synthesis, structural, and physical studies ”

14:50 - O49 - Honzicek, J. (Czech Republic) – ”Ring-substituted vanadocene(IV) and molybdenocene(IV) complexes”

15:10 - O50 - Pombeiro, A. (Portugal) – “Vanadium Catalysts for the Functionalization of Alkanes under Mild Conditions”

15:30 - O51 - Baran, E. (Argentina) – “Oxovanadium (IV) complexes of carbohydrates. Some recent advances”

15:50 - Vanadium Award combined Lecture O52 – Hirao, T. – “Vanadium-Catalyzed Oxidative Bromination Reaction under Molecular Oxygen”

16:40 Coffee break

17:10 - O53 - Krzystek, J. (USA) –” Electron Paramagnetic Resonance of Vanadium(III) Coordination Complexes”

17:30 - O54 - Keramidas, A. (Greece) – “Structure and spectroscopic properties of new VIV/V semiquinone and hydroquinone complexes”

17:50 - O55 - McLauchlan, C.C. (USA) – “ Vanadium Coordination Complexes with the [CpP(OEt,OEt)Co]- ligand : Towards Catalysis “

18:10 - O56 - Carn, F. (France) – “Bio-inspired Synthesis of Bionanocomposites Elastomers via a Complex Coacervation Process Between Gelatin and Decavanadates”

18:30 - 18.45: Closing Remarks

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Scientific Program – Poster Titles

P1 - Daniel Geibig DFT Model Studies of Vanadium Chloroperoxidase: Dissociative or Associative Enzymatic Mechanism and its Dependency on the Degree of Protonation.

P2 - Tamás Jakusch – “Anion “complexes” of diperoxo-vanadate Model compounds for haloperoxidase enzyme?”

P3 - Manuel Aureliano – “Decameric vanadate reduction by physiological concentrations of glutathione in mitochondrial assay conditions”

P4 - Shogo Kamiya – “Template synthesis of a spherical polyoxovanadate(V) by oxidative coupling reaction”

P5 - Pedro Adão – “Asymmetric oxidation of thioanisole catalysed by reduced Schiff base oxovanadium(IV) complexes”

P6 - Amit Kumar – “Oxidation of p-chlorotoluene and cyclohexene catalysed by polymer-anchored oxovanadium(IV) and copper(II) complexes of amino acid derived tridentate ligands”

P7 - Christian Lorber – “Organometallic chemistry of vanadium with B(C6F5)3” P8 - Silvia Lovat – “Vanadium(V) complexes as oxidation catalysts” P9 - Ana M. Martins – “Vanadium diamine bisphenolate complexes: Synthesis, structures and

catalytic activity in sulfoxidations”

P10 - Mannar R. Maurya – “Polystyrene bound dioxovanadium(V) complex of histamine derived ligand for the oxidation of methyl phenyl sulfide, diphenyl sulfide and benzoin”

P11 - Grzegorz Romanowski – “Dioxovanadium(V) Schiff base complexes of R(-)-1,2-diaminopropane and o-hydroxycarbonyl compounds. Synthesis, characterization, catalytic properties and structure”

P12 - Grzegorz Romanowski – “Chiral dioxovanadium(V) complexes of Schiff bases derived from 1,2-diphenyl-1,2-diaminoethane and aromatic o-hydroxyaldehydes. Synthesis, characterization, catalytic properties and structure”

P13 - Valeria Conte – “V-catalysed oxidations with H2O2” P14 - Valeria Conte – “On the nature of V(V) species in hydrophilic ionic liquids: a spectroscopic

approach”

P15 - Fernando Avecilla – “Characterization in the solid state of chiral salen and salan ligands and their vanadium(V) compounds”

P16 - Pabitra Baran Chatterjee – “Intramolecular electron transfer in the solid phase: presenting a unique example of single-crystal-to-single-crystal transformation from a binuclear vanadium(V)-alcoholate to an oligomeric vanadium(IV)-aldehydic compound”

P17 - Debbie C. Crans – “Electron transfer reactions of an amavadin-like complex” P18 - Chryssoula Drouza – “Interaction of Hydroquinonate ligands with VV and MoVI” P19 - Éva Anna Enyedy –“New insight into the lipo-hydrophilic characterisation of a series of

antidiabetic VO(IV) and Zn(II) complexes and their carrier ligands”

P20 - Takeshi Higuchi –“ Syntheses and characterisation of novel [VO(O2)2L](L=ligand) type complexes”

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P21 - Licínia L.G. Justino – “Density functional theory study of structure and NMR chemical shifts of oxoperoxo vanadium(V) complexes of L-lactic acid”

P22 - Licínia L.G. Justino – “Density functional theory study of the oxoperoxo vanadium(V) complexes of glycolic acid. structural correlations with NMR chemical shifts”

P23 - Tatsuya Ueki – “Protein-protein interactions among vanadium-binding proteins and related proteins in a vanadium-rich ascidian”

P24 - Jessica Nilsson – “Synthesis of new oxo-vanadium(IV) coordination compounds and evaluation of their insulin mimetic activity”

P25 - Gloria Omoruyi –“ The analysis and determination of vanadium IV in wastes collected from mining ores in Nigeria”

P26 - Mirta Rubčić – “Vanadium induced cyclization of thiosemicarbazone: formation of heptanuclear mixed valence V(IV)/V(V) complex”

P27 - Athanasios Salifoglou – “A new vanadium(V)-peroxo species in the presence of physiological citrate. The missing link in the structural speciation of the V(V)-peroxo-citrate system”

P28 - Telma F.S. Silva – “New C-functionalized tris(pyrazolyl)methanes and their vanadium complexes”

P29 - Michal Sivák – “Synthesis, molecular and supramolecular structures of oxo compounds formed by biologically active central atom, heteroligand/s and counterions: vanadium(V), pyridine or pyrazine carboxylates and amides”

P30 - Marios Stylianou – “Bi- and Hexanuclear Vanadium (IV) complexes of a p-hydroquinone-based ligand: synthesis and structural characterization”

P31 - Karim Zare – “The effect of ionic strength on the stability constant of vanadium(IV) complex with methionine”

P32 - Gisela Gonçalves – “Interaction of a pyrimidinone-V(IV) complex with human serum transferrin”

P33 - Daniele Sanna – “VIVO complexes with bis(pyridyl) derivatives” P34 - Daniele Sanna – “Interaction of insulin-enhancing vanadium compounds with transferrin and

low molecular mass bioligands”

P35 - Eugenio Garribba – “The effects of the trigonal bipyramidal distortion on the spectroscopic and electrochemical properties of VIVO bis-chelated species”

P36 - Susana B. Etcheverry – “VO(oda): a vanadyl(IV) complex with an OOO-donor group. Bioactivity on human colon adenocarcinoma Caco-2 cell line”

P37 - Dinorah Gambino – “Modifying antiprotozoa activity of organic compounds through complexation with vanadium”

P38 - Maria João Pereira – “Diabetes and vanadium: levels of vanadium in blood samples” P39 - Allison Ross – “Oxovanadium(IV) macrocycles: potential antivirals against HIV” P40 - Jaromír Vinklárek – “Vanadocene complexes of a-amino acids: synthesis, structure and

cytostatic activity”

P41 - Gail R. Willsky – “Biological variability in the anti-apoptotic effects of vanadium” P42 - Sarah Angus-Dunne – “Fenton chemistry revisited: vanadate’s role in the study of

antioxidants”

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P43 - Sarah Angus-Dunne – “Hydroxylamino-vanadate derivatives as protein tyrosine phosphatase inhibitors”

P44 - Rosa F. Brissos – “Vanadium interactions with the calcium pump ATPase: an overview” P45 - Mirjana Colovic – “Decavanadate effect on rat synaptic plasma membrane Na+/K+-ATPase

activity”

P46 - Gil Fraqueza – “Differential interaction of Sarcoplasmic Reticulum Calcium ATPase with Mo, V and W Oxometalates”

P47 - Norifumi Kawakami. – “Vanabin2 extracted from ascidian vanadocyte is a novel vanadium reductase”

P48 - Danijela Krstica – “Inhibition of rat synaptic plasma membrane Ca2+-ATPase activity by decavanadate”

P49 - Ines Lippold – “Modeling supramolecular interactions of vanadium species” P50 - Craig C. McLauchlan – “Vanadium imidazolylcarboxylate complexes: synthesis,

characterization, and phosphatase inhibition”

P51 - Ana M. Pereira - “Functional and structural interactions of three vanadium coordination complexes with the Sarcoplasmic Reticulum Calcium Pump”

P52 - Susana Ramos – “Binding of vanadium (IV) and (V) to actin: effects on function and structure”

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Congratulations

Toshikazu Hirao

on receiving

the

3rd Vanadis Award!


Oral Lectures

Oral lectures


Oral lectures


O1

V-catalysed, MW assisted, oxidations with H2O2

V. Contea, F. Fabbianesia, B. Florisa , P. Gallonia, D. Sordia, I. Arendsb, M. Bonchioc, S. Berardic, D. Rehderd

a Dip. Scienze e Tecnologie Chim., Univ. Roma Tor Vergata, via Ricerca Scientifica, 00133, Roma IT

b Lab. of Biocatalysis and Organic Chemistry, Delft University of Technology, Delft, NL. c ITM-CNR & Università di Padova, Dip. Scienze Chimiche, via Marzolo 1, 35131, Padova, IT

d Inst. Inorganic and Applied Chem., Hamburg University, Martin-Luther-King-Platz 6 D-20146 Hamburg, D e-mail: [email protected]

Vanadium catalysis in oxidation carried out with peroxides is very well known and studied in several research groups.[1] Several different functional groups can be oxidized with good yields and selectivities. More recent is, however, the search for more efficient and sustainable procedure which employs hydrogen peroxide as oxidant. In this respect also the search for more environment friendly solvents is of primary interest for fundamental research. In the last years very interesting results have also been obtained in applying MW activation in metal catalysed reactions carried out in ionic liquids. MW-induced dielectric heating is indeed efficiently used by charged species.[2] In the present work results obtained the performance of vanadium based epoxidation catalysts in oxidations of diverse substrates with hydrogen peroxide will be presented. In particular, alkenes epoxidation and thioethers oxidation will be discussed. Emphasis will be given to the results obtained in reactivity and selectivity improvement observed when hydrophobic ionic liquids and MW activation are used. [1] V. Conte, O. Bortolini, Transition metal Peroxides, Synthesis and role in oxidation reactions. In “The Chemistry of Peroxides” Vol. 2, Part 1, Zvi Rappoport (Editor), ISBN: 0-470-86274-2, (2006), pag.1053-1128. [2] S. Berardi, M. Bonchio, M. Carraro, V. Conte, A. Sartorel, G. Scorrano, J. Org. Chem. 72(23) (2007) 8954-8957.

NN

O OVO

N

O

NH

O

O

V

O OO

NNH

O

N

V

OOMe

N

OCH3

CH3NH

N

V

O O

ON

ONH

O

VO

O

N N

OV

O

O

O

NN

O OV

O

Catalysts

+

EtSO4-

VO(SALen)EtSO4

CH3OH

Cat.1 Cat.2 Cat.3

Cat.4 Cat.5

+

CF3SO3-

VO(3,5-diterzbutylSALOphen)TfO

"Sub"V(V) Catalyst, H2O2

Solvent, TOC"Sub-O"

Sub = alkenes, hydrocarbons, thioethers Solvents: bmimPF6; bmimTf2N

Oral lectures


O2

Directed evolution of C4-symmetric metal vanadate-centered quadruplexes: synergistic metal-specific ion transport and asymmetric

catalysis

Ya-Hui Lin and Chien-Tien Chen

Department of Chemistry, National Taiwan Normal University; Taipei, Taiwan email: [email protected]

We have developed a series of N-Salicylidene-based L-α-amino acids as chiral auxiliaries for chiral vanadyl(V) methoxide complex synthesis. These configurationally well-defined complexes have been examined for kinetic resolution of 2o alcohols. They serve as efficient and highly enantioselective catalysts for asymmetric aerobic oxidation of α-hydroxy acid,1 phosphonic acid,2 and ketone derivatives3 at ambient temperature. X-ray crystallographic analysis of an adduct between N-benzyl-mandelamide and the catalyst allows for probing the origin of the nearly exclusive asymmetric control in the oxidation process. In the case of the 3,5-di-tert-butyl and -chloro analogs, pentanuclear C4-symmetric complexes were formed when a potassium salt was employed. The complexes work synergistically in the asymmetric aerobic oxidations of various racemic α-hydroxy acid derivatives with excellent selectivity factors.4

G

OH

PO

O

5 mol%catalyst

O2/toluenert

(R)48-50% yield

krel: 50 - >100

G = Ar, hetero-Ar, alkenyl, alkynyl, alkyl

O

NV

O

O

O

Br

Br

OCH3O

H

46-50% yield

Ph

catalyst

OPh

G

O

PO

OPh

OPh

G

OH

PO

OPh

OPh

O

N O

O

VO

OVO

Cl

4

M+

ClOH

O

S Ph

1.25 mol%

O

O

S Ph +

OH

O

S Ph

O2, toluenert

K:Cs = 92:8 (8 min)K:Cs = 95:5 (1h)

O

N O

O

VO

OCH3Cl

Cl

CDCl3

H2Ow/M+VO3

-

M = Li, Na, K, CsOH

O

N O

O

VO

OVO

Cl

4

M+

Cl

CDCl3

H2Ow/M'+VO3

-

M' = Li, Na, Cs

An artificial directed evolution process to assemble C4-symmetric, vanadate-centered quadruplexes, for the first time, from a given chiral vanadyl(V) complex allows for highly efficient K+- and Ag+-specific transport from aqueous phase containing three other alkali metal cations into organic solvents, reminiscent of the K+ specific transport exerted by four homochiral glycine residues of the opening site in KcsA membrane protein.

Acknowledgements: We thank the National Science Council of Taiwan for generous financial support of this research. [1] S.-S Weng, M.-W.Shen, J.-Q. Kao, Y. S. Munot, C.-T. Chen, Proc. Natl. Acad. Sci. USA 103 (2006) 3522-3527. [2] V. D. Pawar, S.-S. Weng, S. Bettigeri, J.-Q. Kao, C.-T. Chen, J. Am. Chem. Soc. 128 (2006) 6308-6309. [3] C.-T. Chen, S.-S. Weng, W.-Z. Lee, J. Org. Chem. 72 (2007) 8175-8184. [4] C.-T. Chen, Y.-H. Lin, submitted to Angew. Chem. Int. Ed. 47 (2008) for publication.

Oral lectures


O3

NH NH

O O R1R1

R2R2

V

ONH NH

O O R1R1

R2R2

V

O

Vanadium-salen and salan complexes as catalysts for oxidation reactions

Isabel Correia,a Pedro Adão,a Mannar R. Maurya,b Fernando Avecilla,c Maxim

Kuzvetsova and João Costa Pessoaa

[a] Centro Química Estrutural, Instituto Superior Técnico - TU Lisbon, Av. Rovisco Pais 1049-001, Lisboa, Portugal [b] Department of chemistry, Indian Institute of Technology Roorkee, Roorkee-247667, India

[c] Departamento de Química Fundamental, Facultad de Ciencias, Universidade da Coruña, Zapateira, s/n, 15071, A Coruña, Spain

email: [email protected]

The interest in vanadium complexes as catalysts has been promoted by its ability to catalyze oxidations and oxo transfer reactions.[1] Vanadium complexes containing chiral ligands have shown the capacity to catalyze enantioselectively the oxidation of prochiral sulfides to sulfoxides (and sulfones, in some cases) by hydrogen peroxide or organic hydroperoxides. Moreover, it has been reported that chiral ligands containing a secondary amine group are superior, in terms of reactivity and enantioselectivity to imino analogues.[2] We report the synthesis and characterization of chiral salen (salicylideneimine) and salan (salicylideneamine) type ligands and their vanadium complexes, which are derived from salicylaldehyde or pyridoxal and chiral diamines (1R,2R-cyclohexanediamine, 1S,2S-cyclohexanediamine and 1S,2S-diphenylethylene diamine). The complexes are studied by UV-Vis, circular dichroism and EPR spectroscopy, which provide information on the coordination geometry and conformational chirality of the chelate rings, both being important factors in asymmetric catalysis. The complexes were tested as catalyst in the oxidation of styrene, cyclohexene and cumene with H2O2 as oxidant. Different products were obtained and some catalysts showed good performance and selectivity. Globally the conversions are better with the V-salan complexes than with the V-salen complexes. The complexes were also tested as catalysts for the enantioselective oxidation of methyl phenyl sulphide. Good enantioselective oxidations were achieved and again the results are significantly better with the V-salan complexes than with the V-salen complexes. Possible mechanisms of reactions are outlined and several DFT studies are presented to support the formation of proposed intermediates. Acknowledgement: The authors gratefully acknowledge the financial support of FEDER, Fundação para a Ciência e a Tecnologia, POCI 2010 and PPCDT/QUI/55985/2004 and PPCDT/QUI/56946/2004 projects. Prof. M. R. Maurya acknowledges Fundação Oriente and the Department of Science and Technology, New Delhi for the financial support received. [1] L. Canali and D.C.Sherrington, Chem. Soc. Rev.,1999, 28, 85. [2] J.T.Sun, C.J.Zhu, Z.Y.Dai, M.H.Yang, Y.Pan and H.W.Hu, J. Org. Chem., 2004, 69, 8500.

(VIVO-salan complex)

Oral lectures


O4

From Vanadium(V) to vanadium(IV) – and backwards?

Esther C. E. Rosenthal

Department of Chemistry, Secr. C 2, TU Berlin, Strasse des 17. Juni 135, 10623 Berlin, Germany email: [email protected]

Recently we synthesised and characterised a series of oxovanadium(V) alkoxides with bidentate ligands and investigated their catalytic behaviour.1 Alkoxy and aryloxyalkoxide ligands were chosen due to their ability to stabilise vanadium complexes in high oxidation states by forming chelate structures with the additional oxygen donor coordinated to the vanadium atom. Anyhow not all complexes with alkoxyalkoxide ligands are indefinitely stable under inert conditions. They decompose even in the dark and at low temperatures to the corresponding vanadium(IV) complexes (Figure 1).

Figure 1. From Vanadium(V) to Vanadium(IV) – and backwards?

Advanced reduction is observed by colour change from the yellow, orange or red vanadium(V) compounds to the blue-green colour of vanadium(IV) in solution as well as with exposition to sunlight. Reduction already takes place during the reaction with some of the alkoxy alcohols. Sometimes the reduction products are stable and isolable, but reaction pathways are unknown and often side products are observed. In the majority of cases the stable vanadium(IV) complexes can be synthesised with higher yields by direct methods. Possible decomposition pathways are the oxidation of the alcohol ligands or the formation of chlorine. No positive proof of aldehydes as oxidation products could be made, which had been identified as those for simple alcohols.2 While electrochemical methods are not conclusive on the reduction and oxidation products formed, reaction of the vanadium(V) complexes with several Lewis bases gave crystallographically characterised products with the oxidation state depending on the donor atom. Finally mechanistic investigations showed reversibility for a certain reaction type.

[1] a) E. C. E. Rosenthal, F. Girgsdies, Z. Anorg. Allg. Chem. 628 (2002) 1917, b) E. C. E. Rosenthal, H. Cui, K. C. H. Lange, S. Dechert, Eur. J. Inorg. Chem. (2004) 4681, c) E. C. E. Rosenthal, H. Cui, J. Koch, P. Escarpa Gaede, M. Hummert, S. Dechert, Dalton Trans. (2005) 3108 d) E. C. E. Rosenthal, H. Cui, J. Koch ACS Symp. Ser. 974 (2007) 70. [2] a) H. Prandtl, L. Hess, Z. Anorg. Chem. 82 (1913) 103, b) H. Funk, W. Weiss, M. Zeising, Z. Anorg. Allg. Chem. 296 (1958) 36.

VCl

O

?

!

Oral lectures


O5

OVN

O VN

OO

O

O O

O

(Ra,S,S)-1

Ra

S

S

Chiral dinuclear Vanadium(V) catalyst for dual activation of 2-naphthols in oxidative couplings

Hiroaki Sasai, Shinobu Takizawa, Tomomi Katayama

The Institute of Scientific and Industrial Research (ISIR), Osaka University

Mihogaoka, Ibaraki-shi, Osaka 567-0047, Japan, email: [email protected]

An efficient enantioselective oxidative coupling of 2-naphthol derivatives based on a concept of dual activation catalysis is realized. A chiral dinuclear vanadium(IV) complex (Ra,S,S)-11 possessing (S)-tert-leucine moieties at the 3,3’-positions of the (R)-binaphthyl skeleton was developed, which was found to promote the oxidative coupling of 2-naphthol to afford (S)-BINOL with 91% ee. To verify the dual activation mechanism, mononuclear vanadium(IV) complex (S)-2 was also prepared. Kinetic analysis revealed that the reaction rate of oxidative coupling of 2-naphthol promoted by (Ra,S,S)-1 is 48.3 times faster than that of (S)-2. The two vanadium metals in the chiral complex activate two molecules of 2-naphthol simultaneously in an intramolecular coupling reaction, achieving a high reaction rate with high enantiocontrol. Since (Ra,S,S)-1 was found to be readily oxidized to afford a corresponding vanadium(V) species during preparation in air, a new synthetic procedure using VOCl3 has been developed as shown in Scheme 1.2,3 The structure of (Ra,S,S)-3 was determined by X-ray crystallographic analysis as a NaOH adduct. Corresponding dinuclear vanadium(V) complex (Ra,S,S)-4, bearing octahydrobinaphthyl skeleton, was also prepared from 3,3-diformyl-H8-BINOL. To the best of our knowledge, (Ra,S,S)-3 and (Ra,S,S)-4 show considerably higher catalytic activity than previously reported vanadium complexes for the oxidative coupling of 2-naphthols. Reaction mechanisms of the oxidative coupling reaction promoted by either vanadium(IV) or vanadium(V) complexes will be also discussed.

Scheme 1. Preparation of Dinuclear Vanadium(V) Catalysts.

Scheme 2. Representative Results on Oxidative Coupling of 2-Naphthols. [1] H. Somei, Y. Asano, T. Yoshida, S. Takizawa, H. Yamataka, H. Sasai, Tetrahedron Lett. 45 (2004) 1841-1844. [2] S. Takizawa, T. Katayama, H. Somei, Y. Asano, T. Yoshida, C. Kameyama, D. Rajesh, K. Onitsuka, T. Suzuki, M. Mikami, H. Yamataka, D. Jayaprakash, H. Sasai, Tetrahedron, 64 (2008) 3361-3371. [3] S. Takizawa, T. Katayama, C. Kameyama, K. Onitsuka, T. Suzuki, T. Yanagida, T. Kawai, H. Sasai, Chem. Commun. 2008, 1810-1812.

(S)-2

O VN

OO

O

OHOHOH

Catalyst (5 mol %)

air, CH2Cl2OV

N

O VN

OO

O

O O

O

OHHO

(Ra,S,S)-4Cat 1: 76% (91% ee) (30 oC, 24 h)Cat 3: 100% (90% ee) (0 oC, 72 h)Cat 4: 56% (97% ee) (0 oC, 72 h)

Oral lectures


O6

[ONNO]-type amine bis(phenolate)-based Vanadium catalysts for ethylene homo- and co-polymerization

Christian Lorber

Laboratoire de Chimie de Coordination du CNRS, 205 route de Narbonne, 31077 Toulouse, France


In the past fifteen years, a tremendous amount of effort has been devoted to the design of new "non-metallocene" early transition metal complexes because of their importance as α-olefin polymerization catalysts.[1] Particularly, chelating diamide, dialkoxide, or phenoxyimine ligands have been extensively studied as rigid supporting environments for titanium and zirconium complexes. resulting in the emergence of a great deal of novel and useful chemistry, including the discovery of highly active olefin polymerization precatalysts. Among these new ligands, chelating dianionic [ONNO]-type amine bis(phenolate) ligands associated to group 4 metal complexes have proved to give highly active 1-hexene polymerization catalysts, and in some cases even isospecific living polymerization was possible.[2] As part of an ongoing study of vanadium chemistry with various supporting ligands, in particular directed toward vanadium complexes for olefin polymerization, we have recently used ancillary diamido with sterically demanding protecting groups[3] or imido ligands[4] on vanadium(IV) complexes as a way to overcome the problem of deactivation by stabilization of the formal oxidation state of the vanadium center. Following this concept, we wish to describe the synthesis of a series of vanadium complexes with the ancillary amine bis(phenolate) [ONNO]-type ligand and their use as ethylene homo- and co-polymerization catalyst.[5]

[1] V. C. Gibson, S. K. Spitzmesser, Chem. Rev. 2003, 103, 283-315. [2] E. Y. Tshuva, I. Goldberg, M. Kol, J. Am. Chem. Soc. 2000, 122, 10706-10707. [3] Lorber, C.; Donnadieu, B.; Choukroun, R. Organometallics 2000, 19, 1963-1966. [4] Lorber, C.; Donnadieu, B.; Choukroun, R. J. Chem. Soc., Dalton Trans. 2000, 4497-4498. [5] (a) F. Wolff, C. Lorber, R. Choukroun, B. Donnadieu Inorg. Chem. 2003, 42, 7839-7845. (b) F. Wolff, C. Lorber, R. Choukroun, B. Donnadieu Eur. J. Inorg. Chem. 2004, 2861-2867. (c) C. Lorber, F. Wolff, R. Choukroun, B. Donnadieu, Eur. J. Inorg. Chem. 2005, 2850-2859.

R R

RR

VO

N

O

N

XX

+

α-olefin or cycloolefin

cocata: EtAlCl2

- Linear Low Density PolyEthylenes and CycloOlefin Copolymers- High co-monomer incorporation- Good Molecular Weight Distribution

Oral lectures


O7

On the reactivity of Bromoperoxidase I (Ascophyllum nodosum) in buffered organic media – formation of carbon bromine bonds

Jens Hartung,a Diana Hach,a and Heiko Schulza

aFachbereich Chemie, Technische Universität Kaiserslautern,

Erwin-Schrödinger-Strasse 54,D-67663 Kaiserslautern, Germany email: [email protected]

Vanadium(V)-dependent bromoperoxidase I was isolated from Ascophyllum nodosum [VBrPO(AnI)].1,2 The enzyme was applied as catalyst for conducting sustainable brominations of organic substrates in buffered organic media. In the absence of organic substrates, enzyme stability gradually increased along the series phosphate (pH 6.2) < Tris (pH 9.0) < MES buffer (pH 6.2), as documented with the triiodide assay. A decrease of VBrPO(AnI) stability was furthermore noted by raising the volume percentage of added organic co-solvent. Least pronounced effects on enzyme activity loss was found for co-solvents 1,4-dioxane and tert-butanol in up to 50 % (v/v). Suitable conditions, that balanced VBrPO(AnI) lifetime in buffered organic media, and enzymatic activity for bromide oxidation were applied for converting organic substrates into bromo-derivatives.3 Pyrroles, for example, afforded bromopyrroles on a larger scale. Hydrogen peroxide efficiency was essentially quantitative under newly established conditions. VBrPO activity prevailed for reactions conducted under pH-controlled conditions. The procedure was applied for selective bromohydrine synthesis from olefins. The target products were subjected to detailed stereochemical analysis with the aid of a novel chiral phosphorous-based derivatization reagent.4

Acknowledgements: The authors would like to thank particularly Dr. Hans Vilter for helpful discussions and Prof. Dieter Rehder for donations of VBrPO(AnI) samples for conducting preliminary experiments as well as for his interest in this work. We also wish to express our gratitude to Mrs. Yvonne Dumont for technical assistance and Drs. Philipp Schmidt and Marco Greb for conducting preliminary VBrPO(AnI)-catalyzed oxidations. Financial support was kindly provided by the Stiftung für Innovation (grant 818) des Landes Rheinland-Pfalz and by the Deutsche Bundesstifung Umwelt (grant 2007/885). [1] H. Vilter. Bot. Marina 26 (1983) 331–340. [2] J. Hartung, O. Brücher, D. Hach, H. Schulz, H. Vilter, G. Ruick. Phytochemistry, submitted. [3] D. Hach, H. Schulz, Y. Dumont, H. Vilter, J. Hartung. Manuscript in preparation. [4] M. Amberg, U. Bergsträsser, G. Stapf, J. Hartung. J. Org. Chem. 73 (2008) 3907–3910.

Oral lectures


O8

Synthesis, characterisation, reactivity and catalytic potential of oxovanadium(IV), oxovanadium(V) and dioxovandium(V) complexes

of monobasic tridentate ligand derived from pyridoxal and 2-aminoethylbenzimidazole

Mannar R. Maurya,a Manisha Bisht,a Amit Kumar,b Fernando Avecillac and

João Costa Pessoab

a Department of chemistry, Indian Institute of Technology Roorkee, Roorkee-247667, India;b Centro Química Estrutural, Instituto Superior Técnico - TU Lisbon, Av. Rovisco Pais 1049-001, Lisboa, Portugal;

c Departamento de Química Fundamental, Facultad de Ciencias, Universidade da Coruña Zapateira, s/n, 15071, A Coruña, Spain.

e-mail: [email protected] Interest in the coordination chemistry with particular emphasis on the model character of vanadium(V) complexes having O and N functionalities stems from the structural characterization of three vanadate-dependent haloperoxidases (VHPO). Irrespective of their origin they all have almost identical structural features, with vanadium(V) in a trigonal-bipyramidal coordination environment. In order to model structural features of haloperoxidases, [VO(acac)2] was reacted with two ONN donor ligands, Hpydx-aebmz (I) (Hpydx = pyridoxal and aebmz = 2-aminoethylbenzimidazole) to give oxovanadium(IV) complex, [VO(acac)(pydx-aebmz)] (1). In this complex, one acetylacetonato group remained coordinated and the single crystal X-ray study confirms its octahedral structure. Reaction of Hpydx-aebmz with VOSO4 in refluxing methanol gave [{VO(pydx-aebmz)}2(SO4)] (2). Complex 1 has been used as precursor to prepare other vanadium complexes. Thus, 1 in methanol reacts with aqueous 30 % H2O2 to give oxoperoxovanadium(V) complex, [VO(O2)(pydx-aebmz)] (3), the formation of which has also been established in solution by titrating methanolic solution of 1 with H2O2 dissolved in methanol. Reaction of 1 with catechol (H2cat) and benzohydroxamic (H2bha) acid in refluxing methanol gave octahedral complexes [VO(cat)(pydx-aebmz)] (4) and [VO(bha)(pydx-aebmz)] (5), respectively. All these complexes have been characterised by various physico-chemical techniques. Catalytic activities of some of these complexes for the oxidation of organic substrates are also explored. Acknowledgement: Prof. M. R. Maurya acknowledges Fundação Oriente for the financial support received. Department of Science and Technology, New Delhi is also gratefully acknowledged for financial support of the work, and the authors also thank FEDER, Fundação para a Ciência e a Tecnologia, POCI 2010 (PPCDT/QUI/55985/2004 and PPCDT/QUI/56946/2004 programs).

Oral lectures


O9

Insulin enhancing complexes derived from 3-hydroxy-4-pyridinones Maria Rangel,a Mª João Amorim,b Ana Nunes,b Andreia Leite,b Mariana Andrade,b Ana

Silva,b Paula Gameiro,b Carla Silva,c

aREQUIMTE, Instituto de Ciências Biomédicas de Abel Salazar, Universidade do Porto, Largo Abel Salazar, 2, 4099-003 Porto, Portugal, email: [email protected];

bREQUIMTE, Departamento de Química, Faculdade de Ciências, Universidade do Porto, Rua do Campo Alegre, 4169-007 Porto, Portugal

cREQUIMTE, Faculdade de Ciências da Saúde, Universidade Fernando Pessoa, Rua Carlos da Maia, 4200-150 Porto, Portugal

Metal based drugs are currently in use for both therapeutic and diagnosis purposes. The

identification of abnormal levels of metal ions in the body as a cause of several diseases has

promoted the design of chelators and of metal ion containing molecules with suitable properties

for their use as therapeutic agents.

Since a few years, we have been working on the design of new chelators of the 3-hydroxy-

4-pyridinone family and their complexes with M(II) and M(III) metal ions1. Pyridinone

molecules, apart from its physico-chemical properties, which favour its further use as

therapeutic agents, are synthetically versatile allowing the preparation of polidentate and multi-

functionalized ligands which exhibit strong chelating properties. The work developed on

compounds with potential insulin-enhancing activity will be discussed from the chemical and

biological point of view.

000

0000

00000000

Acknowledgements: I am most grateful to all colleagues and collaborators named in the references above for their invaluable contributions to the research into this field. Financial support from FCT, contract POCTI/QUI/35368/2000, POCI/QUI/56214/2004, PPCDT/QUI/56949/2004 is gratefully thanked. [1] J. Burgess, B. de Castro, C. Oliveira , M. Rangel and W. Schlindwein, Polyhedron, 1997, 16, 789.; M.M.C.A. Castro, C.F.G.C. Geraldes, P. Gameiro, E. Pereira, B. Castro and M. Rangel, J. Inorg. Biochem., 2000, 80, 177; M. Rangel, A. Tamura, C. Fukushima, H. Sakurai, J. Biol. Inorg. Chem., 2001, 6(2), 128.; W. Schlindwein, E. Waltham, J. Burgess, N. Binsted, A. Nunes, A. Leite and M. Rangel, Dalton Trans., 2006, 1313.

Oral lectures


O10

Computationally assisted design of asymmetric sulfoxidation catalysts based on functional models for vanadium dependent Haloperoxidases

Curtis J. Schneider†, Giuseppe Zampella, ‡ Luca De Gioia, ‡ and Vincent L. Pecoraro†,§,

†Department of Chemistry, University of Michigan, Ann Arbor, MI 48109

‡Department of Biotechnology and Biosciences, University of Milano-Bicocca, Milano, Italy §Biophysics Research Division, University of Michigan, Ann Arbor, MI 48109,

Vanadium dependent haloperoxidases are a novel class of vanadium dependent enzymes that

catalyze the two electron oxidation of halides and the asymmetric oxidation of thioethers. Our

group has had a long standing interest in understanding the mechanism of oxidation for VHPOs

through the use of vanadium coordination complexes. We have established that

K[VO(O2)Hheida] is an effective functional model for bromide, iodide, and thioether oxidation.

Using this well defined model complex as a starting point, we have employed modern

computational methods to understand the factors controlling the stereoselectivity for the

oxidation of the synthetically useful and pharmaceutically relevant pro-chiral thioethers to chiral

sulfoxides. This information has assisted in the design of an asymmetric oxidation catalyst and

provided critical insight into the reactivity of this new chiral catalyst. The marriage of modern

computational methods and experimental techniques has developed a catalytic system that is

capable of stereoselective oxidation of thioethers and enhanced the understanding of the factors

controlling the reactivity of vanadium-based catalytic oxidations. Acknowledgements: We thank the Luso-American Development Foundation for financial support.

Oral lectures


O11

Aqueous Vanadium(V) speciation - the Umeå perspective

Lage Pettersson,a Ingegärd Andersson,a András Gorzsásb

aDepartment of Chemistry, Umeå University, SE – 901 87 Umeå, Sweden, email: [email protected]

b Department of Forest Genetics and Plant Physiology, Umeå Plant Science Centre, Swedish Agricultural University, SE – 901 83 Umeå, Sweden

Before studying the speciation in any aqueous vanadium(V) system, the hydrolysis of pentavalent vanadium must be accurately known at a specific ionic medium and temperature. The Umeå group was the first to report the complete speciation in one and the same ionic medium (0.600 M Na(Cl)).1 Vanadates and peroxovanadates have shown insulin enhancing properties. To elucidate their effects, it is vital to know the complete speciation in relevant systems. Detailed and thorough potentiometric (glass electrode) and 51V NMR (Bruker AMX-500 MHz) spectroscopic studies have been performed of H+–H2VO4

––L and H+–H2VO4––H2O2–L

systems at 25 °C in 0.150 M Na(Cl), a medium representing human blood. When studying the ligand(L) systems, the complete speciation in the subsystems H+–H2VO4

– and H+–H2VO4––

H2O2must be known under the same experimental conditions.2 The computer program LAKE,3 designed to simultaneously treat multimethod data, has been used to establish the entire speciation. The ligands we have studied so far include imidazole,2 alanylhistidine,4 alanylserine,5 lactate,6 picolinate,7 citrate,8 phosphate,9 maltol,10,11 and uridine.11 Moreover, studies on the ligands N-hydroxyimino-2,2'-dipropionate (Amavadine ligand) and carbonate are ongoing. The talk will focus on trends in the complexing ability of different ligands to vanadate and peroxovanadate. A common feature is that isomeric species are formed in most systems. When adding hydrogen peroxide, peroxovanadate species are in general formed from already existing vanadate-ligand complexes. In the case of diperoxovanadate complexes, the following donor atoms are preferred: aromatic N only > both aliphatic N and O > exclusively O.12 Equilibrium conditions will be illustrated by distribution diagrams. Models of physiological conditions will also be shown. Acknowledgements: The authors would like to thank the Swedish Research Council and European Union COST projects for financial support. [1] L. Pettersson, B. Hedman, I. Andersson, N. Ingri, Chem. Scripta 22 (1983) 254-264. [2] I. Andersson, S. Angus-Dunne, O. Howarth, L. Pettersson, J. Inorg. Biochem. 80 (2000) 51-58. [3] N. Ingri, I. Andersson, L. Pettersson, A. Yagasaki, L. Andersson, K. Holmström, Acta Chem. Scand. 50 (1996) 717-734. [4] H. Schmidt, I. Andersson, D. Rehder, L. Pettersson, Chem. Eur. J. 7 (2001) 251-257. [5] A. Gorzsás, I. Andersson, H. Schmidt, D. Rehder, L. Pettersson, Dalton Trans. (2003) 1161-1167. [6] A. Gorzsás, I. Andersson, L. Pettersson, Dalton Trans. (2003) 2503-2511. [7] I. Andersson, A. Gorzsás, L. Pettersson, Dalton Trans. (2004) 421-428. [8] A. Gorzsás, K. Getty, I. Andersson, L. Pettersson, Dalton Trans. (2004) 2873-2882. [9] I. Andersson, A. Gorzsás, C. Kerezsi, I. Tóth, L. Pettersson, Dalton Trans. (2005) 3658-3666. [10] K. Elvingson, A. González Baró, L. Pettersson, Inorg. Chem. 35 (1996) 3388-3393. [11] A. González Baró, I. Andersson, L. Pettersson, A. Gorzsás, Dalton Trans. (2008) 1095-1102. [12] L. Pettersson, I. Andersson, A. Gorzsás, Coord. Chem. Rev. 237 (2003) 77-87.

Oral lectures


O12

Simple peroxovanadate-amino acid complexes

Takeshi Higuchia, Masato Hashimotoa and Seichi Okeyaa

aDepartment of Material Science and Chemistry, Faculty of Systems Engineering, Wakayama University, 930 Sakaedani, Wakayama 640-8510, Japan


Several peroxovanadate or peroxovanadium complexes have been investigated mainly from biological point of view, e.g. functional centre of haloperoxdase and insulin-mimetic properties. Many peroxovanadate-organic ligand systems have been analysed and a number of structural data of the complexes have been reported. However, according to CCDC databese, there have not been many structural reports on peroxovanadate-amino acid complexes with rather simple ligands. We therefore tried to examine formation and structural analyses of peroxovanadate complexes bearing simple amino acids such as glycine, L-alanine, L-(+)-arginine, L-gultaminic acid, L-histidine and L-cysteine. A nucleobase adenine was also chosen as a ligand. The formation of complexes in each peroxovanadate-ligand systems were monitored by 51V, 13C and 1H NMR (and 15N for glycinato complexes). Similar tendencies of complex formation were observed for the amino acids used except for L-gultaminic acid. Among the complexes detected a diperoxoglycinatovanadate complex, [VO(O2)2(gly)]2-, was isolated as calcium and

strontium salts, and the structure was determined. The crystals of these complex salts were soluble in water. The solubilities were enhanced by raising ionic strength of the solution up to 3.0 M by NaCl or KCl. The complex formation with adenine ligand has not been confirmed so far. The overall tendency of complex formation as well as results of characterisations of isolated complexes and analyses of behaviour of the complexes in solution after re-dissolution will be discussed. Zn(II) is known to be effective for the metabolic syndrome. Therefore researches on formation of Zn-V mixed metal complexes with some amino acids and adenine ligands and on isolation of the complexes formed are in progress. Formation of complexes were indicated by 51V NMR in the L-histidine system, but their nature has not been confirmed. The result of this attempt will also be discussed in the presentation. Details of some parts of this talk will be presented at the poster entitled ‘Syntheses and characterisation of novel [VO(O2)2L] (L=ligand) type complexes‘ presented by T. Higuchi.

Acknowledgements: The authors would like to thank Prof. Lage Pettersson, Umeå University, for his kind discussion and suggestions.

Oral lectures


O13

The Vanadium-MHCPE system: an evaluation towards bioavailability

Gisela Gonçalves,a João Costa Pessoa,a Isabel Tomaz,a,b M.Margarida C.A. Castro,c Carlos F.G.C. Geraldes,c Fernando Avecillad

aCentro de Química Estrutural, Instituto Superior Técnico – TU Lisbon, Av. Rovísco Pais,

1049-001 Lisbon – Portugal; bCentro de Ciências Moleculares e Materiais, Faculdade de Ciências da Universidade de Lisboa, Campo Grande 1749-016 Lisbon - Portugal; c Dpto. de Bioquímica e Centro de RMN, Universidade de Coimbra, 3001-401 Coimbra - Portugal; d Dpto. de Química Fundamental, Universidade da

Coruña, A Coruña 15071, Spain. email: [email protected]

The pharmacological potential of vanadium compounds has been demonstrated both in Diabetes mellitus treatment, and (more recently) in cancer therapy[1]. VIVO complexes of maltol and ethylmaltol are known for being currently under clinical trials for the oral treatment of type 2 diabetes[2]. Nevertheless the therapeutical use of vanadium-based compounds is still restrained by the full understanding of the factors that account for the performance of the bio-active entity. Vanadium absorption and possibly also its transport to the cells can be improved through coordination by an appropriate ligand thus improving chelating ability, hydrolytic stability and lipo-hydrophilic balance. However in vivo speciation does occur, and metal-protein binding in the plasma serum seems to relate to effectiveness, promoting the cellular uptake and eventualy improving the dose-response ratio[3]. Catecholate derivatives have been widely studied due to their importance as chelating subunits in several ionophores, and these ligands are effective candidates for the transport of vanadium into the cells. We report herein the characterization of vanadium systems with a pyrimidinone-type ligand, MHCPE (2-methyl-3H-5-hydroxy-6-carboxy-4-pyrimidinone ethyl ester), focusing on several factors that can interfere with its performance as a drug candidate. As expected, MHCPE is an efficient ligand for both V(IV) and V(V) in a wide pH range yielding stable and soluble complexes. Serum protein binding of the complexes is studied by Circular Dichroism (CD) and EPR. It is proposed that the MHCPE ligand improves the vanadium binding to apo-transferrin (hTF) as can be concluded from CD spectroscopy (e.g. Fig. 1).

-1

-0.5

0

0.5

400 500 600 700 800 900 1000

λ / nm

Δε

/ M-1cm

-1

hTFhTF:VO(IV):L (1:0.5:0.5)hTF:VO(IV):L (1:1:1)hTF:VO(IV):L (1:1.5:1.5)hTF:VO(IV):L (1:2:2)

Figure 1. Evolution of CD signal with increasing VIVO-MHCPE concentration

(pH 7.4 in HEPES buffer with 25 mM carbonate, [hTF]total= 750 μM; Δε values per mole of hTf present).

Acknowledgements: The authors wish to thank the portuguese Fundação para a Ciência e Tecnologia, (for grants SFRH/BD/32131/2006 and SFRH/BPD/34695/2007, FEDER, POCI 2010 program and project PPCDT/QUI/56949/2004), the Spanish-Portuguese Bilateral Programme (Joint Action E-56/05) and the University of La Coruña for financial support. [1] a) A.Evangelou, Crit.Rev.Oncology/Hematology, 2002, 42, 249-265; b) H.Sakurai, H.Yasui, Y.Adachi, Exp. Opin. Investig. Drugs, 2003, 12, 1189-1203. [2] K. H. Thompson, C. Orvig, J. Inorg. Biochem. 100 (2006) 1925-1935. [3] a) W.H.Ang, P.J.Dyson, Eur. J. Inorg. Chem, 2006, p4003-4018. b) K. Thompson, C. Orvig, 2006, J. Soc. Chem. Dalton Trans., 761-764; c) C. G. Hartinger, S. Zorbas-Seifried, M. A. Jakupec, B. Kynast, H. Zorbas, B. K. Keppler, J. Inorg. Biochem., 100 (2006) 891–904.

Oral lectures


O14

Comparative studies on the biospeciation of antidiabetic vanadium and zinc compounds

Tamás Kiss, Éva Anna Enyedy, Tamás Jakusch

Biocoordination Chemistry Research Group of the Hungarian Academy of Sciences, Department of Inorganic and Analytical Chemistry, University of Szeged, H-6701 Szeged, Hungary

e-mail: [email protected] Intensive studies have been carried out during the last two decades on the antidiabetic (AnD)

effects of several metal ions among others chromium, vanadium, tungsten and zinc. Vanadium

compounds seem to be the most effective, however their non-essential character is a great

disadvantage and their occurrence and potential accumulation in the organism may produce

strong aversion to their practical application. For this reason, the essential Zn compounds may

receive a more positive acceptance.

Due to the presence of numerous endogenous and exogenous metal ion binders the original

AnD complex may undergo transformations in the biological fluids and tissues and thus the real

biological/physiological activity may be bound to an entirely different chemical entity.

In order to say something about the actual solution state(s) of these metal ions during their

transport in the blood stream we studied their interactions with the relevant low molecular mass

(lmm) ligands, such as citrate, lactate, oxalate, phosphate, histidine and cysteine and high

molecular mass (hmm) protein components, such as albumin, transferrin and α-macroglobulin

of blood serum. In this work we give an overview of the work. Solution speciation and spectral

(EPR, UV-Vis) studies revealed that citrate for vanadium, while histidine and cysteine for zinc(II)

are the most important lmm binders, while transferrin for vanadium and α-macroglobulin and

albumin for zinc(II) are the most important hmm binders of the serum. Ultrafiltration studies

helped to separate and determine the two fractions bound metal content of the serum.

In vitro chromatographic separations made on human plasma confirmed our results obtained by

modeling speciation calculations.

Acknowledgements. This work was carried out in the frame of a COST and various bilateral collaborations with Portugese, Japanese and Spanish research groups and supported among others by the Hungarian Science Research Fund (OTKA T49417, NI61786 and PD 050011).

Oral lectures


O15

Vanadium complexes with polipyridyl ligands as potential antiprotozoa agents

Julio Benítez,a Lucía Guggeri,b Gabriel Arrambide,c Isabel Tomaz,c João Costa Pessoa,c Beatriz

Garat,b Dinorah Gambinoa

aCátedra de Química Inorgánica, Facultad de Química, UDELAR, Gral. Flores 2124, 11800 Montevideo, Uruguay; bLaboratorio de Interacciones Moleculares, Facultad de Ciencias, UDELAR, Igua 4225, 11400

Montevideo, Uruguay; cCentro Química Estrutural, IST, Av Rovisco Pais, 1049-001 Lisbon, Portugal email: [email protected]

Parasitic diseases represent a major health problem in Latin America. In particular, Chagas' disease (American Trypanosomiasis), caused by the protozoan parasite Trypanosoma cruzi, is the largest parasitic disease burden in the American continent. The morbidity and mortality associated with this disease are in America more than one order of magnitude higher than those caused by malaria, schistosomiasis or leishmaniasis. Chagas’ disease affects approximately 20 million people from southern United States to southern Argentina. Despite the progress achieved in the study of T. cruzi´s biochemistry and physiology, in which several potential new enzymatic drug targets have been identified, the chemotherapy of this parasitic infection remains undeveloped. The treatment is based on old and quite unspecific drugs that have significant activity only in the acute phase of the disease and give rise to severe side effects. In the search for new therapeutic tools against Chagas' disease metal complexes appear to be a promising approach. Through the strategy of including in a single molecule an organic bioactive ligand and a metal with pharmacological potentiality we have previously developed different bioactive metal complexes and studied their probable mechanism of action.1-4 It has been proposed that the metabolic pathways of kinetoplastid parasites (Leishmania and Trypanosoma parasites) are similar to those present in tumor cells and those compounds that efficiently interact with DNA, like intercalators, could show anti-trypanosomal activity. Under this hypothesis we synthesized, characterized and biologically evaluated vanadyl complexes with polypyridyl ligands capable of intercalate DNA. Vanadyl mixed-ligand complexes, VO(L1)(L2-2H), where L1 = dppz (dipyrido[3,2-a: 2’,3’-c]phenazine) or bipy (2,2’-bipyridine) and L2 = salicylaldehyde semicarbazone derivatives, and VO(dppz)(H2O)2(SO4) were synthesized. The complexes were characterized by elemental analyses, electrospray ionization mass spectrometry (ESI-MS), conductimetric and magnetic measurements and infrared (FTIR) and electronic paramagnetic resonance (EPR) spectroscopies. Complexes were tested on epimastigotes of T. cruzi, Dm28c strain. Results showed activity dependent on the nature of the ligands. Some of the compounds showed excellent antiprotozoal activity, similar to that of the reference drugs Nifurtimox and Benznidazol. Trying to provide insight into the mechanism of anti-trypanosomal action compounds were tested for their DNA interaction ability on plasmid DNA by using gel electrophoresis experiments. Acknowledgements: The authors would like to thank RIDIMEDCHAG CYTED network and Grants of Fonacit G-2005000827. DG would like to thank Technical University of Lisbon for financial support. [1] L. Otero, M. Vieites, L. Boiani, A. Denicola, C. Rigol, L. Opazo, C. Olea-Azar, J. D. Maya, A. Morello, R. Luise Krauth-Siegel, O. E. Piro, E. Castellano, M. González, D. Gambino, H. Cerecetto, J. Med. Chem 49 (2006) 3322-3331. [2] M. Vieites, L. Otero, D. Santos, D. Gajardo, J. Toloza, R. Figueroa, E. Norambuena, C. Olea-Azar, G. Aguirre, H. Cerecetto, M. González, A. Morello, J. D. Maya, B. Garat, D. Gambino, J. Inorg. Biochem. 102 (2008) 1033-1043. [3] C. Urquiola, M. Vieites, G. Aguirre, A. Marín, B. Solano, G. Arrambide, M. L. Lavaggi, M. H. Torre, M. González, A. Monge, D. Gambino, H. Cerecetto, Bioorg. Med. Chem. 14 (2006) 5503-5509. [4] M. Vieites, P. Smircich, B. Parajón-Costa, J. Rodríguez, V. Galaz, C. Olea-Azar, L. Otero, G. Aguirre, H. Cerecetto, M. González, A. Gómez-Barrio, B. Garat, D. Gambino, J. Biol. Inorg. Chem. doi: 10.1007/s00775-008-0358-7.

Oral lectures


O16

Oscillating reaction of a vanadium compound. II What triggers the chaotic reaction?

Kan Kanamori,a Keisuke Fujinami,a Yukie Sakai,a Kenji Kubo,b Naoki Wada,b Seiichi

Matsugo,b and Kenneth Kustinc

aDepartment of Chemistry, University of Toyama, Gofuku 3190, Toyama 930-8555, Japan, email: [email protected] ; bColledge of Science and Engineering, Kanazawa University, Japan;

cBrandeis University, Emeritus, USA.

In the last symposium1 we reported that a new type of oscillating reaction occurred when [V(IV)Cl2(bpy)] or [V(III)Cl3(CH3CN)(bpy)] was added to dichloromethane in a closed system. A similar reaction also occurred for their phenanthroline (phen) analogues. It has been demonstrated that the oscillating color change betwen light green and dark orange is due to a redox reaction between V(IV) and V(V) states and formaldehyde. The latter is a contaminant of dichloromethane; it works as a reducing agent and dissolved oxygen as an oxidizing agent. The color change occurs chaotically rather than periodically, and we have examined what triggers the chaotic reaction. A small temperature change in the reaction system was found to be one of the factors that acts as a trigger. Figure 1 shows the change in darkness of the color of the reaction solution and of the ambient temperature as a function of time. Darkness of the solution was measured by analyzing the darkness of pixels of captured video frames using a graphic software program (Canvas 6). As shown in Fig. 1, there is a tendency to develop the dark orange color when the temperature decreases. However, this phenomenon is not due to thermochromism, because (1) an average temperature does not relate to the color change, and (2) the color change occurred even when the temperature change was negligible. This observation may indicate that a temperature decrease in the solution resulted in an increase of the concentration of dissolved oxygen, and as a result the oxidation reaction from V(IV) to V(V) was promoted.

Figure 1. Temperature-dependent oscillating pattern for [V(IV)OCl2(bpy)] (0.55 mM in CH2Cl2).

Irradiation of UV light was also found to trigger the chaotic reaction. When UV light was irradiated on the reaction solution, the dark orange color developed immediately, and the color of the solution returned to light green when the irradiation was stopped. Irradiation for a long period resulted in prevention of the reduction of the orange species, indicating a decomposition of reducing species present in the solution. [1] K. Kanamori and Y. Shirosaka, “ACS Symposium Series 974, Vanadium: The Versatile Metal”, Eds by

K. Kustin, J. Costa Pessoa, and D. C. Crans, American Chemical Society, 2007, pp. 424-432.

Oral lectures


O17

New ternary and binary species in the structural speciation of insulin mimetic vanadium(V) in the presence of the physiological citrate and

hydrogen peroxide

Athanasios Salifoglou, Catherine Gabriel

Department of Chemical Engineering, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece email: [email protected]

Vanadium has in the past years been investigated for its insulin mimetic capacity1. The underlying premise in this endeavor has been the fundamental chemical reactivity of vanadium to promote interactions with biotargets key to the uptake and catabolism of glucose. Poised to comprehend the molecular chemistry of vanadium to promote interactions with low and high molecular mass substrates, research efforts have been launched in our lab to investigate the requisite chemistry at the cellular level. To this end, starting reagents containing vanadium in the two biologically relevant oxidations states V(IV.V) have been employed in reactions involving the physiological α-hydroxycarboxylic acids (citric and malic) under pH-dependent conditions.2 Guided by the existing aqueous speciation schemes of the relevant binary systems, synthetic efforts led to the isolation of new V(IV,V)-citrate compounds [VV

2O4(C6HxO7)2]n-

(x=4,5,6; n=6,4,2), and [VIV2O4(C6HxO7)(C6H4O7)]

n- (x=4,5; n=4,3) in the solid state.3 Further reactivity toward the physiological reagent H2O2 led to the synthesis and isolation of ternary V(V)-peroxo-citrate complexes [VV

2O2(O2)2(C6HxO7)2]n- (x=2,4; n=2,6) and their corresponding

malate analogs. The derived materials were characterized by numerous spectroscopic (FT-IR, UV-Visible, multinuclear solid state and solution NMR), electrochemical (cyclic voltammetric), and ultimately X-ray crystallographic techniques. The structural characterization of these species denotes the variable coordination geometries of V(V) and V(IV) interacting with citrate and malate. Consistent with these is the chemical reactivity (Figure 1) of the aforementioned systems in acid-base chemical and thermally induced transformations. Collectively, the physicochemical properties of all investigated systems emphasizes the importance of pH-dependent chemical reactivity of binary and ternary vanadium systems with low molecular mass ligands in the structural speciation of vanadium, in biologically relevant fluids, and its potential involvement in chemistries linking the biologically relevant V(IV,V) oxidation states with insulin mimesis.

Figure 1. Acid-base transformation of pH-structural V(V)-peroxo-citrate structural variants. Acknowledgements: This work was supported by and by a ‘‘PENED” grant co-financed by the E.U.-European Social Fund (75%) and the Greek Ministry of Development-GSRT (25%). [1] a) H. Sakurai, Y. Kojima, Y. Yoshikawa, K. Kawabe, H. Yasui, Coord. Chem. Rev. 226(2002) 187-198. b) T. Sasagawa, Y. Yoshikawa, K. Kawabe, H. Sakurai, Y. Kojima, J. Inorg. Biochem. 88(2002) 108-112.c) K. Kanamori, K. Nishida, N. Miyata, K. Okamoto, Y. Miyoshi, A. Tamura, H. Sakurai, J. Inorg. Biochem. 86(2001) 649-656. [2] M. Tsaramyrsi, M. Kaliva, T. Giannadaki, C. P. Raptopoulou, V. Tangoulis, A. Terzis, J. Giapintzakis, A. Salifoglou, Inorg. Chem. 40(2001) 5772. [3] M. Kaliva, C. P. Raptopoulou, A. Terzis, A. Salifoglou, Inorg. Chem. 43(2004) 2895-2905.

pH ~3.5

Oral lectures


O18

Stereospecific formation of dinuclear vanadium(V) tartrato complexes

Peter Schwendt,a Michal Sivák,a Jana Gáliková,a Jozef Tatiersky,a Zdirad Žák,b

aDepartment of Inorganic Chemistry, Comenius University, Faculty of Natural Sciences, Mlynská dolina, 842 15 Bratislava, Slovak Republic b Department of Inorganic Chemistry, Masaryk University

Faculty of Natural Sciences, Brno, Czech Republic email: [email protected]

A study of the aqueous H3O

+ (OH–) / H2VO4– /2R,3R-tartrate system1 revealed that besides a

series of minor species, two species are dominant in acidic solutions: [V4O8(R,R-tart)2]4– (1)

(tart = C4H2O64–; –524 ppm in 51V NMR spectrum) and dinuclear species formulated as “V2L2” (–

550 ppm). The species 1 was characterized in the solid state by X-ray diffraction of the tetraethylammonium salt and an interesting tetranuclear structure was found. Using racemic tartaric acid for the synthesis the compound Na8[V4O8(R,R-tart)2][V4O8(S,S-tart)2] · 24H2O was isolated and characterized by X-ray diffraction as a typical racemic compound. We made efforts to characterize also the “V2L2” species. After many attempts we isolated and structurally characterized the yellow compound (N(CH3)4)2[V2O4(R,R-H2tart)2] · 6H2O (2) (Figure 1). When using racemic tartaric acid for synthesis the red compounds (NR4)2[V2O2(R,R-tart)(S,S-tart)] (R = N(CH3)4 – 3; R = N(C2H5)4 – 4) with a profoundly different structure of the anion (Figure 2) were obtained.

V

O

OOH

O

O

O

O

V

O

O

OO

OH O

O

O

O

H

H

R

R R

R

2–

[V2O4(R,R-H2tart)2]2–

yellow

V

O

OO

OO

OO

V

O

OO

OO

OO

R

R

S

S

2–

[V2O2(R,R-tart)(S,S-tart)]2–

red Figure 1. The structure of the anion in 2. Figure 2. The structure of the anion in 3.

The compounds 2 – 4 crystallized out of water-ethanol media. In the aqueous solution the reaction (1) took place

2[V2O2(R,R-tart)(S,S-tart)]2– + 4H2O → [V2O4(R,R-H2tart)2]2– + [V2O4(S,S-H2tart)2]

2– (1) as proved by spectroscopic methods (51V NMR, Raman and UV-VIS spectra measured for H2O, CH3CN and mixed H2O – CH3CN solutions of 2, 3 and 4).

Acknowledgements: The authors would like to thank the Ministry of Education of the Slovak Republic (grant VEGA 1/4462/07) for the financial support. NMR measurements were performed on the equipment supported by the Slovak State Programme Project No. 2003SP200280203. [1] P. Schwendt, A. S. Tracey, J. Tatiersky, J. Gáliková, Z. Žák, Inorg. Chem. 46 (2007) 3971-3983.

Oral lectures


O19

Chemical and biochemical studies of a 5-hydroxy-4-pyrimidinone V(V) complex

M. Margarida Castroa,b, F. Avecillac, I. Tomazd, G. Gonçalvesd, H. Fanecaa,b,

L. Palacioc, M. Maestroc, M.C.P. Limaa,b, C.F.G.C. Geraldesa,b and João Costa Pessoad a Dpt. of Biochemistry b Center of Neuroscience and Cell Biology; University of Coimbra, 3001-401 Coimbra,

Portugal; email: [email protected] c Dpt. of Fundamental Chemistry, University of A Coruña, A Coruña, Spain;

d Center of Structural Chemistry, Instituto Superior Técnico, TU Lisbon, 1049-001, Lisbon, Portugal,

The importance of Vanadium Compounds (VCs) has greatly increased in the last years since they have shown pharmacological properties, in diabetes and cancer therapy. VCs exhibit anti-cancer activity1 and their potential use as oral insulin mimetics2 has been demonstrated by in vivo and ex vivo studies, as well as in clinical trials. At the present stage the use of VCs as therapeutic agents is limited by the narrow range between beneficial and toxic effects. Thus V(IV) and V(V) complexes containing adequate ligands have been synthesized searching for properties to improve their pharmacological action, such as hydrolytic stability, water solubility, neutral charge and/or lipophilicity, low toxicity and antidiabetic or anticancer activity.3 In this work we report a study of the interaction in aqueous solution of vanadate with a pyrimidinone ligand, the 2-methyl-3H-5-hydroxy-6-carboxy-4-pyrimidinone ethyl ester (MHCPE). Potentiometry and 51V NMR spectroscopy were used to identify and structurally characterize the species formed in solution at different M/L ratios and pH values and the respective formation constants were determined. The results obtained indicated the formation of two main species with stoichiometries 1:1, (VVO2)L, and 1:2 (VVO2)L2 and their most probable binding modes were established according to spectroscopic data. The solution behaviour of these main V(V) species at physiological pH and in different cell culture media was also studied, showing some favorable properties concerning solubility and stability. Their cytotoxic effects were tested in the HeLa tumor cell line and the 3T3-L1 cell line and were demonstrated to be concentration- and time- dependent, being correlated with VC cellular uptake.

Acknowledgements: This work was carried out in the frame of a COST D21 Project. The authors thank the

financial support from FEDER and Fundação para a Ciência e Tecnologia (FCT), Portugal, POCI 2010, Project PPCDT/QUI/56949/2004, the Spanish-Portuguese Bilateral Programme (Acção Integrada E-56/05) and University of A Coruña. [1] M.S.Molinuevo, D.A.Barrio, A.M.Cortizo et al., Cancer Chemotherapy and Pharmacol. 53 (2004) 163-172 [2] H. Sakurai, Y. Kojima, Y. Yoshikawa, K. Kawabe, H. Yasui, Coord. Chem. Rev. 226 (2002) 187-198. [3] D. C. Crans, J. J. Smee, E. Gaidamauskas, L. Yang, Chem. Rev. 104 (2004) 849-902.

Oral lectures


O20

How lipids interfaces affect the coordination chemistry of vanadium compounds

Debbie C. Crans

Department of Chemistry, Colorado State University, Fort Collins, Colorado 80523


As a early transition metal vanadium is small and much of its chemistry is governed by ligand

size and geometry, and this presentation will explore how much a lipid/surface environment can

affect this chemistry. Multiple examples exist of vanadium compounds being able to expand

coordination number and complex with incoming ligands. The increase in coordination number

of the five coordinate triethanolamine complex with vanadate upon addition of an ethanol ligand

generates a six coordinate complex.[1] The four coordinate ethylene glycol complex that forms

upon addition to VOCl3 [2] can expand to a five coordinate species when the alkyl groups are

introduced on the ethylene glycol ligand.[3] The addition of a sixth ligand to the five coordinate

VO(acac)2 [4] and BMOV (bismaltolatooxovanadium(IV)) [5] occurs when dissolved in aqueous

or other polar media. The addition of hydroxylamine derivatives to the dioxodipicolinato

oxovanadium(V) expands the five coordinate vanadium to a seven coordinate species.[6].

Surface interactions are found to affect the properties of simple compounds such as ascorbic

acid, that is much more resistant to reduction in a microemulsion environment [7]. We have

recently been interested in examining the effects of such environments not only on reactivity

but also on the stability and geometry of vanadium coordination compounds. Acknowledgement. We thank the Luso-American Development Foundation for partial travel funds. We also

thank NSF for funding this research.

[1] D. C. Crans, H. Chen, O. P. Anderson and M. M. Miller, J. Am. Chem. Soc. 115 (1993) 6769-6776. [2] D. C. Crans, R. A. Felty, O. P. Anderson and M. M. Miller, Inorg. Chem. 32 (1993) 247-248. [3] D. C. Crans, R. A. Felty and M. M. Miller, J. Am. Chem. Soc. 113 (1991) 265-269. [4] S. S. Amin, K. Cryer, B. Y. Zhang, S. K. Dutta, S. S. Eaton, O. P. Anderson, S. M. Miller, B. A. Reul, S. M. Brichard and D. C. Crans, Inorg. Chem. 39 (2000) 406-416. [5] P. Caravan, L. Gelmini, N. Glover, F. G. Herring, H. L. Li, J. H. McNeill, S. J. Rettig, I. A. Setyawati, E. Shuter, Y. Sun, A. S. Tracey, V. G. Yuen and C. Orvig, J. Am. Chem. Soc. 117 (1995) 12759-12770. [6] J. J. Smee, J. A. Epps, G. Teissedre, M. Maes, N. Harding, L. Yang, B. Baruah, S. M. Miller, O. P. Anderson, G. R. Willsky and D. C. Crans, Inorg. Chem. 46 (2007) 9827-9840. [7] D. C. Crans, B. Baruah, E. Gaidamauskas, B. G. Lemons, B. B. Lorenz, M. D. Johnson, J. Inorg. Biochem. 102 (2008) 1334-1347.

Oral lectures


O21

Development of anti-diabetic vanadium complexes and analysis of their molecular mechanism

Hiromu Sakuraia* and Makoto Hiromurab

a* Faculty of Pharmaceutical Sciences, Suzuka University of Medical Science,

3500-3 Minani-Tamagaki-cho, Suzuka, Mie 513-0816, Japan, E-mail: [email protected] b Metallomics Research Unit, RIKEN 2-1 Hirosawa, Wako, Saitama 351-0198, Japan

e-mail: [email protected] There has been a dramatic worldwide increase in the prevalence of metabolic syndromes involving diabetes mellitus (DM) since the 20th century. To overcome the defects of clinically available pharmaceuticals to treat types 1 and 2 DM, new potent vanadium compounds with +3, +4 and +5 oxidation states have been proposed by many researchers. Since 1990, our group has proposed several types of vanadyl (+4, VO2+) complexes with different coordination environments around vanadium in terms of high anti-diabetic activity, low toxicity, and high bioavailability, that are supported by metallokinetic analysis using BCM-EPR, in types 1 and 2 model animals. Based on the study of structure-activity relationship in vanadyl complexes with picolinate and 3-hydroxy-pyronate as leading compounds, we recently found that vanadyl complexes of 4X-picolinate (X = electron donating and withdrawing substituent) and allixin (alx) are the most potent anti-diabetic complexes. We thus analyzed the molecular mechanism of such complexes with respect to the insulin signaling pathway in cultured adipocytes. The common mechanism of vanadyl complexes have been found to involve the induction of the Akt/PKB and IRβ or PTPase activities leading to the translocation of GLUT4 to the cell membrane. In addition, vanadyl-alx complex regulates the activation of the FoxO transcription factor, which controls the gene expression of G-6-Pase and PEPCK. The obtained results will provide us the development method of novel and more active anti-diabetic vanadyl complexes. Acknowledgements: This study was supported by a Grant-in-Aid for Specially Promoted Research from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of the Japanese Government to H.S. H. Sakurai, Expert Opin. Drug Discov. (2007) 2, 873-887.

Oral lectures


O22

Chemical and biological variability in anti-diabetic and anti-apoptotic effects of vanadium complexes

Gail R. Willsky a, Michael Godzala III a, Paul J. Kostyniak a, Barbara A. Bistram a,

Rebecca Z. Grayson a, Lai-Har Chi a, Martha Clark a, Jason J. Smee b, Debbie C. Crans b

aUniversity at Buffalo (SUNY), Buffalo, NY 14214. USA. b Department of Chemistry, Colorado State University, Ft. Collins CO 80523 USA, email: [email protected]

The biological effects of vanadium (V) vary greatly as the chemical environment of the V or the biological system is modified1. We have previously reported the anti-diabetic effects of V dipicolinic acid complexes with different oxidation states2. We here report the result of modifications of the dipicolinic acid ligand environment on the effects of treatment with V-compounds in oxidation state +5 on hyperglycemia and hyperlipidemia in STZ-diabetic rats. The four V complexes tested in this study are shown in Figure 1 and deviate in structure and electronic properties. Administration of [V(V)O2(dipic)]- lowered diabetic hyperglycemia to levels close to normal, while administration of the other V complexes had a small but often significant effect in lowering the elevated blood glucose. Treatments with all complexes were effective in significantly lowering diabetic hyperlipidemia to near normal levels, as monitored by measurement of serum cholesterol, triglycerides and free fatty acids. The most effective V complex in lowering diabetic hyperlipidemia was [V(V)O(dipic-OH)(NH2O)] which lowered free fatty acids and triglycerides to below normal levels levels and cholesterol to near normal levels.

These results show that subtle alterations of the V environment in dipicolinic acid complexes with the same

+5 oxidation state have a significant effect on the anti-diabetic properties of the metal.

Figure 1. V complexes used in the study of diabetic rats

The effects of changes of the biological system were also monitored using the simple salt vanadate, V(V) in two cell culture systems and the details are given in a separate presentation. V inhibited cell growth in muscle myoblasts (L6) and rat hepatoma cells (H4IIE) cells, affecting cell adhesion before killing the cells. V treatment induced apopoptosis in muscle cells; but not in liver cells. The differences observed appear to be directly related to the different cell types since V as the simple salt vanadate in the +5 oxidation state was administed to both cell lines and the cells were grown in the same type of medium. These results imply that V growth inhibition is mediated via the apoptotic pathway in muscle but not in liver. Varying effects on biological endpoints of V in different tissues and the effects of modification of the V complex, can be effectively used when designing potential therapeutic V compounds. Acknowledgements: We thank the NIH and Luso-American Development Foundation for financial support. [1] A.Tracey,G. Willsky, E.Takeuchi, (2007) Vanadium: Chemistry, Biochemistry, Pharmacology and Technical Applications, CRC Press , Boca Raton FL. 250 pp. [2] P. Buglyó, D. Crans, E. Nagy, R. Lindo, L. Yang, J. Smee, W. Jin, L.-H. Chi, M. Godzala III, and G. Willsky, Inorgan. Chem. 44 (2005)5416-5427.

[V(V)O2(dipic)]-

[V(V)O2(dipic-OH]-

N

O

V

OO

O

O

OM +

M + = NH 4+, Na + , K +

N

O

V

OO

O

O

OM+

M+ = NH4+, Na+

HO

N

O

V

OO

O

OO

H2ON

CH3

CH3

N

O

V

OO

O

OOHO

H2ONH2

[V(V)O(dipic)NMe2O)]

[V(V)O(dipic-OH)(NH2O)]

Oral lectures


O23

Coordination of oxovanadium(IV) to human serum apo-transferrin: a calorimetric comparison study

Chris Orvig,a Khalegh Bordbar,a,b A. Louise Creagh,c Cheri A. Barta,a Katherine H.

Thompson,a Charles A. Haynesd

a Medicinal Inorganic Chemistry Group, Department of Chemistry, University of British Columbia, Vancouver,

BC, V6T 1Z1 Canada; b Present address: Department of Chemistry, Isfahan University, Isfahan, 81746-73441, I.R. Iran; c Centre for BioThermodynamics, Laboratory for Molecular Biophysics, University of British Columbia, Vancouver, BC V6T 1Z4 Canada; d Michael Smith Laboratories and the Department of Chemical

and Biological Engineering, University of British Columbia, Vancouver, BC V6T 1Z4 Canada. email: [email protected]

Bis(maltolato)oxovanadium(IV) (BMOV), and its ethylmaltol analog, bis(ethylmaltolato)-oxovanadium(IV) (BEOV), are candidate insulin-enhancing agents for the treatment of type 2 diabetes mellitus;1 BEOV is currently undergoing phase IIa trials. Results of previous solution studies of the interaction of BMOV with the most common plasma proteins apo-transferrin and (to a lesser extent) albumin indicated an in vivo biomolecular transformation that favors small molecule, readily dissociable, binding for optimal pharmacological efficacy.2 In order to rule out intact binding by complexed vanadium, as in BMOV, to apo-transferrin, we have undertaken a thorough calorimetric determination of heats of association, comparing binding of BMOV to that of vanadyl ion V(IV), and its oxidized counterpart, vanadate ion V(V). Differential scanning calorimetry (DSC) thermograms obtained for all three transferrin-ligand complexes were superimposable. We can conclude from these studies that BMOV dissociates rapidly under the aerobic conditions of calorimetric determination of formation constants, and that the vanadyl ions readily oxidize to vanadate ions. Thus, the formation constant obtained is for vanadate-transferrin binding, and is not strictly relevant to the physiological biodistribution of BMOV. The DSC derived binding constants, both in the range of log K ≈ 5 for vanadate-transferrin binding, are consistent with earlier EPR studies of 0.1 M vanadate binding to apo-transferrin at pH 7.4 at 25° C.3

Acknowledgement is made to NSERC and CIHR (both of Canada) for funding. [1] K. H. Thompson, C. Orvig, J. Inorg. Biochem. 100 (2006) 1925-1935. [2] B. D. Liboiron, K. H. Thompson, G. R. Hanson, E. Lam, N. Aebischer, C. Orvig, J. Am. Chem. Soc. 127 (2005) 5104-5115. [3] W. R. Harris, C. J. Carrano, J. Inorg. Biochem. 22 (1984) 201-218.

Oral lectures


O24

VO(IV) complexes of maltol and ethylmaltol for oral treatment of type 2 diabetes mellitus: lessons from speciation studies and phase I and II

clinical trials

Katherine H. Thompson,a Paloma F. Salas,a John H. McNeill,b Jay B. Lichter,c Michael S. Scaife,c Chris Orviga

aMedicinal Inorganic Chemistry Group, Department of Chemistry, University of British Columbia, 2036 Main Mall, Vancouver, BC, Canada V6T 1Z1; bFaculty of Pharmaceutical Sciences, University of British Columbia, 2146 East Mall, Vancouver, BC, Canada V6T 1Z3; Akesis Pharmaceuticals, Inc., La Jolla, CA, USA 93037


3-Hydroxy-2-methyl-4-pyrone and 2-ethyl-3-hydroxy-4-pyrone (maltol and ethylmaltol, respectively) have proven especially suitable as ligands for vanadyl ions, with the resultant compounds having the desired intermediate stability for prodrug use. Both bis(maltolato)oxovanadium(IV) (BMOV), and the ethylmaltol analog, bis(ethylmaltolato)oxovanadium(IV) (BEOV), are candidate insulin-enhancing agents for the treatment of type 2 diabetes mellitus.1 BEOV has successfully completed phase I clinical trials and is now undergoing phase IIa trials. In preliminary data from the phase II trial, fasting blood glucose (FBG) of some treated diabetic subjects has been observed to decrease markedly. BEOV is being orally administrated at a dose of 20 mg once per day. In one case, a subject had a baseline of 276 mg/dl and dropped to 130 mg/dl after 7 days of treatment. Additional data will be presented. In human volunteers (phase I trial), feeding a standard breakfast immediately following oral dosing with 75 mg BEOV (11 mg V) resulted in an order of magnitude lower maximal concentration of vanadium in serum, when compared to fasted subjects (Cmax= 34.0 ± 25.1 ng/mL vs. 426.1 ± 126.6 ng/mL, fed vs. fasted, respectively, p < 0.0001). Availability of stored vanadium, based on our previous studies of biodistribution and speciation of orally administered BMOV and BEOV,2 will thus vary widely depending on interaction with ligands in food, or lack thereof. A re-examination of these results in light of current Upper Limits of Intake (IOM, FNB) guidelines will be considered. Acknowledgements: The authors would like to thank the Natural Sciences and Engineering Research Council of Canada (NSERC) and Akesis Pharmaceuticals, Inc. for funding. [1] K. H. Thompson, C. Orvig, Vanadium in Diabetes: 100 Years from Phase 0 to Phase I, J. Inorg. Biochem. 100 (2006) 1925-1935. [2] K. H. Thompson, B. D. Liboiron, G. R. Hanson, C. Orvig, In Vivo Coordination Chemistry and Biolocalization of Bis(ligand)oxovanadium(IV) Complexes for Diabetes Treatment, In: Medicinal Inorganic Chemistry (J. L. Sessler, S. R. Doctrow, T. J. McMurry, S. J. Lippard, Eds.) ACS Symposium Series, Vol. 903 (2005) 384-399.

Oral lectures


O25

Evaluation of insulin-mimetic activities of vanadyl complexes from the viewpoint of heterocyclic bidentate ligands

Akira Katoh,a Yuriko Matsumura,a Yutaka Yoshikawa,b Hiroyuki Yasui,b

and Hiromu Sakuraic

a Department of Materials and Life Science, Seikei University, Kichijoji, Musashino-shi, Tokyo 180-8633, Japan, b Department of Analytical and Bioinorganic Chemistry, Kyoto Pharmaceutical University, Misasagi, Kyoto 607-8414, Japan , and c Faculty of Pharmaceutical Sciences, Suzuka University of Medical Science,

3500-3 Minami-Tamagaki-cho, Suzuka, Mie 510-0293, Japan. e-mail: [email protected]

The numbers of patients that suffer from diabetes mellitus (DM) in the world have been

forecasted to increase to approximately 333 million in 2025 from 194 million in 2003.

Untreated DM sometimes causes many severe secondary complications and ocular disorders.

The available treatments for both type 1 and 2 DM have undesirable defects. Therefore, the

developments of new synthetic therapeutics are being explored to improve the lives of diabetic

patients. Over a decade we focused on heterocycles such as hydroxymonoazines,

hydroxydiazines, and 3-hydroxy- thiazole-2(3H)-thiones as bidentate ligands toward a vanadyl

ion. In this paper, we would like to review on synthesis of vanadyl complexes of various

heterocycles and their insulin-mimetic activities.

The following points became clear [1-7]; a) a vanadyl complex with heterocycle 1 showed

the highest insulin-mimetic activity in terms of IC50 value, which is a 50% inhibitory

concentration of the free fatty acid release from isolated rat adipocytes, among four kinds of

vanadyl complexes with heterocycles 1-4, b) blood glucose levels in STZ-induced diabetic rats

apparently were lowered from hyperglycemic to subnormal levels after treatment of vadadyl

complex with 1, c) vanadyl complexes with heterocycles 5 exhibited in vitro insulin-mimetic

activities, in which a correlation between the activity and the Hammett’s substituent constants

of R was found, d) the activity of vanadyl complexes with heterocycles 6 and 7 could not be

observed because they are insoluble in KRB buffer, and e) by plotting IC50 values vs. molecular

weights of 63 samples of vanadyl complexes, it was found that two vanadyl complexes with

molecular weights higher than 1000 (porphyrin structure) showed insulin- mimetic activities and

that a large number of vanadyl complexes with molecular weights of 300~400 showed high

insulin-mimetic activities in terms of IC50 values.

X

Y X

YV

vanadyl complexes

Figure 1 Plots of IC50 values vs. molecular weights of vanadyl complexes

O

N

N

OMe

Me

OH1

N O

OH

Me 2

N S

OH

R 7

N

O

MeMe

OH

3

N

N Me

OOH

Me

Me4

N

SS

OHR 5

N S

OHMe

R

6

0

0.5

1

1.5

2

2.5

3

3.5

4

4.5

0 200 400 600 800 1000 1200 1400M olecular W eight

IC50 (mM)

[1-7] A. Katoh et al.: Chem. Lett. 29, 866-867 (2000), 31, 114-115 (2002), and 33, 1274-1275 (2004); Heterocycles, 60, 1147-1159 (2003), 73, 603-615 (2007); J. Inorg. Biochem., 100, 260-269 (2006), Bull. Chem. Soc. Jpn.(Accounts), 79, 1645-1664 (2006).

Oral lectures


O26

The insulin-mimetic properties of vanadium with its effects on the gene expression profiling of the insulin signaling pathway in diabetic

mellitus

Wenjun Ding,a Dan Wei, Ming Li, Jianhong Yang

a College of Life Sciences, Graduate University of Chinese Academy of Sciences, No. 19A Yuquan Road,

Beijing 100049, P. R. China email: [email protected]

The insulin-mimetic properties and antidiabetic effects of vanadium compounds have been widely documented. Vanadium and its compounds stimulate glucose transport and oxidation, glycogen synthesis, lipogenesis, and they inhibit lipolysis and gluconeogenesis. In vitro and in vivo studies demonstrated that vanadium has a clear role in the effect on the insulin signaling pathway, such as increases of insulin receptor binding, stimulation of down-regulation of insulin receptors, inhibition of protein phosphotyrosine phosphatases, activation of nonreceptor protein tyrosine kinases and inhibition of glucose-6-phosphatase. Vanadium compounds appear to have a profound impact on insulin action through the insulin signaling cascade, but the underlying mechanism is not fully understood. Several previous studies also showed that the gene transcripts were up-regulated in diabetic rats. It has been reported that the activities of MAPK, ERK1/2 and S6 kinase were stimulated by vanadyl sulphate. Also, the PI3K pathway in vivo and in vitro was activated by vanadium compounds. In vitro studies showed that vanadium compounds could increase ERK1/2 protein level and inhibit cell proliferation via the MAPK pathway in a dose-response manner. In our previous study, of 96 genes surveyed, transcriptional patterns of 19 genes (20%) showed alterations in diabetic rats compared with controls. Although most of these changed gene expressions were improved after treatment with NaVO3 (14, 74%) and insulin (16, 84%), NaVO3 and insulin treatment resulted in the alteration of 20 and 12 additional gene transcripts compared with no treatment. Comparison of the gene expression profiling indicates that there is a significant difference between the NaVO3-treated group and the insulin-treated group. Several candidate genes of the insulin signaling pathway involved in the effect of vanadium treatment on hyperglycemia. We believe that these findings in the gene expression advance the current of level of understanding of glucose-lowering action of vanadium in diabetes mellitus. Acknowledgements: The authors acknowledge the financial support received from NSFC (20571084) and “Hundred Talents Program” of CAS. [1] M. Z. Mehdi, S. K. Pandey, J. F. Theberge, et al, Cell Biochem Biophys 44 (2006) 73-81 [2] H. Sakurai, K. Tsuchiya, M. Nukatsuka, et al, J. Endocrinol. 126(1990) 451-459 [3] R. Sreekumar, P. Halvatsiotis, J. C. Schimke, K.S. Nair, Diabetes 51(2002) 1913-1920 [4] G. Willsky, L. Chi, Y. Liang, D. Gaile, Z. Hu, D. Crans, Physiol Genomics 26(2006) 192-201 [5] J. H. McNeill, H. L.Delgatty, M. L. Battell, Diabetes 40(1991) 1675-1678

Oral lectures


O27

Arylalkylamine vanadium salts as a new generation of antidiabetic

compounds

Antonio Zorzano

Institute for Research in Biomedicine. Universitat de Barcelona. CIBERDEM.

Vanadium compounds show insulin-like effects which has been demonstrated both in vivo and in vitro. The most widely studied compounds in animal models are vanadyl sulfate and sodium orthovanadate. Some clinical studies have been performed using vanadium compounds and they have shown efficacy in type 2 diabetic subjects. A major concern is safety, which calls for the development of more potent vanadium compounds. The semicarbazide-sensitive amine oxidase (SSAO)/vascular adhesion protein-1 (VAP-1) is a bifunctional membrane protein highly expressed in adipose cells. On one hand, SSAO/VAP-1 is a copper-containing ectoenzyme with amine oxidase activity and produces hydrogen peroxide. On the other hand, SSAO/VAP-1 is an inflammation-inducible endothelial molecule involved in leukocyte subtype-specific rolling under physiological shear. In this regard, substrates of SSAO, such as benzylamine, in combination with low concentrations of vanadate strongly stimulate glucose transport and GLUT4 recruitment in 3T3-L1 and rat adipocytes and show antidiabetic effects in different animal models of diabetes. Chronic administration of benzylamine and vanadate exerts potent antidiabetic effects in streptozotocin (STZ)-induced diabetic rats or in Goto-Kakizaki diabetic rats. As far as mechanisms of action, we have found that benzylamine/vanadate causes enhanced tyrosine phosphorylation of proteins and reduced protein tyrosine phosphatase activity in adipocytes. In addition, incubation of human recombinant SSAO, benzylamine, and vanadate generates peroxovanadium compounds in vitro. Based on these data, we have proposed that benzylamine/vanadate administration generates peroxovanadium locally in pancreatic islets, which stimulates insulin secretion and also produces peroxovanadium in adipose tissue, activating glucose metabolism in adipocytes and in neighboring muscle. This opens the possibility of using the SSAO/VAP-1 activity as a local generator of protein tyrosine phosphatase inhibitors in antidiabetic therapy. We have recently characterized a novel class of arylalkylamine vanadium salts that exert potent insulin-mimetic effects downstream of the insulin receptor in adipocytes. These compounds trigger insulin signaling, which is characterized by rapid activation of insulin receptor substrate-1, Akt, and glycogen synthase kinase-3 independent of insulin receptor phosphorylation. Administration of these compounds to STZ diabetic rats or to ob/ob mice lowered glycemia and normalized the plasma lipid profile. In addition, arylalkylamine vanadium salts exerted antidiabetic effects in STZ-diabetic rats with undetectable levels of plasma insulin. The use of arylalkylamine vanadium salts represents a novel therapeutic approach in diabetes.

Oral lectures


O28

Can Vanadyl chelates help to detect cancer?

Marvin W. Makinena, Shengrong Shena, Suzanne D. Conzenb, Antonio J. Machado IIc,

Dong Yund, Qing Guo Xiec, Chien-Min Kaoc, and Chin-Tu Chenc

aDepartment of Biochemistry & Molecular Biology, bSection on Hematology & Oncology, Department of

Medicine, cDepartment of Radiology, The University of Chicago, Chicago, Illinois 60637 and dDepartment of Biomedical Engineering, Illinois Institute of Technology, Chicago, Illinois 60616 USA


Detection of malignant tumors by positron emission tomography (PET) with 2-(fluorine-18)-2-deoxy-D-glucose (FDG) as the tracer molecule is based on the high rate of glucose uptake and increased glycolytic activity associated with cancer. In the clinical setting, PET detection of neo-plasms is dependent on the intensity contrast between tumor sites and surrounding normal tissue and is generally limited to tumors of ca. 10 mm in maximum dimension. Increased FDG uptake by neoplastic tissue could lead to improved detection of small tumors and enhanced diagnostic capability. To this end we have investigated the capacity of

bis(acetylacetonato)oxovanadium(IV) [VO-(acac)2] to increase uptake of FDG by cultured MDA-

MB-231 cells, a well defined breast carcinoma cell line. MDA-MB-231 cells, grown in Dulbecco’s modified Eagle medium and Ham's F-12 containing 10% (v/v) fetal calf serum, penicillin, streptomycin, D-glucose, vitamins, salts, and essential amino acids, were trypsinized and transferred to Krebs-Ringer buffer containing 0.3 mM BSA and varying concentrations of D-glucose according to assay conditions. In contrast to cultured 3T3-L1 adipocytes [J. Biol. Inorg. Chem. 2005, 10, 874-886], SDS PAGE and phosphotyrosine immunoblots showed only low levels of phosphorylated insulin receptor and insulin receptor substrate-1 when MDA-MB-

231 cells were incubated in the presence of 1–300 nM insulin. Addition of 50–250 µM VO(acac)2

markedly increased the levels of these tyrosine phosphorylated proteins. The uptake of radioactive FDG by MDA-MB-231 cells in the absence of D-glucose showed that 100 µM

VO(acac)2 greatly enhanced FDG uptake within the initial 30 min incubation period compared to

cells in the absence of added VO(acac)2. In the presence of 5 mM D-glucose, equivalent to a

normal fasting blood glucose level in adult patients, 250 µM VO(acac)2 enhanced FDG uptake

within the initial 30–60 min period of incubation. PET imaging of single layers of MDA-MB-231 cells in culture flasks in the presence of 5 mM D-glucose showed increased intensity due to FDG

uptake when incubated in the presence of 250 µM VO(acac)2 compared to cells incubated

without VO(acac)2. The results of these preliminary investigations suggest that VO(acac)2 and

possibly other organic chelates of VO2+ may facilitate increased FDG uptake by neoplasms in

vivo, enhancing the sensitivity of PET imaging for detection of cancer. The ultimate applicability

of VO2+-chelates to enhance FDG uptake in human cancer will depend on the relative sensitivity

of tumor versus normal tissue to VO(acac)2 activity. Therefore, future experiments will be

directed towards PET imaging of transgenic and xenograft models of human breast cancer in

mice with and without administration of VO(acac)2.

Acknowledgements: We thank the Luso-American Development Foundation for travel support. This research was supported by grants from the National Institutes of Health (P50 CA125183, P30 CA14599, and S10 RR022520).

Oral lectures


O29

Lewis bases in Vanadium(V) catalyzed oxygen transfer catalysis

Silvia Lovat, Miriam Mba, Marta Pontini Giulia Licini* and Cristiano Zonta*

a Dipartimento di Scienze Chimiche, Università di Padova, via Marzolo 1, 35131 Padova, Italy email: [email protected]

Oxidation mediated by vanadium compounds has been revitalized by vanadium dependent

enzymes haloperoxidases, producing an ever growing number of studies on biomimetic

complexes.1 The main interest has been directed toward oxidations of sulfides, halides, and

olefins.2 In the oxidation pathway performed by these complexes it has been largely accepted

that the mechanism follows an electrophilic activation of the peroxide followed by a nucleophilic

attack by the substrate on the η2 coordinated peroxide.3 During the course of these studies we

noticed that the presence in solution of a LB was distinctively enhancing the catalytic activity of

the complex (Figure 1).

S SOROOH

VV complex

Lewis Base

SO

+O

Figure 1. Vanadium metal complexes used in sulfoxidations with the addition of Lewis Bases.

The Lewis Base (LB) is able to bind to the metal in addiction to the ligand, and capable to

selectively modify the catalytic properties of the complex. This approach not only offers the

opportunity to module the catalytic systems with a defined reactivity and selectivity profile, but

also to better understand the basic principles behind metal activation in synthetic and biological

systems. Acknowledgements: The authors would like to thank FIRB-2003 CAMERE-RBNE03JCR5 project, COST Action D40 ‘Innovative Catalysis, MIUR and University of Padova for their financial support. [1] D.C Crans, J. Smee, E. Gaidamauskas, L. Yang Chem.Rev. 104 (2004) 849. [2] A.G.J. Ligtenbarg, R. Hage, B.L. Feringa Coord. Chem. Rev. 237 (2003) 83 [3] C. J. Schneider, J. E.Penner-Hahn, V. L. Pecoraro 130 (2008) J. Am. Chem. Soc. 2712.

Oral lectures


O30

Octahedral-square pyramidal equilibrium in bis-chelated VIVO species: spectroscopic and DFT characterization

Eugenio Garribba,a Giovanni Micera,a Daniele Sanna,b

aDipartimento di Chimica, Università di Sassari, Via Vienna 2, 07100 Sassari, Italy; email: [email protected]

bIstituto C.N.R. di Chimica Biomolecolare, Trav. La Crucca 3, 07040 Li Punti, Sassari, Italy

The “additivity rule” assumes that an axial ligand does not contribute to 51V anisotropic hyperfine coupling constant along z axis (Az), so that its presence cannot be demonstrated by EPR spectroscopy;1 therefore, the possibility of an equilibrium between the VIVO species with and without a solvent (or ligand) molecule in the sixth coordination position usually is not taken into account. Few exceptions to the “additivity rule” have been reported: the octahedral complexes [VOX(capca)] where Hcapca is N-{2-[(2-pyridylmethylene)amino]phenyl}pyridine-2-carboxamide and X is Cl−, SCN− or CH3COO−,2 and the bis-chelated complexes formed in DMF by several amidrazone derivatives3 and in water by 6-methylpicolinate.4 In this work we demonstrate the existence of an equilibrium between the octahedral and the trans square-pyramidal forms of bis-chelated VIVO complexes. The characterization was performed through the combined application of EPR spectroscopy and DFT methods. The complexes studied were formed in aqueous solution by 6-methylpicolinate (6-mepic) and 6-methyl-2,3-pyridinedicarboxylate (6-me-2,3-dpc). EPR spectra of the VIVO bis-chelated species of 6-mepic and 6-me-2,3-dpc consist of two set of resonances, the inner with an anomalously low value of Az (~148x10−4 cm−1) and the outer with a “normal” value (~161x10−4 cm−1). With increasing the ionic strength, the inner signals disappear and the outer ones increase in intensity. This result has been explained postulating an equilibrium between the octahedral and square-pyramidal form, similar to the octahedral-square planar transition of the tetra-aza NiII complexes.5

N

CH3

O O–

V

O

N

H3C

O–ON

CH3

O O–

V

O

N

H3C

O–O

OH2

+ H2OIonic strength

Figure 1. Equilibrium between the six and five-coordinated bis-chelated VIVO complex of 6-methylpicolinate.

DFT calculations performed with Gaussian 03 software allow to prove these assumptions. We reached a consistent improvement in the prediction of Az, calculating it for 24 representative VIVO complexes with different charge, geometry, coordination mode and donor sets; deviations < 5% and, in most of the cases, < 3% with respect to the experimental values were obtained. The calculated values of Az for the octahedral species [VO(6-mepic)2(H2O)] and [VO(6-me-2,3-pdc)2(H2O)]2−, and for the square-pyramidal [VO(6-mepic)2] and [VO(6-me-2,3-pdc)2]

2− are in good agreement with those measured. Moreover, DFT methods correctly predict the unusual low value of Az for [VOX(capca)] and for [VOL2(dmf)]2+ formed by the amidrazone derivatives in DMF.2,3 This suggests that the disagreement with the “additivity rule” is probably due to an incompleteness of the EPR theory rather than to a real anomaly of the Az value.

[1] N. D. Chasteen, in Biological Magnetic Resonance; Plenum Press: 1981, vol. 3, pp. 53-119. [2] E. J. Tolis, K. D. Soulti, C. P. Raptopoulou, A. Terzis, Y. Deligiannakis, T. A. Kabanos, J. Chem. Soc., Chem. Commun. (2000) 601-602. [3] M. T. Cocco, V. Onnis, G. Ponticelli, B. Meier, D. Rehder, E. Garribba, G. Micera, J. Inorg. Biochem. 101 (2007) 19-29. [4] E. Kiss, E. Garribba, G. Micera, T. Kiss, H. Sakurai, J. Inorg. Biochem. 78 (2000) 97-108. [5] A. Anichini, L. Fabbrizzi, P. Paletti, R. M. Clay, Inorg. Chim. Acta 24 (1977) L21-L23.

Oral lectures


O31

Vanadium in Life

Dieter Rehder

Department Chemie, Universität Hamburg, 20146 Hamburg, Germany email: [email protected]

As summarised in the phylogenetic tree, Fig. 1,1 vanadium is employed by a plethora of organisms. There are at least three different levels, on which vanadium can act in living organisms: (1) The ease of exchange between the oxidation states +V and +IV (and, to some extent, also +III) classifies this element as a redox catalyst: Amavadin from Amanitae mushrooms (e.g. the fly agaric) may be a relic of an evolutionary overcome oxygenase. Several protobacteria gain energy from respiration based on vanadate(V) as electron acceptor. Further, the presence of vanadium in alternative nitrogenases in Azotobacter and Anabaena reflects its ability to take part in the activation and electron delivery to N2. (2) The VV centre in vanadate-dependent peroxidases from marine macro algae, fungi and lichens exerts Lewis acidity and thus activates peroxide in the 2e- oxidation of substrates such as halides and sulphides. (3) The similarity between vanadate and phosphate makes vanadate an apt regulator for phosphate-metabolising enzymes, essentially through the inhibition of phosphatases, also in high developed organisms, viz. plants and animals, a fact which has implications for the insulin-mimetic/enhancing effect of vanadium. Figure 1. The phylogenetic tree, including organisms (in italics) which (can) use vanadium in life processes.1 LUCA = last uniform common ancestor. In plants and animals, vanadium may have a regulatory function.

[1] D. Rehder, Org. Biomolec. Chem. 6 (2008) 957-964.

CyanobacteriaAnabaena

ProteobacteriaPseudomonasShewanellaGeobacterAzotobacterThioalkalivibrio A r c h a e a

B a c t e r i a

PhaeophytaAscophyllum

AscomycotaCurvularia

BasidiomycotaAmanita

F u n g i

P l a n t a e

RhodophytaCorallina

ChlorophytaHalimeda

LichenXanthoria

E u c a r y o t a

3.5

3.0

2.11.2

0.5

109 a

LUCA

A n i m a l e s

E u c a r y a

Oral lectures


O32

Biological Effects and Cytotoxicity of a complex of Vanadium(V) with salicylaldehyde semicarbazone in osteoblasts in culture

Josefina Rivadeneiraa,b, Daniel A. Barrioa, Gabriel Arrambidec, Dinorah Gambino c,

Liliana Bruzzonea, Susana B. Etcheverrya,b*

aFacultad de Ciencias Exactas, UNLP. 47 y 115 (1900) La Plata, Argentina bCEQUINOR (CONICET-UNLP), Facultad de Ciencias Exactas, UNLP, La Plata, Argentina

cFacultad de Química, Universidad de la República, Montevideo, Uruguay * Corresponding author e-mail: [email protected]

Interaction of simple vanadium species with ligand groups bearing pharmacological activity, particularly those with antitumoral and insulin-mimetic properties, is of growing scientist interest. Vanadate mimics various insulin actions on different cell types and also in cell free systems. Semicarbazones are versatile compounds of considerable interest because of their chemistry and potentially beneficial pharmacological effects, such as antitumor, antibacterial, antiviral and antimalarial activities. The biological effects of these ligands are considered to be related to their ability to form chelates with metals. Biological activities of metal complexes differ from those of either ligands or the metal ions, and increased or decreased biological activities have been reported for several transition metal complexes. In the frame of our continuing studies devoted to the biological and potential pharmacological properties of vanadium compounds we report herein the biological actions of VVO2(salicylaldehydesemicarbazone) (V(V)-SalSem) on two osteoblast cell lines in culture (MC3T3E1 and UMR106). Cell proliferation, differentiation, morphological alterations, oxidative stress, activation of the extracellular regulated kinases (ERK) cascade and apoptosis have been investigated. V(V)-SalSem inhibited cell proliferation in a dose response manner as determined by the crystal violet bioassay, with the same potency and efficacy in both cell lines (IC50: >100 μM). The inhibition at high doses (100μM) could be partially reversed by the free radical scavengers NAC (N-acetylCysteine) and a mixture of vitamins E and C. Changes in cell proliferation correlated with morphological alterations as could be determined by ligt microscopy with Giemsa staining. Alterations began at 10 μM and increased with complex concentration. Stress fibers were also desorganized in a dose response manner being the network lost between 50-100 μM. Specific activity of alkaline phosphatase (ALP) and collagen content, two mature osteoblast phenotype markers, were inhibited in a dose response manner by the complex in UMR106 cells. In an atempt to elucidate the mechanisms of action involved in the toxicity actions of V(V)-SalSem, the oxidative stress and the activation of ERK pathway were analyzed. The determination of oxidative stress through the fluorometric measurement of free radical levels, showed that complex promoted the production of free radicals (Dihydrorhodamine oxidation to rhodamine) in a dose response manner reaching a two-fold value at 100 μM in comparison with basal conditions. This effect could be partially reversed by free radical scavengers. ERK cascade was activated by the complex as it was determined by Western blot using two specific inhibitors (PD98059) and wortmannin. These events correlated with the enhancement of apoptosis over necrosis as could be seen using AnnexinV-Propidium Iodide. In conclusion, the complex formed between vanadium(V) and salicylaldehyde semicarbazone displays cytotoxic effects on osteoblasts in culture through the production of free radicals and the activation of ERK cascade. These mechanisms triggered the apoptotic events that convey to cell death. Acknowledgements: S. B. Etcheverry thanks the Reitoria da Universidade Técnica de Lisboa, Portugal, the financial support for travelling.

Oral lectures


O33

Interaction of Dioxovanadium(V) with Iminodiacetic Acid and Phenylalanine Using SIT

Kavosh Majlesi,a Karim Zare,a,b Saghar Rezaienejad a

aChemistry Department, Islamic Azad University, Science & Research Campus, Tehran, Hesarak, Iran

bChemistry Department, Shahid Beheshti University, Tehran, Evin, Iran email: [email protected]

When the required Pitzer parameters are evaluated accurately from extensive data, the Pitzer model is a preferred, standard method in presentation of experimentally determined thermodynamic properties of electrolytes. However, the specific ion interaction theory(SIT) because of its advantages in mathematical simplicity and its less parameterized nature, may find application when the experimental data are less extensive, or the accuracy provided by the SIT model is deemed to be satisfactory, or in systems where complex formation occurs. This is especially true in cases in treatment of equilibrium constants. The shortcoming of the SIT model is its rather low accuracy in reproduction of mean activity coefficients in comparison with Pitzer model. However, the error is usually less than 10% at ionic strength up to 6-10 m at 25 ºC. The less-parameterized SIT model gives quite reasonable estimations of equilibrium constants in different media at various ionic strengths, provided that the necessary interaction coefficients are known. Consequently, the SIT model has the potential to become a useful method to estimate medium effects on equilibrium constants in concentrated solution in high temperature chemistry. There is a project on the IUPAC web site about the ionic strength corrections for stability constants using SIT which has been completed in 2005, but to our knowledge no reports of the ionic strength dependence of dioxovanadium(V) complexes with iminodiacetic acid(IDA) and phenylalanine has appeared. Therefore this research has been undertaken to show the application of specific ion interaction theory1 for the aforementioned complexes at different ionic strengths from 0.1 to 1.0 mol dm-3 of sodium perchlorate and pH range 1.00 to 4.00. The temperature was kept constant at 25 ºC. Stoichiometry and stability constants of the formed complexes were determined2 from a combination of potentiometric and UV spectroscopic measurements based on the relationship A=f(pH). The semi-empirical parameters3-5 for ionic strength dependence have been calculated on the basis of minimizing the error function using Gauss-Newton nonlinear least squares method in Microsoft Excel 2000 program. Debye-Huckel theory applies well for both of the complexes but phenylalanine complex data fit better in the specific ion interaction theory. Finally the values of interaction coefficients ∆ε= -0.7643, 0.7389 have been calculated for the IDA and phenylalanine complexes respectively. [1] K. Majlesi, S. Rezaienejad, Chin. J. Chem. 25 (2007) 1815-1820. [2] K. Majlesi, K. Zare, J. Mol. Liq. 125 (2006) 62-65. [3] K. Majlesi, K. Zare, J. Mol. Liq. 125 (2006) 66-71. [4] K. Majlesi, K. Zare, F. Najafi, Russ. J. Inorg. Chem. 52 (2007) 1299-1303. [5] K. Majlesi, K. Zare, Phys. Chem. Liq. 44 (2006) 257-268.

A

Oral lectures


O33

Complexation of dioxovanadium(V) with nitrilotriacetic acid in different sodium perchlorate aqueous solutions using SIT

Saghar Rezaienejad,a Kavosh Majlesi,a Karim Zarea,b

aChemistry Department, Islamic Azad University, Science & Research Campus, Tehran, Hesarak, Iran

bChemistry Department, Shahid Beheshti University, Tehran, Evin, Iran email: [email protected]

In investigations of systems where complex formation takes place, a method of constant ionic medium is usually adopted. There are difficulties in determination of activity coefficients of reaction species in a constant ionic medium. Usually only a value of equilibrium constant in a certain medium can be determined, and the number of equilibrium constants obtained is generally small. Second, the accuracy of equilibrium constants is relatively low in comparison with that of mean activity coefficients and osmotic coefficients. Accordingly, owing to these two facts, it is sensible to use an activity model with fewer parameters when dealing with experimental equilibrium constants, as it is often impractical to determine more than one or two empirical parameters from a small number of such constants with limited accuracy. The specific ion interaction theory (SIT) model can be regarded as a simplified version of the Pitzer formalism without consideration of triple interactions and interactions between ions of the same charge sign. The SIT model is most useful in the ionic strength range up to 3.5-4.0 mol dm-3 and successful applications of the SIT model at 25 ºC in NaCl solutions up to the saturation of halite have also been demonstrated. Thus, ionic strength effects for dioxovanadium(V) complexes with nitrilotriacetic acid(NTA) have been studied in an ionic strength range of 0.1 to 1.0 mol dm -3 of sodium perchlorate at 25 ºC using SIT.1 Acidic solutions of dioxovanadium(V) were titrated with basic solutions of NTA at different ionic strengths. The absorbance data in the UV range(245 to 280 nm) and pH = 1.00-2.50 were used for minimizing the error function on the basis of Gauss-Newton nonlinear least squares method in Microsoft Excel 2000 program. Two species, VO2H2L and VO2HL-, have been detected according to curve fitting, which allows us to calculate the formation constants. There are descending patterns for the dioxovanadium(V) complexes with NTA according to the SIT model without any maximum or minimum, but there are combination of ascending and descending patterns on the basis of extended Debye-Huckel model.2-6 Ultimately it can be concluded that SIT model applies well for the NTA complexation with dioxovanadium(V). [1] K. Majlesi, S. Rezaienejad, Chin. J. Chem. 25 (2007) 1815-1820. [2] K. Majlesi, K. Zare, S. M. Shoaie, J. Chem. Eng. Data 50 (2005) 878-881. [3] K. Majlesi, K. Zare, Phys. Chem. Liq. 44 (2006) 257-268. [4] K. Majlesi, K. Zare, J. Mol. Liq. 125 (2006) 66-71. [5] K. Majlesi, K. Zare, J. Mol. Liq. 125 (2006) 62-65. [6] K. Majlesi, K. Zare, F. Najafi, Russ. J. Inorg. Chem. 52 (2007) 1299-1303.

B

Oral lectures


O34

Recent advances in decameric vanadate biochemistry

Manuel Aureliano

CCMAR, University of Algarve; Dept. Chemistry and Biochemistry and Pharmacy, FCT, University of Algarve; email: [email protected]

Great care is needed when utilising vanadate solutions because decavanadate species can occur even at physiological pH values through a slight acidification of the medium. Few studies point out that that the effects cannot be taken as evidence that monomeric vanadate is the inhibiting species and that individual vanadate species can differently affect the biological processes, being in some cases decavanadate the only effector. Decavanadate interacts with the polyphosphate, nucleotide, inositol 3-phosphate binding sites of enzymes either in the substrate domain or in an allosteric effector site does not tend to follow a simple model of action1,2. Recently in vivo vanadium toxicological studies following decavanadate administration point out to specific effects induce by this vanadium oxoanions. Apparently, in hepatic and cardiac muscle cells, the degree of vanadate toxicity depends on the mode of administration such as intraperitoneal or intravenous, and is also dependent; at some extend, at the vanadate species such as decavanadate3, which induces different changes in vanadium accumulation, lipid peroxidation and oxidative stress markers, than the ones observed for vanadate4.

ADPRS

Δψ

Δψm

ROSATP

V10

V10

V10 in CS

V10

V10

ATP

Ca2+

V10

V10 ⇔ V1

Ca2+

ADPCa2+

Ca2+ V10

Figure 1. Cellular targets and cellular responses for V10: Pumps, ionic channels, contractile system, cytoskeleton, mitochondria, extracellular matrix and ROS changes. RS, sarcoplasmic reticulum, CS, Contractile system, ROS, reactive oxygen species, V10 decameric and V1, monomeric vanadate species. Membrane potential, Δψm.

In mitochondria, where vanadium was shown to be particularly accumulated following decavanadate in vivo administration, nM concentration of decavanadate induces membrane depolarization besides oxygen consumption inhibition5. Other recent studies from ours and others research groups, included, for instance, the use of decavanadate or decavanadate compounds as a probe in comprehension of muscle contraction6,7, modulation of ionic channels8,9, interaction with lipid interfaces10, calcium homeostasis11 cytoskeleton structures dynamics12, cell growth and extracellular matrix mineralization13, and as a prodrug of insulin mimetics14 or in mechanisms of cell death15 induce by vanadate. We believe that these and other recent studies with decavanadate species and compounds described in the present review will allow a better understanding of decavanadate targets in cellular biology (Figure 1). [1] D.C. Crans, Comments Inorg. Chem. 16 (1994) 1-33; [2] M. Aureliano, V.M.C Madeira, In Vanadium in the Environment; John Wiley & Sons, New York, 1998, 333-357 ; [3] M. Aureliano, and R. M. C. Gândara, J. Inorg. Biochem., 99 (2005) 979-985; [4] S.S Soares, H. Martins, J. Coucelo, C Gutiérrez-Merino, and M. Aureliano, J. Inorg. Biochem. 101, (2007) 80-88 ; [5] S.S. Soares, C. Gutiérrez-Merino, and M. Aureliano, J. Inorg. Biochem. 101 (2007) 789-796. ; [6] T. Tiago, M. Aureliano, C. Gutiérrez-Merino, Biochemistry 43 (2004) 5551-5562.; [7] T. Tiago, P Martel, C. Gutiérrez-Merino, M. Aureliano Biochem. Biophys. Acta, 1771 (2007) 474-480.; [8] B. Nilius, J. Prenen, A. Janssens, T. Voets, and G. Droogmans, J. Physiol.- London, 560 (2004) 753-765. ; [9] M. Gutierrez- Aguilar, Perez et al, Biochem. Biophys. Acta 1767 (2007) 1245-1251 ; [10] D.C. Crans in: Vanadium Biochemistry, Research Signpost, Kerala, India, 2007 ; [11] M. Aureliano, S. S Soares, T. Tiago, S. Ramos, C. Gutierrez-Merino In: Vanadium: The versatile metal, ACS Symposium Series. 974, (2007), 249-263; [12] S Ramos, M. Manuel, T. Tiago, R. O., Duarte, J Martins, C Gutiérrez-Merino, J.J.G Moura, M. Aureliano, J. Inorg.Biochem.100 (2006) 1734-1743.; [13] D.M. Tiago, M.L. Cancela, M. Aureliano and V. Laize, FEBS Lett., 582 (2008) 1381-1385.; [14] F. Yraola et al, Chem Biol Drug Des. 69 (2007) 423-428 ; [15] S.S. Soares, F. Henao, M. Aureliano, C. Gutiérrez-Merino, Chem. Res. Toxicol. 21 (2008) 607-618.

Oral lectures


O35

A novel function of Vanabin2 and the relationship among proteins involved in the accumulation and reduction of vanadium by ascidians

Hitoshi Michibata,Tatsuya Ueki, Norifumi Kawakami Department of Biological Science, Graduate School of Science, Hiroshima University, Higashi-Hiroshima 1-3-

1, Hiroshima 739-8526, Japan, e-mail: [email protected]

Ascidians, known as sea squirts, accumulate high levels of vanadium ions. Their blood cells can

contain vanadium ions at concentrations up to 350 mM, a 107-fold increase over its dissolved

concentration in seawater (35 nM). Accumulated vanadium ions (VV) are first reduced to VIV in

ascidian vanadocytes and stored in their vacuoles containing high levels of protons and sulfate

ions where they are finally reduced to VIII and seem to exist as free ions[1]. Ongoing research

over the last decade has identified many proteins involved in the accumulation and reduction of

vanadium in vanadocytes, blood plasma and digestive tract of ascidians, such as H+-ATPase,

chloride channels, AsSUL1 (sulfate transporter), enzymes of the pentose-phosphate pathway,

AsGST (glutathione transferase), Vanabin1–4, VanabinP, CiVanabins, VBP-129 (vanadium-

binding protein 129), VIP1 (Vanabin-interacting protein 1) and metal-ATPase. To elucidate

overall mechanisms of vanadium accumulation and reduction in ascidians, not only individual

functions of the proteins but also the relationship between the proteins should be clarified from

now on. Thus, in this talk, we will describe a novel function of Vanabin2 as a VV reductase in

which the thiol-disulfide exchange reactions are involved and the relationship among NADPH,

GSH, Vanabin family, AsGST, VBP-129, VIP1, AsSUL1 which may provide sufficient knowledge

how these proteins and coenzymes share their roles to accumulate vanadium in ascidians.

VanabinPSulfate TransporterH+-ATPaseVBP-129

VIP1

Metal-ATPase

AsGST

Vanabin1�4

VanabinPSulfate TransporterH+-ATPaseVBP-129

VIP1

Metal-ATPase

AsGST

Vanabin1�4

[1] H. Michibata, M. Yoshinaga, M. Yoshihara, N. Kawakami, N. Yamaguchi, T. Ueki, In “Vanadium the Versatile Metal”, K. Kustin, J. C. Pessoa, D. C. Crans Eds., ACS Symp. Ser., 974, Oxford University Press: (2007) pp. 264-280.

Figure 1. Schematic representation of vanadium accumulation and reduction by ascidians. The concentration of vanadium dissolved in sea water is only 35 nM in the +5 oxidation state. While, the highest concentration of vanadium in ascidian blood cells attains up to 350 mM. In addition 500 mM of sulfate is contained. The contents of vacuoles are maintained in an extremely low pH of 1.9 by H+-ATPases. Under the environment, almost all vanadium accumulated is reduced to VIII via VIV. The first step of vanadium uptake may occur at a branchial sac or digestive organs, where AsGST was identified as a major vanadium carrier protein. VBP-129 and VanabinP were isolated in the blood plasma. Vanabin1-4 and VIP1 were in the cytoplasm of vanadocytes. The pentose phosphate pathway, which produces NADPH, was disclosed to localize in the cytoplasm. A metal-ATPase and AsSUL1 were also found in vacuolar membrane.

Oral lectures


O36

Vanadium induces AIH: implications for the pulmonary immune system

Mitchell D. Cohena, Ph.D. and Andrew J. Ghiob, M.D.

aNIEHS Center of Excellence, Dept. of Environmental Medicine, NYU School of Medicine, Tuxedo, NY 10987

USA ([email protected]) and bClinical Research Branch, Human Studies Division, U.S. EPA, Research Triangle Park NC 27711 USA ([email protected])

Residents of urban centers are routinely exposed to airborne pollution containing a variety of particles, gases, biologics, and acids. While risk to human health from pollution is correlated with the cumulative concentration of all pollutants present, many of the individual constituents have their own potential to induce alterations in pulmonary inflammatory status and immunocompe-tence. We believe one mechanism leading to these outcomes could be an induction of altered iron homeostasis (AIH) in the lungs wherein airway and cellular levels of biologically active iron (Fe) are affected. We propose that an AIH in the lungs following pollution exposure is mediated by effects on proteins critical to Fe import, storage, and/or export. Among the metals commonly associated with particulate matter (PM) is vanadium (V), a known pulmonary immunomodulant. To determine whether V could induce changes in Fe homeostasis in lung epithelial (BEAS-2B) cells and in alveolar macrophages (NR8383 cells), in vitro studies were performed to assess effects of V on cell Fe import. The impact of V on select Fe-dependent proteins and on the production of specific cytokines whose genes contain a promoter that can be activated during states of cell Fe deficit were also assessed. To attempt to relate outcomes of the in vitro studies to potential effects in situ, in vivo inhalation studies using V (soluble and insoluble forms) were performed. Following their exposures (100 µg V/m3, 5 hr/d, 5 consecutive days,), F344 rats were assessed for lung V burden as well as lavage concentrations of Fe, Fe-dependent proteins, as well as select cytokines and chemokines, or infected with Listeria monocytogenes and monitored for pathogen clearance over a 72-hr period. The in vitro study results indicated that the presence of V significantly reduced the ability of the cells to maintain normal Fe status. With both penta- and tetravalent V, cell Fe levels were reduced in comparison to those when cells were presented Fe alone. Further evidence of V-induced effects were reflected in reductions in levels of the major Fe storage protein ferritin, increases in the expression/binding activity of iron response protein-1 (IRP-1), and the increased formation/release of IL-8 whose gene contains a promoter (i.e., HRE) whose activation is affected by low cell Fe levels. Effects of V upon Fe delivery out of the lung lining fluid and into resident cells were noted in the in vivo studies. Further, the lavages of rats that inhaled the V agents consistently had higher concentrations of non-heme Fe and ferritin. The lavages also contained significant amounts of TNFα and MIP-2, AM and epithelial cell products whose genes also contain an HRE promoter. Lastly, those rats that were exposed to soluble V had significantly reduced abilities to clear viable bacteria; oddly, rats that had inhaled the insoluble form of the metal had no change in (or actually even lower) bacterial levels compared to air-exposed infected counterparts. The results of these studies demonstrate that V can affect iron homeostasis in the lungs, and in particular, among cells critical to maintaining pulmonary immunocompetence. Further studies are needed to clarify whether the presence of V in the lungs also affects proteins critical to cell Fe storage and efflux. These results illustrate that commonly-encountered airborne V compounds have a potential to induce AIH in situ, and thus should be considered toxicologically-significant pollutants during assessments of daily risk to health among the citizens of urban areas. Acknowledgements: The Authors would like to thank Dr. João Costa Pessoa and the Fundação Luso-Americana para o Desenvolvimento (Luso-American Development Foundation) for their help and financial support in making this presentation possible.

Oral lectures


O37

DNA cleavage activity of VO(acac)2 and derivatives

Isabel Cavaco,a,b Ofelia Nouri,a Vera Ribeiro,c Esther Escribano,d Virtudes Moreno,d Sofia Gama,e Isabel Tomaz,f João Costa Pessoab

aDepartamento de Química, Bioquímica e Farmácia, Universidade do Algarve, Campus de Gambelas, 8005-139 Faro, Portugal, email: [email protected]; b Centro de Química Estrutural, Instituto Superior Técnico, TU

Lisbon, Av Rovisco Pais, 1049-001 Lisboa, Portugal; c Centro de Biomedicina Molecular e Estrutural, Universidade do Algarve, Campus de Gambelas, 8005-139 Faro, Portugal; dUniversidad de Barcelona,

Departamento de Química Inorgánica, Martí i Franquès 1-11, 08028-Barcelona, Spain; e Química Inorganica

e Radiofarmacêutica, Instituto Tecnológico e Nuclear, Estrada Nacional 10, 2686-953 Sacavém, Portugal f Centro de Ciências Moleculares e Materiais, Faculdade de Ciências – Univ. Lisboa, Campo Grande 1749-

016 Lisbon - Portugal;

Inorganic nucleases are inorganic compounds which have demonstrated activity in DNA cleavage, as is the case of some vanadium complexes1,2. In previously reported cases of DNA cleavage by vanadium complexes, this activity must be initiated by an activating agent, usually an oxidant (KHSO3, H2O2), or UV radiation. Studies of nuclease activity are carried out at micromolar metal concentrations, at which metal speciation is unknown. Our objective is to determine which species are actually active towards DNA cleavage. We are particularly interested in analysing the nuclease activity of vanadium compounds that have been proposed as therapeutic agents for diabetes mellitus, due to their known insulin-like properties. Evaluating the possibility and extent of DNA damage is an important preliminary step when considering these new therapeutic compounds. We compared the nuclease activity of several insulin-mimetic vanadium complexes. VO(acac)2 (1) is a known insulin-mimetic compound which shows a remarkably high nuclease activity in the apparent absence of activation by radiation and oxidizing or reducing agents. In order to understand this process, derivatives 2 – 6 were prepared and their nuclease activity was studied by plasmid gel electrophoresis, atomic force microscopy and circular dichroism.

O

O O

O

V

O O

O O

O

V

O O

O O

O

NH2

V

O

H2N

O

O O

O

N

V

O

N

O

O O

O

V

O

O

O O

O

V

O

1 2 3 4

5 6 It is concluded that VO(acac)2 and derivatives are very efficient DNA cleavers. Unlike all previously reported cases of vanadium nucleases, except for vanadium phenanthroline complexes, VO(acac)2 complexes require no activating agents to degrade DNA. It is proposed that the bichelated complexes, or possibly their monochelated equivalents, interact directly with DNA to promote cleavage. Acknowledgements: The authors wish to thank the Fundação para a Ciência e Tecnologia, FEDER, POCI 2010 and PPCDT/QUI/56949/2004 for financial support. [1] Q. Jiang, N. Xiao, P. Shi, Y. Zhua, Z. Guoa, Coord Chem Rev 251 (2007) 1951-1972 [2] D.C.Crans, J.J. Smee, E. Gaidamauskas, L.Yang, Chem. Rev., 104 (2004) 849-902

Oral lectures


O38

Vanadium Haloperoxidases as versatile biological matrix: Mechanistic aspects towards cofactor and substrate specificity

Winfried Plass

Institut für Anorganische und Analytische Chemie, Friedrich-Schiller-Universität Jena, Carl-Zeiss-Promenade 10, 07745 Jena, Germany; email: [email protected]

Vanadium haloperoxidases (V-HPOs) are enzymes capable of the two electron oxidation of halides and organic sulfides. The x-ray structure of the resting state and peroxide bound forms of the enzyme have been previously reported and indicate that their general reactivity is governed by the hydrogen bonding network provided by the protein matrix.1 Implications of this hydrogen bonding network on the structure of the resting state have been deduced, indicating a two-fold protonation in the resting state of the enzyme.2,3 Nevertheless, the mode of action for the formation of the initial peroxo species still remains unclear as to what extend a dissociative or an associative mechanism is employed in the catalytic cycle of the enzyme. Experimental, spectroscopic and computational methods are employed to understand the reactivity appropriate model systems,4,5,6 with special emphasize on the modeling of hydrogen bonding interactions and the formation of peroxo species. Attempts to rationalize the cofactor and substrate specificity will be discussed.

[1] R. Wever, W. Hemrika in Handbook of Metalloproteins, Vol. 2 (Eds.: A. Messerschmidt, R. Huber, T. Poulos, K. Wieghardt), John Wiley and Sons Ltd., Chichester, 2001, pp. 1417–1428. [2] M. Bangesh, W. Plass, J. Mol. Struct. Theochem 725 (2005) 163-175. [3] W. Plass, M. Bangesh, S. Nica, A. Buchholz, ACS Symp. Ser. 974 (2007) 163-177. [4] I. Lippold, H. Görls, W. Plass, Eur. J. Inorg. Chem. (2007) 1487–1491. [5] S. Nica, A. Buchholz, M. Rudolph, A. Schweitzer, M. Wächtler, H. Breitzke, G. Buntkowsky, W. Plass, Eur. J. Inorg. Chem. (2008) 2350–2359. [6] A. Schweitzer, T. Gutmann, M. Wächtler, H. Breitzke, A. Buchholz, W. Plass, G. Buntkowsky, Solid State Nucl. Magn. Reson. (2008) doi:10.1016/j.ssnmr.2008.02.003.

Oral lectures


O39

Vanadium Haloperoxidases – a biocatalyst for iodination reactions

Marisa Nicolaia, Gisela Gonçalvesb, Filipe Natálioc, Marise Almeidad, Madalena Humanesa

aCentro de Química e Bioquímica do Departamento de Química e Bioquímica da Faculdade de Ciências da

Universidade de Lisboa, Edifício C8, Campo Grande, 1749-016 Lisbon, Portugal. b Centro de Química Estrutural, IST, TU, Av. Rovisco Pais, 1049-001 Lisbon, Portugal.

c Institut für Physiologische Chemie, Abteilung Angewandte Molekularbiologie, Mainz Universität, Duesbergweg 6, D-55099 Mainz, Germany.

dUICOB- Faculdade de Medicina Dentária de Lisboa, Cidade Universitária, 1649-003 Lisbon, Portugal, email: [email protected]

The iodinated compounds are recognized for many years as important and versatile intermediates in organic synthesis. Their applications cover several processes as diverse as nucleophilic displacement and radical or transition metal mediated coupling reactions. The synthesis of iodinated compounds is often carried out using elemental iodine but due to its low electrophilicity, an extra increment of reactivity is necessary what is usually accomplished by a solvent, an acid and more recently by the introduction of several oxidation systems1. The discovery of enzymes that are able to catalyze halogenation reactions which containing vanadium as active site was a breakthrough in the biocatalysis field. Here, we show the high versatility of the reactions performed by the vanadium haloperoxidase (V-HPO) extracted from the brown algae Laminaria saccharina, at the expense of hydrogen peroxide and in the presence of iodide and several aminoacids and related molecules. We have previously demonstrated that this enzyme catalysed the conversion of L-tyrosine to the iodotyrosine derivatives, monoiodo- and diiodotyrosine and it can also acts directly upon monoiodotyrosine producing the diiododerivative. The kinetic data suggest, for the monoiodotyrosine formation, a sequential mechanism for the binding of the two substrates (hydrogen peroxide and iodide). The experimental data also support the existence of an L-tyrosine binding site in the enzyme2. The versatility of this enzyme is demonstrated since a totally different reaction was obtained when the V-HPO catalyse the peroxidative iodination of the amino acid L-DOPA. A melanin type black precipitate was obtained. The reaction is a multistep one with a crucial role developed by the iodide as in the initial quinone formation, which is supported by similar results with cathecol and guaiacol, as well as in the subsequent enzyme catalysed peroxidative production of dopachrome, a well known intermediate in the synthesis of melanin. Dopachrome is then converted to a synthetic form melanin3. This black precipitate, characterized by FT-IR and XPS and SEM shows some similar properties to the commercially available melanin. The reaction with epinephrine was also studied showing some similarities with the reaction with L-DOPA, except that no black precipitate was observed. Other amino acids such as L-phenylalanine, L-hystidine and L-tryptophan were also studied in this context, but at a preliminary level. They showed quite distinct reactional behaviour when compared with L-tyrosine and L-DOPA. Despite their evident synthetic utility, the production of iodinated compounds, specially containing aromaticity, remains a synthetic challenge. The demand for efficient, tuneable and ecofriendly procedures are still ongoing development1. In this context, V-HPO from L. saccharina revealed a significant contribution due to its intrinsic and interesting features, e.g., its capability to catalysed iodination reactions with a high operational stability.

[1] G. David, C. Boyer, J. Tonnar, B. Ameduri, P. Lacroix-Desmazes, B. Boutevin, Chem. Rev. 106 (2006) 3936-3962. [2]- M.Almeida, C. Duarte, A. Alexandre, M. Humanes, J.J.R. Fraústo da Silva J. Inorg. Biochem. 86 (2001) 321. [3] S. Ito, K. Wakamatsu, Photochem. Photobiol. 84 (2008) 582-592.

Oral lectures


O40

Directed evolution of Vanadium Chloroperoxidase: a mutant with high bactericidal activity at alkaline pH

Rokus Renirie,a Zulfiqar Hasan,a Anny de Wilde,b Christel Pierlot,c Didier Hober, b

Jean-Mary Aubry,c and Ron Wevera

aVan ′t Hoff Institute of Molecular Sciences, University of Amsterdam, The Netherlands

Amsterdam, Nieuwe Achtergracht 129, 1018 WS Amsterdam, The Netherlands. bDépartement Universitaire de Microbiologie. Faculté de Médecine UPRES-EA3610, Universite de Lille 2, Laboratoire de Virologie, Lille, France, cLCOM, Equipe ‘Oxydation et formulation’, UMR CNRS 87009, ENSCL, Villeneuve d’Ascq, France,


Vanadium haloperoxidases (VHPO’s) catalyze the oxidation of halides to hypohalous acids (Eqn. 1), an industrially interesting reaction: these enzymes can be used to halogenate various organic compounds (Eqn. 2). In addition they may provide an alternative biocide in antifouling applications, or may be used as a component in disinfectants and in detergent-formulations for bleaching purposes.

H2O2 + X- + H+ → HOX + H2O [1] HOX + AH → AX + H2O [2]

X = Cl, Br, I and A = organic nucleophilic acceptor

The major drawback of the VHPO’s is that they are mainly active at mildly acidic pH values, whereas for many applications activity at mildly alkaline pH values is required. In this study we have used directed evolution techniques on vanadium chloroperoxidase from the fungus Curvularia inaequalis to increase its brominating activity at mildly alkaline pH. After successful expression of the enzyme in Escherichia coli, two rounds of screening and selection, saturation mutagenesis of a ‘hot spot’ and rational recombination, a triple mutant (P395D/L241V/T343A) was obtained that showed a 100-fold increase in activity at pH 8 (kcat = 100 s-1). The brominating activity at pH 5 was increased by a factor of 6 (kcat = 575 s-1) and the chlorinating activity at pH 5 by a factor of 2 (kcat = 36 s-1), yielding the ‘best’ vanadium haloperoxidase known thus far. The mutations are in the first and second coordination sphere of the vanadate cofactor and the catalytic effects suggest that fine-tuning of residues Lys353 and Phe397, along with addition of negative charge or removal of positive charge near one of the vanadate oxygens, is very important. Lys353 and Phe397 were previously assigned to be essential in peroxide activation and halide binding. The antimicrobial activity of the triple mutant obtained (P395D/L241V/T343A) was investigated at pH 8 and the activity of this mutant and its wild type counter part was compared towards the Gram-negative Pseudomonas aeruginosa and the Gram-positive Staphylococcus aureus. Strong microbial reduction was observed and the bactericidal activity was three to six order of magnitude higher than the wild type enzyme. The observed activity is an important step forward in the application of this robust enzyme as a component in disinfection formulations.

[1] Z. Hasan, R. Renirie, R. Kerkman, H.J. Ruijssenaars. A.F. Hartog and R. Wever, J. Biol. Chem. 281 (2006) 9738-9744 [2] R. Renirie, A. Dewilde, C. Pierlot, R. Wever, D. Hober, and J.-M.Aubry, J. Appl. Microbiol.(2008) doi:10.1111/j.1365-2672.2008.03742.x

Oral lectures


O41

Vanadium containing Bromoperoxidase – Insights into the enzymatic mechanism using X-ray crystallography

Jennifer Littlechild

Henry Wellcome Building for Biocatalysis, School of Biosciences, University of Exeter, Exeter, EX4 4QD, UK


The vanadium bromoperoxidase enzymes from two members of the red algal species, Corallina, have been studied in detail at a structural level1,2. These enzymes forms a large dodecameric structure with 12 protein subunits each containing vanadium V which is essential for its activity. The structural information has allowed an understanding of the halide specificity of the enzymes and a mutant enzyme has been constructed which also has chloroperoxidase activity3. The crystal strucure of this mutant protein has been determined and differences in the active site will be discussed in the context of its altered halide specificity. With knowledge of the overall structure of the dodecameric enzyme an active mutant dimeric enzyme has been made where a substantial portion of the N-terminus of each monomer has been deleted4. This enzyme can be over-expressed in Escherichia coli in the soluble fraction whereas the dodecameric form is only overexpressed as inclusion bodies. However it has been possible to refold this fraction in vitro to produce an active dodecameric form that resembles the wild type enzyme isolated from the Corallina species5. Structural studies in the presence of potential substrates of the bromoperoxidase enzyme have demonstrated that the substrates do bind to a site close to the active site of the enzyme and that the binding site of the halide can be located close to the vanadate in the active site. The binding of the halogen involves the displacement of a specific leucine amino acid residue towards the incoming ion to establish a hydrophobic interaction, excluding solvent from the active site cavity. This is accompanied by the rotation by 25 degrees of a nearby phenylalanine residue. In the non-halide bound structure the positions of the halogen and the leucine are occupied by water. Once the halide is bound this is accompanied by exclusion of solvent and a reduction in the entrance to the active site6.

Figure 1. Bromine in the active site of the vanadium haloperoxidase enzyme, shown as a sphere bound

between the vanadate and residue Arg397 at a H-bonding distance of 2.8-3.1Å. These studies have increased our understanding of the structure of the bromoperoxidase enzymes and the role of the vanadium which is essential for the enzymatic mechanism. Acknowledgements: The author would like to thank the BBSRC UK for their help and financial support. [1] M. Isupov, A. Dalby, A. Brindley, T. Izumi, T. Tanabe, and J.Littlechild, J. Mol. Biol., 299,(2000) 1035-1049. [2] J. Littlechild and E. Garcia-Rodriguez Coordination Chemistry Reviews, 237, (2003) 65-76. [3] T. Ohshiro, J. Littlechild, E. Garcia-Rodriguez and M. Isupov, Y. Iida , T. Kobayashi and Y. Izumi, Protein Science 13, (2004) 1566-1571 [4] E. Coupe, R. Hall and J. Littlechild, Protein Engineering, 2008, manuscript in preparation. [5] E. Coupe, M.G. Smyth, A. Fosberry, R. Hall and J. Littlechild, Protein Expression and Purification 52, (2007) 265-272 [6] E. Garcia-Rodriguez, PhD thesis Exeter, 2005

Oral lectures


O42

The organizers

are sorry that

no Title or Abstract

are available

for this

Lecture

Oral lectures


O43

Crystallographic statistical studies of the decavanadate anion: toward a prediction of the non-covalent interactions.

Anne Spasojević-de Biré,a Nada Bosnjaković-Pavlović,a,b Nour Eddine Ghermani,a,c

aLaboratoire SPMS UMR CNRS 8580, Ecole Centrale Paris, 92295 Châtenay-Malabry, France bFaculty of Physical Chemistry, University of Belgrade, P.O.Box 137, 11001 Belgrade, Serbia

cLaboratoire de Physique Pharmaceutique UMR CNRS 8612, Faculté de Pharmacie, 92296 Châtenay-Malabry, France, email :[email protected]

A large number of crystal structures containing the [V10O28 Hx]

6-x anion has already been published. We have retrieved from the inorganic database (ICSD), the organic-organometallic database (CSD), the protein data base (CSD) and an extensive bibliographic search has lead to about 100 different structures. From a geometric point of view, the decavanadate anion appears very rigid with really small variations in interatomic distances or bond angle values. In a previous study1, we have experimentally determined the electron and electrostatic properties of Na3V10O28(C4N3OH5)3(C4N3OH6)3 ·10H20. From these results we have predicted the preferential non-covalent interactions (figure 1) with the different oxygen atoms of the decavanadate anion. These predictions are confirmed, in this study, by the observation of the non-covalent interactions existing in the almost 100 crystalline structures found in the literature. The non-covalent interactions are strongly different depending on the oxygen atom type. The Ob and Oc oxygen atoms, for which the electrostatic potential in the vicinity have the lowest value, are involved mainly in the strong O-H…O, N-H…O while Of or Og are mainly involved in weakest hydrogen bonds such as C-H…O or cation interactions. The cation with the highest positive charge forms a coordination polyhedron with the water molecule. The less positive cation includes the decavanadate anion in its coordination polyhedron. This occurs generally with the Of oxygen atom. The main protonation sites for the protonated decavanadate anion are Ob and Oc. These results are important in the context of the various biological applications of the decavanadate such as, for example, inhibition of the Ca2+ ATPase2, myosin ATPase3, and new development in insulin mimetic4.

Figure 1. Schematic representation of the main expected non-covalent interactions with a decavanadate

anion. [1] N.E. Ghermani, N. Bosnjaković-Pavlović, I. Tomaz, N. Bouhmaida, F. Avecilla, A. Spasojević-de Biré, U. Mioc, and J.Costa Pessoa, 6th International Vanadium Symposium, 17-19 July 2008, Lisboa, Portugal [2] D.L. Stokes, N.M. Green, Biophys. J. 78 (2000) 1765-1776 [3] T. Tiago, P. Martel, C.G.Merino, M. Aureliano, Bioch. Bioph. Acta 1774 (2007) 474-480 [4] S. Garcia-Vicente, Yraola F., L. Marti L., E. Gonzalez-Munoz, M.J. Garcia-Barrado, C. Canto, A. Abella, S. Bour , R. Artuch, C. Sierra, N. Brandi, C. Carpéne, J. Moratinos, M. Camps, M. Palacin, X. Testar, A. Guma, F. Alberici, M. Royo, A. Mian, A. Zorzano, Diabetes, 56 (2007) 486-493

Oral lectures


O44

Influence of polydentate ligands in the structure of dinuclear V(V) compounds

Fernando Avecilla,a Pedro Adão,b Isabel Correiab and João Costa Pessoab

a Departamento de Química Fundamental, Universidade da Coruña, Campus da Zapateira s/n, 15071, A

Coruña, Spain. email: [email protected] b Centro de Química Estrutural, Instituto Superior Técnico, TU Lisbon, Av. Rovisco Pais,

1049-001 Lisboa, Portugal

A variety of vanadium complexes have been introduced as structural and/or functional models for biologically active vanadium compounds.[1] Schiff base complexes with functional amine groups constitute a specific subfamily within this group. A wide range of asymmetric Schiff base compounds containing primary amine functions can be prepared in one step by the reaction of corresponding aldehyde and the appropriate diamine. Although the initial mixture contain VIV and Schiff base ligands, a VV complex with the half Schiff-base monoanionic ligand were obtained in some cases, where one of the imine bonds hydrolyzed.[2] The oxidation of VIV was probably due to diffusion of air into the solution. The resulting VO2L complexes contained tridentate ligands with phenolate, imine, and amine coordination to the dioxovanadium(V) ion. X-ray structures of these compounds demonstrate that they form dimers in the solid state with a V2O4 core, which is in equilibrium with the monomer in solution. There have been many O-bridged dinuclear vanadium (IV and/or V) complexes the structures of the which have been determined by X-ray diffraction, although those involving the OVV(μ-O)VVO unit (V2O3 core) with tridentate or tetradentate ligands are relatively rare.[3] Water molecules can block the second μ-O bridge such as in the complex [{VO(van-L-ser)H2O}2-μ-O],[4] but this effect can be exercised by the ligand itself when it acts as polydentate. We present the structures of a series of dinuclear vanadium complexes with Schiff base and functional amine ligands. This work illustrates the high propensity of the vanadium center to increase its coordination number via dimerization of two pentacoordinate monomers if the steric control exercised of the ligands allow it.

Acknowledgements: The authors thank FEDER, Fundação para a Ciência e a Tecnologia, POCI 2010 (PPCDT/QUI/55985/2004 and PPCDT/QUI/56946/2004 programs). [1] D. Rehder, Coord. Chem. Rev. 1999, 182(1), 297-322. [2] I. Correia, J. Costa Pessoa, M. T. Duarte, R. T. Henriques, M. F. M. Piedade, L. F. Veiros, T. Hakusch, T. Kiss, A. Dörnyei, M. M. C. A. Castro, C. F. G. C. Geraldes and F. Avecilla, Chem. Eur. J. 2004, 10, 2301-2317. [3] I. Cavaco, J. Costa Pessoa, M. T. Duarte, R. T. Henriques, P. M. Matias and R. D. Gillard, J. Chem. Soc., Dalton Trans., 1996, 1989-1996. [4] C. Grüning, H. Schmidt and D. Rehder, Inorg. Chem. Commun. 2, 1999, 57-59.

Oral lectures


O45

Hexavanadate core and discovery of double stranded octadecavanadate

Yoshihito Hayashi, and Kiyoshi Isobe

Departament of Chemistry, Graduate School of Natural Science, Kanazawa University, Kanazawa 920-1192, Japan


The chemistry of polyoxovanadates have been explained by the equilibrium between metavanadate and decavanadate which has a structure with fused hexavanadate, one of the well-established hexametalate core in polyoxometalate chemistry. The growing process that turns monovanadate into decavanadate, are not fully rationalized in terms of step-by-step reaction mechanisms, and there are certain possibilities of an involvement of un-realized intermediate such as hexavanadate in those processes. In vanadate chemistry, the negative charge build up through the formation of hexavanadate may result in the failure of isolation. The efforts to isolate the hexavanadate core had been established by the introduction of protecting ligand such as organometallic groups or multidentate-alkoxo ligands for compensation of the build up negative charge. In this study, we disclose a simple method to synthesize a hexaalkoxohexavanadate from the infinite vandate sheets. The hexavanadate was stabilized by symmetrically coordinated hexamethoxo ligands. The hexamethoxo-hexavanadate was unstable in terms of isomerization as well as hydrolysis reaction. By the utilization of the hydlorytic nature of the hexavanadate core, we could condensate the units into the bowl-type dodecavanadate in dichloromethane. The resulting dodecavanadate has unlike predecessor, no acetonitrile template was included at the center, instead, a dichloromethane molecule was located on top of the open mouse of the bowl. In other view, we synthesized the empty bowl which may be suitable for the insertion of the other type of template. The condensation reaction can be viewed as the transition of two hexavanadate core into the one decavanadate core, the 6+6 addition reaction. In this structure, the open-end of the bowl was constructed by cyclic octavanadate. The octavanadate ring was also observed in reduced decavanadate. The reduced decavanadate can be converted to octadecavanadate species with nitrate template. The discovery of the octadecavanadate which has a double stranded octavanadate ribbons in the spherical molecule capped by two square pyramidal VO5 units at the both end of the strands, may lead a new bioinorganic vanadate chemistry. The valence state of the two octavanadate ribbons are V(V), while the capping two VO5 pyramidal groups are V(VI). This molecule is a pure inorganic chiral molecule, and the chirarity arose from the inorganic structure itself. The absolute structure has been determined for a given crystal in a solid state. However, we could not optically resolve those crystals by hand-picking, except for the crystallography which need only one crystal. To address the question whether the inorganic chiral core is maintained or not in a solution, we tried the structural investigations in an acetonitrile through the XAFS studies. The XAFS absorption edge show a clear splitting according to the different oxidation state of V(V) and V(VI). The EXAFS interpretation supports the existence of DNA-like inorganic molecule in a solution. The vanadium K-edge signals of a solid state sample and a sample in acetonitrile has an close match. The corresponding Fourier transform also show close match through the region less than 2.8 Å which are attributable to V=O, V-O and V-V distances, but 3-4 Å region show a slight shifts.

Figure 1. Polyhedral representation of double stranded octadecavanadate. Capped square-pyramidal V(VI)

group are showed in hatched pyramid, the octavanadate ribbons are represented as a gray ribbon and a white ribbon. Both ribbon are constructed by the edge sharing of eight VO5 pyramids.

Oral lectures


O46

Structural and electrostatic properties of a decavanadate-cytosine co-crystallized complex

Nour Eddine Ghermani,a,f Nada Bosnjakovic-Pavlovic,a Isabel Tomaz,b Nouzha Bouhmaida,c Fernando Avecilla,d Anne Spasojević-de Biré,a Ubavka Mioce and

João Costa Pessoab

aEcole Centrale Paris, Laboratoire SPMS UMR CNRS 8580 1, Grande Voie des Vignes 92295 Châtenay-Malabry, France

bCentro de Quimica Estrutural, Instituto Superior Tecnico, TU Libon, Av. Rovisco Pais, 1049-001 Lisboa, Portugal

cLaboratoire des Sciences des Matériaux, LSM, Université Cadi Ayyad, Faculté des Sciences Semlalia, Boulevard Prince Moulay Abdallah, BP 2390, 40000 Marrakech, Morocco

dDepartamento de Química Fundamental, Facultad de Ciencias, Universidade da Coruña, Campus da Zapateira s/n, 15071 A Coruña, Spain

eFaculty of Physical Chemistry, University of Belgrade, P.O.Box 137, 11001 Belgrade, Serbia fLaboratoire de Physique Pharmaceutique UMR CNRS 8612, Faculté de Pharmacie 5 rue Jean-Baptiste

Clément, 92296 Châtenay-Malabry, France ; email: [email protected] Polyoxometalates (POM’s) of general formula: H6-xAxM10O28⋅nH2O, (A = K, Na, M = W, V, n = 0-30) crystallize with a various (generally large) number of water molecules. The primary structure of POM’s is formed by polyanions, whereas the secondary structure corresponds to an arrangement of interacting polyanions, cations, protons and water molecules. The interest on POM’s recently increased due to their medicinal applications (antiviral and antitumoral activity). Since the biological properties result from interactions with viral enzymes or with viral cell envelope, the understanding of these interactions at a molecular level is essential for the interpretation and the development of potent compounds with selective enzymatic affinity. For a better understanding of these interactions, accurate structure determinations from a single-crystal X-ray diffraction experiment are more than necessary. In our investigations, among the polyoxometalate compounds, we focused on the study of polyoxovanadates (POV’s); vanadium being less toxic than tungsten in biological mediums. POV’s interact with biomolecules with various and versatile activities (enzymes inhibitor or activator). For example, POV’s inhibit many phosphate-metabolizing enzymes like kinases [1], phosphorilases [2], Ca2+ ATP-ase [2], aldolase. In this context, the decavanadate-cytosine complex Na3V10O28(C4N3OH5)3(C4N3OH6)3 ·10H20 has been synthesized and its crystal structure has been determined from a single-crystal X-ray diffraction experiment at different temperatures. At room temperature, the crystal structure is dominated by an extensive network of hydrogen bonds involving the protonation-deprotonation of the cytosine molecules. We have observed a phase transition occurring below 200K from P-1 to P1 space group due to the protonic stabilization of one cytosine molecule in the unit cell. A high resolution X-ray diffraction experiment at 210K (in P-1 space group phase) was carried out. The data were refined using a pseudo-atom multipole model [3] in order to obtain the charge density distribution and the electrostatic properties of the decavanadate-cytosine DNA base complex. The nature of interactions between decavanadate anions and the cytosine base were carefully highlighted and analyzed. [1] D.W.Boyd, K.Kustin, M.Niwai, Biochim. Biophys.Acta (1985) 827, 472-475. [2] P. Csermely, A. Martonosi, G.C. Levy and A.J. Ejchart, Biochem.J (1985) 230, 807-815. [3] N. Hansen, P. Coppens, Acta Crystallogr. (1978) A34, 909-921.

Oral lectures


O47

A new oxo-Vanadium complex employing an imidazole rich tripodal ligand

Octávio A. C. Antunes, Tatiana L. Fernandez, Lorenzo C. Vinsetin and

Marciela Scarpellini

Departamento de Química Inorgânica, IQ/UFRJ, Av.Athos da Silveira Ramos, 149, Rio de Janeiro, RJ, Brazil, email: [email protected]

Vanadium complexes have been investigated for several applications including biomimetic model compounds, insulin mimics and catalysts. Aiming to develop new vanadium catalysts for oxidation processes we have used the imidazole rich tripodal ligand BMIMAPY1, [(bis(1-methylimidazol-2-yl)methyl)(2-(pyridyl-2-yl)ethyl)amine]. The reaction of stoichiometric amounts of BMIMAPY, [VO(acac)2] and NaClO4, in methanol, afforded slightly violet single crystals of [VO(acac)(BMIMAPY)]ClO4 suitable to X-ray analysis. The crystal structure (Figure 1) reveals a mononuclear oxovanadium cation complex in a distorted octahedral geometry. The two imidazole nitrogen atoms and the two oxygen atoms from the acac ligand comprise the equatorial plane, in an arrangement where the atoms of the same nature are cis to each other. Completing the coordination sphere are the tertiary amine nitrogen atom and one oxygen at 1.590 (4) Å, indicating the oxo character of the bond. It is also observed that the pyridine group stays uncoordinated.

Figure 1. Ortep view of the cation complex [VO(acac)(BMIMAPY)]+.

The infrared spectrum of the complex [VO(acac)(BMIMAPY)]ClO4 presents typical bands of the ligand skeletal overloaded with those from the acac coordinated in a bidentate mode. It is also observed two strong bands at 1092 cm-1, typical of the perchlorate anion, and at 990 cm-1 tentatively attributed to the stretching of the V=O bond. Analytical calculated for VC22H32ClN6O7 (found): C, 45.64 (45.06); H, 5.57 (5.28); N, 14.52 (14.07). Electronic spectrum recorded in acetonitrile solution (1x10-2 molL-1) shows two weak bands at 736 nm (ε = 30 mol-1Lcm-1) and 547 nm (ε = 10 mol-1Lcm-1) assigned to d-d transitions. The redox behavior of [VO(acac)(BMIMAPY)]ClO4 is under investigation by cyclic voltammetry, and the results will be presented. Acknowledgements: The authors would like to thank Faperj and Capes for their help and financial support. [1] M. Scarpellini et al. Inorg. Chim. Acta 357 (2004) 704-715.

Oral lectures


O48

Oxovanadium(V) compounds with bis(hydroxyamino)-triazines: Synthesis, structural, and physical studies

Vladimiros A. Nikolakis,a John T. Tsalavoutis,b Michael P. Sigalas,b Marios Stylianou,c Evgenios Evgeniou,c Artem Melman,d Tamas Jakusch,e Tamas Kiss,e Anastasios D.

Keramidas,c and Themistoklis A. Kabanosa

aDepartment of Chemistry, Section of Inorganic and Analytical Chemistry, University of Ioannina, 45110 Ioannina, Greece.

bDepartment of Chemistry, Laboratory of Applied Quantum Chemistry, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece,

cDepartment of Chemistry, University of Cyprus, 1678 Nicosia, Cyprus dThe Institute of Chemistry, The Hebrew University of Jerusalem, Givat Ram, Jerusalem 91904, Israel,

eDepartment of Inorganic and Analytical Chemistry, Attila Joszef University, Szeged, Hungary.

Bis-(hydroxyamino) triazines constitute a new, general and highly versatile group of tridentate vanadium(V) chelating agents exhibiting higher affinity to vanadium(V) than other tridentate vanadium(V) chelators. Two vanadium(V) compounds of hydroxyamino-1,3,5,-triazine ligand 1,2 were synthesized and characterized both in solution and in the solid state. Compound 2 is very stable in a large region of the pH scale, from 2.0 to 11.5, as it was evidenced by multinuclear NMR and potentiometric studies.

1 2

Acknowledgement. This research is part of the PENED03 research project, implemented within the framework of the “Reinforcement Program of Human Research Manpower” (PENED) and co-financed by National and Community Funds (25% from the Greek Ministry of Development-General Secretariat of Research and Technology and 75% from E.U.-European Social Fund).

Oral lectures


O49

Ring-substituted vanadocene(IV) and molybdenocene(IV) complexes

Jan Honzíček,a Carlos C. Romãoa and Jaromír Vinklárekb

a Instituto de Tecnologia Química e Biológica da Universidade Nova de Lisboa, Av. da República, EAN, 2780-

157, Oeiras, Portugal, email: [email protected]; b The Department of General and Inorganic Chemistry, University of Pardubice, nám.Čs. Legií 565, 532 10 Pardubice, Czech Republic.

Among other applications, bent metallocene complexes of the type [Cp2MCl2] (M = Ti, V, Nb, Mo) have also been investigated for biological applications ever since their antitumor activity was discovered.[1] Due to the particular requirements of such applications considerable attention has been given in the last few years to the synthesis of modified complexes.[2] Substitution of halide ligands leaves the “Cp2M” moiety unchanged and the properly chosen substituents can help overcoming some problems that complicate application of the parent compounds such as low water solubility or biological incompatibility. However, modification of the Cp rings seems to be a more promising approach for solving the above-mentioned problems. Such modification enables the fine tuning of cytostatic properties. Moreover, it allows the introduction of reactive groups that offer an anchor to append biologically active molecules capable of directing the final complex to the target receptors or diseased tissues. Ring-substituted vanadocene compounds were prepared using the reaction between (acac)2VCl and MgCl salt of appropriate substituted cyclopentadiene (Cp’MgCl). The obtained monochloride complexes (Cp’2VCl) were then oxidized to desired dichlorides (Cp’2VCl2). This method is suitable for synthesis of symmetrically disubstituted (Cp’2VCl2) and ansa-bridged vanadocene compounds (A-(C5H4)2VCl2), see Fig.1b, c. Compounds containing amines and ethers in the side chain were prepared using this pathway. Molybdenocene compounds were prepared using multistep route starting from allyl complex [(η3-C3H5)Mo(CO)2(NCMe)2Cl]. Subsequent bonding of Cp ring together with mild reaction conditions enable to assembly of the Cp’CpMo moiety containing ether and carboxylic acid ester function groups in the side chain (Fig.1a). This route is even suitable for synthesis of compounds with reactive function groups. Haloethyl-substituted compounds were obtained applying ring-opening reaction of spiro[2.4]hepta-4,6-diene.[3]

a) b) c)

Figure 1. a) monosubstituted compound b) 1,1’-disubstituted compound; c) ansa-metallocene.

Acknowledgements: We are grateful to Fundação para a Ciência e Tecnologia (FCT, Portugal) for supporting through postdoctoral project SFRH/BPD/24889/2005. [1] H. Köpf, P. Köpf-Maier, Angew. Chem.-Int. Edit. Engl. 18 (1979) 477-478. [2] P. M. Abeysinghe, M. M. Harding, Dalton Trans. (2007) 3474-3482. [3] J. Honzíček, F. A. A. Paz, C. C. Romão, Eur. J. Inorg. Chem. (2007) 2827-2838.

Oral lectures


O50

Vanadium catalysts for the partial oxidation of alkanes under mild conditions

Armando J.L. Pombeiro, Telma F. S. Silva, Gopal S. Mishra, Marina V. Kirillova,

Elisabete C.B.A. Alegria, Luísa M.D.R.S. Martins, Alexander M. Kirillov, Maria F.C. Guedes da Silva, Maxim L. Kuznetsov, António Palavra, José A.L. da Silva, João J. R.

Fraústo da Silva

Centro de Química Estrutural, Complexo I, Instituto Superior Técnico, Av. Rovisco Pais, 1049-001 Lisboa, Portugal.

e-mail: [email protected]

Partial oxidation reactions of saturated hydrocarbons under mild conditions are expected to

provide promising methods towards the use of such unreactive compounds as raw materials for

organic syntheses. This general aim constitutes a challenge to modern Chemistry and the field

is also of biological significance in view of the ability of a few enzymes to catalyse the partial

oxidation of alkanes.

Our initial studies by using, as a catalyst, Amavadin, a natural bare vanadium complex with a

still unknown biological role, have been extended to other vanadium catalysts which are shown

to be particularly active for the following general types of oxidation reactions:

- Peroxidative oxidations of alkanes to alcohols and ketones, typically with aqueous

hydrogen peroxide (a “green” oxidant), at room temperature.

- Oxidations of alkanes with dioxygen (the ideal oxidant) in solvent free systems, by

using supported catalysts on modified silica.

Such reactions will also be compared with alkane carboxylations leading to carboxylic acids.

Some of the V-systems provide the highest catalytic activity so far reported in the field of

alkane functionalization under mild or moderate conditions. They are compared with those

based on other metals, and plausible radical mechanisms are discussed on the basis of radical

trap and 13C-labelled experiments, and of DFT theoretical studies.

Acknowledgements: This work has been partially supported by the Fundação para a Ciência e a Tecnologia and its POCI 2010 programme (FEDER funded). [1] T.F.S. Silva, E.C.B.A. Alegria, L.M.D.R.S. Martins, A.J.L. Pombeiro, Adv. Synth. Cat., 2008, 350,706. [2] G.S. Mishra, J.J.R. Fraústo da Silva, A.J.L. Pombeiro, J. Mol. Cat. A: Chem., 2006, 265, 59-69. [3] M.V. Kirillova, M.L. Kuznetsov, P.M. Reis, J.A.L. Silva, J.J.R. Fraústo da Silva, A.J.L. Pombeiro, J. Am Chem. Soc., 2007, 129, 10531. [4] M.V. Kirillova, M.L. Kuznetsov, J.A.L. Silva, M.F.C. Guedes da Silva, J.J.R. Fraústo da Silva, A.J.L. Pombeiro, Chem. Eur. J., 2008, 14, 1828. [5] M.V. Kirillova, J.A.L. da Silva, J.J.R. Fraústo da Silva, A.F. Palavra, A.J.L. Pombeiro, Adv. Synth. Cat., 2007, 349, 1765. [6] M.V. Kirillova, A.M. Kirillov, P.M. Reis, J.A.L. Silva, J.J.R. Fraústo da Silva, A.J.L. Pombeiro, J. Cat., 2007, 248, 130.

Oral lectures


O51

Oxovanadium (IV) complexes of carbohydrates. Some recent advances

Enrique J. Baran

Centro de Química Inorgánica (CEQUINOR; CONICET/UNLP), Facultad de Ciencias Exactas,

Universidad Nacional de La Plata, C. Correo 962, 1900-La Plata, Argentina email: [email protected]

Carbohydrates and their derivatives are the most abundant class of biomolecules and have a

large variety of biological functions. The interaction of these poly-functional molecules with

metal cations in living organisms is of special interest as it occurs during many important

biological processes. In particular, the interaction of carbohydrates with different vanadium

species has great relevance for vanadium biochemistry, especially in relation to its metabolism

in the higher forms of life1,2 and to its biological detoxification1-4. Therefore, it constitutes an

area of increasing research interest. In fact, most sugars can reduce vanadium (V) to

oxovanadium (IV), VO2+, and strongly complex this cation. Some years ago we analyzed the

most interesting and characteristic aspects of these complexes5. In this communication we

present some relevant results from recent studies in this field, which include:

1) Synthesis and characterization of some new oxovanadium (IV) complexes derived from a

variety of carbohydrates and related species.

2) First studies on the formation of VO2+ complexes with conduritols.

3) Spectroscopic investigation of the interaction of VO2+ with chitosan.

In all cases, the complexes were characterized by a combination of spectroscopic techniques,

including infrared, Raman and UV-visible measurements.

Acknowledgements: The author acknowledges the continuous support from the “Consejo Nacional de Investigaciones Científicas y Técnicas de la República Argentina” (CONICET). [1] E.J. Baran, J. Inorg. Biochem. 80 (2000) 1-10. [2] E.J. Baran, J. Braz. Chem. Soc. 14 (2003) 878-888. [3] E.J. Baran, In Vanadium in the Environment (J.O. Nriagu, Edit.), Vol. 2, 317-345, J. Wiley, New York (1998). [4] E.J. Baran, Chem. Biodivers., in the press. [5] E.J. Baran, J. Carbohydr. Chem. 20 (2001) 769-788.

Oral lectures


O52

Vanadis Awardee

Vanadium-catalyzed oxidative bromination reaction under molecular oxygen

Toshikazu Hirao, Toshiyuki Moriuchi, and Kotaro Kikushima

Department of Applied Chemistry, Graduate School of Engineering, Osaka University, Yamada-oka, Suita,

Osaka 565-0871, Japan. email: [email protected]

Bromination of organic compounds is one of the most important reactions in organic

synthesis. Conventional bromination involves the use of hazardous and tedious elemental

bromine. To avoid the use of bromine, an alternative environmentally friendly method is

required. From these points of view, considerable efforts have been focused on to develop an

efficient bromination reaction based on function of vanadium bromoperoxidase (VBrPO), which

is found in marine algae. We have already demonstrated the efficient bromination reaction

under relatively mild conditions by using NH4VO3 catalyst combined with H2O2, KBr, and HBr in

an aqueous media.1 This result prompted us to develop a more environmentally favorable

catalytic bromination reaction as described herein.

The oxidative bromination reaction of 1,3,5-trimethoxybenzene with 10 mol% of NH4VO3,

200 mol% of tetrabutylammonium bromide (TBAB), and 200 mol% of p-toluenesulfonic acid

monohydrate (PTS·H2O) in MeCN under oxygen smoothly proceeded to afford the corresponding

bromination product in a high conversion. In the case of α-methylstyrene as an alkene

substrate, the corresponding dibromo and bromohydrin derivatives were obtained in 100%

conversion at room temperature.

Br

Br

Br

OH

33% 62%

NH4VO3TBABPTS·H2O

MeCN, O2, reflux, 40 hMeO

OMe

OMe MeO

OMe

OMe

Br

10 mol%200 mol%200 mol%

NH4VO3TBABPTS·H2O

MeCN, O2, rt, 6 h

1 mol%200 mol%200 mol%

+

79%

[1] T. Moriuchi, M. Yamaguchi, K. Kikushima, T. Hirao, Tetrahedron Lett. 48 (2007) 2667-2670.

Oral lectures


O53

Electron Paramagnetic Resonance of Vanadium(III) coordination complexes

Jurek Krzystek

National High Magnetic Field Laboratory, Florida State University, Tallahassee, Florida, 32310 USA


Vanadium has long been an appealing transition metal for study due to its wide range of

oxidation states and associated beautiful colors of its complexes. Among these oxidation states,

V(III) has traditionally been less studied than V(IV) or V(V), which have better defined

biological/physiological roles. However, V(III) has recently become more intensely investigated

due to the its observation in marine organisms, namely in the blood cells of ascidians. An exotic

biological role for a given metal ion is sure to pique the interest of the inorganic community, and

if that metal ion happens to be also of the open-shell type, it will surely make an odd EPR

spectroscopist interested, too. At the same time V(III) (3d2 “non-Kramers” configuration)

complexes, which have long been considered “EPR-silent” due to the typically large zero-field

splitting in their ground spin triplet state, have now become amenable to EPR detection through

the availability of high microwave frequencies, and magnetic fields [1, 2].

Indeed, our interest in V(III) also stems from a biological role, however quite different from the

above; it is due to the presence of vanadium-containing nitrogenase (V-N2ase). An EPR study of

V(III) in this enzyme is still ahead of us; however, we concentrate on V(III) complexes with

sulfur-rich ligands that are model compounds for V-N2ase. In the course of high-frequency and -

field EPR investigations of these systems, we also realized the need for comparison studies on

complexes of V(III) with more “innocent” ligands, as complexes of sulfur donors can often

exhibit ambiguous oxidation states and are decidedly “non-innocent”. We will thus cover two

other classes of V(III) complexes containing only oxygen- and nitrogen-donating ligands:

aminocarboxylates such as EDTA and related compounds, and heterocycles. Of particular

interest to us is the relationship between magnetic properties of the investigated complexes,

and their electronic and geometric structure. Experimental investigations will be complemented

by preliminary calculations of the spin Hamiltonian parameters using DFT-related methods.

Acknowledgements: I am greatly indebted to my collaborators on this project: Joshua Telser (Roosevelt University, Chicago, USA), Hua-Fen Hsu (National Cheng Kung University, Tainan, Taiwan) and Marcin Brynda (University of California, Davis, USA). [1] J. Krzystek, S. A. Zvyagin, A. Ozarowski, S. Trofimenko, J. Telser, J. Magn. Reson. 178 (2006) 174-183. [2] J. Krzystek, A. T. Fiedler, J. J. Sokol, A. Ozarowski, S. A. Zvyagin, T. C. Brunold, J. R. Long, L. C. Brunel, J. Telser, Inorg. Chem. 43 (2004) 5645-5658.

Oral lectures


O54

Structure and spectroscopic properties of new VIV/V semiquinone and hydroquinone complexes

Anastasios D. Keramidas,a Chryssoula Drouza,b Marios Stylianoub

aDepartment of Chemistry, University of Cyprus,1678 Nicosia, Cyprus, email: [email protected];

bDepartment of Agriculture Production, Biotechnology and Food Science, Cyprus University of Technology, 3603, Limasol, Cyprus, email: [email protected]

The investigation of the association between the electron and proton transfer in the metal ion -

hydroquinone/semiquinone/quinone interacting systems is particularly important in order to

understand the factors which regulate the redox potentials and the pathways in electron

transfer reactions between transition metal centers and p-semiquinone radicals. The interaction

of p-hydroquinones with vanadium in high-oxidation states presents additional interest due to

the participation of vanadium in redox reactions in biological systems [1] such as the reduction of

vanadium(V), present in sea water, to vanadium(III) in the blood cells of tunicates [2, 3].

Our focus in this work is on the synthesis and characterization in solid state and solution of

stable complexes of vanadium with p-semiquinonate radicals as well as the investigation of the

H+ induced electron transfer between the VIV/VV metal centers and the coordinated

semiquinonate/hydroquinonate ligands. Substituted hydroquinones with chelate groups

(Scheme 1) were used to stabilize vanadium complexes. The VIV/VV –

semiquinonate/hydroquinonate tetranuclear and dinuclear species produced from this electron

transfer were isolated from aqueous or acetonitrile solutions and the oxidation states of the

ligand were indisputably determined by X-ray crystallography. UV-Vis and NMR spectroscopies

and electrochemistry were employed for the investigation of the speciation and redox properties

of these complexes in aqueous solution.

Scheme 1. Hydroquinone ligands.

Acknowledgements: The authors would like to thank PRF of Cyprus (TEXNO/0506/19) for their financial support . [1] D. Rehder, Coordination Chemical Reviews 182(1999) 197. [2] P. Frank, P., K.O. Hodgson, Inorganic Chemistry 39(2000) 6018. [3] C. Drouza, V. Tolis, V. Gramlich, C. Raptopoulou, A. Terzis, M.P. Sigalas, T.A. Kabanos, A.D. Keramidas, Chem. Commun. (2002) 2786.

Oral lectures


O55

Vanadium coordination complexes with the [CpP(OEt,OEt)Co]- ligand : Towards catalysis

Craig C. McLauchlan, Michael P. Weberski, Jr.

Department of Chemistry, Illinois State University, Normal, IL 61790-4160 USA,


Broadly stated, my laboratory is interested in vanadium coordination chemistry. In the course of our investigations of vanadium-containing compounds for use as potential oxidation catalysts, we have generated a series of metal coordination complexes with tridentate ligands that effectively oxidize catechols to quinones. We recently communicated some of the preliminary work focusing on complexes with the [CpP(OEt,OEt)Co]- ligand, specifically [CpP(OEt,OEt)Co]VCl2(DMF), 1, where DMF is N,N-dimethylformamide.1 Here we discuss the reactivity of 1 and clarify the products produced. X-ray structural analysis has allowed us to positively identify products 5-7 in the shown reaction scheme, but crystallization of complexes 2-4 remain elusive. These octahedral vanadium(III) phosph(on)ate cluster complexes with a V4P4O12core can be synthesized by varying the phosphonate salt used (RPO(O)2, R = Me, tBu, Ph). In a parallel project more focused on bioinorganic chemistry, we are also investigating complex 1 for its alkaline phosphatase inhibition properties using enzyme kinetics studies. Our most recent results will be presented here.

Figure 1. Reactivity scheme for CpP(OEt,OEt)Co]VCl2(DMF), 1.

Acknowledgements: The authors would like to thank the National Science Foundation (U.S., CHE-0645081) and the American Chemical Society- Petroleum Research Fund (46064-B3) for financial support. [1] M. P. Weberski, Jr., C. C. McLauchlan, Inorg. Chem. Commun. 10 (2007) 906-908.

Oral lectures


O56

Bio-inspired synthesis of bionanocomposites elastomers via a complex coacervation process between gelatin and decavanadates

Florent Carn,a Olivier Durupthy,a Nathalie Steunou,a,* Thibaud Coradin,a,* Madeleine

Djabourov,b Bruno Fayolle,c François Ribot a and Jacques Livage a

aLaboratoire de Chimie de la Matière Condensée de Paris, UPMC Univ. Paris 6, Collège de France, France, bLaboratoire de Physique Thermique, E.S.P.C.I., Paris, France,

cLaboratoire d’Ingénierie des Matériaux, E.N.S.A.M. Paris, France. *email : [email protected] ; [email protected]

Vanadium (V) oxide materials are well-known for their physical properties such as redox, semi-conducting and intercalation properties. Thus, they are currently used as antistatic coatings, cathode for Li-batteries or catalytic materials. A possible challenge consists i) in improving the conduction, mechanical and/or intercalation properties by combination with an organic polymer with specific functionalities and ii) in optimizing the morphology at different length scales. Such hybrid materials with tailored morphologies can be obtained in soft reaction conditions via bio-inspired strategies where the inorganic network growth is spatially directed by an organic polymer. Besides, this biopolymer may improve or even induce some new physical properties. Following this approach, we have synthesized a new vanadium oxide-gelatin hybrid material showing a striking rubber-like elastic character (figure 1). This elastomer is formed at a temperature higher than 25°C whereas the sol-gel transition of gelatin occurs at T<25°C.

1 2 4 60

2

4

6

σ =

F/S

0 (MPa

)

λ

a ) b )

Neo-Hookeenbehavior

Experimentaldata

1 2 4 60

2

4

6

σ =

F/S

0 (MPa

)

λ

a ) b )

1 2 4 60

2

4

6

σ =

F/S

0 (MPa

)

λ

a ) b )

Neo-Hookeenbehavior

Experimentaldata

Figure 1. a) Photopraph of a decavanadate-gelatin bionanocomposite showing a rubber-like character ; b)

Cauchy stress (F/S0) as a function of the drawing ratio (λ). The red curve presented is a fit corresponding to

a neo-hookeen behavior with a rubbery modulus of 0.6 MPa.

First of all, we have studied the influence of pH, gelatin and vanadate relative concentrations on nanocomposite formation. Then, the material structure and morphology has been fully characterized by 51V MAS NMR, XRD, SEM, TEM while its mechanical behavior has been quantified under tensile load. 51V MAS NMR spectroscopy suggests that the cohesion of this hybrid material arises from electrostatic interactions between decavanadate anions [H2V10O28]

4- and positively charged chains of gelatin. Under aging conditions, we have observed by XRD and TEM that these interactions at the organic-inorganic interface strongly affect the V2O5 network growth by slowing down the condensation process and preventing the regular layers stacking in the material. Finally, we have proposed a mechanism of formation based on an analogy with complex coacervation process1 in good agreement with 51V NMR, DLS, rheological and calorimetric measurements. [1] F. Carn, N. Steunou, M. Djabourov, T. Coradin, F. Ribot, J. Livage, Soft Matter, 4 (2008) 735-738.


Poster Presentations

Poster presentations




P1

DFT model studies of vanadium chloroperoxidase: dissociative or associative enzymatic mechanism and its dependency on the degree of

protonation

Daniel Geibig, Winfried Plass

Friedrich-Schiller-Universität Jena, Institut für Anorganische und Analytische Chemie Carl-Zeiss-Promenade 10, 07745 Jena, Germany, email: [email protected]

It has been shown that for particular modes of action of vanadium chloroperoxidase different pH optima are observed:1 At the one hand the enzyme shows its highest activity at pH 5.0 but on the other hand the reaction rate of the formation of the peroxovanadate species is higher at pH 8.3. Although doubly protonated form of the vanadate cofactor is commonly accepted,2,3 it remains unclear whether the first reaction step of the enzymatic cycle proceeds in a dissociative or associative manner. There are molecular dynamics simulations which imply an associative mechanism4 as well as DFT model studies suggesting a dissociative mechanism.5 The results of our DFT model studies point towards a pH dependency for the reaction mechanism of the formation of the initial peroxovanadate species: Whereas a high degree of protonation promotes a dissociative pathway, this kind of reaction mechanism can be ruled out for a lower degree of protonation because of the high reaction barrier. Further studies concerning the influence of the degree of protonation on an associative mechanism are in progress.

Figure 1. With TURBOMOLE/RI-DFT/BP86/TZVP optimized structures of the native site (left) and the

peroxovanadate species (right).

As model system a cutout of the active site of the vanadium chloroperoxidase crystal structure (1IDQ)6 containing the important hydrogen bonds in the direct environment of the vanadate cofactor is utilized (see Figure 1). All heavy atoms of the backbone are fixed for maintaining the enzymatic structure while side chains and all hydrogen atoms are free to move.

[1] R. Renirie, W. Hemrika, S.R. Piersma, R. Wever, Biochemistry 39 (2000) 1133-1141. [2] M. Bangesh, W. Plass, J. Mol. Struct. Theochem 725 (2005) 163-175. [3] W. Plass, M. Bangesh, S. Nica, A. Buchholz, ACS Symp. Ser. 974 (2007) 163-177. [4] S. Raugei, P. Carloni, J. Phys. Chem. B 110 (2006) 3747-3758. [5] G. Zampella, P. Fantucci, V.L. Pecoraro, L. De Gioia, Inorg. Chem. 45 (2006) 7133-7143. [6] A. Messerschmidt, L. Prade, R. Wever, Biol. Chem. 378 (1997) 309-315.



P2

Anion “complexes” of diperoxo-vanadate Model compounds for haloperoxidase enzyme?

Tamás Jakusch, Tamás Kiss

Departament of Analitical and Inorganic Chemistry Department, SZTE, H-6721 Szeged, Dóm tér 7, Hungary,


The vanadium dependent haloperoxidase enzymes and their active sites are very well known. The X-ray structures revealed that the anionic cofactor, vanadate, is mainly bound via electrostatic interaction and a hydrogen-bond network from the positively charged amino acid residues, except of a single coordinating bond from Nε2 of a histidine to the metal center.1 Although almost in all functional model compounds of these enzymes, developed until now, the ligand(s) coordinate(s) via 2-4 covalent bound to the central vanadium atom. The typically oxoperoxo vanadium(V) compounds does not have hydrogen-bound network environment. These complexes practically capable oxidize just iodine and bromine but not chlorine and only in special condition: non-aqueous solutions and in presence of strong acid.2,3 However the enzyme are oxidize chlorine in water at pH ~5.5.1 Based on the vanadate-phosphate structural analogy, phosphate receptors/sensors can be used vanadate/peroxo-vanadate binders too, as earlier works showed already.4-6 Since the vanadate speciation is quite complicated in aqueous solution and the monoperoxo-vanadate is not stabile in such conditions, we focused on the diperoxo-vanadate which has more simple speciation in water.7

0.0

0.2

0.4

0.6

0.8

1.0

2 4 6 8 10 12pH

V fr

actio

n

[HVO2(OO)2]2-[H2VO2(OO)2]

-

[HV2O3(OO)4]3-

10 mM

[V2O5(OO)3]6-

A

0.0

0.2

0.4

0.6

0.8

1.0

2 4 6 8 10 12pH

V fr

actio

n

[HVO4]2-10 mM

[V2O7]4-

[HV2O7]3-

[V4O12]4-

[HV10O28]5-[H2V10O28]

4-

[V5O15]5-

[H2VO4]2-

[H2V2O7]3-

VO2+

[V10O28]6-

[H3V10O28]3-

B

Figure 1. A: Speciation of diperoxo-vanadate7, B: Speciation of vanadate

A promising ligand can be seen in Figure 2. The detailed studies are still in progress in our laboratory.

NN

O

O

NN

NN

H

H

H

H

Figure 2. A potentian diperoxo-vanadate binder8

Acknowledgements: The author (TJ) would like to thank the “Magyary Zoltán Felsőoktatási Közalapítvány” for the financial support. [1] R. Wever, W. Hemrika, Vanadium haloperoxidases. Handbook of Metalloproteins (2001), 2 1417-1428. [2] J.Y. Kravitz,; V.L. Pecoraro, Pure and Appl. Chem. 77(9) (2005) 1595-1605. [3] A. Butler, M.J. Clague, G.E. Meister, Chem. Rev. 94(3) (1994) 625-38. [4] X. Zhang, M. Meuwly, W.D. Woggon, J. Inorg. Biochem. 98(11) (2004) 1967-1970. [5] X. Zhang, W.D. Woggon, J. Am. Chem. Soc. 127(41) (2005) 14138-14139. [6] S. Tapper, J.A. Littlechild, Y. Molard, I. Prokes, J.H.R. Tucker, Supramol. Chem. 18(1) (2006) 55-58. [7] I. Andersson, S. Angus-Dunne, O. Howarth, L. Pettersson, J. Inorg. Biochem. 80 (2000) 51–58 [8] H.F.M. Nelissen, D.K. Smith, Chem. Commun. (2007) 3039–3041.



P3

Decameric vanadate reduction by physiological concentrations of glutathione in mitochondrial assay conditions

Sandra S. Soaresa,b, Rui O. Duartec, Carlos Gutiérrez-Merinod, José J.G. Mourac,

Manuel Aurelianob,e

aFCMA, University of Algarve, Portugal; bCCMAR, University of Algarve; cREQUIMTE, Dept. Chemistry, FCT, University Nova of Lisbon; dDept. Biochemistry and Molecular Biology, University of Extremadura, Spain;

eDept. Chemistry and Biochemistry, FCT, University of Algarve; email: [email protected]

It is well known that vanadate and vanadyl interconvert easily under physiological conditions1. Vanadate seems to be more toxic for living systems and its conversion to vanadyl can be seen as an intracellular detoxification mechanism2. Moreover, the characterization of the composition of vanadate solutions is of extreme importance in order to correlate the vanadate promoted effects in biological systems with the oligomeric species and/or oxidation states present in these solutions3,4. The aim of this work is to determine if specific in vitro experimental conditions, such as the usual composition of mitochondrial assay buffers, physiological concentrations of reduced glutathione (GSH) or the presence of mitochondrial protein in the assay media, may contribute to vanadate reduction particularly at the polymerized state of vanadate, the decameric vanadate species. Changes in absorbance at 700 nm, for reduced vanadium form, were monitored by spectrophotometry, as previously described5. The reduction of decameric and monomeric vanadate species (1 mM total vanadium) was recorded in a reaction medium containing mitochondrial respiration buffer (0.2 M sucrose, 5 mM KH2PO4, 10 mM KCl, 5 mM MgCl2 and 10 mM Tris-HCl, pH 7.4 plus 5 mM pyruvate and 0.5 mM malate) and a physiological concentration of GSH (5 mM), in the absence or presence of rat hepatic mitochondria (0.5-2.0 mg protein/ml) (Figure 1). Vanadate reduction products were also recorded by Electron Paramagnetic Resonance (unpublished results).

Reduction of vanadate to a 700 nm-absorbing blue colored product, a form of vanadyl, was demonstrated _in the absence or presence of rat hepatic mitochondria using GSH as the reducing agent6. It was also observed that the increase in absorbance at 700 nm depends on the presence of decameric vanadate species, whereas no reduction of monomeric vanadate was noticed under the same experimental conditions. Reduction of decameric vanadate is accompanied by the loss of absorbance at 400 nm, pointing out that it induced decameric vanadate

decomposition (not shown). The presence of a tetravalent form of vanadium in these experimental conditions was confirmed by EPR, nevertheless, the weak signals obtained correspond to amounts of reduced products below the detection limit of the EPR instrument used (<10 µM). Note that, once vanadyl radical concentration keep lower than 10 µM it means that the vanadyl radical must be rapidly reacting with another vanadyl radical or with other chemical specie(s) present in the medium once formed by the reaction between GSH and vanadate, thus leading to a fairly low steady-state concentration. Therefore, in the presence of physiological concentrations of GSH the redox state of vanadate in neutral pH appears to be dependent on the decamerization of vanadate. Putting it al together, we can not exclude the possibility of a cross talk between oligomerization of vanadate and decavanadate reduction in biological systems, which can account, at least in part, for the role of vanadium in biological systems. Acknowledgements: Portuguese Foundation for Science and Technology (SFRH/BD/8615/2002 to SSS and project POCTI/38191/QUI/2001 to MA), joint Spanish-Portuguese Grant (HP2004-0080 to CG-M and MA). [1] D.C. Crans, Comments Inorg. Chem. 16 (1994) 1-33. [2] N.D. Chasteen, Struct. Bonding 53 (1983) 105-138. [3] M. Aureliano, and R. M. C. Gândara, J. Inorg. Biochem., 99 (2005) 979-985;[4] S.S. Soares, F. Henao, M. Aureliano, C. Gutiérrez-Merino, Chem. Res. Toxicol. 21 (2008) 607-618. [5] T. Ramasarma, A.V.S. Rao, Mol. Cell. Biochem. 281 (2006) 139-144. [6] I.G. Macara, K. Kustin, L.C.C. Cantley Jr., Biochim. Biophys. Acta 629 (1980) 95-106.

Time (min)0 50 100 150 200 250 300 350

Abs

orba

nce

(700

nm

)

0.00

0.02

0.04

0.06

0.08 DecavanadateMetavanadate



P4

Template synthesis of a spherical polyoxovanadate(V) by oxidative coupling reaction

Shogo Kamiya, Yoshihito Hayashi, Kiyoshi Isobe

Department of Chemistry, Graduate School of Natural Science, Kanazawa

University, Kakuma, Kanazawa 920-1192, Japan

Redox coupling of polyoxovanadates in non-aqueous solvent under mild conditions may be suitable for conversion of certain series of polyoxovanadates into larger species. With the utilization of redox chemistry of vanadium, the isolation of a series of reduced polyoxovanadates with reductive coupling have been investigated. Alternatively, the oxidative coupling of polyoxometalates may be possible for the synthesis of fully oxidized polyoxovanadates. The nucleophilic species and electrophilic V(V) species produced by the controlled oxidation may prompt to couple two species into a larger polyoxovanadate. In this study, the structure and the coordination ability of the template molecules are also important for the synthesis of novel polyoxovanadates. By the addition of the template anions to the condensation reaction, we isolated a spherical triacontavanadate (V30) with V(V) oxidation state.

Figure. V30 structure of the left-handed type (left) and that of the right-handed type (right).

The shape of the V30 vanadate looks like reflecting the structure of the template anion. Furthermore, we found that this V30 vanadate has optical isomer. By the asymmetric crystallization, we characterized both structures with single crystal X-ray structural analysis.



P5

Asymmetric oxidation of thioanisole catalysed by reduced Schiff base oxovanadium(IV) complexes

Isabel Correiaa, Pedro Adãoa, João Costa Pessoaa, Fernando Avecillab

aCentro de Química Estrutural, Instituto Superior Técnico,TU Lisbon, 1049-001 Lisboa, Portugal,

email: [email protected] bDepartamento de Química Fundamental, University of Coruña, Spain

Vanadium complexes of the chiral reduced Schiff base ligands, prepared from 1S,2S-cyclohexanediamine or and 1S,2S-diphenylethylenediamine and 2-hydroxybenzaldehydes, [VO(sal(1S,2S-chan))] or [VO(sal(1S,2S-dpan))], catalyze the sulfoxidation of thioanisole with hydrogen peroxide, showing high conversions and moderate enantioselectivities1. Various parameters were tested such as solvent, temperature, catalyst loading, catalyst concentration and phenolic ring substituent effect on overall conversion and enantioselectivity. Methoxy substituents adjacent to the phenolate group improve chiral induction2. Lower temperatures also have a positive effect on chiral induction. The catalyst concentration also required optimization. Catalyst loadings higher or lower than 1 mol % seem to slow down the catalysis and decrease enantioselectivity. In the case of vanadium catalyzed sulfoxidations, it is very likely that the active species is an oxomonoperoxovanadium(V) complex3.

S

NH NH

O O

R R

M

S*

O

H2O2,

1: R=H-; R'=H-; M=VO2+

2: R=MeO-; R'=H-; M=VO2+

3: R=t-Bu-; R'=t-Bu-; M=VO2+

0-10ºC

R'R'

Scheme 1 – Asymmetric sulfoxidation of thioanisole catalysed by VO(sal(1S,2S-chan)) complexes. Acknowledgements. We thank the financial support of Fundo Europeu para o Desenvolvimento Regional, Fundação para a Ciência e Tecnologia, POCI 2010, project PPCDT/QUI/55985/2004 and the grant SFRH/BD/40279/2007.

[1] G. Romanowski, E. Kwiatkowski, W. Nowicki, M. Kwiatkowski, T. Lis, Polyhedron, 27 (2008) 1601-1609 [2] K. Nakajima, K. Kojima, M. Kojima, J. Fujita, Bull. Chem. Soc. Jpn., 63 (1990) 2620-2630 [3] A. Butler, M.J. Clague, G.E. Meister, Chem. Rev., 94 (1994) 625-638.



P6

Oxidation of p-chlorotoluene and cyclohexene catalysed by polymer-anchored oxovanadium(IV) and copper(II) complexes of amino acid

derived tridentate ligands

Amit Kumar,a Mannar R. Maurya,b Maneesh Kumar,b and João Costa Pessoaa

aCentro Química Estrutural, Instituto Superior Técnico, TU Lisbon, Av Rovisco Pais, 1049-001 Lisboa,

Portugal, email: [email protected] b Department of Chemistry, Indian Institute of Technology Roorkee, Roorkee-247667, India

3-Formylsalicylic acid (Hfsal) covalently bound to chloromethylated polystyrene (PS) cross-linked with 5% divinylbenzene reacted with DL-alanine (DL-Ala) and L-isoleucine (L-Ile) to give the Schiff-base tridentate ligand PS-H2fsal-DL-Ala and PS-H2fsal-L-Ile, respectively. These polymer-anchored ligands upon reaction with VOSO4 and Cu(CH3COO)2 form the polymer-bound complexes PS-[VO(fsal-DL-Ala)(H2O)], PS-[Cu(fsal-DL-Ala)(H2O)], PS-[VO(fsal-L-Ile)(H2O)] and PS-[Cu(fsal-L-Ile)(H2O)] (see Scheme). Structures of these immobilized complexes have been established on the basis of scanning electron micrographs, FTIR, UV-Vis, EPR, thermo gravimetric and elemental analyses studies. Non-polymer-bound CuII- and VIVO-complexes have also been prepared with these ligands, namely the vanadium complexes [VIVO(fsal-DL-Ala)(H2O)] and [VIVO(fsal-L-Ile)(H2O)].

These complexes have been used with success as catalysts for the oxidation of p-chlorotoluene and cyclohexene by H2O2 and reaction conditions have been optimised to obtain maximum conversion. EPR studies were especially useful to confirm that the VIVO- and CuII-complexes are magnetically diluted and well dispersed in the polymer matrix, and to give evidence for the binding modes proposed. Recycling studies indicated that these catalysts can be reused at least three times without any

N

R

O

OOO

OV

O

OH2

Proposed structure for the polymer-bound vanadium complexes: R = -CH3 (DL-Ala) or R = -CH(CH2CH3)CH3 (L-Ile). The ball represents the polystyrene matrix.

significant loss in their catalytic potential. However, EPR studies indicated that while the polymer supported VIVO-complexes did not change upon use, the EPR spectra of the Cu-complexes showed significant changes. Several EPR, 51V NMR and UV-Vis studies have been carried out to detect intermediate species, and outlines of the mechanisms of the catalytic reactions are proposed.

Acknowledgements: The authors thank the financial support from FEDER, Fundação para a Ciência e a Tecnologia, POCI 2010 (PPCDT/QUI/55985/2004 and PPCDT/QUI/56946/2004 programs) and grant SFRH/BPD/34835/2007. Prof. M. R. Maurya acknowledges the financial support received from the Council of Scientific and Industrial Research, New Delhi



P7

Organometallic chemistry of vanadium with B(C6F5)3

Christian Lorber and Robert Choukroun

Laboratoire de Chimie de Coordination du CNRS, 205 route de Narbonne, 31077 Toulouse, France, email: [email protected]

Vanadocene, which is the unique, stable, and easily accessible metallocene of the early transition metals, is an electronically and coordinatively unsaturated molecule. Other metallocenes of the early transition metals, such as titanocene and zirconocene do not exist in their original sandwich structure and need subtle ligand (alkyne, butadiene) to stabilize the metallocene fragment. A contrario the reactivity of the vanadocene [VCp2] compound, in spite of its accessibility, was scarcely studied probably due to the formation of various paramagnetic VIII and VIV compounds which prevent further spectroscopic informations.[1,2] The chemistry of the strongly Lewis acidic tris(pentafluorphenyl)borane B(C6F5)3 is the subject of numerous applications. Although the main interest was its established role in the formation of cationic derivatives for polymerization, different organic, organometallic, and catalytic applications have been reported the last few years.[3] As part of our long term interest in the organometallic chemistry of early-transition metal group 4 and 5 complexes,[4] in particular directed towards olefin polymerization and small molecule or unsaturated bond activation, we have investigated the reactivity of several vanadium compounds (including Cp2V) with B(C6F5)3. Some of these studies will be presented here,[5] with sometimes a comparison with group 4 metal analogue complexes.

[1]. R. Choukroun, C. Lorber Eur. J. Inorg. Chem. (2005), 4683. (Review on Vanadocene). [2]. C. Lorber, ‘Vanadium’ in Comprehensive Organometallic Chemistry III, Eds. Robert H. Crabtree and D. Michael P. Mingos, Elsevier: Oxford (2007), Vol. 5, pp. 1-60 (ISBN: 008044590X). [3]. W. E. Piers, Adv. Organomet. Chem. (2005), 1-76. [4] (a) C. Lorber et al, Organometallics (2000), 19, 1963. (b) C. Lorber et al, Dalton Trans. (2000), 4497. (c) F. Wolff et al, Inorg. Chem. (2003), 42, 7839. (d) F. Wolff et al, Eur. J. Inorg. Chem. (2004), 2861. (c) C. Lorber et al, Eur. J. Inorg. Chem. (2005), 2850. (d) R. Choukroun et al, Chemistry- Eur. J. (2002), 8, 2700. (e) R. Choukroun et al, Organometallics (2002), 21, 1124. (f) C. Lorber et al, Inorg. Chem., (2002), 41, 4217 (g) C. Lorber et al, Inorg. Chem. (2007), 46, 3192. [5] (a) F. Wolff et al, Eur. J. Inorg. Chem. (2003), 628. (b) R. Choukroun et al, Organometallics (2003), 22, 1995. (c) C. Lorber et al, Organometallics (2004), 23, 5488. (d) R. Choukroun et al, Organometallics (2006), 25, 1551. (f) R. Choukroun et al, Organometallics (2006), 25, 4243. (g) R. Choukroun et al, Organometallics (2006), 25, 4243. (h) R. Choukroun et al, Organometallics (2007), 26, 3604.

Cp2V(CO)V

Cp HCOB(C6F5)3

VCp CO

COB(C6F5)3 Cp

VCp CO

COV

Cp

B F

FFF

F

C6F5 C6F5

+ +Cp

VCp

+ H B(C6F5)3[HB(C6F5)3]B(C6F5)3

VN

N

N

N

B(C6F5)3(C6F5)3B

VCp2Cp2V

TCNQ TCNE

N

N

(C6F5)3B

Cp2V

NN

B(C6F5)3

VCp2

N

N

B(C6F5)3

NN

(C6F5)3B

- TCNE- and TCNQ-vanadium complexes as structural models for molecule-based magnet.

O

VEt2N

NEt2

NEt2

BC6F5C6F5

C6F5

VO

VO

R

R

OR

RO

O

OC6F5

C6F5V

OV

O

R

R

OR

RO

RO

ORC6F5

C6F5

- Reactivity of B(C6F5)3 with oxo, alkyl or alkoxide complexes

CVCp2

NR' BR3

BR3 = BCl3, BPh3, B(C6F5)3

- Reactivity of Metallocenes towards small molecules and/or unsaturated C-X bonds

Cp2V + R'C≡N•BR3

+

2 B(C6F5)3

n

n = 2 n = 1

adduct Cp2VMe

L[B(C6F5)4]-

-C6F5 transfer alkyl abstraction



P8

Vanadium(V) complexes as oxidation catalysts

Silvia Lovat, Miriam Mba, Marta Pontini and Cristiano Zonta* and Giulia Licini*

Dipartimento di Scienze Chimiche, Università di Padova, via Marzolo 1, 35131 Padova, Italy email: [email protected]

Vanadium(V) centres are usually strong Lewis acids, which makes them suitable for the activation of peroxidic reagents.1 Accordingly, vanadium(V) complexes have been found to act as catalysts in various oxidation reactions like epoxidations of alkenes and allylic alcohols, hydroxylations of alkanes and arenes, oxidations of primary and secondary alcohols to the corrisponding aldehydes and ketones, haloperoxydation and oxidations of sulphide ethers.2 More recently we have studied the coordination chemistry of various ligands, such as trialkanolamines 1, and triphenolamines 2, with vanadium(V). We have demonstrated that these ligands form thermally robust tetradentate, C3-symmetric, V(V)complexes. In addition to these ligands, we have recently expanded our attention to silsequioxane ligands. These ligands are a a class of three-dimensional oligomeric organosilica compounds with a cage framework 3.3 The preliminary results on the capability to transfer oxygen of these complexes will be presented.

N

VOOO

O

R

RR

VN

O OO

OR

RR SiO

O

OR

SiR O

O

Si

OO

Si

SiO

O Si

OOSi

R O V

R

R

RR

O

31 2 Figure 1. Vanadium metal complexes used in catalytic oxidations.

Acknowledgements: The authors would like to thank FIRB-2003 CAMERE-RBNE03JCR5 project, COST Action D40 ‘Innovative Catalysis, MIUR and University of Padova for their financial support. [1] D.C Crans, J. Smee, E. Gaidamauskas, L. Yang Chem.Rev. 104 (2004), 849. [2] A.G.J. Ligtenbarg, R. Hage, B.L. Feringa Coord. Chem. Rev. 237 (2003) 83 [3] F. Carniato, E. Boccaleri, L. Marchese, A. Fina, D. Tabuani, G. Camino 9 (2007) Eur. J. Inorg. Chem 585.



P9

Vanadium diamine bisphenolate complexes: synthesis, structures and catalytic activity in sulfoxidations

Sónia Barroso,a Pedro Adão,a João Costa Pessoa,a Ana M. Martinsa*

aCentro de Química Estrutural, Instituto Superior Técnico, 1049-001 Lisboa, Portugal


Nowadays, there are two main reasons which stimulate research in the field of the sulfoxidation catalytic reactions: the synthesis of sulfoxides, an important class of compounds widely utilized in the pharmaceutical industry and academia, and the removal of sulfur compounds from fuels and industrial effluents, in order to satisfy the new environmental legislations. A number of vanadium-dependent haloperoxidases mediate the oxidation of sulfides by hydrogen peroxide.1 In an attempt to gain an insight into the biological roles of vanadium, many recent studies have been focused in the design of model compounds that mimic the metal coordination sphere in the active sites of these vanadium-dependent enzymes, as well as their reactivity in the oxidation states +3, +4 and +5.2 It was previously observed that vanadium and other early transition metal complexes of tetra-(N2O2)-dentate diamine-bisphenolate ligand have proved to be highly active catalysts in olefin polymerization3 and in the Ring Opening Polymerization of lactones.4 Moreover, Diamino-bisphenolate (N2O2 ligand = [Me2N(CH2)2N{CH2−(2−OC6H2−But

2−3,5)2}]) complexes of molybdenum and tungsten revealed to be very active catalysts in olefin epoxidation.5 In this work we present results on the synthesis and structural characterization of N2O2

complexes of V(III) and V(V) and the catalytic activity of VVO[N2O2]X (X = Cl, OiPr) in the sulfoxidation of thioanisole. The highest conversion (93%) was obtained with VVO[N2O2]O

iPr and H2O2 almost without further reaction to the sulfone (5%). Preparation of a chiral version of this complex is in course in order to test the enantioselectivity.

N

VN

O

But

tBuO

tBu

tBu

XO

SH2O2

SO

X = Cl, OiPr

Acknowledgements: We thank the FCT, Portugal, for financial support (SFRH/BD/28762/2006, SFRH/BD/40279/2007, PPCDT/QUI/55744/2004 and PPCDT/QUI/55985/2004) [1] I. Fernández, N. Khiar, Chem. Rev. 103 (2003) 3651–3705. [2] D. C. Crans, J. J. Smee, E. Gaidamauskas, L. Yang, Chem. Rev. 104 (2004) 849. [3] S. Gendler, S. Groysman, Z. Goldschmidt, M. Shuster, M. Kol, J. Polym. Sci. 44 (2006) 1136. [4] A. J. Chmura, M. G. Davidson, M. D. Jones, D. Lunn, M. F. Mahon, A. F. Johnson, P. Khunkamchoo, S. L. Roberts, S. S. F. Wong, Macromolecules, 39 (2006) 7250. [5] C. Trindade, S. Barroso, S. Namorado, P. M. Reis, A. M. Martins, B. Royo, manuscript in preparation.



P10

Polystyrene bound dioxovanadium(V) complex of histamine derived ligand for the oxidation of methyl phenyl sulfide, diphenyl sulfide and

benzoin

Mannar R. Maurya* and Aarti Arya

Department of chemistry, Indian Institute of Technology Roorkee, Roorkee-247667, India, e-mail: [email protected]

Ligand H2sal-his derived from salicylaldehyde and histamine has been covalently bonded to chloromethylated polystyrene cross-linked with 5 % divinylbenzene. Upon treatment with [VO(acac)2] in dimethylformamide (DMF), the polystyrene bound ligand (abbreviated as PS-Hsal-his, I) gave the stable intermediate polystyrene bound oxovanadium(IV) complex, which on oxidation yielded the dioxovanadium(V) PS-[VO2(sal-his)](1) complex. The corresponding non-polymer bound complex, [VO2(sal-his)](2) and its peroxo analogue [VO(O2)(sal-his)](3) have also been isolated. These complexes have been characterized by IR, electronic and 1H NMR spectral studies, magnetic susceptibility measurements, and thermal as well as scanning electron micrographs studies. Complex PS-[VO2(sal-his)](1) has been used as catalyst for the oxidation of methyl phenyl sulfide, diphenyl sulfide and benzoin with 30% H2O2 as an oxidant. Under the optimised reaction conditions, a maximum of 95.3% conversion of methyl phenyl sulfide with 63.7% selectivity towards methyl phenyl sulfoxide and 36.3% towards methyl phenyl sulfone has been achieved in 2 h of contact time. Under similar conditions, diphenyl sulfide gave 83.4% conversion where selectivity of reaction products varied in the order: diphenyl sulfoxide (71.8%) > diphenyl sulfone (28.2%). A maximum of 91.2% conversion of benzoin has abeen achieved within 6 h of reaction time where selectivity of the obtained reaction products varied in the order: methylbenzoate (45.3%) > benzyl (22.5%) > dimethylacetal (20.9%) > benzoic acid (11.3%). The polymer-anchored heterogeneous catalyst is free from leaching during catalytic action and is recyclable. Catalytic activities of the polymer bound catalyst have also been compared with the corresponding non-polymer bound complex, [VO2(sal-his)].

Acknowledgements: Prof. M. R. Maurya acknowledges Fundação Oriente for the financial support received and Department of Science and Technology, New Delhi is also gratefully acknowledged for financial support of the work



P11

Dioxovanadium(V) Schiff base complexes of R(-)-1,2-diaminopropane and o-hydroxycarbonyl compounds. Synthesis, characterization, catalytic properties and structure

Grzegorz Romanowski,a Waldemar Nowicki,a Artur Sikorski,a Andrzej Wojtczak,b

aFaculty of Chemistry, University of Gdansk, Sobieskiego 18/19, PL-80952 Gdansk, Poland

bFaculty of Chemistry, N. Copernicus University, Gagarina 7, PL-87100 Torun, Poland email: [email protected]

Vanadium plays active roles in many biologically important reactions such as

halogenation of organic substrates, activation or fixation of nitrogen through an alternative pathway1, potent inhibitor of phosphate-metabolizing enzymes2 and a cofactor in haloperoxidases and nitrogenases3. Some of the vanadium compounds stimulate glucose uptake and inhibit lipid breakdown in a manner remarkably reminiscent of insulin effects4,5 or exert preventive effects against chemical carcinogenesis on animals6. Recently, it has been established that vanadium(V) complexes with Schiff bases, which are excellent models for active sites of vanadium haloperoxidases, are able to catalyze the oxidation of organic sulfides to the corresponding sulfoxides7-9.

A series of dioxovanadium(V) complexes, obtained by monocondensation of R(-)-1,2-diaminopropane and aromatic o-hydroxycarbonyl compounds, were prepared in high yields. The complexes were characterized in the solid state (IR) and in solution (UV-Vis, CD, 1H and 51V NMR). Single crystal X-ray analyses were performed with dimeric and monomeric form of the complexes. The complexes comprising ligands derived from 3-methoxy and 5-methoxysalicylaldehyde catalyze the oxidation of thioanisole to the corresponding sulfoxide by cumene hydroperoxide.

Figure 1. The molecular structure of the one of the vanadium(V) complexes.

Acknowledgements: This scientific work has been supported from funds for science in years 2007-2009 as a research project (N N204 0355 33, BW/8000-5-0399-8, DS/8210-4-0086-8). [1] A. Butler, J.V. Walker, Chem. Rev. 93 (1993) 1937. [2] D. Rehder, Angew. Chem. Int. Ed. Engl. 30 (1991) 148. [3] J.S. Martinez, G.L. Carrol, R.A. Tschirret-Guth, G. Altenhoff, R.D. Little, A. Butler, J. Am. Chem. Soc. 123 (2001) 3289. [4] K.H. Thompson, C. Orvig, Coord. Chem. Rev. 219–221 (2001) 1033. [5] D.C. Crans, L. Yang, J.A. Alfano, L.-H. Chi, W. Jin, M. Mahroof-Tahir, K. Robbins, M.M. Toloue, L.K. Chan, A.J. Plante, R.Z. Grayson, G.R. Willsky, Coord. Chem. Rev. 237 (2003) 13. [6] A.M. Evangelou, Crit. Rev. Onco./Hematol. 42 (2002) 249. [7] E. Kwiatkowski, G. Romanowski, W. Nowicki, M. Kwiatkowski, K. Suwinska, Polyhedron 22 (2003) 1009. [8] E. Kwiatkowski, G. Romanowski, W. Nowicki, M. Kwiatkowski, K. Suwinska, Polyhedron 26 (2007) 2559. [9] G. Romanowski, E. Kwiatkowski, W. Nowicki, M. Kwiatkowski, T. Lis, Polyhedron 27 (2008) 1601.



P12

Chiral dioxovanadium(V) complexes of Schiff bases derived from 1,2-diphenyl-1,2-diaminoethane and aromatic o-hydroxyaldehydes. Synthesis, characterization, catalytic properties and structure

Grzegorz Romanowski,a Waldemar Nowicki,a Tadeusz Lis,b

aFaculty of Chemistry, University of Gdansk, Sobieskiego 18/19, PL-80952 Gdansk, Poland bFaculty of Chemistry, University of Wroclaw, F. Joliot-Curie 14, PL-50283 Wroclaw, Poland


The discovery of vanadium in active sites of biological systems of nitrogenase1 and bromoperoxidase2 and recognition of its environment increased the interest in the vanadium complexes with ligands bearing oxygen and nitrogen atoms for mimicking the biological activity in natural systems. Structural models for the active site in haloperoxidases have already been reported3-5. Recently, it has been established that vanadium(V) complexes with Schiff bases, which are excellent models for active sites of vanadium containing haloperoxidases, are able to catalyze the oxidation of organic sulfides to the corresponding sulfoxides6,7. Vanadium haloperoxidases catalyze the oxidation of halides in the presence of hydrogen peroxide to highly reactive intermediate, a hypohalous acid, which may react either with suitable nucleophilic acceptor, if present, forming a halogenated compound or with hydrogen peroxide yielding 1O2.

A series of dioxovanadium(V) complexes, obtained by monocondensation of R,R(+)-1,2- diphenyl-1,2-diaminoethane or S,S(-)-1,2-diphenyl-1,2-diaminoethane and aromatic o-hydroxyaldehydes, were prepared in high yields. The complexes were characterized in the solid state (IR) and in solution (UV-Vis, CD, 1H and 51V NMR). Single crystal X-ray analyses were performed with two of such complexes and revealed different conformations of the five-membered chelate rings. Complexes, which incorporate singly condensed products with 3- or 5-methoxysalicylaldehyde act as catalyst to the oxidation of thioanisole by cumene hydroxyperoxide.

Figure 1. The molecular structure of the one of the vanadium(V) complexes.

Acknowledgements: This scientific work has been supported from funds for science in years 2007-2009 as a research project (N N204 0355 33, BW/8000-5-0399-8, DS/8210-4-0086-8). [1] R.L. Robinson, R.R. Eady, T.H. Richardson, R.W. Miller, M. Hawkins, J.R. Postgate, Nature 322 (1986) 388. [2] H. Vilter, Phytochemistry 23 (1984) 1387 [3] M. Casny, D. Rehder, Chem. Commun. (2001) 921. [4] C. Gruning, D. Rehder, J. Inorg. Biochem. 80 (2000) 185. [5] C. Kimblin, X. Bu, A. Butler, Inorg. Chem. 41 (2002) 161. [6] E. Kwiatkowski, G. Romanowski, W. Nowicki, M. Kwiatkowski, K. Suwinska, Polyhedron 22 (2003) 1009. [7] E. Kwiatkowski, G. Romanowski, W. Nowicki, M. Kwiatkowski, K. Suwinska, Polyhedron 26 (2007) 2559.



P13

V-catalysed oxidations with H2O2 V.Contea, F. Fabbianesia, B. Florisa , P. Gallonia, D. Sordia, I. Arendsb, D. Rehderc

a Dip. Scienze e Tecnologie Chim., Univ. Roma Tor Vergata, via Ricerca Scientifica, 00133, Roma IT

b Lab. of Biocatalysis and Organic Chemistry, Delft University of Technology, Delft, NL. c Inst. Inorganic and Applied Chem., Hamburg University, Martin-Luther-King-Platz 6 D-20146 Hamburg, D

e-mail: [email protected]

In the present paper, the performance of some vanadium based catalysts will be presented.[1]

High TON’s and selectivities were obtained by using trifluoroethanol as a solvent, which is known to activate H2O2. The potential of the V complexes shown in the scheme, in the oxidation of thioethers, alcohols, and alkenes with both dioxygen and H2O2 in a variety of ILs, has been screened. Between the ILs studied, the hydrophobic bmim+PF6

- gives in general the best feats.

[1] D. Sordi : WG1COST-STSM-D40-1773 from Rome to Delft.

N

O

NH

O

O

VO O

O

NNH

O

N

VO

OMe

N

OCH3

CH3NH

N

VO O

ON

ONH

O

VO

ON N

OVO

O

O NN

O OV

O

+

CF3SO3-

Cat.4 Cat.5 VO(SALen)TfO

CH3OH

Cat.1 Cat.2 Cat.3

NN

O OVO

+

EtSO4-

VO(SALen)EtSO4

N N +

[(CF3SO2)2N]-

BMImTf2N

OHF

F

F

TFE

N N +PF6

-

BMImPF6

N N

BMImNO3

+NO3

-

OH

SCH3

N N OH

"Sub"V(V) Catalyst, oxidant

Solvent, TOC"Sub-O"

Catalysts

Solvents

Substrates

Oxidants

H2O2, O2

HOPMImNO3

+NO3

-



P14

On the nature of V(V) species in hydrophilic ionic liquids: a spectroscopic approach

István Bányai,a Valeria Conte,b Lage Pettersson,c Adriano Silvagnib

a Dept. of Colloid and Environmental Chemistry, University of Debrecen, H-4010, Debrecen, Pf 31, Hungary

b Dip. Scienze e Tecnologie Chim., Univ. Roma Tor Vergata, via Ricerca Scientifica, 00133, Roma, Italy c Department of Chemistry, Umeå University, SE-90187, Umeå, Sweden


Aqueous solutions of V(V) peroxovanadates with high ionic concentrations have the potential to be more effective oxidising agents than the corresponding simple aqueous solutions.1 However, they have received little investigation. The present study uses mainly 51V NMR in order to understand the effects of increasing ionic concentrations, using three different ionic compounds that also exist as hydrophilic ionic liquids.

51V NMR and other experiments partially elucidated the nature of aqueous vanadates and peroxovanadates to which the hydrophilic ionic liquids [bmim][BF4], [bmim][TfO] and [bdmim][BF4] have been added. These ionic liquids alter the solution chemistry of aqueous vanadate by increasing aggregation (with and without H2O2) and also increase the rate of peroxide consumption in reactions catalysed by vanadium. In ionic liquids containing BF4

-, the formation of vanadate-fluoride and tetrafluoroborate adducts is suggested, based on the appearance of new 51V NMR resonances at -465, -503, -612 ppm. The results also include reactivity data for peroxovanadates in ionic liquids.

Acknowledgements: A. Silvagni COST-STSM-D29-02097 from Rome to Debrecen. [1] V. Conte, B. Floris, A. Silvagni, Vanadium catalyzed oxidation in Ionic Liquids, in ACS Symposium Series 974: Vanadium: the Versatile Metal, K. Kustin, J. Costa Pessoa and D.C. Crans Eds. (2007) 28-37.

V4O124- (-577 ppm)

[bmim][BF4]

Vanadate-fluoride adducts? (-465, -548, -612 ppm)

Decavanadates (-422, -503, -521 ppm)

[VO(O2)2]- (-690 ppm)[bmim][BF4]

[VO(O2)2F]2- (-700 ppm)

H2VO4- (-560 ppm)

V5O155- (-586 ppm)

N

N

N

N

N

N++ + BF4

-

BF4- CF3SO3

-

[bdmim][BF4][bmim][BF4] [bmim][TfO]



P15

Characterization in the solid state of chiral salen and salan ligands and their vanadium(V) compounds

Fernando Avecilla,a Pedro Adão,b Isabel Correiab and João Costa Pessoab a Departamento de Química Fundamental, Universidade da Coruña, Campus da Zapateira s/n, 15071,

A Coruña, Spain. email: [email protected] b Centro de Química Estrutural, Instituto Superior Técnico, TU Lisbon, Av. Rovisco Pais,

1049-001 Lisboa, Portugal

We report the characterization in solid state of chiral salen and salan type ligands, which are derived from salicylaldehyde and chiral diamines (cyclohexane and diphenyletylenediamine), and some dinuclear vanadium(V) compounds with them. A variety of vanadium complexes have been introduced as structural and/or functional models for biologically active vanadium compounds.[1] The vanadium compounds reported can be studied as models in oxidation catalysis.

In solution salen ligands have the disadvantage of the hydrolysis of the C=N bond, particularly in water containing solvents, and we have worked with salan ligands where the imine bonds have been reduced to amines. The salen reduced derivatives exhibit different structural and chemical properties, increasing the stability of the complexes and their flexibility, which are also more resistant to hydrolysis.

We prepared the complexes starting from VIVOCl2. The oxidation of VIV was probably due to diffusion of air into the solution during the crystallization.[2] The resulting VO2L complexes precipitated as dinuclear species containing tetradentate ligands with phenolate and amine coordinated to the dioxovanadium(V) ion. X-ray structures of these compounds demonstrate that they form dimers in the solid state with a OVV(μ-O)VVO unit (V2O3 core) with tetradentate ligands and one μ-oxo bridge, which are relatively rare.[3] In fact, only two examples were found in the literature of amine derivatives which act as tetradentate ligands and both of them are mixed valence(IV/V) dimers.[4]

This work illustrates the high propensity of the vanadium centre to increase its coordination number via dimerization of two pentacoordinate monomers if the steric control exercised of the ligands allow it.

Acknowledgements: The authors thank FEDER, Fundação para a Ciência e a Tecnologia, POCI 2010

(PPCDT/QUI/55985/2004 and PPCDT/QUI/56946/2004 programs).

[1] D. Rehder, Coord. Chem. Rev. (1999), 182(1), 297-322. [2] I. Correia, J. Costa Pessoa, M. T. Duarte, R. T. Henriques, M. F. M. Piedade, L. F. Veiros, T. Hakusch, T. Kiss, A. Dörnyei, M. M. C. A. Castro, C. F. G. C. Geraldes and F. Avecilla, Chem. Eur. J. (2004), 10, 2301-2317. [3] I. Cavaco, J. Costa Pessoa, M. T. Duarte, R. T. Henriques, P. M. Matias and R. D. Gillard, J. Chem. Soc., Dalton Trans., (1996), 1989-1996. [4] a) A. Kojima, K. Okazaki, S. Ooi and K. Saito, Inog. Chem., (1983), 22, 1168-1174; b) J-P. Launay, Y. Jeannin and M. Daoudi, Inorg. Chem., (1985), 24, 1052-1059



P16

Intramolecular electron transfer in the solid phase: presenting a unique example of single-crystal-to-single-crystal transformation from a binuclear vanadium(V)-a lcoholate to an oligomeric vanadium(IV)-

aldehydic compound

Pabitra Baran Chatterjee,a Muktimoy Chaudhury,*,a

aDept. of Inorganic Chemistry, Indian Association for the Cultivation of Science, Kolkata-700 032, India,


Single-crystal-to-single-crystal (SCSC) transformations in the solid state involve coordinated movement of atoms in the matrices. Most of these transformations are reversible, triggered by light with a few thermally induced incidences are also known. Majority of these studies involve organic molecules since crystals of metallo-organic frameworks can hardly retain their single crystallinity after the rearrangements that happen in the solid phase. However, several similar transformations involving coordination compounds have been reported in recent years, accompanied by many interesting changes in properties such as host-guest behavior, magnetism and photochemical reactivity. In the present work, we report an unprecedented coordination driven oligomerization of a red colored dinuclear oxovanadium(V) compound [V2O2L2] 1 involving 2,6-bis(hydroxymethyl)-p-cresol (H3L) as a bridging ligand to an infinite 1D chain of greenish brown oxovanadium(IV) entity [V2O2(L

*)2]α 2 through a SCSC irreversible transformation pathway. The solid-state constitutional rearrangement of 1 to 2 is probably the first case where an intramolecular-redox process, triggered by the oxidation of a coordinated alkoxy group to an aldehydic moiety, generating two equivalents of electron which are consumed by one equivalent each of vanadium(V) and hydrogen ion followed by solid-state self-assembly to generate the product in almost 100 % yield. Confirmations in favor of this novel SCSC transformation have come from time interval IR spectroscopy, magnetic susceptibility and epr spectrum for the oligomeric vanadium(IV) compound 2 and more precisely from single-crystal X-ray diffraction analyses. Perhaps the most interesting structural feature behind this serendipitous SCSC transformation is the generation of a new ligand viz. 2-formyl-6-hydroxymethyl-p-cresol (H2L

*) involving two types of C-O bonds attached as side arms to the aromatic ring unlike its predecessor (H3L).

Oxidation

Reduction

Curing

1 2



P17

Electron transfer reactions of an amavadin-like complex

Jeremy M. Lenhardt,a Michael D. Johnson,a Debbie C. Crans,b Bharat Baruahb

aDepartment of Chemistry and Biochemistry, New Mexico State University, Las Cruces, NM 88003 bDepartment of Chemistry, Colorado State University, Fort Collins, CO 80523

email : [email protected]

The kinetics of the electron self-exchange process of amavadin and an amavadin model have

been studied using the Marcus cross relationship and directly measured using 51-V NMR line

broadening techniques with good agreement between the two methods. Outer-sphere electron

transfer reaction pathways are ascribed to both complexes. Exchange rates approximately two

orders of magnitude larger than other vanadium (IV/V) couples are reported. The results are

compared to previous studies with the natural product amavadin [1] and little change is found.

The significance of these studies will be discussed.

We thank the Luso-American Development Foundation for partial travel funds. We also thank NSF for

funding this research.

[1] J. Lenhardt, B. Baruah, D. C. Crans and M. D. Johnson, Chem. Comm. (2006) 4641-4643.



P18

Interaction of hydroquinonate ligands with VV and MoVI

Chryssoula Drouza,a Anastasios D. Keramidas,b

aDepartment of Agriculture Production, Biotechnology and Food Science, Cyprus University of Technology, 3603, Limasol, Cyprus, email: [email protected]

bDepartment of Chemistry, University of Cyprus,1678 Nicosia, Cyprus

Study of the interaction of hydroquinones with redox active metal ions is of great importance

because such combination represents model systems for the electron and proton transfer

reactions in biological systems. Hydroquinone Vanadium and molybdenum participate in redox

reactions in biological systems like those of oxygen transfer systems (xanthine oxidases,

sulphate oxidases, nitrate reductases etc).1-4 On the other hand modified hydroquinone can

serve as connecting bridge between two redox centres, such as metal ions, thus allowing the

investigation of electronic interactions throughout the bridge.5 Hydroquinone has very low

oxidation potential thus does not stabilize metals in high oxidation state. In order to stabilize

the coordination of VIV/V and MoVI with hydroquinone we have synthesized modified

hydroquinones, one is shown in scheme 1. These ligands chelate and stabilize VIV/V and MoVI

ions forming stable complexes characterized with X-ray single crystal analysis.

OH

HON

OHO

OH

O

N

OH

O

O OH

Scheme 1. Ligand used in this work.

1D and 2D 1H NMR spectroscopies were used to characterize all complexes and investigate the

lability in aqueous solution. 2D EXSY spectra show an intramolecular exchange in aqueous

solution, and the mechanism is investigated.

Acknowledgements: The authors would like to thank PRF of Cyprus (TEXNO/0506/19) for their financial

support.

[1] Hille, R. Chem. Rev. 96, 2757 (1996). [2] Collison, D., Garner, C. D., Joule, J. A., Chem. Soc. Rev. 25 (1996). [3] D. Rehder, Coordination Chemical Reviews 182(1999) 197. [4] C. Drouza, V. Tolis, V. Gramlich, C. Raptopoulou, A. Terzis, M.P. Sigalas, T.A. Kabanos, A.D. Keramidas, Chem. Commun. (2002) 2786. [5] Drouza, C., Keramidas, A. D. J. Inorg. Biochem. 80, 75 (2000).



P19

New insight into the lipo-hydrophilic characterisation of a series of antidiabetic VO(IV) and Zn(II) complexes and their carrier ligands

Éva Anna Enyedy,a Tamás Kissa

aDepartment of Inorganic and Analytical Chemistry, University of Szeged, H-6701 Szeged, Hungary,


The main target of the design of novel antidiabetic vanadium(IV) and zinc(II) complexes is obviously to achieve compounds with higher biological activity and reduced side effects. Complexation of these metal ions with carrier ligands leads to the protection against the hydrolytic processes and to the formation of neutral, bis complexes enhancing their lipophilic character and the scale of absorption from the digestive tract. Since the insulin-enhancing effects of these complexes are closely correlated many times to their octanol-water distribution coefficients among other factors [1], in the development of new metal complexes the determination of this basic physico-chemical property is an important issue. The octanol-water distribution coefficient of the carrier ligands has also effect on the binding to serum proteins, which may have significant role in the metabolism of the antidiabetic complexes. The lipo-hydrophilicity of a series of vanadium(IV) and zinc(II) complexes and their carrier ligands were reinvestigated in the present work. It has involved a wide pH range study to determine the pH independent constants (log P) for the ligands and the bis complexes considering the actual chemical speciations and the individual UV-visible spectra of all species formed in the systems with classic shake-flask method by the means of ICP-AES and UV-visible spectrophotometry.

Acknowledgements: The authors would like to thank to the Hungarian Science Research Fund (OTKA PD050011, T49417) for financial support. [1] H. Sakurai, A. Katoh, Y. Yoshikawa, Bull. Chem. Soc. Jpn. 79 (2006) 1645-1664.



P20

Syntheses and characterisation of novel [VO(O2)2L](L=ligand) type complexes

Takeshi Higuchi,a Masato Hashimoto,a Seichi Okeya,a Yutaka Yoshikawa,b

Hiromu Sakuraic

a Department of Material Science and Chemistry, Faculty of Systems Engineering, Wakayama University Skaedani 930, Wakayama 640-8510, Japa, email: [email protected]

b Department of Bioinorganic Chemistry, Kyoto Pharmaceutical University, 5 Nakauchi-cho, Misasagi, Yamashina-ku, Kyoto 607-8414, Japan

c Institute of Oriental Medicine,Suzuka University of Medical Science, 1001-1 Kishioka-cho, Suzuka, Mie 513-0816, Japan, email: [email protected]

Some vanadyl and [VO(O2)2L] type peroxo complexes are known to show the insulin-mimetic effects. We therefore aimed at syntheses and X-ray and NMR structural analyses of novel [VO(O2)2L] type complexes as well as analyses of their behaviour in aqueous media by NMR (51V, 13C, 1H, 15N). The ligands used were amino acids which are common organic matters in the biological systems, having various compositions and donor sites.

Structure of M[VO(O2)2(OCOCH2NH2)]·4H2O (M=Sr, Ca)

Amino acids such as glycine, L-alanine, L(+)-arginine, L-glutaminic acid, L-histidine, and L-cysteine as well as a nucleobase adenine, have been tested as organic ligands. Formation of several V-containing peroxo complexes were detected by 51V NMR. Among these complexes we have been so far successful to crystallise M[VO(O2)2(OCOCH2NH2)]·4H2O (M=Sr, Ca) having a glycinato ligand, and structurally analysed by a single crystal X-ray diffraction technique (see figure). Attempts to crystallise other complexes are still ongoing. The decrement of a 51V signal at about -750 ppm in the reaction solution after the crystallisation suggests that the signal can be assigned to this complex. This complex was further characterised by IR, TG-DTA, 1H NMR, 13C NMR, and organic elemental analyses. The complex salts were not soluble in organic solvents such as ethanol, methanol, acetone and acetonitrile but soluble in water. The solubilities were enhanced by adding NaCl or KCl. The detailed behaviour concerning dissolution of the complex salts are now in investigation. Phosphate buffer (pH 7.2), in contrast, forced immediate decomposition of the complexes which were detectable by 51V NMR. This behaviour encouraged us to make biological tests, which are going on at present. Furthermore, attempts to incorporate Zn(II), which is also known to be effective as an insulin-mimetic material, into the peroxovanadate complexes are in progress. The results of these ongoing investigations will also be presented in the poster. Acknowledgements: The authors would like to thank Prof. Lage Pettersson at Umeå University for his kind discussion and suggestions.

glycinato ligand

V

O

N



P21

Density functional theory study of structure and NMR chemical shifts of oxoperoxo vanadium(V) complexes of L-lactic acid

Licínia L.G. Justino,a,b M. Luísa Ramos,a,b Fernando Nogueira,c Abilio J.F.N Sobral,a Carlos F.G.C. Geraldes,d,b Martin Kaupp,e Hugh D. Burrows,a Carlos Fiolhaisc and

Victor M.S. Gila

aDepartamento de Química, Faculdade de Ciências e Tecnologia, Universidade de Coimbra, 3004-535 Coimbra, Portugal, email: [email protected]

bCentro de Neurociências e Biologia Celular, Universidade de Coimbra, Portugal. cDepartamento de Física e Centro de Física Computacional, Faculdade de Ciências e Tecnologia,

Universidade de Coimbra, 3004-516 Coimbra, Portugal dDepartamento de Bioquímica, Faculdade de Ciências e Tecnologia, Universidade de Coimbra,

3001-401 Coimbra, Portugal. eInstitut für Anorganische Chemie, Universität Würzburg, Am Hubland, D-97074 Würzburg, Germany

Vanadium occurs in nature as a trace element. It is essential for several organisms and, in particular, is implicated in the synthesis of chlorophyll in green plants and in the normal growth of some animals.1 It is, possibly, also essential for humans.2 In recent decades, in vivo and in vitro studies of the biological effects of this metal have revealed other important effects. These include the ability to inhibit certain enzymes, the possibility of mimicking the effects of insulin, the capacity to reduce cholesterol biosynthesis,3 in addition to antitumorigenic properties.4 Peroxo V(V) complexes show antitumorigenic activity and also enhanced insulinomimetic2,5 activity compared with the anionic salts of the higher oxidation states of vanadium. Additionally, these complexes have been studied as functional models6 for the haloperoxidase enzymes,7 and they are efficient oxidants for a variety of substrates.8 Previously,9 we have reported a study of the system V(V)–L-lactic acid–H2O2 in aqueous solution using multinuclear NMR spectroscopy and have proposed structures for the corresponding peroxo V(V) complexes of this acid. The solid state structure of one of these complexes has been presented,10 but detailed information is lacking on the structures of the other complexes found in aqueous solution. In this study we have applied density functional theory (DFT) methods to study the structures, and to simulate the solution NMR chemical shifts of the complexes. Various combinations of density functionals and pseudopotentials with associated valence basis-sets were compared for reproducing the known solid-state data. Gas-phase optimizations at the B3LYP/SBKJC level have been found to provide the overall best results. This method was subsequently applied to all the V(V)-lactate-peroxide complexes found in solution. The NMR chemical shifts were computed in all-electron DFT-IGLO calculations (UDFT-IGLO-PW91 level). This provides a way to evaluate how close the theoretical structures are from the solution ones. The chosen methodology was, additionally, able to predict and analyze a number of interesting structural features for V(V) oxoperoxocomplexes of α-hydroxycarboxylic acids, such as the bridging of the V(V) atoms in the V2O2 core of dinuclear complexes in the solid state by hydroxy bridges and the preference for 1:1 V(V):peroxide stoichiometry and the very low stability of complexes with 1:2 V(V):acid stoichiometry in aqueous solution. Acknowledgments: LLGJ thanks “Fundação para a Ciência e a Tecnologia” for the postdoctoral grant SFRH/BPD/26415/2006 and the “Laboratório de Computação Avançada”, of the Department of Physics of the University of Coimbra, for the computing facilities (Milipeia cluster). [1] D. Rehder, Angew. Chem. Int. Ed. Engl. 30 (1991) 148-167 and references therein. [2] D.C. Crans, J.J. Smee, E. Gaidamauskas, L. Yang, Chem. Rev. 104 (2004) 849-902. [3] N.D. Chasteen, Struct. Bonding 53 (1983) 105-138. [4] C. Djordjevic, Met. Ions Biol. Syst. 31 (1995) 595-616. [5] K.H. Thompson, J.H. McNeill, C. Orvig, Chem. Rev. 99 (1999) 2561-2572. [6] G.J. Colpas, B.J. Hamstra, J.W. Kampf, V.L. Pecoraro, J. Am. Chem. Soc. 116 (1994) 3627-3628. [7] A. Butler, J.V. Walker, Chem. Rev. 93 (1993) 1937-1944. [8] T. Hirao, Chem. Rev. 97 (1997) 2707-2724. [9] L.L.G. Justino, M.L. Ramos, M.M. Caldeira, V.M.S. Gil, Eur. J. Inorg. Chem. (2000) 1617-1621. [10] P. Schwendt,; P. Švančárek, I. Smatanová, J. Marek, J. Inorg. Biochem. 80 (2000) 59-64.



P22

Density functional theory study of the oxoperoxo vanadium(V) complexes of glycolic acid. structural correlations with

NMR chemical shifts

Licínia L.G. Justino,a,b M. Luísa Ramos,a,b Martin Kaupp,c Hugh D. Burrows,a Carlos Fiolhaisd and Victor M.S. Gila

aDepartamento de Química, Faculdade de Ciências e Tecnologia, Universidade de Coimbra,

3004-535 Coimbra, Portugal, email: [email protected] bCentro de Neurociências e Biologia Celular, Universidade de Coimbra, Portugal.

cInstitut für Anorganische Chemie, Universität Würzburg, Am Hubland, D-97074 Würzburg, Germany dDepartamento de Física e Centro de Física Computacional, Faculdade de Ciências e Tecnologia,

Universidade de Coimbra, 3004-516 Coimbra, Portugal

In view of the relevance of vanadium compounds for both their biological and industrial applications, we have carried out a DFT study of the structures and structural correlations with NMR chemical shifts of oxoperoxo and dioxo V(V) complexes of glycolic acid. Peroxovanadium complexes with α-hydroxycarboxylic acids are of particular relevance in biochemistry, since the anions of many of these exist in biological media and are involved in a number of fundamental physiological processes. Previously,1 we have studied the system V(V)–glycolic acid–H2O2 in aqueous solution using multinuclear NMR spectroscopy and proposed structures for the oxoperoxo V(V) complexes of this acid present in solution. The solid state structure of one of these complexes is known.2 In this work we have applied the DFT B3LYP/SBKJC method, which we previously validated for related systems,3 to calculate the gas-phase optimized geometries of the V(V)–glycolate–peroxide complexes. Subsequently, we have calculated the 51V, 17O, 1H and 13C chemical shifts for the theoretical geometries in all-electron DFT calculations at the UDFT-IGLO-PW91 level. The theoretical chemical shifts have been compared with the experimental solution values to assess the quality of the theoretical structures. With the objective of understanding the major structural features determining the metal and oxo oxygen chemical shifts in the NMR spectra of α-hydroxycarboxylate V(V) complexes, we have carried out a study of the effects of structural changes on the 51V and 17O NMR chemical shifts for several glycolate V(V) complexes, using the referred computational methodologies. The coordination of a small ligand to the metal, the replacement of a fragment of a ligand by a different fragment and changing the geometry of the complex have been considered. This investigation has shown, for example, that structural modifications far from the metal nucleus do not significantly affect the metal chemical shift, explaining why it is possible to establish reference scales that correlate the type of complex (type of metal centre associated with a certain type of ligand) with its typical range of metal chemical shifts, such as that formulated by Rehder.4 These studies have been extended to small molecules used in quantitative analysis. Acknowledgments: LLGJ thanks “Fundação para a Ciência e a Tecnologia” for the postdoctoral grant SFRH/BPD/26415/2006 and the “Laboratório de Computação Avançada”, of the Department of Physics of the University of Coimbra, for the computing facilities (Milipeia cluster). [1] L.L.G. Justino, M.L. Ramos, M.M. Caldeira, V.M.S. Gil, Inorg. Chim. Acta 311 (2000) 119-125. [2] P. Švančárek, P. Schwendt, J. Tatiersky, I. Smatanová, J. Marek, Monatsh. Chemie 131 (2000) 145-154. [3] See poster in this symposium. [4] D. Rehder. C. Weidemmann, A. Duch, W. Priebsch, Inorg. Chem. 27 (1988) 584-587.



P23

Protein-protein interactions among vanadium-binding proteins and related proteins in a vanadium-rich ascidian

Tatsuya Ueki, Koki Shintaku, Masao Yoshihara, Hitoshi Michibata

Department of Biological Science, Graduate School of Science, Hiroshima University, 1-3-1 Kagamiyama,

Higashi-Hiroshima 739-8526, Japan, email: [email protected]

Several species of ascidians can accumulate extremely high levels of vanadium ions in their blood cells. We have been trying to identify and isolate proteins involved in this process. So far we obtained several vanadium-binding proteins (Vanabins [1-3], GSTs, and VBPs) and putative membrane transporters for vanadium, sulfate and protons from several species of ascidians. By using one of Vanabins, we isolated a Vanabin-interacting protein 1 (VIP1) from blood cells of Ascidia sydneiensis samea [4]. VIP1 was localized in the cytoplasm of signet ring cells and giant cells. Using a two-hybrid method, we revealed that VIP1 interacted with Vanabins 1, 2, 3, and 4 but not with VanabinP. Furthermore, we found that Vanabin1 interacted with all of the other Vanabins. From the blood plasma, we isolated a novel vanadium-binding protein named VBP-129, and revealed that VBP-129 interacted with VanabinP regardless of the presence or absence of vanadium ions [5]. These results indicated that two protein-protein interaction system functions in A. sydneiensis samea; Vanabins and VIP1 in cytoplasm of signet ring cells, and VanabinP and VBP-129 in blood plasma.

Figure 1. Known and putative protein-protein interaction network in vanadocytes.

Acknowledgements: The authors thank Mr. T. Morita and the staff at the International Coastal Research Center of the Ocean Research Institute, The University of Tokyo, Otsuchi, Iwate, Japan, for their help in collecting adult ascidians. This work was supported in part by Grants-in-Aids from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (#17370026 and 17651048 to H.M. and #18570070 to T.U.) and a grant from the Toray Science Foundation (03-4402 to T.U.). [1] T. Ueki, T. Adachi, S. Kawano, M. Aoshima, N. Yamaguchi, K. Kanamori, H. Michibata, Biochim. Biophys. Acta 1626 (2003) 43-50. [2] K. Fukui, T. Ueki, H. Ohya, H. Michibata, J. Am. Chem. Soc. 125 (2003) 6352-6353. [3] T. Hamada, M. Asanuma, T. Ueki, F. Hayashi, N. Kobayashi, S. Yokoyama, H. Michibata, H. Hirota, J. Am. Chem. Soc. 127 (2005) 4216-4222. [4] T. Ueki, K. Shintaku, Y. Yonekawa, N. Takatsu, H. Yamada, T. Hamada, H. Hirota, H. Michibata, Biochim. Biophys. Acta 1770 (2007) 951-957. [5] M. Yoshihara, T. Ueki, N. Yamaguchi, K. Kamino, H. Michibata, Biochim. Biophys. Acta 1780 (2007) 256-263.



P24

Synthesis of new oxo-vanadium(IV) coordination compounds and evaluation of their insulin mimetic actvity

Jessica Nilsson,a Matti Haukka,b Eva Degerman,c Dieter Rehder,d Ebbe Nordlandera

a Inorganic Chemistry Research Group, Chemical Physics, Center for Chemistry and Chemical Engineering,

Lund University, Getingevägen 6, SE-22100 Lund, Sweden b Department of Chemistry, University of Joensuu, Box 111, FI-80101 Joensuu, Finland

c Department of Experimental Medical Science, Biomedical Center, Lund University, SE-221 48 Lund, Sweden

d Institut für Anorganische und Angewandte Chemie, Universität Hamburg, Martin-Luther-King-Platz 6, D-20146 Hamburg, Germany, email: [email protected]

With the intention of preparing new insulin mimetic compounds, two new V(IV) oxo complexes of the tetradentate ligand N-(2-hydroxybenzyl)-N,N-bis(2-pyridylmethyl)amine, L, (Figure 1a) have been prepared and characterized by NMR and IR spectroscopy, mass spectrometry, elemental analysis and X-ray diffraction. In vitro effects on the insulin signaling pathways of the new complexes [VIVO(HSO4)(L)] (Figure 1b) and [VIVO(Cl2)(L)].MeOH as well as of a related V(IV) oxo complex of trispyridylmethylamine1 have been investigated. Neither of the complexes did, however, show the insulin mimetic effect observed for VOSO4 or Na3VO4 salts. In fact this type of tetradentate coordinating ligands seems to inhibit the inherent insulin mimetic effect of vanadium. To investigate this further we are now in the process of developing complexes containing derivates of the original ligand, altering the coordination mode as well as the hydro/lipophilicity. a) b)

Figure 1. a) The ligand, N-(2-hydroxybenzyl)-N,N-bis(2-pyridylmethyl)amine, used for synthesis of the new complexes, one of which is b) [VIVO(HSO4)(L)].

Acknowledgements: The authors would like to thank The Research School in Pharmaceutical Science (FLÄK), The Swedish Foundation for International Cooperation in Research and Higher education (STINT), The European Cooperation in the Field of Scientific and Technical Research (COST Action D21) and The Royal Physiographic Society in Lund for financial support. [1] Y. Tajika, K. Tsuge and Y. Sasaki, Dalton Trans. (2005), 1438-1447

NN

OH

N



P25

The analysis and determination of vanadium IV in wastes collected from mining ores in Nigeria.

Gloria Omoruyi, Olakunlemi Akinsulire, Oluwaseun Alao

Department of Chemistry, Obafemi Awolowo University, Adeyemi Campus, P.M.B 520, Ondo, Ondo State,

Nigeria. [email protected]

1-(2-Hydroxy-4-methoxybenzophenone)-4-phenylthiosemicarbazone (HMBPT) was investigated

as a new reagent for the flotation of vanadium(IV). At pH �1.5, vanadium(IV) forms a 1:1 pale-

violet complex with HMBPT in aqueous solution. An intense clear violet layer was formed after

flotation, by adding an oleic acid (HOL) surfactant. The composition of the float was 1:1

[V(IV)]:[HMBPT]. A highly selective and sensitive spectrophotometric procedure was proposed

for the determination of microamounts of V(IV) as its floated complex. The molar absorptivities

of the V(IV)-HMBPT and V(IV)-HMBPT-HOL systems were 0.4 × 104 and 0.12 × 105 L mol-1 cm-1

at 560 nm, respectively. The formation constants of the species formed in the presence and

absence of HOL were 4.6 × 107 and 8.7 × 105 L mol-1, respectively. Beer's law was obeyed up

to 1 × 10-4 mol L-1 in the aqueous layer as well as in the oleic acid layer. The HMBPT-V(IV)

complexes formed in the aqueous solution and scum layer were characterized by elemental

analysis, infrared and UV spectrophotometric studies. The mode of chelation between V(IV) and

HMBPT is proposed to be due to a reaction between the protonated bidentate HMBPT ligand and

V(IV) through the S=C and N=C groups. Interferences from various foreign ions were avoided

by adding excess HMBPT and/or Na2S2O3 as a masking agent. The proposed flotation1 method

was successfully applied to the analysis of V(IV) in synthetic mixtures, wastes of power stations,

simulated samples and in real ores. The separation mechanism is discussed.

G . A. Whittlow, S. E. Lee, R. R. Mullir, R. A. Wenglar and T. P. Sherlock, J. Eng. For Power, (1988), 105, 88. A. I. Vogel “A Text Book of Quantitative Inorganic Analysis”, (1994), Longman, London. Koleso, A.O, Chemistry of Vanadium, (2000).



P26

Vanadium induced cyclization of thiosemicarbazone: formation of heptanuclear mixed valence V(IV)/V(V) complex

Mirta Rubčić,a Ivica Đilović,a Marina Cindrić,a Dubravka Matković-Čalogovića

a Laboratory of General and Inorganic Chemistry, Department of Chemistry, Faculty of Science, University of

Zagreb, Horvatovac 102a, Zagreb, Croatia, e-mail: [email protected]

Thiosemicarbazones, a small organic molecules which belong to a family of thiourea derivatives, are associated with various biological activities including antibacterial, antiviral and antitumor.[1] As ligands, they can coordinate to metal ions in diverse manners due to the number of mixed soft-hard donor atoms and conformational flexibility.[2] Furthermore, under the influence of metal cations as oxidants they can easily undergo ring closure process affording variety of heterocyclic rings.[3] Data in the literature reveal that various metal cations, such as Ag(I), Zn(II), V(IV) etc., are capable of inducing cyclization reactions of thiosemicarbazone or related dithiocarbazate systems.[4]

Recently, we have reported two new thiazoline compounds obtained by vanadium induced cyclization of acetylacetone and thiosemicarbazone ligands.[5] As a continuation of the previous research, we have investigated the reactions of oxovanadium(IV) acetylacetonate and salicylaldehyde 4-phenylthiosemicarbazone (H2L) in the presence of different bases (imidazole, 4-picoline and pyridine) under inert atmosphere. When imidazole (im) or 4-picoline (4-pic) were used mononuclear vanadium(IV) complexes, [VO(L)(im)] (Figure 1(a)) and [VO(L)(4-pic)] were obtained. Interestingly, in the case of pyridine we isolated previously reported thiazoline compound [5] and polinuclear mixed-valence V(IV)/V(V) complex, [V7O14(Lcycl)3(py)3] (Figure 1(b)). In the polinuclear complex with unprecented [V7O14]

3- core, vanadium atoms are coordinated by bridging ligands containing 1,2,4-thiadiazole ring, as a product of vanadium induced oxidative cyclization, and pyridine as ancillary ligands.

(a) (b)

Figure 1. (a) [VO(L)(im)]; (b) [V7O14(Lcycl)3(py)3].

All isolated products were identified and characterised by means of chemical analysis (C H, N, S), IR spectroscopy, thermogravimetric methods and when possible by single crystal X-ray diffraction method. [1] (a) W.-X. Hu, W. Zhou, C.-N. Xia, X. Wen, Bioorg. Med. Chem. Lett. 16 (2006) 2213–2218. (b) N. Bharti, K. Husain, M. T. G. Garza, D. E.Cruz-Vega, J. Castro-Garza, B. D. Mata-Cardenas, F. Naqvi, A. Azam Bioorg. Med. Chem. Lett. 12 (2002) 3475–3478. (c) D. F. Smee, R. W. Sidwell Antiviral Research 57 (2003) 41–52. [2] J.S.Casas, M.S.Garcıa-Tasende, J. Sordo, Coord. Chem. Rev. 209 (2000) 197-261. [3] P. Lo Meo, M.Gruttadauria, R. Noto Arkivoc i (2005) 114-129. [4](a) A. Castineiras, I. Garcıa-Santos, S. Dehnen, P. Sevillano Polyhedron 25 (2006) 3653-3660. (b) J. S. Casas, M. V. Castano, E. E. Castellano, J. Ellena, M. S. Garcıa-Tasende, A. Gato, A. Sanchez, L. M. Sanjuan, J. Sordo Inorg. Chem. 41 (2002) 1550-1557. (c) S. K. Dutta, S. Samanta, D. Ghosh, R. J. Butcher, M. Chaudhury Inorg. Chem. 41 (2002) 5555-5560. [5]M. Cindrić, M. Rubčić, I. Đilović, G. Giester, B. Kamenar Croat. Chem. Acta 80 (2007) 583-590.



P27

A new vanadium(V)-peroxo species in the presence of physiological citrate. The missing link in the structural speciation of the V(V)-

peroxo-citrate system.

Athanasios Salifoglou, Catherine Gabriel

Department of Chemical Engineering, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece email: [email protected]

Vanadium is an essential element, which exists in all organisms at low concentration. Vanadium participation in a plethora of biological systems and abiotic applications, has spawn considerable research over its role in nature, its potential use in pharmaceutical therapeutics and generally its biological action.1 The latter is supported by the fact that vanadium plays a catalytic role in metalloenzyme systems such as nitrogenase and haloperoxidases.2 As an inorganic cofactor, vanadium possesses and promotes bioactivities, ranging from antitumorigenicity to mitogenicity, inhibition of metabolic enzymes such as phosphoglucomutases2,3 and others.1 Outstanding in this regard is its influence in the heterogeneous syndrome of Diabetes mellitus through its insulin mimetic action.4,5 In an effort to understand the aqueous chemistry of insulin mimesis exhibited by vanadium in its biologically relevant oxidation states V(IV,V), well-designed synthetic approaches were developed at the binary and ternary level with physiological ligands. Among the various ligand-substrates studied in the presence of vanadium were α-hydroxycarboxylate-containing organic ligands, the most biologically relevant of which was citric acid. Citric acid exists in human plasma6, promoting chemical interactions with metal ions and variably influencing key metabolic functions. In view of the significance of the above mentioned (bio)chemistry, aqueous vanadium-peroxo-citrate complexes were targeted.7 Consequently, the chemical reactivity of V(V)-peroxo-citrate system was investigated under control of the molar stoichiometry and pH-dependent conditions leading to a new ternary complex [V2O2(O2)2(C6H5O7)2][quanidiniumH]4

.6H2O (1). The synthesized complex was fully characterized by numerous spectroscopic (FT-IR, UV-Visible, and multinuclear NMR), electrochemical (cyclic voltammetric), and ultimately X-ray crystallographic techniques. The structural nature of this species emphasizes the degree of deprotonation of citric acid in formulating the coordination environment of V(V) in the presence of H2O2. To this end, the existence of such a ternary species emerges in consonance with the other existing analogous species and justifies its presence on the requisite speciation scheme as a competent structural variant. Hence, species 1 is the missing link in the structural speciation of the ternary V(V)-peroxo-citrate, completing the family of species bearing deprotonated forms of citrate and exhibiting variable structural features as a result of their synthetic assembly and isolation from solutions covering the physiological pH range. Collectively, the physicochemical properties of 1 formulate the profile of ternary V(V)-peroxo-citrate species arising in aqueous media and shed light onto the chemical reactivity of vanadium participating in insulin mimetic activity. Acknowledgements: This work was supported by and by a ‘‘PENED” grant co-financed by the E.U.-European Social Fund (75%) and the Greek Ministry of Development-GSRT (25%). [1] In Metal Ions in Biological System: Edited by Sigel, H., and Sigel, A.. Marcel Dekker, Inc., New York NY, (1995), pp. 325-362, 407-425, 558-560. [2] a) J. K. Klarlund, Cel, 41, (1985), 707-717. b) J. B. Smith, Proc. Natl. Acad. Sci. USA 80, (1983), 6162-6167. [3] a) K. M. Walton, J. E. Dixon, Annu. Rev. Biochem. 62, (1993),101-120. b) K.-H. W. Lau, J. R. Farley, D. J. Baylink, Biochem. J. 257, (1989), 23-36. [4] H. Sakurai, Y. Kojima, Y. Yoshikawa. K. Kawabe, H. Yasui, Coord.Chem. Rev. 226, (2002), 187. [5] D. L. Flynn, J. Med. Chem. 35, (1992), 1489-1491. [6] H. A. Krebs, W. A. Johnson, Enzymologia 4, (1937), 148-156. [7] a) M. Kaliva, C. P. Raptopoulou, A. Terzis, A.Salifoglou, J. Inorg. Biochem. 93, (2003), 161-173. b) M. Kaliva, E. Kyriakakis, C. Gabriel, C.P. Raptopoulou, A. Terzis, J.-P. Tuchagues, A.Salifoglou, Inorganica Chimica Acta 359, 14, (2006),4535-4548.



P28

New C-functionalized tris(pyrazolyl)methanes and their vanadium complexes

Telma F.S. Silva,a,c Riccardo Wanke,c Luísa M.D.R.S. Martins,b,c

Armando J.L. Pombeiroc

aÁrea Científica de Física, ISEL, R. Conselheiro Emídio Navarro, 1959-007 Lisbon, Portugal, bDepartamento de Engenharia Química, ISEL, R. Conselheiro Emídio Navarro, 1959-007 Lisbon, Portugal,

cCentro de Química Estrutural, IST, TU, Av. Rovisco Pais, 1049-001 Lisbon, Portugal, email: [email protected]

Recently, we have initiated the study of the coordination chemistry of hydrotris(1-pyrazolyl)methane, HC(pz)3 (pz = pyrazolyl), and its derivatives bearing substituents on the pyrazolyl rings (e.g., hydrotris(3,5-dimethyl-1-pyrazolyl)methane, HC(3,5-Me2pz)3) or the C- methine carbon-substituted tris(1-pyrazolyl)methanesulfonate (as its lithium salt Li[SO3C(pz)3]), towards V, Fe, Cu or Re centres.1-5 In addition, we have found that some of the synthesized scorpionate complexes of those metals can act as selective catalysts in the single-pot oxidation of ethane to acetic acid and in the peroxidative oxidation of cyclohexane to cyclohexanol and cyclohexanone. Herein we report the study of the reactivity of hydrotris(1-pyrazolyl)methane towards the methine carbon functionalization and the coordination of the obtained C-functionalized scorpionates to a V centre. Hence we have prepared C-functionalized tris(pyrazolyl)methane derivatives RC(pz)3, R= CH2OH or new CH2OCH2(py) (py = pyridyl ring), and investigated their behavior at vanadium(III) centres:

NNN N

NN

CV

Cl

Cl

ClMeOH or THF, refluxVCl3 R

R = HOCH2 or pyCH2OCH2

NNC 3HO NNC 3ONor

The synthesis and characterization of the new scorpionate and V-complexes are reported. Acknowledgements: The work has been partially supported by the Fundação para a Ciência e Tecnologia (FCT) and its POCI 2010 programme (FEDER funded). [1] T.F.S. Silva, L.M.D.R.S. Martins, E.C.B.A. Alegria, A.J.L. Pombeiro, Adv. Synth. Catal. 350 (2008) 706. [2] E.C.B. Alegria, M.V. Kirillova, L.M.D.R.S. Martins, A.J.L. Pombeiro, Appl. Catal. A: Gen. 317 (2007) 43. [3] T.F.S. Silva, L.M.D.R.S. Martins, M.F.C.G. Silva, A.J.L. Pombeiro, Acta Cryst. E, 63 (2007) m1979. [4] E.C.B. Alegria, L.M.D.R.S. Martins. M. Haukka, A. J.L. Pombeiro, Dalton Trans (2006) 1. [5] E.C.B. Alegria, L.M.D.R.S. Martins, M.F.C.G. Silva, A.J.L. Pombeiro, J. Organomet. Chem. 690 (2005) 1947.



P29

Synthesis, molecular and supramolecular structures of oxo compounds formed by biologically active central atom, heteroligand/s and

counterions: vanadium(V), pyridine or pyrazine carboxylates and amides

Michal Siváka, Peter Schwendta, Silvia Pacigováa and Gyepes Róbertb

aDepartment of Inorganic Chemistry, Comenius University, Faculty of Natural Sciences, Mlynská dolina,

842 15 Bratislava, Slovak Republic, b Department of Inorganic Chemistry, Charles´ University, Faculty of Natural Sciences, Prague, Albertov, 128 00 Prague, Czech Republic, e-mail: [email protected]

In the reaction systems V2O5 – H2O2 – L1 – L2 – H2O, the interaction of vanadium(V) with organic compounds L1 and L2: dipicolinate (dipic), picolinate (pic), quinolinate (1-) (Hquin), pyrazinate (pca), picolinamide (pa), nicotinamide (1-Hnica), isonicotinamide (inica) or pyrazinamide (pcaa), which exhibit either as free substances or bonded in coordination compounds different biological activities, resulted in formation of crystalline oxo, and oxo peroxo compounds: (Hpa)[VO(O2)dipic(H2O)]•H2O (1), (Hnica)[VO(O2)dipic(H2O)] (2), [VO(O2)(pic)(pa)]·H2O (3), [VO(O2)(Hquin)(pa)]·2H2O (4) (Figure 1, left) , [VO(O2)(pca)(pa)] (5), (1-Hnica)6V10O28·2H2O (6) and (H-inica)4H2V10O28· inica (7). The coordination of two bidentate ligands in pentagonal bipyramidal complexes 3 – 5 to the VO(O2)

+ group with a triple V≡O(oxo) bond1 too confirm our empirical stereochemical rules2.

Figure 1. Molecular structure of 4 (left) and anion- π interactions between pca ligands in 5 (right).

The supramolecular structures of 1-7 are constructed by hydrogen bonds („classical“ and C-H•••O) and interactions between the π - electrons of aromatic rings: parallel/non-parallel displaced π - π or the rare anion- π interactions in 3 and 5 (Figure 1, right), the latter also confirmed by DFT calculations of electrostatic potential distributions and MOs for the solid state. Acknowledgements: Authors would like to thank the Ministries of Eduction of: the Slovak Republic (grant VEGA 1/4462/07) and Czech Republic (grant GA 203/99/M037 ), and Comenius University Bratislava (grant UK 172/2007) for their financial support. [1] S. Pacigová, R. Gyepes, J. Tatiersky, M. Sivák, , Dalton Trans. (2008), 121-130 [2] J. Tatiersky, P. Schwendt, M. Sivák, J. Marek, Dalton Trans. (2005), 1-7



P30

Bi- and hexanuclear vanadium (IV) complexes of a p-hydroquinone-based ligand: synthesis and structural characterization

Marios Stylianou and Anastasios D. Keramidas

Department of Chemistry, University of Cyprus, Nicosia 1678, Cyprus,


It is well established that the electron transfer reactions of p-quinones, along with their redox products, p-semiquinones and p-hydroquinones play an important role in biological systems.1,2 Vanadium also participates in biological processes as a catalyst in the active sites of metalloenzymes. Consequently, vanadium chemistry with hydroquinone-based ligands, may have immediate implications on its role in its action as a biological agent and thus, may give fundamental aspects of the electron transfer reactions between transition metal centres and p-quinone cofactors.3 In an effort to comprehend the interaction and the aqueous chemistry of vanadium (IV) and p-dioxolene ligands, reactions of vanadium (IV) salts and an electron-active bis-substituted p-hydroquinonate ligand were pursued in water and led to isolation of V(IV)-p-hydroquinonate complexes, the structure and properties of which depend strongly on the solution pH. X-ray crystallography revealed the formation of bi- (1) and hexa-nuclear (2) vanadium (IV) complexes where the metal atom in both molecules coordinated in an octahedral geometry. In 1, three binuclear complexes formed an open triangular array where the average distance between the neighboring metal centres is 8.6 Å while in 2, three binuclear complexes, analog to 1, are connected to each other via VIV-O-VIV bridges forming the hexanuclear structural motif illustrated in Figure 1. For both compounds, BVS calculations confirmed vanadium's oxidation state as IV, and in conjuction with X-ray crystallography ligand’s oxidation state was assigned as p-hydroquinone. FT-IR confirmed metal atom’s coordination and thus ligand’s oxidation state in both complexes, while elemental analysis (CHN) confirmed their purity. Magnetic susceptibility measurements in the solid state at room temperature for 1 and 2 supported their paramagnetism.

Figure 1. Molecular structure of the hexanuclear VIV-p-hydroquinonate complex 2.

Acknowledgements: The authors would like to thank the Research Promotion Foundation of Cyprus for the financial support of this work with the proposal TEXNO/0506/19 (BYKH). [1] M. R. A. Blomberg, P. E. M. Siegbahn, and G. T. Babcock, J. Am. Chem. Soc. 120 (1998) 8812-8824. [2] M. S. Craige, M. L. Paddock, J. M. Bruce, G. Feher, and M. Y. Okamura, J. Am. Chem. Soc. 118 (1996) 9005-9016. [3] C. Drouza, V. Tolis, V. Gramlich, C. Raptopoulou, M. P. Sigalas, T. A. Kabanos, and A. D. Keramidas, Chem. Commun. (2002) 2786-2787.



P31

The effect of ionic strength on the stability constant of vanadium(IV) complex with methionine

Karim Zare,a,b Saied Abedini Khorrami,c Bahareh Khorramdinc

aChemistry Department, Shahid Beheshti University, Tehran, Evin, Iran

bChemistry Department, Islamic Azad University, Science & Research Campus, Tehran, Hesarak, Iran cChemistry Department, Islamic Azad University, North Tehran Branch, Tehran, Iran


The equilibrium of vanadium(IV) complex formed by methionine in acidic media has been

investigated by a combination of potentiometric and spectrophotometric techniques. The metal-

ligand equilibria were studied at 25 ± 0.1ºC in the ionic range of interest 0.1 < I < 1 mole dm-3 of sodium perchlorate. Oxyvanadium has been reported as VO2+ ion in the pH range of 1.3 < pH

< 2.5. Under these experimental conditions, hydrolysis of vanadium(IV) was negligible and the

1:1 complex has the formula VOHY, where Y- represents the fully dissociated amino carboxylate

anion. All of the stability constants have been determined at various wavelengths. Comparison

of the ionic strength effect on this complex formation reaction has been made using a Debye-

Huckel type equation. The method based on the relationship A=f(pH) was employed, on account

of the high stability of the complexes studied. Absorbance and pH was measured for solution

containing a large excess of the ligand.1-4

[1] K. Majlesi, K. Zare, J. Mol. Liq. 125 (2006) 62-65. [2] P. Lagrange, M. Schneider, K. Zare, J. Lagrange, Polyhedron 13 (1994) 861-867. [3] F. Gharib, K. Zare, S.A. Khorrami, J. Chem. Eng. Data 40 (1995) 186-189. [4] K. Zare, P. Lagrange, J. Lagrange, J. Chem. Soc. Dalton Trans. (1979) 1372-1376.



P32

Interaction of a pyrimidinone-V(IV) complex with human serum transferrin

Gisela Gonçalves,a João Costa Pessoa,a Isabel Tomaz,a,b M.Margarida C.A. Castro,c

Carlos F.G.C. Geraldes,c Fernando Avecillad

a Centro de Química Estrutural, Instituto Superior Técnico, Av. Rovísco Pais, TU Lisbon, 1049-001 Lisboa Portugal, email: [email protected]

b Centro de Ciências Moleculares e Materiais, Faculdade de Ciências da Universidade de Lisboa, Campo Grande 1749-016 Lisboa - Portugal;

c Dpto. de Bioquímica e Centro de RMN, Universidade de Coimbra, 3001-401 Coimbra, Portugal; d Dpto. de Química Fundamental, Universidade da Coruña, A Coruña 15071, Spain.

In the last years, research in vanadium chemistry has gained new impetus: in addition to the potential benefits of vanadium compounds for the oral treatment of Diabetes, its anti-tumour potential has also been recognized 1.

It has been proposed that in higher organisms the delivery of vanadium into cells can be promoted by natural carriers such as plasma proteins, particularly by the human serum transferrin 2.

The vanadium complexes of maltol and ethylmaltol are promising compounds for the oral treatment of Diabetes, 1 and pyridinone complexes have also been considered. We prepared a pyrimidinone ligand MHCPE (2-methyl-3H-5-hydroxy-6-carboxy-4-pyrimidinone ethyl ester), and studied its complexation with VIVO2+ and VVO2

+ by potentiometry, UV-Vis, EPR and NMR spectroscopy. MHCPE is an an efficient ligand for both V(IV) and V(V). The complexes are quite stable, complex formation starting at pH lower than two.

In this work we report and discuss some results regarding the interaction of vanadium, and vanadium(IV)-MHCPE complexes with human serum transferrin (hTF) by circular dichroism (CD) and EPR spectroscopy. By CD the 200-250 nm, 250-330 nm and 400-1000 nm were examined separately, as give distinct information regarding the interaction of V-species with hTf. Namely, the existence of CD signal in the 400-1000 nm is a clear indication of the binding of VIVO-species to chiral hTf sites. It is concluded that the ternary system, VIVO-MHCPE-transferrin, leads to a stronger binding than for the binary VIVO-transferrin species. Moreover, the order of mixing the reagents (VIVO + MHCPE + hTF) appears to have influence upon the CD spectra recorded.

We anticipate MHCPE can be an effective ligand to improve vanadium transport in blood plasma if the MHCPE ligand is also absorbed in the gastro-intestinal tract.

N

NH

OH

OH3C

O O

Figure 1. Structure of the ligand MHCPE (2-methyl-3H-5-hydroxy-6-carboxy-4-pyrimidinone ethyl ester)

Acknowledgements: The authors wish to thank to the Fundação para a Ciência e Tecnologia, (SFRH/BD/32131/2006 and SFRH/BPD/34695/2007), FEDER POCI 2010 and PPCDT/QUI/56949/2004, the Spanish-Portuguese Bilateral Programme (Acção Integrada E-56/05) and University of A Coruña for financial support. [1] K.H. Thompson and C. Orvig, J. Inorg. Biochem., 100 (2006) 1925-1953. [2] T. Kiss, T. Jakusch, D. Hollender, A. Dörnyei, E. A. Enyedy, J. Costa Pessoa, H. Sakurai and A. Sanz-Medel, Coord. Chem. Rev., Vol. 252 (2008) 1153-1162.



P33

VIVO complexes with bis(pyridyl) derivatives

Daniele Sanna,a Giovanni Micera,b Luisa Pisano,b Eugenio Garribba,b Dóra Kiss,c Katalin Várnagy,c

aIstututo CNR di Chimica Biomolecolare, I-07040 Sassari, Italy, email: [email protected];

bDipartimento di Chimica, Università di Sassari, Via Vienna 2,I-07100 Sassari, Italy cDepartment of Inorganic and Analytical Chemistry, University of Debrecen, H-4010 Debrecen, Hungary

Oxovanadium(IV) complexes of bis(imidazolyl) derivatives of amino acids have been recently examined by some of us.1 The bis(imidazolyl) moiety acts as an anchoring group and avoids hydrolysis and precipitation of vanadium hydroxide allowing the deprotonation and coordination of the amide nitrogen. Pyridine nitrogen is known as a good donor group in vanadium coordination chemistry2 and bis(pyridyl) derivatives of amino acids could keep VO2+ ion in solution in the acidic pH range and favour the binding of the amide nitrogen. In this context we studied the coordinating properties of a series of bis(pyridyl) derivatives through the combined application of potentiometric and spectroscopic methods. In particular we examined 2,2’-dipyridylmethane and its derivatives, 2,2’dipyridylketone, 2,2’-dipyridylmethanol and 2,2’-dipyridylamine and two amino acid derivatives of 2,2’-dipyridylmethylamine (DPMA), namely N-glycyl-DPMA and N-histidyl-DPMA. The results show that the simple bis(pyridyl) derivatives, having only Npyridine donor atoms, form mono-chelated complexes, while the derivatives with a carbonyl or hydroxyl groups also complexes with (Npyr, CO/O–) coordination. To assign the binding modes to the various species bidentate ligands, 2-acetylpyridine and 2-pyridinemethanol, have been used as simple models. The 51V hyperfine coupling constant (Az) of the complexes with 2x(N, O–) coordination shows an anomalously low value. This anomalous reduction will be discussed and possible explanations will be proposed. With the two amino acid derivatives, N-glycyl- and N-histidyl-DPMA, the metal binding starts with the formation of complexes with bis(pyridyl) coordination and continues at higher pH values with the coordination of the amino and deprotonated amide groups.

Figure 1. Calculated structure of the complex [VO(N-glycyl-pyridylmethylamine)(OH)].

DFT calculations were performed to obtain information on the structure of the species formed by N-glycyl-DPMA and N-histidyl-DPMA. DFT methods were also used to predict the 51V hyperfine coupling constant for vanadyl-pyridine complexes. The calculations on the model complex [VO(pyridine)(H2O)4]

2+, with an equatorially coordinated pyridine, show that Az value depends on the orientation of the pyridine ring with respect to the V=O bond, analogously to what experimentally and theoretically found for the species with imidazole.3, 4 [1] K. Várnagy, T. Csorba, D. Kiss, E. Garribba, G. Micera, D. Sanna, Eur. J. Inorg. Chem. (2007) 4884–4896. [2] T. Duma, R. Hancock, J. Coord. Chem. 32 (1994) 135-146. [3] T. S. Smith II, C. A. Roof, J. W. Kampf, P. G. Rasmussen, V. L. Pecoraro, J. Am. Chem. Soc. 122 (2000) 767-775. [4] A. C. Saladino, S. C. Larsen, J. Phys. Chem. A 106 (2002), 10444-10451.



P34

Interaction of insulin-enhancing vanadium compounds with transferrin and low molecular mass bioligands

Daniele Sanna,a Giovanni Micera,b Eugenio Garribba,b

aIstututo CNR di Chimica Biomolecolare, I-07040 Sassari, Italy, email: [email protected];

bDipartimento di Chimica, Università di Sassari, I-07100 Sassari, Italy

The interaction of human serum transferrin (hTf) with VO(IV) and a series of insulin-enhancing vanadium compounds, namely cis-[VO(picolinato)2(H2O)], [VO(6-methylpicolinato)2], [VO(acetylacetonato)2], and [VO(maltolato)2]) has been examined in aqueous solutions using frozen solution electron paramagnetic resonance (EPR) spectroscopy. Moreover the interaction of insulin-enhancing vanadium compounds with transferrin and low molecular weight ligands of the blood serum (lactic and citric acids) has been considered. For comparison the system hTf-VO(IV) has been reexamined. The results show that in the binary system VO(IV)-hTf, as previously reported,1 the metal ion can occupy three different binding sites, A, B1 and B2, identified with the two N- and C-terminal coordination sites of hTf for Fe(III). The synergic anion bicarbonate is necessary for the metal binding analogously as reported in the case of iron; this ligand, however, can be replaced by different anions like citrate or lactate. When considering the interaction of the insulin-enhancing compounds with hTf, the prevalent vanadium complexes present in solution depend on the stability of the binary VO(IV)-carrier species. With strong carriers the main species present in solution can be identified as a ternary complex with hTf and a carrier molecule; with intermediate carriers mixed complexes VO(IV)-hTf-carrier and VO(IV)-hTf-lactate (or citrate) are formed, while with weak carriers the vanadium is present in solution mainly as (VO)2hTf, the binary complex with hTf. Besides hTf, human serum albumin (HSA), can be involved in the transport of the insulin mimetic vanadium compounds in the blood serum.2 Since the relative stabilities of the vanadium complexes with hTf and HSA are unknown we examined the ternary system VO(IV)-hTf-HSA at different ratios and concentrations. EPR results show that human serum transferrin seems to be the preferred ligand for the oxovanadium(IV) ion. However, as it will be explained in detail, the vanadium binding to human serum albumin cannot be completely excluded and this means that both these high molecular mass ligands of the blood serum (i.e. hTf and HSA) contribute to the transport of the insulin-enhancing vanadium compounds to the target organs, with hTf being the preferred one.

Figure 1. Anisotropic EPR spectra of the systems VO(IV)-hTf, VO(IV)-hTf-lactate and VO(IV)-lactate. [1] N. D. Chasteen, in Biological Magnetic Resonance; Plenum Press: 1981, vol. 3, pp. 53-119 and references therein. [2] B. D. Liboiron, K. H. Thompson, G. R. Hanson, E. Lam, N. Aebischer, C. Orvig, J. Am. Chem. Soc. 127 (2005) 5104-5115.



P35

The effects of the trigonal bipyramidal distortion on the spectroscopic and electrochemical properties of VIVO bis-chelated species

Eugenio Garribba,a Giovanni Micera,a Daniele Sanna,b Elzbieta Lodyga-Chruscinska,c

aDipartimento di Chimica, Università di Sassari, Via Vienna 2, 07100 Sassari, Italy, email: [email protected];

bIstituto C.N.R. di Chimica Biomolecolare, Trav. La Crucca 3, 07040 Li Punti, Sassari, Italy cInstitute of General Food Chemistry, Technical University of Lodz, ul. Stefanowskiego, 90924 Lodz, Poland

Among the five-coordinated VIVO complexes, those with square-pyramidal geometry are the most common. Only few examples of a geometry close to the trigonal bipyramid were described in the literature.1 In this work the behaviour of the bis-chelated VIVO complexes formed by simple (glycolic, 2-hydroxyisobutiric, 2-ethyl-2-hydroxybutiric and benzilic) and complex (citric and D-, L-, DL-tartaric) α-hydroxycarboxylic acids was studied. The structure of the VOL2H−2 species in aqueous solution was simulated by DFT methods with Gaussian 03 software, which provide a valid tool for the optimization of the structures of complexes in absence of X-ray single crystal analysis. EPR spectra of trigonal bipyramidal distorted species are rhombic with three g (gx ≠ gy ≠ gz) and three A values (Ax ≠ Ay ≠ Az), whereas electronic absorption spectra are characterized by four transitions between 400 and 850 nm: this is due to the loss of degeneracy of the dxz and dyz atomic orbitals.2 It was found that in aqueous solution the distortion follows the steric hindrance of the substituents on the α-carbon atom and the hydrophobicity of the ligands. The trigonal bipyramidal distortion, expressed by the structural index of trigonality τ,3 can be correlated with the values of: i) |Ax – Ay|, where Ax and Ay are the 51V hyperfine coupling constants along the x and y axes in the anisotropic EPR spectrum; ii) Δλ = λ2 – λ3, where λ2 and λ3 are the central bands in the electronic absorption spectrum; and iii) the half-wave potential E1/2 for the oxidation of [VIVO(LH−1)2]

x− to the corresponding VVO2 species [VVO2(LH−1)2](x−1)− in

the cyclic voltammogram. The results are confirmed by DFT calculations which show that the trigonal bipyramidal distortion results in a four-band electronic spectrum.

Figure 1. Effect of the trigonal bipyramidal distortion τ of VIVO complexes of α-hydroxycarboxylates on Δλ.

We think that the results are of general validity and can be applied to every penta-coordinated VIVO complex formed by bidentate ligands to determine its trigonal bipyramidal distortion. [1] C. R. Cornman, K. M. Geisre-Bush, S. R. Rowley, P. D. Boyle, Inorg. Chem. 36 (1997) 6401-6408. [2] E. Garribba, G. Micera, A. Panzanelli, D. Sanna, Inorg. Chem. 42 (2003) 3981-3987. [3] A. W. Addison, T. N. Rao, J. Reedijk, J. van Rijn, G. C. Verschoor, Dalton Trans. (1984) 1349-1356.



P36

VO(oda): a vanadyl(IV) complex with an OOO-donor group. Bioactivity on human colon adenocarcinoma Caco-2 cell line.

Josefina Rivadeneiraa,b,Cecilia I. Mugliaa, Enrique J. Barana,b, Liliana Bruzzonea,

Susana B. Etcheverrya,b

aFacultad de Ciencias Exactas, UNLP. 47 y 115 (1900) La Plata, Argentina [email protected] bCEQUINOR (CONICET-UNLP), Facultad de Ciencias Exactas, UNLP, La Plata, Argentina

Vanadium is a trace element widespread distributed in nature. Vanadium compounds have attracted scientific attention due to their potential therapeutic applications. The pharmacological effects of vanadium include insulin mimetic actions, osteogenic and antitumoral effects. In particular, the antitumoral actions of vanadium can be evaluated by the determination of different parameters such as cell proliferation, morphology and disruption of cellular architecture. Vanadium compounds exert their antineoplastic actions by different mechanisms (inhibition of key protein tyrosine phosphatases, changes in cell cytoskeleton proteins, and disturbance of redox equilibria in the cells that causes an increment in the oxidative stress and alterations in the ratio GSH/ GSSG). Altogether, these effects may lead to the induction of apoptosis and/or necrosis, and finally to cell death. On the other hand, strong chelating ligands are very important in aqueous media because they offer the opportunity of trapping different metal species. This process becomes particularly significant in living systems, where different metals are acquired, transported and stored mostly by low-molecular-weight compounds involving multidentate oxygen donors. Among the family of multidentate oxygen donor species, oda= oxodiacetate, O(CH2COO-)2, stands as a versatile complexing agent. It holds an OOO donor group and can complex metal ions by forming chelate rings. The synthesis of the complex VO2+-oda has been previously reported. The aim of the present study is to extend our previous observations on the bioactivity of VO2+-oda on tumoral cells, focusing the attention on its cytotoxicity effects on the human colon adenocarcinoma cell line Caco-2, trying to understand its mechanisms of action. The complex caused an inhibitory effect on cell proliferation in a dose response manner in the range of 10-100 µM (p<0.001) (Crystal violet assay). Nevertheless, this inhibitory effect was lower than the inhibition in other tumoral cell line (UMR106 rat osteosarcoma) studied in our laboratory. IC50 for the complex in Caco-2 cell line was >> 100 µM. This inhibition of Caco-2 proliferation was reversed by scavengers of free radicals as a mixture of vitamin C and E (50 µM). The reversion was complete in the range of low doses of the complex (10-25 µM) and only partial at higher concentrations (50-100 µM). Morphological studies were carried out using Giemsa staining and light microscopy. In basal conditions, the cells displayed polygonal shape and big nuclei with numerous nucleoles. Cells present also numerous connections between each other. Upon incubation with the complex, the nuclei showed different alterations in their form and some membrane blebs could be seen. Besides, the cytoplasm of the cells also showed important transformations such as numerous irregular vacuoles and lost of neighbouring connections. These changes increased with the doses and correlated with a decrease in number of cells per field. Moreover, the investigation of the effects of VO2+-oda on the actin filaments, indicated a disassembly of the network as a function of complex concentration. Thus, the morphological alterations were in parallel with the results of proliferation study. In order to get a deeper insight into the mechanisms underlying the cytotoxicity of VO2+-oda, we determined its effect on the oxidative stress using two parameters: the oxidation of dihydrorhodamine 123 to rhodamine (measured by spectrofluorometry) and the changes in the ratio of reduced glutathione (GSH) to oxidized glutathione (GSSG). The complex produced a great increment in the levels of rhodamine in the range of 50-100 µM while a decrease in the GSH/GSSG ratio could be observed. Besides, the mixture of vitamins C and E, scavenger of free radicals, caused a partial reversion of the VO2+-oda effect in the range of complex concentration 50-100 µM. Altogether these results suggest that VO2+-oda exerts its cytotoxicity effects on human colon adenocarcinoma (Caco-2) cells through, at least in part, an increment in the oxidative stress and the alterations of actin cellular network. Acknowledgements: S. B. Etcheverry thanks the Reitoria da Universidade Técnica de Lisboa, Portugal, the financial support for travelling.



P37

Modifying antiprotozoa activity of organic compounds through complexation with vanadium

Dinorah Gambino,a Julio Benítez,a Marisol Vieites,a Lucía Guggeri,b Pablo Smircich,b

Beatriz Garat,b Miriam Rolón,c Celeste Vega,c Antonieta Rojas de Arias,c Daniel Figueroa,d Tanof Celmar Costa França,d Edgar Marchán,e Zulay Simonie

aCátedra de Química Inorgánica, Facultad de Química, UDELAR, Gral. Flores 2124, 11800 Montevideo, Uruguay; bLaboratorio de Interacciones Moleculares, Facultad de Ciencias, UDELAR, Igua 4225, 11400

Montevideo, Uruguay; cCEDIC, Fundación M. Bertoni/Laboratorios Díaz Gill, Asunción, Paraguay; dDepartamento de Quimica, IME, 22290-270, Rio de Janeiro, Brazil; eInstituto de Investigaciones en

Biomedicina y Ciencias Aplicadas, Universidad de Oriente, Venezuela; email: [email protected]

According to the World Health Organization infectious and parasitic diseases are major causes of human disease worldwide. Chagas´s disease and Leishmaniasis, diseases caused by kinetoplastid parasites of the genus Trypanosoma and Leishmania respectively, are large burdens in the American continent. Chagas´ disease affects nearly 20 million people in Latin America. Leishmaniasis threatens 88 countries around the world, 72 of which are developing ones. Currently, Leishmania and HIV co-infection is a serious world problem. Chemotherapy is unsatisfactory, available treatments suffering from limited efficacy and/or undesirable side effects and/or development of resistance. Searching for new therapeutic tools against Chagas' disease, we have been working on the development of metal-based drugs by including in a single molecule an organic bioactive ligand and a metal with pharmacological potentiality. This approach could lead to a metal-drug synergism, produce an additive effect or improve bioavailability of the organic drug. By means of this strategy we developed different bioactive metal complexes and studied their mechanism of action. Among them a family of vanadyl complexes of bioactive 3-aminoquinoxaline-2-carbonitrile-N1,N4-dioxide derivatives, VO(L)2, showed improved anti-trypanosomal activity when compared with the free ligands. We were able to explain this behaviour on the basis of lipophilicity and electronic characteristics of the quinoxaline substituents. Taking into account these results, more recently, we have been working with another aromatic amine N-oxide bearing in vitro anti-trypanosomal and anti-Leishmania activities, namely pyridine-2-thiol-N-oxide (mpo), and its vanadium, platinum, palladium and gold complexes. It has been previously demostrated that mpo blocks Trypanosoma cruzi´s growth in culture and in infected mammalian myoblasts, affecting all stages of its life cycle and showing low IC50 values. Although it may have other intracellular targets, it inhibits the parasite specific enzyme NADH-fumarate reductase, enzyme responsible of the conversion of fumarate to succinate which is required by the parasite for energy production. We evaluated the antiprotozoa activity of its vanadyl complex VO(mpo)2. It showed a threefold increase of activity against T. cruzi epimastigotes (CL-B5 strain) when compared with mpo sodium salt, showing an IC50 value in the micromolar range and higher activity than the anti-trypanosomal drugs Nifurtimox and Benznidazol. It also showed high in vitro leishmanicidal activity against Leishmania(L.) mexicana (NR strain) and Leishmania(V.) braziliensis (M2903 strain). In addition, it demonstrated highly selective anti-parasite activity since no unspecific citotoxicity on mammalian cells (J774 macrophages and NCTC clone 929 fibroblasts) was observed at the doses where it showed activity. Trying to provide insight into its mechanism of action NADH-fumarate reductase was evaluated as potential parasite target. In addition, the enzyme was theoretically modelled and preliminary docking studies with VO(mpo)2 are being performed. All data strongly suggest that the potent antiprotozoa action of VO(mpo)2 could mainly rely on the inhibition of the enzyme, although other secondary targets cannot be discarded. VO(mpo)2 could constitute a new antiprotozoa chemotherapeutic alternative to be further evaluated in experimental models. Acknowledgements: The authors would like to thank RIDIMEDCHAG CYTED network and Grants of Fonacit G-2005000827. DG would like to thank Technical University of Lisbon for financial support.



P38

Diabetes and vanadium: levels of vanadium in blood samples

Maria João Pereiraa; Cláudia Pedroa; Filipa Rodriguesa; Hélio Martinsb; Hercília Martinsc; Mª João Faíscac; Mª João Melod; Eugénia Carvalhoe and Manuel Aurelianoa

(a) CCMAR, University of Algarve, Campus das Gambelas, 8005-139 Faro, Portugal (b) FCT, University of Algarve, Campus das Gambelas, 8005-139 Faro, Portugal

(c) SPC, Faro Hospital, 8005 Faro, Portugal (d) SIH, Faro Hospital, 8005 Faro, Portugal

(e) Center for Neuroscience and Cell Biology, University of Coimbra, 3000 Coimbra

A promising application for vanadium in human’s health arises from recent studies that evaluated vanadium to have benefits affects in the treatment and prevention of diabetes. Vanadium is an essential element well known as a metabolic regulator, a mitogenic activator, an insulin-mimetic agent and by reversing drug resistance. Since it displays insulin-like activity through correction of metabolic disorders associated with insulin deficiency, vanadium can be used in diabetes treatment. However, the pharmacological and toxicological effects of vanadium are far from a clear identification. Type 2 diabetes mellitus (T2DM) is associated with a clinical phenotype known as the metabolic syndrome. The metabolic syndrome is characterized by visceral obesity, pathogenic dyslipidemia, glucose intolerance, insulin resistance and markers of cardiovascular disease. T2DM is considered a modern disease once it is highly related with modern style of life favouring sedentary and obese people. In the present study, realised in the University of Algarve collaboration with the Immune Therapy Service and the Pathology Service of the Hospital of Faro (HDF), it was analysed and correlated several parameters associated with type 2 diabetes such as age, fasting serum concentration of glucose, insulin, glycated haemoglobin (HbA1c), triglycerides (TGs), total cholesterol (TC), low density lipoprotein- and high density lipoprotein – cholesterol (LDL-C and HDL-C), markers of insulin resistance (HOMA-IR and QUICKI) in individuals with normal glucose tolerance (NGT, n=66) and T2DM (n=625). In addition, we also studied the vanadium content in blood samples (NGT=34 and T2DM=41), by furnace atomic absorption spectroscopy. We demonstrate that TC, LDL-C, TG, did not differ among NGT and T2DM, although individuals with T2DM present mean HDL concentrations of 47.35 ± 9.5 mg/dL, lower than the NGT with 53.27 ± 10.5 mg/dL (p<0.05). The NGT present mean HbA1c of 4.7 ± 0.4 %; while T2DM with 8.21 ± 1.1 % (p<0.001). The calculated values of insulin sensitivity (QUICKI) differ from 0.37 ± 0.03 to 0.30 ± 0.03 (p<0.05) between the NGT and the T2DM population; and the index of insulin resistance (HOMA) differ from 1.71 ± 1.1 to 7.93 ± 8.7 (p<0.05) between the NGT and the T2DM population. Individuals with NGT present mean vanadium concentrations of 77.63 ± 19.9 ng/mL, higher than the T2DM with 59.35 ± 17.7 ng/mL (p<0.001). These results show that NGT individuals present means vanadium concentrations 1.3 higher than T2DM. Putting it all together, although preliminary, the obtained results may contribute to a better understanding of vanadium metabolism and its relationship with biochemical parameters associated with diabetes. Acknowledgements: The authors would like to thank FCT – The Portuguese Foundation for Science and Technology (SFRH/BD/41044/2007) and project POCI/SAU-MMO/57598/2004 for their help and financial support.



P39

Oxovanadium(IV) macrocycles: potential antivirals against HIV

Allison Ross,1 Neil Robertson,1 Simon Parsons1 and Peter J. Sadler1,2

1School of Chemistry, University of Edinburgh, West Mains Road, Edinburgh, EH9 3JJ, UK and 2Department

of Chemistry, University of Warwick, Gibbet Hill Road, Coventry CV4 7AL, UK Email: [email protected]

Some macrocycles, including cyclam derivatives, show promise as stem cell mobilizers and antivirals, including activity against HIV and AIDS. The specific configurations adopted by metal cyclam complexes may be important for receptor recognition and biological activity1. Natural macrocyclic compounds with complexed metal ions play a role in many biological processes. Cyclic polyamines in particular bind to a wide range of metals and in many cases show configurational changes during binding2. In this work, novel vanadium complexes have

Figure 1: Oxovanadium(IV) cyclam chloride

been characterized and oxovanadium(IV) bicyclam complexes show high antiviral activity against HIV. In particular, an oxovanadium(IV) bicyclam chloride species has shown antiviral activity comparable with AMD3100, an effective entry inhibitor against HIV (and now a successful stem-cell-mobilizing drug). Intriguingly, oxovanadium(IV) cyclam complexes were completely inactive, and each crystallised in the thermodynamically stable trans-III configuration with a 6th ligand trans to the oxygen of the characteristic V=O group. Magnetic susceptibility measurements and FTIR spectroscopy confirmed the presence of V(IV). The complexes have been studied by EPR, which revealed differences in behaviour between the bicyclams and cyclams in aqueous solution. Protein recognition is being investigated since the CXCR4 coreceptor is involved in HIV entry into cells and stem cell anchoring. Acknowledgements: We thank the BBSRC (studentship for A Ross) and RCUK (Rasor) for support, Drs. Abraha Habtemariam and Ana Pizarro for assistance and advice. [1] Liang X, Parkinson J A, Weishaupl M, Gould R O, Paisey S J, Park H, Hunter T M, Blindauer C A, Parsons S, Sadler P J (2002) J Am Chem Soc 124: 9105-9112 [2] Hunter T M, McNae I W, Liang X, Bella J, Parsons S, Walkinshaw M D, Sadler P J (2005) Proc Natl Acad Sci USA 102: 2288-2292.



P40

Vanadocene complexes of α-amino acids: synthesis, structure and cytostatic activity

Jaromír Vinklárek,a Hana Paláčková,a Jana Holubová,a Jan Honzíček,b Lenka

Zárybnická,c Zuzana Šinkorovác

aThe Department of General and Inorganic Chemistry, Faculty of chemical-technology, University of Pardubice, nám.Čs. Legií 565, 532 10 Pardubice, Czech Republic, email:[email protected]

bInstituto de Tecnologia Química e Biológica da Universidade Nova de Lisboa, Av. da República, EAN, 2780-157, Oeiras Portugal.

cThe Department of Radiobiology, Faculty of Military Health Sciences, University of Defence, Třebešská 1575, 500 01 Hradec Králové, Czech Republic.

Bent metallocenes Cp2MCl2 (Cp = η5-C5H5, M = Ti, V, Nb, Mo) are representatives of recently developed non-platinum-group metal antineoplastic agents exhibiting pronounced in vivo and in vitro activity against various tumor cell lines and markedly inhibiting the growth of several human carcinomas heterotransplanted into athymic mice.[1-2] Mechanism of antitumor action of metallocene compounds at the molecular level is still not sufficiently solved. However, biological, cytological and chemical studies show that active metallocene species inhibits DNA replication through interaction with DNA molecule or with DNA processing enzymes.[3] The interaction between vanadocene dichloride (Cp2VCl2) and proteins was studied using model system metallocene - amino acid. The first vanadocene(IV) complexes of α-amino acids were prepared using reaction of vanadocene dichloride and α-amino acids in aqueous solution of neutral pH.[4] All prepared complexes have been characterized by analytical and spectroscopic methods. Molecular structures of fourteen compounds were determined by X-ray diffraction analysis (Figure 1.). EPR spectroscopy was used for investigation of their behaviour in solutions. It was found that majority of α-amino acids without further function group is coordinated to vanadocene fragment through oxygen atom of carboxylic group and nitrogen of amino group giving chelate complexes [Cp2V(N,O-aa)]Cl. Only L-proline forms monodentate complex [Cp2V(O-pro)2]Cl2 with two amino acids bonded through oxygen atoms of carboxylic groups. Reaction of Cp2VCl2 with L-cystein gives other structural types. Chelate complexes [Cp2V(N,S-cys)] and [Cp2V(O,S-cys)]Cl with amino acid bonded though sulphur are formed. The considerable attention was also paid to antitumor properties of these amino acid complexes. The cytostatic activity towards human leukaemia cell line HL-60 was comparable with starting vanadocene dichloride and even better then in case titanocene dichloride (Cp2TiCl2) that was clinically tested structural analogue of vanadocene dichloride. Acknowledgements: The authors would like to thank Ministry of Education of the Czech Republic Research Project MSM0021627501 for help and financial support. [1] P. Köpf-Maier, H. Köpf, Chem. Rev. 87 (1987) 1137-1152. [2] K. Mross, P. Robben-Bathe, L. Edler, J. Baumgart, W. E. Berdel, H. Fiebig, C. Unger Onkologie 23 (2000) 576-579. [3] Waern, J. B.; Harding, M. M. J. Organomet. Chem. 2004, 689, 4655-4668. [4] J. Vinklárek, H. Paláčková, J. Honzíček, J. Holubová, M. Holčapek, I. Císařova Inorg. Chem. 45 (2006) 2156-2162.

Figure 1. Structure of [Cp2V(ile)][PF6]



P41

Biological variability in the anti-apoptotic effects of vanadium

Gail R. Willsky a, Barbara A. Bistram a, Rebecca Z. Grayson a, Lai-Har Chi a, Martha Clark a, Debbie C. Crans b

aUniversity at Buffalo (SUNY), Buffalo, NY 14214. USA. b Department of Chemistry, Colorado State

University, Ft. Collins CO 80523 USA, email: [email protected]

The biological effects of vanadium (V) vary greatly in different biological systems1. This fact explains, in part, why differring biological endpoints are reported by different research groups with slightly different cells and V compounds. In these studies, the effects of changes of the biological system were observed using the simple salt vanadate, V(V) in two cell culture systems. Induction of apoptosis by V treatment was explored using caspase inhibitors in growth experiments and monitoring of apoptotic cells using DNA labeling (TUNEL assay) with flow cytometry. We have previously reported the inhibitory effects of V(V) on muscle cell growth2. Here V inhibited cell growth in both muscle myoblasts (L6) and rat hepatoma cells (H4IIE) cells. In both cell lines V affected cell adhesion before killing the cells as expected since V is known to affect cytoskeleton elements such as actin. Caspase inhibitors protected muscle cells from cell death, but not liver cells. Since Caspases are activated by apoptosis, the protection of cells from growth inhibition by caspase inhibitors is indicative of the induction of apoptosis.

Figure 1 TUNEL assay for apoptosis in cell culture Cells were grown to approximately 40% confluence and treated with different concentrations of vanadate from 0 to 500 uM for 12 hours. A. H4IIE liver cells, B. L6 myoblasts.

Vanadate treatment induced apopoptosis in muscle cells (Figure 1B); but not in liver cells (Figure 1A) in the TUNEL assay. Induction of apoptosis results in the shift of the cell population to the right, indicative of increasing amounts of fluorescent dye being incorporated in the cells at the site of apoptosis-induced breaks in the DNA. These studies imply that V growth inhibition is mediated via the apoptotic pathway in muscle but not in liver. The differential results observed could be due to the induction of different vanadium-sensitive components in the two cell lines, differential uptake of vanadium in the two cell types or other factors. Liver and muscle cells frequently have different metabolic pathways activated, or different levels of activation are seen in response to a stimuli. For example, glucose transport in muscle is strongly stimulated (4- 20 fold) by insulin, while glucose transport in liver only shows a 2 fold stimulation after insulin treatment. Both tissues are differently affected by the onset of diabetes. The results reported here show the benefits for directing vanadium therapies to specific tissues, and thus presents new directions of research for this class of compound. Acknowledgements: We thank the NIH and Luso-American Development Foundation for financial support. [1] A.Tracey, G. Willsky, E.Takeuchi, (2007) Vanadium: Chemistry, Biochemistry, Pharmacology and Technical Applications, CRC Press , Boca Raton FL. 250 pp. [2]G. Willsky, M. Godzalla III, P. Kostyniak, L.-H. Chi , R. Gupta,V. Yuen, J. McNeill, M. Mahroof-Tahir, J. Smee, L. Yan, A. Lobernick, S. Watson, and D. Crans, ACS Symposium Series 974 (2007) 93-109.

A. B.



P42

Fenton chemistry revisited: vanadate’s role in the study of antioxidants

Wu Lisha,a Leif A. Eriksson b, Åke Stridb, Simon Dunne a, Sarah Angus-Dunnea

a Institution for Biology and Chemical Engineering, Mälardalens University, Eskilstuna (Sweden) bDepartment of Natural Sciences and Örebro Life Science Centre, Örebro University (Sweden)

Fenton chemistry is generally known as the reaction of Fe(II) or Fe(III) salts with peroxide to

create hydroxyl free radicals1. Several other metals including vanadium(IV) and (V) are known

to create a similar effect2. The generation of free radicals is generally an unwanted effect, which

most biological systems have effective defenses against. We will report how both the

Fe/peroxide and the V/peroxide systems along with NMR spectroscopy can be employed to

probe the effectiveness of various natural compounds as antioxidants.

[1] Stadtman, E.R., Berlett, B.S., J. Biol. Chem., (1991), 266 (26): 17201 -17211. [2] Valko, M., Morris, H., Cronin, M. T.D. Current Medicinal Chemistry, (2005), 12(10), pp. 1161-1208(48); Natarajan S. Venkataramanan, Gopi Kuppuraj and Seenivasan Rajagopal, Coord. Chem. Reviews, (2005), 249, (11-12), 1249-1268.



P43

Hydroxylamino-vanadate derivatives as protein tyrosine phosphatase inhibitors

Xu Zhou,a Leif A. Eriksson b, Simon Dunne a, Sarah Angus-Dunnea

a Institution for Biology and Chemical Engineering, Mälardalens University, Eskilstuna (Sweden) bDepartment

of Natural Sciences and Örebro Life Science Centre, Örebro University (Sweden)

Protein tyrosine phosphatases (PTPs), are known targets for the treatment of diabetes as they

regulate phosphorylation in the insulin signaling pathway. Vanadate acts as an inhibitor of PTPs

and leads to amplified insulin receptor signaling. Vanadate itself is active only in doses which

are unsuitable for long-term therapeutic treatment of diabetes, due to deposition of vanadium in

bones leading to osteoporosis. Hydroxylamino-vanadium derivatives are potential PTPs

inhibitors in smaller amounts and thus have possible use as oral pharmaceuticals for the

treatment of diabetes.

The compounds which show strong affinity for the active site on PTP1B through molecular

modeling have been synthesized and their speciation under physiological conditions as

determined by using 51V NMR spectroscopy techniques will be reported.

S

NOH

1



P44

Vanadium interactions with the calcium pump ATPase: an overview

Rosa F. Brissos,a,b Fábio L. Fontes,a,b Hélio Martins,a Gil Fraqueza,a,b Teresa Tiago,a,b Jorge Martins,a,c Rui O. Duarte,d José J.G. Moura,d Manuel Aurelianoa,b

aDept. Chemistry Biochemistry and Pharmacy, FCT, University of Algarve, Faro, Portugal; bCentre for Marine

Sciences (CCMAR), University of Algarve, Faro, Portugal; cCBME, University of Algarve, Faro, Portugal; dDept. Chemistry, FCT, New University of Lisbon, Monte da Caparica, Portugal

It is well known that vanadium inhibits the calcium pump ATPase1. Back then, only the monomeric vanadate species (V1) was recognized as the active specie having biological roles, disregarding the possible contribution of other vanadate oligomers. Among them, decameric vanadate species (V10) was later recognized also to interact with Ca2+-ATPase inducing protein dimmers2 besides inhibiting the Ca2+ translocation coupled to ATP hydrolysis3. Whereas V1 was described as interacting with aspartate binding site, blocking the enzyme in the E2 conformation V10 was also found to interact with several protein conformations1,3 through binding to the nucleotide binding site4. The ability of vanadate to act either as a phosphate analog or as a transition state analog with enzymes catalysis phosphoryl group transfer suggests that vanadium coordination compounds may reveal mechanistic preferences in these classes of enzymes. Recent studies from our group, proposed that different vanadium compounds such as pyridine-2,6-dicarboxylatedioxovanadium(V) (PDC-V(V)), and two vanadium(IV) compounds, bis(maltolato)oxovanadium(IV) (BMOV) and an analog of amavadine, bis(N-hydroxylamidoiminodiacetato)vanadium(IV) (HAIDA-V(IV)) affect differently the SR Ca2+-ATPase being the relative order of inhibition: PDC-V(V) > BMOV > vanadate > HAIDA-V(IV), with IC50 values of 25, 40, 80 and 325 µM, respectively5 lower than the one observed for vanadate-citrate complexes (0.5 mM)6. Once that the Ca2+-ATPase can adopt several conformations, the specific nature of the interactions of each of the vanadium compounds with the sarcoplasmic reticulum Ca2+-ATPase is an important scope of investigation.

In the present work, we study the interaction between monomeric (V1) and decameric

(V10) vanadate species with the Ca2+-ATPase at several conformations, by using atomic absorption spectroscopy and UV/Vis spectrophotometry. The preliminary results suggest that although being more negatively charged the V10 stoichiometry of interaction with the sarcoplasmic reticulum (SR) Ca2+-ATPase is apparently not different from V1. Further studies, will confirm if the interaction of the different vanadium oligomers is, at least in part, dependent on the different protein conformations that occurs during the mechanism of calcium translocation. It is expected that these studies will allow an extended and improved understanding of vanadium mode of interaction and its effects in calcium homeostasis and muscle contraction regulation through the SR Ca2+-ATPase. Acknowledgements: T. Tiago thanks to the fellowship (SFRH/BPD/20777/2004) from (FCT). [1] Y. Dupont, and N. Bennett, FEBS Lett. 139 (1982) 237-240. [2] L. Dux, and A. Martonosi, J. Biol. Chem. 258 (1983) 2599-2603; [3] M Aureliano, V.M.C. Madeira, Biochim. Biophys. Acta 1221 (1994) 259-271; [4] S. Hua, G. Inesi, and C. Toyoshima, J. Biol. Chem. 275 (2000) 30546.; [5] M. Aureliano, F. Henao, T. Tiago, R.O. Duarte, J.J.G. Moura, B. Baruah, and D.C. Crans, Inorganic Chemistry. (2008) in press.; [6] M, Aureliano, T. Tiago, R. M Gândara, A. Sousa, A. Moderno, M Kaliva, A. Salifoglou, R. O Duarte, J. J. G Moura, Inorg. Biochem, 99 (2005) 2355-2361.

LUMEN CYTOPLASM



P45

Decavanadate effect on rat synaptic plasma membrane Na+/K+-ATPase activity

Mirjana Colovic,a Nada Bosnjakovic-Pavlovic,b Anne Spasojevic-de Bire,c Vesna Vasic,a

a Vinča Institute of Nuclear Sciences, P.O.Box 522, 11001 Belgrade, Serbia, e-mail: [email protected] bFaculty of Physical Chemistry, University of Belgrade, P.O.Box 47, 11158 Belgrade, Serbia cEcole Centrale Paris, Laboratoire SPMS UMR CNRS 8580 1, Grande Voie des Vignes

92295 Châtenay-Malabry, France Decameric vanadate species interact, in vitro, with high-affinity with many proteins such as myosin and SR calcium pump and also inhibit these biochemical systems involved in energy transduction1. The purpose of this study was the investigation of the in vitro effect of (NH4)6V10O28.5H2O on rat synaptic plasma membrane (SPM) sodium pump activity. The method of Chinea et al2 was used for synthesis of ammonium decavanadate crystals. SPM were isolated from the whole rat brain. The Na+/K+_ATPase activity was assayed in the absence (control) and presence of decavanadate (within the range 1x10-10 to 1x10-1) in standard medium containing 50 mM Tris-HCl (pH 7.4), 100 mM NaCl, 20 mM KCl, 5 mM MgCl2, 2 mM ATP and 25 μg enzyme in a final volume of 200 μl. Incubation mixtures were preincubated for 10 min at 37oC in the presence of investigated compound or distilled water (control). The inorganic orthophosphate (Pi) liberated from the hidrolysis of ATP, was measured using modified spectrophotometric procedure3. The increasing concentrations of decavanadate induced inhibition of enzymatic activity in a concentration-dependent manner (Fig 1). The dependence of enzyme activity, expressed as a percentage of the control value (obtained without inhibitor) on inhibitor concentration fit a sigmoidal function. The obtained half-maximum inhibitory concentration (IC50) of decavanadate for sodium pump, determined by sigmoidal fitting, was (4.7 ± 0.1) x 10-7 mol/L.

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Figure 1. The concentration dependent inhibition of SPM sodium pump induced by ammonium decavanadate. The values are expressed as mean ± S.E.M.

[1] M. Aureliano, R. Gandara, J. Inorg. Biochem. 99 (5) (2005) 979-985. [2] B. Chinea, D. Dakternieks, A. Duthie, C.A. Ghilardi, P. Gili, A. Mederos, S. Midollini, A. Orlandini, Inorg. Chim. Acta 298 (2000) 172-177. [3] V. Vasić, D. Jovanović, D. Krstić, G. Nikezić, Lj. Vujisić, N. Nedeljković,Toxicol. Let. 110 (1-2) (1999) 95-104.



P46

Differential interaction of Sarcoplasmic Reticulum Calcium ATPase with Mo, V and W Oxometalates

Gil Fraquezaa,b, Emilie Ritob,c, Rosa Brissosb,c, Teresa Tiagob,c, Jorge Martinsb,d, Rui O.

Duartee, José J.G. Mourae and Manuel Aurelianob,c

a Escola Superior de Tecnologia, Universidade do Algarve, 8005-139 Faro, Portugal; b Departamento de Química, Bioquímica e Farmácia, FCT, Universidade do Algarve, Faro, Portugal;

c CCMar, Universidade do Algarve, Faro, Portugal; d IBB-CBME, Universidade do Algarve, Faro, Portugal; e REQUIMTE, Departamento de Química, FCT,

Universidade Nova de Lisboa, Monte da Caparica, Portugal.

Vanadium (V), tungsten (W) and molybdenum (Mo) oxometalates are widely applied as analytical reagents for the determination of numerous pharmacologically active substances and different biochemical parameters1. It has been shown that these compounds act on some cellular enzymatic systems leading to the normalization of blood pressure, blood glucose and serum lipid levels1. The insulin mimetic effects of these compounds have been associated to the specific regulation of protein kinase receptors, including the insulin receptor. We have recently reported that organic vanadium compounds, some of them with insulin mimetic properties, inhibit the activity of sarcoplasmic reticulum calcium ATPase (SR-Ca2+-ATPase), and may therefore also regulate the muscle contraction process through this ATPase2. In the present study we aim to clarify the interaction between V, W and Mo, with the calcium pump, by combining spectroscopic with kinetic studies. We found that the hydrolytic activity of SR-Ca2+-ATPase was inhibited by all four oxometalates, however the decameric specie of vanadate exhibit the lower value of IC50. The relative order of inhibition was V10 > V1> W > Mo whit IC50 values of 0.015 mM, 0.05 mM, 0.4 mM and 45 mM, respectively. Upon incubation of SR-Ca2+-ATPase with V1, V10, W and Mo at 25ºC, the results show an increase in the hydrolytic activity, after 15 minutes for all four oxometalates. After 60 minutes of incubation, the relative order of decrease in the SR-Ca2+-ATPase activity was V10 ≈ W > Mo. V1 oxometalate appears to increase the hydrolytic activity of SR-Ca2+-ATPase. In order to clarify the type of the inhibition effects caused by V10, this phenomenon can be reverted by adding DTT to the incubation preparation. It is suggested that clearing up the interaction between SR-Ca2+-ATPase with V, W and Mo oxometalates can help to further understand the modulation of some cellular enzymatic systems, such as the SR-Ca2+-ATPase, by different oxometalate compounds. Acknowledgements: T. Tiago is the recipient of a post-doctoral fellowship (SFRH/BPD/20777/2004) from the Portuguese Foundation for Science and Technology (FCT). [1] Stankov,M.J.;Markovic, S.U.; Antunovic,I.H.; Todorovic,M. and Djurdevic,P. Journal of Trace Elements in Medicine and Biology (2007), 21, 8-16. [2] Aureliano,M.; Henao,F.; Tiago,T.; Duarte, R.O.; Moura, J.J.G.; Baruah, B. and Crans, D.C. Inorganic Chemistry. (2008) in press.



P47

Vanabin2 extracted from ascidian vanadocyte is a novel vanadium reductase

Norifumi Kawakami,a Tatsuya Ueki,a Yusuke Amata,b Kan Kanamori,b Koichi Matsuo,c

Kunihiko Gekko,c and Hitoshi Michibataa

aDepartment of Biological Science and cDepartment of Mathematical and Life Sciences, Graduate School of Science, Hiroshima University, 1-3-1 Kagamiyama, Higashi-Hiroshima 739-8526, Japan, and bDepartment of Chemistry, Graduate School of Science and Engineering, University of Toyama, Gofuku 3190, Toyama 930-

8555, Japan, email: [email protected]

The unusual phenomenon found in the ascidians with exceptional ability to accumulate vanadium ions at concentrations up to 350 mM, a107-fold increase over its concentration in seawater (35 nM), has been attracting the interdisciplinary attention of chemists, physiologists, and biologists. Accumulated vanadium ions (VV) are first reduced to VIV in ascidian vanadocytes and stored in their vacuoles where they are finally reduced to VIII and seem to exist as free ions[1]. Reducing agents must, therefore, participate in the reduction of vanadium[2]. A family of vanadium-binding proteins, Vanabins, were found in a vanadium-rich ascidian[3-5]. Among them, Vanabin2 analyzed its solution structure has been revealed to be a rare protein with 9 disulfide bonds per a molecule[6]. The disulfide bonds were cleaved by GSH, which resulted in the reduction of VV to VIV. In fact, 10 μM Vanabin2 evoked a strong EPR signal intensity due to VIV species when it was added to the reaction mixture containing 2 mM VV and 2 mM GSH at room temperature. Thus, Vanabin2 can act as a VV reductase in vandocytes.

[mT]

Scheme1 (left). Possible VV reduction cascade in vanadocytes. Figure 1 (right). EPR signal obtained from Scheme 1 assay system. Dashed line, immediately after the addition of 10 μM Vanabin2 to the reaction mixture of 2 mM VV and 2 mM GSH; Solid line, 24 hr after the addition of 10μM Vanabin2 to the reaction mixture of 2 mM VV and 2 mM GSH.

Acknowledgements: The authors thank Mr. T. Morita and the staff at the International Coastal Research Center of the Ocean Research Institute, The University of Tokyo, Otsuchi, Iwate, Japan, for their help in collecting adult ascidians. This work was supported by Research Fellowships of the Japan Society for the Promotion of Science for Young Scientists. [1] J. Hirata H. Michibata, J. Exp. Zool. 257 (1991) 160-165. [2] K. Kanamori, M. Sakurai, T. Kinoshita, T. Uyama, T. Ueki, H. Michibata, J. Inorg. Biochem. 77 (1999) 157-161. [3] T. Ueki, T. Adachi, S. Kawano, M. Aoshima, N. Yamaguchi, K. Kanamori, H. Michibata, Biochim. Biophys. Acta 1626 (2003) 43-50. [4] K. Fukui, T. Ueki, H. Ohya, H. Michibata, J. Am. Chem. Soc. 125 (2003) 6352-6353. [5] M. Yoshihara, T. Ueki, T. Watanabe, N. Yamaguchi, K. Kamino, H. Michibata, Biochim. Biophys. Acta 1730 (2005) 206-214. [6] T. Hamada, M. Asanuma, T. Ueki, F. Hayashi, N. Kobayashi, S. Yokoyama, H. Michibata, H. Hirota, J. Am. Chem. Soc. 127 (2005) 4216-4222.

V(V)

V(IV) GSH

GSSG Vanabin2 SH

SH

Vanabin2 9

S

S

n

261 286 311 336 361 386 411



P48

Inhibition of rat synaptic plasma membrane Ca2+-ATPase activity by decavanadate

Danijela Krstica, Nada Bosnjakovic-Pavlovicb, Anne Spasojevic-de Birec, Vesna Vasicd

aInstitute of Chemistry, School of Medicine, University of Belgrade, Serbia, e-mail: [email protected]

bFaculty of Physical Chemistry, University of Belgrade, P.O.Box 47, 11158 Belgrade, Serbia cEcole Centrale Paris, Laboratoire SPMS UMR CNRS 8580 1, Grande Voie des Vignes

92295 Châtenay-Malabry, France d Vinča Institute of Nuclear Sciences, P.O.Box 522, 11001 Belgrade, Serbia

Decavanadate has a strong inhibitory effect on some nucleotide binding enzymes such as sarcoplasmic reticulum calcium pump which belongs to the P-type ATPase family1. The aim of this work was the investigation of the in vitro effect of ammonium decavanadate, (NH4)6V10O28.5H2O on rat synaptic plasma membrane Ca2+-ATPase (PMCA) activity, which also belongs to the P-type ATPase family. Orange crystals of (NH4)6V10O28.5H2O were prepared according to the method of Chinea et al2. The SPM were isolated from the whole rat (albino, vistar) brain according to the standard method3. The rat synaptic PMCA activity was assayed in the absence (control) and presence of decavanadate (within the range 1x10-10 to 1x10-1) in standard medium containing 50 mM Tris-HCl (pH 7.4), 0.5 mM EGTA, 0.5 mM CaCl2, 5 mM MgCl2, 2 mM ATP and 25 μg enzyme in a final volume of 200 μl. Incubation mixtures were preincubated for 10 min at 37oC in the presence of investigated compound or distilled water (control). The inorganic orthophosphate (Pi) liberated from the hidrolysis of ATP, was measured spectrophotometricly at 690 nm. The obtained results show (Figure 1) that decameric vanadate species inhibited rat synaptic calcium pump in a concentration-dependent manner. Dependence of the AChE activity, expressed as the percent of control value (obtained without inhibitor) on the inhibitor concentration has a sigmoidal shape. The concentrations that reduce the response by 50% (half-maximum inhibitory concentration-IC50) obtained by Hill analyse (Figure 1, inset) of inhibition curve was (3.1 ± 0.1) x 10-8 mol/L.

Figure 1. The concentration dependent inhibition of SPM Ca2+-ATPase induced by ammonium decavanadate. Hill plot of inhibition curve (inset) The values are expressed as mean ± S.E.M.

[1] M. Aureliano, R. Gandara, J. Inorg. Biochem. 99 (5) (2005) 979-985. [2] B. Chinea, D. Dakternieks, A. Duthie, C.A. Ghilardi, P. Gili, A. Mederos, S. Midollini, A. Orlandini, Inorg. Chim. Acta 298 (2000) 172-177 [3] RS. Kohen, F.Blomberg, K. Berzins, P. Siekevits J. Cell Biol. 74 (1977) 181-203

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ivity

))

log C (of decavanadate)

activ

ity (%

of c

ontro

l)

decavanadate (M)



P49

Modeling supramolecular interactions of vanadium species

Ines Lippold and Winfried Plass

Institut für Anorganische und Analytische Chemie, Friedrich-Schiller-Universität Jena, Carl-Zeiss-Promenade 10, 07745 Jena, Germany, email: [email protected]

Supramolecular interactions are a prominent feature in biological systems. A specific example is given by the vanadium haloperoxidases (V-HPOs) for which a hydrogen bonding network is observed that governs their reactivity.1 Therefore, models are desired to contain suitable donors that generate a polar protic surrounding, capable of generating an appropriate hydrogen bonding environment. Cyclodextrins (CDs) are hosts that provide hydrophobic cavities with hydrophilic outer walls. They form inclusion compounds with various apolar groups that partially or completely included in the cavity. Parts of the guest protruding out of the CD-cavity could take part in the hydrogen bonding system.2 Herein we present new cis-dioxovanadium(V) complexes with appropriate side chains that fit in CD cavities (Figure 1).

Figure 1. Syntheses of the inclusion compounds K[VO2(aldhyguest)@xCD]. Hydrazone ligands H2aldhyguest are synthesized via Schiff-base condensation of aromatic ortho-hydroxy-aldehyds (ald) and different apolar acid-hydrazides (hyguest). The reaction of potassium vanadate with H2aldhyguest in the presence of 1 or 2 equivalents of α− or β-CD in water yield the chiral 1:1 or 1:2 inclusion compounds K[VO2(aldhyguest)@xCD].3 For selected examples their solid state and solution structures will be discussed. [1] R. Wever, W. Hemrika in Handbook of Metalloproteins, Vol. 2 (Eds.: A. Messerschmidt, R. Huber, T. Poulos, K. Wieghardt), John Wiley and Sons Ltd., Chichester, 2001, pp. 1417–1428. [2] J. Szejtli, Chem. Rev. 98 (1998) 1743–1753. [3] I. Lippold, H. Görls, W. Plass, Eur. J. Inorg. Chem. (2007) 1487–1491.



P50

Vanadium imidazolylcarboxylate complexes: synthesis, characterization, and phosphatase inhibition

Craig C. McLauchlan, Bradley A. Greiner, Nicole A. Dorner, Emily A. Backhus, and

Jamie E. Meyer

Department of Chemistry, Illinois State University, Normal, IL 61790-4160 USA, email: [email protected]

In the course of our investigations of vanadium-containing compounds for use as insulin enhancing agents, we have generated a series of novel vanadium coordination complexes with bidentate ligands. Specifically we have focused on two ligands meant to mimic naturally occuring ligands, namely imidizole-4-carboxylate (imc, shown) and anthranilate. For each ligand, we have generated a series of complexes containing the V(III), V(IV), and V(V) oxidation states. Each complex is being investigated using alkaline phosphatse inhibition studies as prima facia evidence for potential use as an insulin enhancing agent. Under our experimental conditions, for instance, V(imc)3 appears to be as potent an inhibitor of alkaline phosphatase as vanadyl sulfate. Here we report the syntheses, characterization, reactivity, and phosphatase inhibition activity of our newly formed complexes, focusing on complexes analogous to the known picolinate complexes.

Figure 1. A series of V/imc complexes

Acknowledgements: The authors would like to thank the National Science Foundation (U.S., CHE-0645081) for financial support.

O O

NNH

OO

NHN

V

O

O

OV

O

O N

NH

O

O

NHN

-

VO(imc)2 [VO2(imc)2]-

O O

NNH

VO

O N

NH

O

O

NHN

V(imc)3



P51

Functional and structural interactions of three vanadium coordination complexes with the Sarcoplasmic Reticulum Calcium Pump

Ana M.Pereiraa,b, Teresa Tiagoa,b,c, Fernando Henaoc, Carlos Gutiérrez-Merinoc, Bharat

Baruahd, Debbie C.Cransd and Manuel Aurelianoa,b

aDept de Química, Bioquímica e Farmácia, FCT, Universidade do Algarve, 8005-139 Faro, Portugal, email: [email protected]; bCCMar, Universidade do Algarve, Faro, Portugal; cDept Bioquímica y Biologia Molecular,

Faculdad de Ciências, Universidad de Extremadura, Badajoz, Spain; dDept of Chemistry, Colorado State University, Fort Collins, Colorado 80523-1872,USA

Sarcoplasmic Reticulum Ca2+-ATPase (SERCA) is a complex transmembrane and energy transducting system that is extensively studied and well understood. Recently, we have demonstrated that three different classes of vanadium coordination complexes including pyridinedicarboxylate vanadium (V) (PDC-V(V)), oxovanadium(IV)-bis(maltolato) (BMOV) and an analogue of amavadine, bis(N-hydroxylamidoiminodiacetato)vanadium(IV) (HAIDA-V(IV)) (Figure 1) inhibit the hydrolytical activity of this pump1. While the first two are known to induce insulin enhancing effects, the third one is a well-known analogue of a vanadium-containing natural product. A relative inhibition order of PDC-V(V) > BMOV > vanadate > Amavadine (with IC50 values of 25, 40, 80 and 325 µM, respectively) has been established. To this end, intrinsic and extrinsic fluorescence studies as well as kinetic measurements on the 45Ca transport and binding to the ATPase were performed to evaluate the effects of these three vanadium complexes on the ATPase bioenergetic and structural function.

Figure 1. Molecular structures of PDC-V(V), BMOV, [VO2(ma)2]- and HAIDA-(IV). Both BMOV and PDC were able to stimulate SR 45Ca binding in a similar way to metavanadate solutions. Nevertheless, BMOV and PDC levels around the IC50 values for inhibition of hydrolysis did not significantly inhibit the 45Ca uptake, irrelevant of incubation time. Such inhibition was only observed at higher vanadium levels. Fluorescence studies with FITC labelled SERCA have shown that BMOV and PDC shift the calcium pump to the E2 (like decavanadate and monovanadate solutions) and E1 (like metavanadate solutions) conformations, respectively. Together, these observations are consistent with an adduct formation between protein and V compounds and with their complexation to the catalytic site of Ca2+-ATPase, as previously suggested1. Although amavadine favoured the E1 conformation (a high Ca2+ affinity state), it significantly inhibited 45Ca binding, suggesting that amavadine may interact with calcium binding sites of the pump. Collectively, these results indicate that the three coordination compounds could promote a response in the calcium homeostasis and muscle contraction systems through the SERCA pump. Acknowledgments: Work supported by Joint Spanish-Portuguese Project CRUP-E-106/05 and by the POCTI program financed through FEDER: project 38191/QUI/2001 (to M.A.). Dr. T. Tiago is the recipient of a post-doctoral fellowship (SFRH/BPD/20777/2004) from the Portuguese Foundation for Science and Technology (FCT). [1] M. Aureliano, F. Henao, T. Tiago, R.O. Duarte, J.J.G. Moura, B. Baruah, D.C. Crans. Inorganic Chemistry in press.



P52

Binding of vanadium (IV) and (V) to actin:effects on function and structure

Susana Ramosa,b, Teresa Tiagob,c, Rui Duartea, José J. G. Mouraa, Manuel Aurelianob

a REQUIMTE/CQFB, Dpto. Química, Faculdade de Ciências e Tecnologia, Universidade Nova de Lisboa,

2829-516 Caparica, PORTUGAL; b CCMar, Dpto. Química e Bioquímica, Faculdade de Ciências e Tecnologia, Universidade do Algarve,

8000-139 Faro, PORTUGAL; c Dpto. De Bioquímica y Biología Molecular, Facultad de Ciencias, Universidad de Extremadura,

Av. Elvas s/n, 06071 Badajoz, SPAIN email: [email protected]

The chemistry of vanadium is characterized by multiple oxidation states (+2 to +5), being largely found in the +4 and +5 oxidation states, both of which are readly accessible under physiological conditions [1]. In aqueous solutions, the chemistry of tetravalent vanadium is centered on VO2+ ion. This ion forms complexes with a diversity of ligands and is known to bind to numerous proteins [2]. In vanadium (+5) solutions different oligoanions can occur simultaneously in equilibrium such as monomeric (V1), dimeric (V2), tetrameric (V4) and decameric (V10) species. Actin is one of the major components in the microfilament system of the eukaryotic cells, being involved in many cellular processes, such as the maintenance of cell shape, cytoplasmic streaming and cell division. The ability of actin monomers (G-actin) to polymerize into filamentous form (F-actin) is crucial in structural and motile functions of the cells. A major role of actin lies in the generation of force by striated and smooth muscle cells [3]. Previous results from our group demonstrated that decameric species inhibit G-actin polymerization and enhance F-actin depolymerization, disturbing the G-actin/F-actin equilibrium. Besides V10, tetrameric vanadate species may also contribute to the inhibition of actin polymerization [4]. We now show that incubation of F-actin with decavanadate inhibits 70 % the myosin-S1-ATPase activity stimulated by F-actin (IC50 = 0,80 ± 0,15 μM), while metavanadate and vanadyl ion have a much lower effect (only 25 % inhibition for the maximum vanadium concentrations used, 50 μM). The cysteine oxidation observed upon G- and F-actin incubation with decavanadate may play a key role to the functional alterations described above. To gain a deeper knowledge about the interactions of vanadyl ions with actin, EPR studies are being developed. Preliminary results indicate binding of 8 VO2+ ions/actin molecule, probably in amino acid residues containing the group – NH2, such as asparagine (Asn), glutamine (Gln) and lysine (Lys). Susana Ramos and Teresa Tiago are supported by a PhD grant (SFRH/BD/29712/2006) and a post-doctoral grant (SFRH/BPD/20777/2004) from the Portuguese Foundation for Science and Technology (FCT), respectively. [1] Chasteen, N. D., Structure and Bonding, Springer-Verlag Berlin Heidelberg, 1983; [2] Chasteen, N. D., Biological Magnetic Ressonance, Vol. 3 (eds.) Berliner, L. Reuben, J., p 53, New York, Plenum Press, 1981; [3] Lorinczy, D. et al., Thermochimica Acta, (1988) 322, 95; [4] Ramos, S. et al., J Inorg Biochem, (2006) 100, 1734.


List of Participants

Oral lectures



V6 Symposium ∷∷∷∷ Lisbon 2008

LP1

ARGENTINAARGENTINAARGENTINAARGENTINA

Baran, Enrique

Centro de Quimica Inorgânica - CEQUINOR

Universidad Nacional de La Plata

Calle 47 esquina 115

1900 La Plata

[email protected]

Etcheverry, Susana

Facultad de Ciencias Exactas

Universidad Nacional de La Plata

Calle 47 esquina 115

1900 La Plata

[email protected]

BRAZILBRAZILBRAZILBRAZIL

Antunes, Octávio

Departmento de Química Inorgânica, UFRJ

Centro de Tecnologia

Bloco A, Lab 641

Cidade Universitária

21.941-590 Rio de Janeiro

[email protected]

CANADACANADACANADACANADA

Orvig, Chris

Department of Chemistry

University of British Columbia

2036 Main Mall

Vancouver, BC

V6T1Z1 Vancouver

[email protected]

Thompson, Katherine


University of British Columbia

2036 Main Mall

V6T 1Z1 Vancouver

[email protected]

CHINACHINACHINACHINA

Ding, Wenjun

College of Life Sciences

Graduate University of Chinese Academy of

Sciences

No. 19A Yu Quan Road

100049 Beijing

[email protected]

CROATIACROATIACROATIACROATIA

Cindrić, Marina

Chemistry Department, University of Zagreb,

Faculty of Science

Horvatovac 102a

10000 Zagreb

[email protected]

Rubčić, Mirta

Chemistry Department, University of Zagreb,

Faculty of Science

Horvatovac 102a

10000 Zagreb

[email protected]

CYPRUSCYPRUSCYPRUSCYPRUS

Drouza, Chryssoula

Department of Agricultural Production and Food

Science, Cyprus University of Technology

3036 Lemesos

[email protected]

Keramidas, Anastasios

Department of Chemistry, University of Cyprus

1678 Nicosia

[email protected]

Stylianou, Marios

Department of Chemistry, University of Cyprus

1678 Nicosia

[email protected]

CZECH REPUBLICCZECH REPUBLICCZECH REPUBLICCZECH REPUBLIC

Vinklárek, Jaromír

Department of General and Inorganic Chemistry,

University of Pardubice

nám. Čs. legií 565

532 10 Pardubice

[email protected]

FRANCEFRANCEFRANCEFRANCE

Carn, Florent

Chimie de la Matière Condensée de Paris UPMC

Colège de France

4 place Jussieu

T.54-55 - Case 174

75252 PARIS

[email protected]



LP2

Ghermani, Nour Eddine

U.F.R. Pharmacie, Université Paris-Sud 11

Laboratoire Physico-Chimie - Pharmacotechnie -

Biopharmacie

UMR CNRS 8612

5 rue J.B. Clément

92296 Châtenay-Malabry

[email protected]

Lorber, Christian

Laboratoire de Chimie de Coordination

Centre National de la Recherche Scientifique –CNRS

205 route de Narbonne

31077 Toulouse

[email protected]

Spasojevic, Anne

SPMS, Ecole Centrale Paris

UMR 8580 CNRS

Grande voie des Vignes

92295 Chatenay-Malabry

[email protected]

GERMANYGERMANYGERMANYGERMANY

Geibig, Daniel

Institut für Anorganische und Analytische Chemie

Friedrich-Schiller-Universität Jena

Carl-Zeiss-Promenade 10

07745 Jena

[email protected]

Hartung, Jens

Technische Universität Kaiserslautern

Fachbereich Chemie

Organische Chemie

Erwin-Schrödinger-Strasse 54

D-67663 Kaiserslautern

[email protected]

Lippold, Ines


Friedrich-Schiller-Universität Jena


07745 Jena

[email protected]

Plass, Winfried


Friedrich-Schiller-Universität

Lehrstuhl für Anorganische Chemie II


07745 Jena

[email protected]

Rehder, Dieter

Chemistry Department, University of Hamburg

Martin-Luther-King-Platz 6

20146 Hamburg

[email protected]

Rosenthal, Esther

Technische Universität Berlin

Secr. C2

Strasse des 17. Juni 135

10623 Berlin

[email protected]

GREECEGREECEGREECEGREECE

Kabanos, Themistoklis

Section of Inorganic and Analytical Chemistry,


University of Ioannina

45110 Ioannina

[email protected]

Salifoglou, Athanasios

Laboratory of Inorganic Chemistry

Department of Chemical Engineering

Aristotle University of Thessaloniki

University Box 462

54124 Thessaloniki

[email protected]

HUNGARYHUNGARYHUNGARYHUNGARY

Enyedy, Éva

Department of Inorganic and Analytical Chemistry

University of Szeged

Dóm tér 7.

PO Box 440

6701 Szeged

[email protected]

Jakusch, Tamas



Dóm tér 7.

PO Box 440

H-6721 Szeged

[email protected]

Kiss, Tamás



Dóm tér 7.

P.O.Box 440

H-6701 Szeged

[email protected]



LP3

INDIAINDIAINDIAINDIA

Chatterjee, Pabitra

Department of Inorganic Chemistry

Indian Association for the Cultivation of Science

2A, 2B Raja S. C. Mallik Road

Jadavpur, Kolkata

700032 West Bengal

[email protected]

Maurya, Mannar


Indian Institute of Technolog Roorkee

Uttrakhand

247 667 Roorkee

[email protected]

IRAN, ISLAMIC REPUBLIC OFIRAN, ISLAMIC REPUBLIC OFIRAN, ISLAMIC REPUBLIC OFIRAN, ISLAMIC REPUBLIC OF

Majlesi, Kavosh

Chemistry Department

Islamic Azad University

Science & Research Campus

Hesarak

1477893855 Tehran

[email protected]

Rezaienejad, Saghar

Chemistry Department

Islamic Azad University


Hesarak

1477893855 Tehran

[email protected]

Zare, Karim

Chemistry Department, Islamic Azad University,


Hesarak

1477893855 Tehran

[email protected]

ITALYITALYITALYITALY

Conte, Valeria

Chemical Sciences and Technology

Università di Roma Tor Vergata

Via Ricerca Scientifica

00133 Roma

[email protected]

Garribba, Eugenio

University of Sassari

Via Vienna, 2

I-07100 Sassari

[email protected]

Lovat, Silvia

Department of Chemical Sciences

University of Padova

via Marzolo 1

35131 Padova

[email protected]

Sanna, Daniele

C.N.R. Istituto di Chimica Biomolecolare

Traversa La Crucca, 3

Baldinca-Li Punti

I-07040 Sassari

[email protected]

Zonta, Cristiano

Department of Chemical Sciences

University of Padova

via Marzolo 1

35131 Padova

[email protected]

JAPANJAPANJAPANJAPAN

Hashimoto, Masato

Fac. Syst. Eng., Dept. Mater. Sci. Chem.

Wakayama University

Sakaedani 930

640 8510 Wakayama

[email protected]

Hayashi, Yoshihito

Chemistry Department, Kanazawa University

Kakuma

920-1192 Kanazawa

[email protected]

Higuchi, Takeshi

Fac. Syst. Eng., Dept. Mater. Sci. Chem.

Wakayama University

Sakaedani 930

640 8510 Wakayama

[email protected]

Hirao, Toshikazu

Department of Applied Chemistry, Graduate School

of Engineering, Osaka University Yamada-oka

565-0871 Suita

[email protected]



LP4

Kanamori, Kan

Department of Chemistry, Faculty of Science,

University of Toyama

Gofuku 3190

930-8555 Toyama

[email protected]

Kamiya, Shogo

Chemistry Department, Kanazawa University

Kakuma

920-1192 Kanazawa

[email protected]

Katoh, Akira

Department of Materials and Life Science

Seikei University

3-3-1 Kichijoji-kitamachi, Musashino-shi

180-8633 Tokyo

[email protected]

Kawakami, Norifumi

Biological Science, Hiroshima University

Kagamiyama1-3-1,

Higashi-hiroshima

739-8526 Hiroshima

[email protected]

Michibata, Hitoshi

Department of Biological Science

Hiroshima University, Graduate School of Science

Kagamiyama 1-3-1

739-8526 Higashi-Hiroshima

[email protected]

Sasai, Hiroaki

Inst. of Scientific and Industrial Research

Osaka University

8-1 Mihogaoka, Ibaraki-shi

567-0047 Osaka

[email protected]

Sakurai, Hiromu

Department of Pharmaceutical Sciences

Suzuka University of Medical Science

3500-3 Minami-tamagaki-chou, Mie

513-0816 Suzuka

[email protected]

Ueki, Tatsuya

Department of Biological Science

Hiroshima University

Graduate School of Science

1-3-1 Kagamiyama

739-8526 Higashi-Hiroshima

[email protected]

Yamamoto, Tomohiro

Research & Development headquarters

Asahi soft drinks co., ltd.

1-1-21, Midori

302-0106 Moriya-shi

[email protected]

NETHERLANDSNETHERLANDSNETHERLANDSNETHERLANDS

Wever, Ron

University of Amsterdam

Nieuwe Achtergracht 129

1018 WS Amsterdam

[email protected]

NIGERIANIGERIANIGERIANIGERIA

Omoruyi, Gloria

Chemistry, Obafemi Awolowo University

Adeyemi Campus

p.m.b 520

Ondo state

23434 Ondo

[email protected]

POLANDPOLANDPOLANDPOLAND

Romanowski, Grzegorz

Faculty of Chemistry, University of Gdańsk

Sobieskiego 18/19

PL-80952 Gdańsk

[email protected]

PORTUGALPORTUGALPORTUGALPORTUGAL

Adão, Pedro

Centro de Química Estrutural

Instituto Superior Técnico

Av. Rovisco Pais, 1

1049-001 Lisboa

[email protected]

Almeida, Maria Marise

UICOB- Laboratório de Biomateriais

Faculdade de Medicina Dentária de Lisboa

Cidade Universitária

1649-003 Lisboa

PORTUGAL

[email protected]



LP5

Aureliano, Manuel

Departamento de Química, Bioquímica e Farmácia,

Faculdade de Ciências e Tecnologia

Universidade do Algarve

Campus de Gambelas

8005-139 Faro

[email protected]

Brissos, Rosa




Casa Brissos Vale Formoso

8100-267 Loulé

[email protected]

Butenko, Nataliya




Campus de Gambelas

8005-139 Faro

[email protected]

Castro, Maria Margarida

Departamento de Bioquímica


Universidade de Coimbra

P.O.Box 3126

3001-401 Coimbra

[email protected]

Cavaco, Isabel




Campus de Gambelas

8005-139 Faro

[email protected]

Fontes, Fábio




Rua das Oliveiras, n.º 23

8500-601 Portimão

[email protected]

Fraqueza, Gil

Escola Superior de Tecnologia


Campus da Penha

8000 Faro

[email protected]

Gama, Sofia

Química Inorgânica e Radiofarmacêutica

Instituto Tecnológico e Nuclear

Estrada Nacional 10

2686-953 Sacavém

[email protected]

Geraldes, Carlos

Departamento de Bioquímica



POBox 3126

3001-401 Coimbra

[email protected]

Gonçalves ,Gisela



Av. Rovisco Pais, 1

1049-001 Lisboa

[email protected]

Honzicek, Jan

Instituto de Tecnologia Química e Biológica

Av. da República

2780-157 Oeiras

[email protected]

Humanes, Madalena

Faculdade de Ciências da Universidade de Lisboa

Campo Grande

1749-016 Lisboa

[email protected]

Justino, Licínia

Departamento de Química


Rua Larga

3004 – 535 Coimbra

[email protected]

Pereira, Ana




Campus de Gambelas

8005-139 Faro

[email protected]

Pereira, Maria João

Centro de Ciências do Mar


Urbanização Forte Novo Bloco C - r/c H

8125-214 Quarteira

[email protected]



LP6

Pessoa, João da Costa



Av. Rovisco Pais, 1

1049-001 Lisboa

[email protected]

Pombeiro, Armando



Av. Rovisco Pais, 1

1049-001 Lisboa

[email protected]

Ramos, Susana

REQUIMTE/CQFB, Departamento de Química,


Universidade Nova de Lisboa

2829-516 Caparica

[email protected]

Rangel, Maria

Chemistry, Instituto de Ciências Biomédicas de

Abel Salazar

Largo Abel Salazar, 2

4099-003 PORTO

[email protected]

Silva, Telma

Instituto Superior de Engenharia de Lisboa

Rua Conselheiro Emídio Navarro

1950-062 Lisboa

[email protected]

Tomaz, Isabel

Centro de Ciências Moleculares e Materiais

Faculdade de Ciências da Universidade de Lisboa

Campo Grande

1749-016 Lisboa

[email protected]

Tyagi, Amit



Av. Rovisco Pais, 1

1049-001 Lisboa

[email protected]

SLOVAKIASLOVAKIASLOVAKIASLOVAKIA

Schwendt, Peter


Comenius University

Mlynska dolina

842 15 Bratislava

[email protected]

Sivak, Michal


Comenius University

Mlynska dolina CH2

842 15 Bratislava

[email protected]

SPAINSPAINSPAINSPAIN

Porto Avecilla, Fernando

Departamiento de Quimica Fundamental,

Universidade da Coruña

Zapateira s/n

15071 A Coruña

[email protected]

Zorzano, António

Head, Molecular Medicine Programme

Institute for Research in Biomedicine - IRB

Baldiri Reixac, 10

08028 Barcelona

[email protected]

SWEDENSWEDENSWEDENSWEDEN

Angus-Dunne, Sarah

Chemical Engineering, Mälardalens University

HST Box 325

63105 Eskilstuna

[email protected]

Nilsson, Jessica

Department of Chemistry, Lund University

Kemisk Fysik

Kemicentrum

Getingevägen 60

22241 Lund

[email protected]

Pettersson, Lage

Department of Chemistry, Umeå University

SE-901 87 Umeå

[email protected]



LP7

TAIWANTAIWANTAIWANTAIWAN

Chen, Chien-Tien

Department of Chemistry,

National Taiwan Normal University

#88, Sec. 4, Ding-jou Road

11650 Taipei

[email protected]

UNITED KINGDOMUNITED KINGDOMUNITED KINGDOMUNITED KINGDOM

Correia, Maria

Chemistry Department, Imperial College

South Kensington

SW7 2AZ London

[email protected]

Littlechild, Jennifer

Henry Wellcome Building for Biocatalysis

School of Biosciences, University of Exeter

Stocker Road

EX4 4QD Exeter

[email protected]

Ross, Allison

Chemistry Departement, University of Edinburgh

Office 96, Joseph Black Building, Kings Buildings,

West Mains Road

EH9 3JJ Edinburgh

[email protected]

UNITED STATESUNITED STATESUNITED STATESUNITED STATES

Butler, Alison

Department of Chemistry & Biochemistry,

University of California

93196-9510 Santa Barbara

[email protected]

Cohen, Mitchell

Environmental Medicine

New York University School of Medicine

7 Old Forge Road

10987 Tuxedo

[email protected]

Crans, Debbie C.

Chemistry Department, Colorado State University

1301 Center Av , CO 80523

80523 Fort Collins

[email protected]

Krzystek, Jurek

National High Magnetic Field Laboratory

1800 E. Dirac Dr.

32310 Tallahassee

[email protected]

Makinen, Marvin

Biochemistry & Molecular Biology Department,

University of Chicago

Center for Integrative Science

929 East 57th Street

60637 Chicago, Illinois

[email protected]

McLauchlan, Craig

Chemistry Department, Illinois State University

CB 4160

61790-4160 Normal, IL

[email protected]

Pecoraro, Vincent

Chemistry Department, University of Michigan

930 N. University Avenue

48109-1055 Ann Arbor

[email protected]

Willsky, Gail

Biochemistry Department, University at Buffalo

School of Medicine and Biomedical Sciences

140 Farber Hall

14214 Buffalo

[email protected]

URUGUAYURUGUAYURUGUAYURUGUAY

Gambino, Dinorah

Inorganic Chemistry Department

Faculty of Chemistry

Gral Flores 2124

11800 Montevideo

[email protected]

YUGOSLAVIAYUGOSLAVIAYUGOSLAVIAYUGOSLAVIA

Colovic, Mirjana

Department of Physical Chemistry

Institute of Nuclear Sciences

Mike Petrovica 12-14

Vinca, P.O.Box 522

11001 Belgrade

[email protected]

Krstić, Danijela

Biochemistry Department

Institute of Medicinal Chemistry, School of Medicine

University of Belgrade

Višegradska 26

11000 Belgrade

[email protected]


Author Index

Author Index


AI1

AAAA

Adão, P. – O3, O44, P5, P9, P15

Alegria, E. C. B. A. – O50

Almeida, M – O39O39O39O39

Amata, Y. – P47

Amorim, M. J. – O9

Andersson, I. – O11

Andrade, M. – O9

Angus-Dunne, S. – P42, P43

Antunes, O. – O47O47O47O47

Arends, I. – O1, P13

Arias, A. R. – P37

Arrambide, G. – O15, O32

Arya, A. – P10

Aubry, J.-M. – O40

Aureliano, M. - O34O34O34O34, P3, P38, P44, P46, P51, P52

Avecilla, F. – O3, O8, O13, O19, O44O44O44O44, O46, P5, P15,

P32

BBBB

Backhus, E. A. – P50

Bányai, I. – P14

Baran, E. J. – O51O51O51O51, P36

Barrio, D. A. – O32

Barroso, S. – P9

Barta, C. A. – O23

Baruah, B. – P17, P51

Benítez, J. – O15, P37

Berardi, S. – O1

Biré, A. S. – O43, O46, P45, P48

Bisht, M. – O8

Bistram, B. A. – O22, P41

Bordbar, K. – O23

Bonchio, M. – O1

Bosnjakovic-Pavlovic, N. – O43, O46, P45, P48

Bouhmaida, N. – O46

Brissos, R. F. – P44, P46

Bruzzone, L. – O32, P36

Burrows, H. D. – P21, P22

CCCC

Carn, F. - O56O56O56O56

Carvalho, E. – P38

Castro, M. M. C. A. – O13, O19O19O19O19, P32

Cavaco, I. - O37O37O37O37

Clark, M. – O22, P41

Chatterjee, P. B. – P16

Chaudhury, M. – P16

Chen, C.T. - O2O2O2O2, O28

Chi, L.-H. – O22, P41

Choukroun, R. – P7

Cindrić, M. – P26

Colovic, M. – P45

Cohen, M. D. – O36O36O36O36

Conte, V. – O1, P13, P14

Conzen, S. D. – O28

Coradin, T. – O56

Correia, I. – O3O3O3O3, O44, P5, P15

Costa Pessoa, J. – O3, O8, O13, O15, O19, O37,

O44, O46, P5, P6, P9, P15, P32

Crans, D. C.- O20O20O20O20, O22, P17, P41, P51

Creagh, A. L. – O23

DDDD

Degerman, E. – P24

De Gioia, L. – O10

Ding, W - O26O26O26O26

Dilović, I. – P26

Djobourov, M. – O56

Dorner, N. A. – P50

Drouza, C. – O54, P18

Duarte, R. O. – P3, P44, P46, P52

Dunne, S. – P42, P43

Durupthy, O. – O56

EEEE

Enyedy, E. A. – O14, P19

Escribano, E. – O37

Etcheverry, S.B. – O32O32O32O32, P36

Eriksson, L. A. – P42, P43

Evgeniou, E. – O48

FFFF

Fabbianesi, F. – O1, P13

Faísca, M. J. – P38

Faneca, H. – O19

Fayolle, B. – O56

Fernandez, T. L. – O47

Figueroa, D. – P37

Fiolhais, C. – P21, P22

Floris, B. – O1, P13

Fontes, F. L. – P44

Fraqueza, G. – P44, P46

Fraústro da Silva, J. J. – O50

França, T. C. C. – P37

Fujinami, K. – O16

GGGG

Gabriel, C. – O17, P27

Gáliková, J. – O18

Galloni, P. – O1, P13

Gama, S. - O37

Gambino, D. – O15O15O15O15, O32, P37

Gameiro, P. – O9

Garat, B. – O15, P37

Garribba, E. – O30O30O30O30, P33, P34, P35

Geibig, D. – P1

Gekko, K. – P47

Geraldes, C.F.G.C. – O13, O19, P21, P32

Ghermani, N.E. – O43, O46O46O46O46

Ghio, A. J. - O36

Gil, V. M. S. – P21, P22

Author Index


AI2

Godzala III, M. – O22

Gonçalves, G. - O13, O19, O39, P32

Gorzsás, A. – O11

Grayson, R. Z. – O22, P41

Greiner, B. A. – P50

Guedes da Silva, M. F. C. – O50

Guggeri, L. – O15, P37

Gutiérrez-Merino, C. – P3, P51

HHHH

Hach, D. – O7

Hartung, J. – O7O7O7O7

Hasan, Z. – O40

Hashimoto, M. - O12O12O12O12, P20

Haukka, M. – P24

Hayashi, Y. - O45O45O45O45, P4

Haynes, C. A. – O23

Henao, F. – P51

Higuchi, T. – O12, P20

Hirao, T. - O52 O52 O52 O52

Hiromura, M. – O21

Hober, D. – O40

Holubová, J. – P40

Honziček, J. - O49O49O49O49, P40

Humanes, H. – O39

IIII

Isobe, K. – O45, P4

JJJJ

Jakusch, T. – O14, O48, P2

Johnson, M. D. – P17

Justino, L. L. G. – P21, P22

KKKK

Kabanos, T. A. - O48O48O48O48

Kanamori, K. - O16,O16,O16,O16, P47

Kamiya, S. – P4

Kao, C.-M. – O28

Katayama, T. – O5

Katoh Akira – O25O25O25O25

Kaupp, M. – P21, P22

Kawakami, N. – O35, P47

Keramidas, A. D. – O48, O54 O54 O54 O54, P18, P30

Kikushima, K. – O52

Kirillov, A. M. – O50

Kirillova, M. V. – O50

Kiss, D. – P33

Kiss, T. – OOOO14141414, O48, P2, P19

Khorrami, S. A. – P31

Khorramdin, B. – P31

Kostyniak, P. J. – O22

Krstic, D. – P48

Krzystek, J. - O53O53O53O53

Kubo, K. – O16

Kumar, A. – O8, P6

Kumar, M. – P6

Kustin, K. – O16

Kuznetsov, M. – O50

Kuzvetsov, M. – O3

LLLL

Leite, A. – O9

Lenhardt, J. M. – P17

Li, M. – O26

Lichter, J. B. – O24

Licini, G. – O29, P8

Lima, M. C. P. – O19

Lin, Y.-H. – O2

Lippold, I. – P49

Lis, T. – P12

Lisha, W. – P42

Littlechild, J. - O41O41O41O41

Livage, J. – O56

Lodyga-Chruscinska, E. – P35

Lorber, C. – O6O6O6O6

Lovat, S. – O29, P8

Lorber, C. – P7

MMMM

Machado II, A. J. – O28

Maestro, M. – O19

Majlesi, K. – OOOO33333333AAAA, O33B

Makinen, M. W. - O28O28O28O28

Marchán, E. – P37

Martins, A. M. – P9

Martins, H. – P38, P44

Martins, H. – P38

Martins, J. – P44, P46

Martins, L. M. D. R. S. – O50, P28

Matković-Čalogović, D. – P26

Matsugo, S. – O16

Matsumura, Y. - O25

Matsuo, K. – P47

Maurya, M. R. – O3, O8O8O8O8, P6, P10

Mba, M. – O29, P8

McLauchlan, C. C. - O55O55O55O55, P50

McNeill, J. H. – O24

Meyer, J. E. – P50

Melman, A. – O48

Melo, M. J. – P38

Michibata, H. - O35O35O35O35, P23, P47

Micera, G. – O30, P33, P34, P35

Mioc, U. – O46

Mishra, G. S. – O50

Moreno, V. – O37

Moriuchi, T. – O52

Moura, J. J. G. – P3, P44, P46, P52

Muglia, C. I. – P36

Author Index


AI3

NNNN

Natálio, F. – O39

Nicolai, M. – O39

Nikolakis, V. A. – O48

Nilsson, J. – P24

Nogueira, F. – P21

Nordlander, E. – P24

Nouri, O. – O37

Nowicki, W. – P11, P12

Nunes, A. – O9

OOOO

Okeya, S. – O12, P20

Olakunlemi, A. – P25

Oluwaseun, A. – P25

Omoruyi, G. – P25

Orvig, C – O23O23O23O23, O24

PPPP

Pacigová, S. – P29

Palacio, L. – O19

Paláčková, H. – P40

Palavra, A. – O50

Parsons, S. – P39

Pecoraro, V. L. - O10O10O10O10

Pedro, C. – P38

Pereira, A. M. – P51

Pereira, M. J. – P38

Pettersson, L. - O11O11O11O11, P14

Pierlot, C. – O40

Pisano, L. – P33

Plass, W. - O38O38O38O38, P1, P49

Pombeiro, A. J. L. - O50O50O50O50, P28

Pontini, M. – O29, P8

RRRR

Ramos, M. L. – P21, P22

Ramos, S. – P52

Rangel, M. C. ---- O9 O9 O9 O9

Rehder, D. – O1, O31O31O31O31, P13, P24

Renirie, R. – O40

Rezaienejad, S. – O33A, OOOO33333333BBBB

Ribeiro, E. – O37

Ribot, F. - O56

Rito, E. – P46

Rivadeneira, J. – O32, P36

Róbert, G. – P29

Robertson, N. – P39

Rodrigues, F. – P38

Rolón, M. – P37

Romão, C. C. – O49

Romanowski, G. – P11, P12

Rosenthal, E. C. E. - O4 O4 O4 O4

Ross, A. – P39

Rubčić, M. – P26

SSSS

Sadler, P. J. – P39

Sakai, Y. – O16

Sakurai, H. – O21O21O21O21, O25, P20

Salas, P. F. - O24

Salifoglou, A. - O17O17O17O17, P27

Sanna, D. – O30, P33, P34, P35

Sasai, H. - O5O5O5O5

Scaife, M. S. – O24

Scarpellini, M. – O47

Schneider, C. J. – O10

Schulz, H. – O7

Schwendt, P. – O18O18O18O18, P29

Shen, S. – O28

Shintaku, K. – P23

Sigalas, M. P. – O48

Sikorski, A. – P11

Silva, A. – O9

Silva, C. – O9

Silva, J. A. L. – O50

Silva, T. F. S. – O50, P28

Silvagni, A. – P14

Simoni, Z. – P37

Šinkorová, Z. – P40

Sivák, M. – O18, P29

Smee, J. J. – O22

Smircich, P. – P37

Soares, S. S. – P3

Sobral, A. J. F. N. – P21

Stylianou, M. – O48

Sordi, D. – O1, P13

Spasojević, Anne – O43O43O43O43, O46

Steunou, N – O56

Strid, A. – P42

Stylianou, M. – O54, P30

TTTT

Takizawa, S. – O5

Tatiersky, J. – O18

Thompson, K. H. – O23, O24O24O24O24

Tiago, T. – P44, P46, P51, P52

Tomaz, I. – OOOO13131313, O15, O19, O37, O46, P32

Tsalavoutis, J. T. – O48

UUUU

Ueki, T. – O35, P47, P23

VVVV

Várnagy, K. – P33

Vasic, V. – P45, P48

Vega, C. – P37

Vieites, M. – P37

Vinklárek, J. – O49, P40

Vinsetin, L. C. – O47

Author Index


AI4

WWWW

Wada, N. – O16

Wanke, R. – P28

Weberski, M. P. – O55

Wei, D. - O26

Wever, R. - O40O40O40O40

Wilde, A. – O40

Willsky, G. R. - O22O22O22O22, P41

Wojtczak, A. – P11

XXXX

Xie, Q. G. – O28

YYYY

Yang, J. – O26

Yoshikawa, Y. – P20, O25

Yoshihara, M. – P23

Yun, D. – O28

ZZZZ

Žák, Z. – O18

Zampella, G. – O10

Zare, K. – O33A, O33B, P31

Zárybnická, L. – P40

Zhou, X. – P43

Zonta, C. – O29O29O29O29, P8

Zorzano, A. - O27O27O27O27

v6 symposium: the 6th international vanadium symposium” july 17 to 19th, 2008 lisbon, portugal

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