21

Foreword

The 12th EUCHEM Conference on Organic Free Radicals will take

place in Bologna, Italy, from June 28 to July 2, 2010. The conference

is intended primarily to stimulate new topics of growth and improve

interdisciplinary in free radicals research. In conjunction, the annual

meeting of the COST Action CM0603 on "Free Radicals in Chemical

Biology" will be held in Bologna on July 1-2, 2010. Therefore, we

share two days of activities between the two scientific audiences.

About 170 scientists from areas of free radical chemistry and from all

over the world will gather for this meeting to exchange and discuss

their research, and to meet colleagues and friends. It is worth

underlining that a large number of young participants is registered.

This is a success for the meeting and also demonstrates the

attractiveness of free radical research, foreseeing a period of further

growth for this field.

The Research Area of Consiglio Nazionale delle Ricerche (CNR) in

Bologna (Italy) is the venue of the EUCHEM Conference 2010. Top-

class facilities are available for the scientific sessions as well as

spaces for formal and informal meetings discussions. Also the city of

Bologna with its architectural features, art and history is an ideal

venue for the social activities programmed for the Conference.

This volume contains the abstracts received up to May 10th of the

planned 14 plenary lectures, 23 invited talks, and 84 contributed

papers that are presented as posters. The abstracts have been

reproduced as submitted by the authors, they are grouped in

22

alphabetical order of the first author that gives the lecture or presents

the poster. I am grateful to all participants who submitted abstracts for

the creation of this volume, that clearly indicate the strong interest

and wide applicability of free radical research in many scientific areas.

The EUCHEM conference on Organic Free Radicals is an event for

the free radical scientific community held in various places in Europe

since 1966. The following table summarizes the history of this

conference. I wish the free radical community keep its enthusiasm

and continuity in organizing successful Conferences for many years

to come.

EUCHEM Conferences on Organic Free Radicals and Organizers 1 – Schloss Elmau (D) October 23-29, 1966 K. Dimroth

E. Müller 2 – Schloss Elmau (D) October , 1972 H. Fischer

3 – Schloss Elmau (D) October 19-24, 1975 C. Rüchardt

4 – Cirencester (UK) September 10-14,1979 A. G. Davies

5 – Schloss Elmau (D) October 17-21, 1983 R. Sustmann

6 – Assisi (I) September 22-26, 1986 M. Tiecco

7 – Arles (F) September 17-21, 1990 P. Tordo

8 – Champery (CH) August 21-26, 1994 B. Giese

9 – Grottaferrata (I) July 4-9, 1998 E. Baciocchi

10 – York (UK) July 21-25, 2002 B.C. Gilbert

11 – Bergen (N) July 9-13, 2006 H.-R. Bjørsvik L. Engman T. Skrydstrup

12 – Bologna (I) June 28-July 2, 2010 C. Chatgilialoglu

23

I am grateful to the Scientific Committee (M.-L. Bennasar, K.

Bobrowski, J. Cadet, C. J. Easton, L. Engman, B. T. Golding,

M. Malacria, J. A. Murphy, M. Orfanopoulos, G. F. Pedulli, N. A.

Porter, I. Ryu and A. Studer) and the Organizing Committee (C.

Ferreri, A. Pitzus, A. Torreggiani, and L. Valgimigli) for their

advices and assistance in arranging the scientific and technical

programs and providing all local arrangements. The publisher Aracne

has to be thanked for its efforts in printing of these Proceedings.

Finally, I address a warm welcome to all participants and I am looking

forward to this event, wishing that new contacts and ideas can be

realized to strengthen the relevance of free radical chemistry in the

multidisciplinary tasks of scientific research.

Bologna, May 10th, 2010

Chryssostomos Chatgilialoglu

24

LIGHT-ACTIVATED pH-GATED ALKYNE AND ENEDIYNE CONJUGATES FOR EFFICIENT DOUBLE-STRANDED DNA

CLEAVAGE AND CANCER THERAPY

Igor V. Alabugin, Wang-Yong Yang, Kerry Gilmore

Dep.Chemistry and Biochemistry, Florida State University, Tallahassee, FL.

First, I will present new photochemical and radical reactions of alkynes which illustrate how the two alkyne π-orbitals can be utilized for a) the formation of four new single C-C bonds with the creation of two contiguous quaternary centers,1 b) attachment of =CH2 methylene fragments to both of the alkyne carbons2 and c) coupling of a C=C bond formation at one of the alkyne carbons of a bis-alkyne with simultaneous formation of two C-H bonds at the other alkyne carbons.3

In the main part, I will discuss how the diverse chemical reactivity of excited alkynes matches the chemical diversity of DNA and leads to the design of light-activated reagents with unprecedented efficiency of ds DNA cleavage and greater selectivity for cancer cells. Spatial and temporal selectivity for the activation stems from the use of light which can activate prodrugs once they accumulate in the cancer cells. Incorporation of Photoinduced Electron Transfer (PET) from DNA as a condition for the prodrug activation contributes to the selectivity towards the correct cellular target (DNA).

25

Two additional levels of biological selectivity were added via the attachment of DNA-damaging “warheads” to the DNA-binding groups which display a) the ability to locate a site of initial DNA damage site and to transform it into therapeutically important ds-DNA damage,4 and b) pH-gated behavior associated with a dramatic increase in the efficiency at the lower pH of cancer cells.5

1) Zeidan, T.; Kovalenko, S. V.; Manoharan, M.; Clark, R. J.; Ghiviriga, I.; Alabugin I. V. J. Am. Chem. Soc. 2005, 127, 4270-4285. 2) Alabugin, I. V.; Gilmore, K.; Patil, S.; Manoharan, M.; Kovalenko, S. V.; Clark, R. J.; Ghiviriga, I. J. Am. Chem. Soc., 2008, 30, 11535-11545. 3) Alabugin I. V.; Kovalenko, S.V. J. Am. Chem. Soc. 2002, 124, 9052-9053. Alabugin I. V.; Manoharan, M. J. Am. Chem. Soc. 2003, 125, 4495-4509. Kovalenko, S. V.; Alabugin I. V. Chem. Comm. 2005, 1444. Breiner, B.; Schlatterer, J. C.; Kovalenko, S. V.; Greenbaum, N. L.; Alabugin I. V. Angew. Chem. 2006, 45, 3666. 4) Breiner, B.; Schlatterer, J. C.; Kovalenko, S. V.; Greenbaum, N. L.; Alabugin I. V. Proc. Natl. Acad. Sci., 2007, 104, 13016-13021. 5) Yang, W.-Y.; Breiner, B.; Kovalenko, S. V.; Ben, C.; Singh, M.; LeGrand, S. N.; Sang, A. Q.-X.; Strouse, G. F., Copland, J. A.; Alabugin I. V. J. Am. Chem. Soc., 2009, 131, 11458–11470.

26

EFFECTS OF BASES ON PEROXYL RADICAL SCAVENGING ACTIVITY OF ANTIOXIDANTS

Riccardo Amorati,# Luca Valgimigli,# Gian Franco Pedulli,# Stanislav A. Grabovskiy,§ Chryssostomos Chatgilialoglu§

#Dipartimento di Chimica Organica, Università di Bologna;§ISOF, Consiglio Nazionale delle Ricerche, Via P. Gobetti 101, 40129, Bologna, Italy

The reaction of peroxyl radicals (ROO•) with chain-breaking antioxidants occurs by the formal transfer of a H-atom from the antioxidant to the radical. Recently, it has been shown that this reaction can proceed at faster rates in the presence of organic acids, via the formation of small amounts of protonated peroxyl radicals which are able to react through an electron-transfer mechanism in polar solvents.1 On the other hand, little is known about the role of bases on the reactivity of peroxyl radicals, as until now most studies have focused mainly on dpph• (diphenylpicrylhydrazyl) radical.2 In this poster, we report some of our preliminary results obtained by measuring the rate constants (kinh) for the reaction of peroxyl radicals with several phenolic and non-phenolic antioxidants in the presence of substituted pyridines in acetonitrile. We have found that compounds with pKa(H2O) smaller than 8, such as HMU (see figure), show a noticeable increase in their ability to inhibit AIBN initiated styrene autoxidation after the addition of pyridine (figure 1A). The increase kinh is dependent on the strength of the base, being 4-NMe2pyridine > pyridine > 3-Br-pyridine (Figure 1B). Relatively acidic polyphenols (quercetin, esculetin, caffeic acid) also display a similar behavior, while the reactivity of α-tocopherol is not influenced by the presence of pyridine.

1) L.Valgimigli, R. Amorati, S. Petrucci, G.F. Pedulli, D. Hu, J.J. Hanthorn, D.A. Pratt. Angew. Chem. Int. Ed. 2009, 48, 8348-8351. 2) G. Litwinienko, K. U. Ingold, Acc. Chem. Res. 2007, 40, 222-230.

27

NOVEL TYPES OF PERSISTENT SILYL RADICALS

Yitzhak Apeloig, Dennis Sheberla, Dmitry Bravo-Zhivotovskii, Mark Botoshansky and Boris Tumanskii Department of Chemistry and the Lise Meitner-Minerva Center for Computational Quantum Chemistry, Technion-Israel Institute of Technology, Haifa 32000, Israel.

Silyl radicals are important reactive intermediates. Yet, fundamental knowledge for these intriguing reactive species is quite scarce. In this lecture we report the generation and spectroscopic characterization of several novel types of persistent silyl radicals and some aspects of the chemistry of analogous carbon and germanium radicals. Several radical adducts of metallylenes 1–3 with free radicals of different chemical nature (O-, P-, Re-, Mn-, etc) were studied by EPR and DFT calculations (eq. 1). A detailed EPR study of the phosphoryl radical adducts 4-6 shows that the unpaired electron is delocalized over the 5-membered ring, with the spin density on E decreasing in the order: C > Si > Ge. Isolable branched polysilyl radicals 7 have enhanced photo-activity. For example, irradiation of 7 (yellow solution in hexane) yields the corresponding disproportionation products, silane and disilene (blue color) (eq. 2). Irradiation of 8 yields the first Pt-centered radical 9 which was characterized by EPR spectroscopy (eq. 3). The observation of Pt-centered radicals of type 9 opens new opportunities for studying the role of radicals in Pt-catalyzed reactions.

28

TUNING RADICAL REACTIVITY IN POLYMERIZING SYSTEMS: INITIATION, CONTROL AND SYNTHESIS

Christopher Barner-Kowollik,1 Fabian Günzler, Sandy P. S. Koo, Dominik Voll, Anna-Marie Zorn, Mathias Dietrich, Edgar H. H. Wong, Leonie Barner, Thomas Junkers

1Preparative Macromolecular Chemistry, Institut für Technische Chemie und Polymerchemie, Karlsruhe Institute of Technology (KIT), Engesserstr. 18, 76128 Karlsruhe

Fine tuning radical reactivity and understanding the reaction pathways of free radicals is essential for the design and control of polymerization processes. The present lecture will address distinct areas of radical reactivity in the context of free radical polymerization: (i) (Photo)-initiation processes – standing at the start of any free radical polymerization – can be efficiently studied via the combination of high frequency pulsed laser techniques with high resolution mass spectrometry. It will be demonstrated how the reactivity of individual photolytically generated radical fragments towards variable monomers can be quantified and used to design photoinitiators. Applications of photo-induced grafting-to processes to biosubstrates may also be discussed. (ii) Rapidly pulsing laser systems (500 Hz) open the opportunity

Scheme 1: Quantitative mass spectrometric analysis of photochemically induced polymerization processes.

29

to determine accurate propagation rate coefficients for high reactivity propagating radicals, specifically (functional) acrylates. The lecture will provide examples thereof as well as discuss how the complexities of acrylate free radical polymerization can be controlled to achieve a uniform polymer product distribution as well as provide ready access to oligomeric macromolecular building blocks. (iii) Finally, the lecture will highlight how spin traps – for example thioketones and nitrones – can be employed to impart control onto radical polymerization processes. It will be addressed how two related control protocols, namely thioketone mediated polymerization (TKMP) and enhanced spin capturing polymerization (ESCP) can be derived from these species. A focus of the discussion will be the radical chemistry of both processes as well as the provision of rate coefficients for the relevant elemental reactions. Time permitting, synthetic applications of spin traps will be highlighted.

30

SPIN LABELS AND SPIN PROBES: A COMPUTATIONAL JOURNEY

Vincenzo Barone

Scuola Normale Superiore, piazza dei Cavalieri 7, 56126, Pisa, Italy

Magnetic spectroscopic techniques such as Electron Paramagnetic Resonance (EPR) and Paramagnetic Nuclear Magnetic Resonance (PNMR) are valuable tools for understanding the structure and dynamics of complex systems, like e.g. bio-molecules or nano-materials labeled with suitable free radicals. Unfortunately, such spectra do not give direct access to the radical structure because of the subtle interplay of several different effects not easily separable and evaluable by experimentalists alone. In this respect computational spectroscopy is becoming a needful and versatile tool for the assignment and interpretation of experimental spectra. In this contribution, the integrated computational strategy developed in recent years in our research group are reviewed. Methods rooted into the density functional theory (DFT) are providing very encouraging results and the development of carefully optimized medium size basis sets is allowing the contemporary computation of reliable structural and magnetic properties. Inclusion of solvent effects by last generation discrete-continuum models and proper account of vibrational effects by effective time-dependent and time-independent models completes the definition of a promising integrated computational strategy. Such approaches have been applied to some widely used spin-probes showing that proper account of stereo-electronic, environmental and dynamical effects leads to magnetic properties in quantitative agreement with experimental results.

P. Cimino, A. Pedone, E. Stendardo, V. Barone, Interplay of stereo-electronic, environmental, and dynamical effects in determining the EPR parameters of aromatic spin-probes: INDCO as a test case, PCCP 12, 3741-3746 (2010); V. Barone, P. Cimino, Validation of the B3LYP/N07D and PBE0/N07D computational models for the calculation of electronic g-tensors, J.Chem.Th.Comp. 5, 192-199 (2009); V. Barone, P. Cimino, Accurate and feasible computations of structural and magnetic properties of large free radicals: the PBE0/N07D model, Chem.Phys.Lett. 454, 139-143 (2008); Pavone, P.Cimino, F.De Angelis, V.Barone, Interplay of stereo-electronic and enviromental effects in tuning the structural and magnetic properties of a prototypical spin probe: insights from a first principle dynamical approach, J.Am.Chem.Soc. 128, 4338-4347 (2006); V. Barone, A. Polimeno, Integrated computational approaches to modelling of ESR observables, PCCP 8, 4609-4629 (2006).

31

6-ENDO CYCLIZATIONS OF 3-INDOLYLACYL RADICALS UPON TETRAHYDROPYRIDINES:

ACCESS TO THE AZAERGOLINE RING SYSTEM

M.-Lluïsa Bennasar and Tomàs Roca

Laboratory of Organic Chemistry, Faculty of Pharmacy, and Institut de Biomedicina (IBUB), University of Barcelona, Barcelona 08028, Spain

The indole nucleus is a common substructure found in many biologically active compounds and occupies an important position in medicinally relevant heterocyclic systems. Therefore, there is a demand for general strategies that can efficiently provide variously substituted and functionalized indoles. In the last years we have developed a novel general indole annulation procedure using selenoester derived 2-indolylacyl radicals.1-4 Thus, indolo 1,2- and 2,3-fused carbo- and heterocyclic ketones were efficiently assembled by intramolecular reaction of these intermediates with indole-tethered alkene acceptors under reductive conditions. On the basis of our previous work, we present here the use of 6-endo cyclizations of 4-(tetrahydropyridyl)-3-indolylacyl radicals for the construction of indolo 3,4,5-fused isoquinolines, which are related to the natural ergoline ring system. Interestingly, the nucleophilic benzyl-type radical resulting from cyclization (A) undergoes oxidation or reduction depending on the reductive protocol (Bu3SnH, Et3B, air or Bu3SnH-AIBN) applied.

1. Bennasar, M.-L.; Roca, T.; Ferrando, F. Org. Lett. 2004, 6, 759-762. 2. Bennasar, M.-L.; Roca, T.; Ferrando, F. J. Org. Chem. 2006, 71, 1746-1749. 3. Bennasar, M.-L.; Roca, T.; García-Díaz, D. J. Org. Chem. 2007, 72, 4562-4565. 4. Bennasar, M.-L.; Roca, T.; García-Díaz, D. J. Org. Chem. 2008, 73, 9033-9039.

32

•OH RADICAL ADDITION ON TYROSINE, PHENYLALANINE OR METHIONINE? TOWARDS UNDERSTANDING

THE METENKEPHALINE OXIDATION PROCESSES

J. Bergèsa,b, P. Trouillasc, C. Houée-Levind

aLaboratoire de chimie théorique, Université Pierre et Marie Curie and

bUniversité Paris Descartes, Paris, France. cEA 4021 Faculté de Pharmacie 2 Rue du Dc Marcland 87025 Limoges Cedex, France. dLaboratoire de chimie-physique, Université Paris-Sud 11, Orsay, France. The Enkephalines are opiate pentapeptides that lower the sensation of pain in inflammation processes. One of them is is Methionine enkephaline (MetEnk), the sequence of which is Tyr-Gly-Gly-Phe-Met.

Since this peptide intervenes in situations of oxidative stress, it is submitted to high amounts of oxygen free radicals. Oxidation may lower the anti-pain action of the peptide, and understanding the oxidation process might lead to strategies of protection. We have performed the study of the one-electron oxidation of this peptide by radiolysis. The two oxidized residues are Tyr and Met. The first step of this oxidation should be the addition of OH radicals on the aromatic ring of Tyr or on the S atom of Met. In order to investigate the ability of this OH addition, we performed calculations with B3P86 method on both residues and their corresponding adducts, in vacuum and in the solvated states using the IEFPCM continuum model. In all cases, the addition is thermodynamically favoured on Tyr.

33

A TIME-RESOLVED KINETIC STUDY OF THE REACTIONS OF THE BENZYLOXYL AND CUMYLOXYL RADICALS

WITH HYDROGEN ATOM DONORS. THE ROLE OF STRUCTURAL EFFECTS

Gloria Anastasi, Massimo Bietti, and Michela Salamone

Dipartimento di Scienze e Tecnologie Chimiche, Università "Tor Vergata", Via della Ricerca Scientifica, 1 I-00133 Rome, Italy

Recent studies on the hydrogen abstraction reactions from carbon by the tert-butoxyl radical have indicated that steric effects in the abstracting radical may play an important role, showing moreover that most of these reactions are entropy controlled.1 In order to obtain new information on the role of structural effects on these processes and to provide a comprehensive picture of hydrogen abstractions from carbon by alkoxyl radicals we have extended these studies to the benzyloxyl and cumyloxyl radicals. The time-resolved kinetic data obtained for the reactions of these radicals with a series of hydrogen atom donors will be presented and discussed in comparison with those determined previously for the reactions of the tert-butoxyl radical.

Finn, M.; Friedline, R.; Suleman, N. K.; Wohl, C. J.; Tanko, J. M. J. Am. Chem. Soc. 2004, 126, 7578-7584.

34

•OH-INDUCED OXIDATION OF MET-MET DIPEPTIDES: INFLUENCE OF GEOMETRIC AND STERIC FACTORS

Krzysztof Bobrowski,1 Gordon L. Hug,2 Tomasz Pędziński,3 Franciszek Kaźmierczak,3 Paweł Wiśniowski,1 Bronisław Marciniak3 1 Institute of Nuclear Chemistry and Technology, 03-195 Warszawa, Poland; 2 Radiation Laboratory, University of Notre Dame, Notre Dame, IN 46556, USA; Faculty of Chemistry, Adam Mickiewicz University, 60-780 Poznań, Poland Oxidation of multifunctional organic compounds can lead to a variety of interesting mechanistic pathways through the neighboring group participation [1]. Peptides containing methionine (Met) are a case in point. There have been several studies on the OH-induced oxidation of small peptides containing Met [2-4]. Stabilizations, through neighboring group participation, of the resulting monomeric sulfur radical cations (>S+•) were seen when the Met residues were C- or N-terminal [2,3]. It was commonly thought that such bond formation would not occur with the heteroatoms involved in the peptide bonds because their electron lone pairs were considered to be too delocalized throughout the amide/carbonyl moieties to be able to participate in the bonding. Recently, studies were undertaken on the OH-induced oxidation of three Met-containing cyclic dipeptides. It has now been confirmed that >S+• can also been stabilized by bonding to the heteroatoms involved in peptide bonds [5,6]. So, in this paper, •OH-induced oxidation of the linear (open chain) L-Met-L-Met dipeptide protected on the N- and C-terminal was studied. The side chains of Met residues in the L,L-configured linear dipeptides are forced to point in opposite directions in space due to a tendency towards formation of trans conformers which makes it more difficult for them to come into close contact. The geometric preferences are exactly reversed in the cyclic L-Met-L-Met dipeptide due to a tendency towards formation of cis conformers. The contrasting behavior of these two dipeptides will be discussed in terms of a change of tendency towards formation of σ*-type 2c-3e S∴O, S∴N, and S∴S-bonds in linear vs. cyclic peptides resulting from their conformation and geometric preferences.

[1] R. S. Glass, in Sulfur-Centered Reactive Intermediates in Chemistry and Biology, vol. 97, ed. by C. Chatgilialoglu, K.-D. Asmus (Plenum Press, New York) 1990, 213; [2] K. Bobrowski, J. Holcman, J. Phys. Chem. 1989, 93, 6381; [3] K. Bobrowski, J. Holcman, Int. J. Radiat. Biol. 1987, 52, 139; [4] K. Bobrowski, C. Schöneich, Radiat. Phys. Chem. 1996, 47, 507; [5] K. Bobrowski, G. L. Hug, D. Pogocki, B. Marciniak, C. Schöneich, J. Phys. Chem. B. 2007, 111, 9608; [6] G. L. Hug, K. Bobrowski, D. Pogocki, G. Hörner, B. Marciniak, ChemPhysChem 2007, 8, 2202.

35

BIOLOGICAL BIRCH REDUCTION BY BENZOYL-CoA REDUCTASES

Matthias Boll

Institute of Biochemistry, Brüderstr. 34, University of Leipzig, 04103 Leipzig, Germany

Dearomatizing benzoyl-coenzyme A reductases (BCRs) are key enzymes in the anaerobic degradation of aromatic compounds.1 They catalyze the reduction of the aromatic ring of the substrate benzoyl-CoA yielding cyclohexa-1,5-diene-1-carboxyl-CoA with the two hydrogen atoms stereospecifically added in trans.2 A reduced ferredoxin serves as natural electron donor; no further reduction of the cyclic dienoyl-CoA formed is observed. The reaction by BCR is considered to be analogous to the Birch reduction of aromatic rings in chemical synthesis. Kinetic studies and isotope exchange reactions confirmed that benzoyl-CoA proceeds via radical intermediates.2,3 There are two completely different classes of benzoyl-CoA reductases in nature4. Class I enzymes couple electron transport to the aromatic ring to a stoichiometric ATP hydrolysis and consists of 4 subunits with 3 [4Fe-4S] clusters. Class II enzymes are independent of ATP hydrolysis and consist of 8 subunits with a tungsten cofactor at the active site; in addition they contain selenocysteine, FeS-cluster and flavin cofactors. The ATP-independent electron activation machinery in class II enzymes is unknown so far.

1Boll, M. (2005) J Mol Biotechnol 10, 132-42. 2Thiele, B., Rieder, O., Golding, BT, Müller, M. and Boll, M. (2008) J Am Chem Soc 130, 14050-1. 3Möbitz, H. and Boll, M. (2002) Biochemistry 41, 1752-8. 4Kung, JW, Löffler, C., Dörner K.,and Boll et al., (2009) Proc Natl Acad Sci 106, 17687-92.

36

EFFECT OF TYROSINE PHOSPHORYLATION AND NITRATION ON INTRAMOLECULAR LONG-RANGE

ELECTRON TRANSFER IN PEPTIDES

Weiqun Shi, Anastasia Domazou, Patricia L. Bounds, and Willem H. Koppenol*

Laboratory of Inorganic Chemistry, Department of Chemistry and Applied Biosciences, ETH-Zurich, CH-8093 Zurich, Switzerland

Long-range electron transfer (LRET) in proteins occurs in a wide range of biological processes, including oxidative phosphorylation, photosynthesis, and a variety of enzyme-catalyzed redox reactions1. Free radical damage and repair is largely mediated by LRET; although generation of radicals on proteins and peptides can initially be at various residues, intramolecular LRET generally ultimately leads to radicals being resident on tyrosine sidechains. The impact of LRET on ultimate formation of tyrosine radicals in proteins may play a role in cellular signaling pathways that function via reversible phosphorylation of tyrosine residues2, which are modulated by the redox status of the cell3. Nitration of tyrosine residues is another important post-translational modification of proteins, and 3-nitrotyrosine is recognized as a tissue biomarker for exposure to oxidative stress4.

We have studied effects of tyrosine phosphorylation and nitration on LRET in a model peptide (YPPW) and in peptide fragments from the proteins β-tubulin and α-synuclein. Radical formation on tryptophan was initiated by pulse radiolysis in the presence of azide in N2O saturated solution, and electron transfer from tyrosine to the tryptophan radical was observed by UV/VIS spectrophotometry. Intra-molecular LRET reactions were clearly observed in the peptides, and rate constants were evaluated. We produced the tyrosine phosphorylated and nitrated forms of these peptides for study by pulse radiolysis; phosphorylation or nitration of the tyrosine residue blocks LRET. We suggest that responses to oxidative stress might be mediated in part by modulation of the flow of electrons in the impacted proteins by phosphorylation and nitration of tyrosine residues.

Acknowledgement: This work was supported by ETH-Zurich.

1. R. A. Marcus, N. Sutin, Biochim. Biophys. Acta, 1985, 811, 265–322. 2. T. Hunter, Cell, 1995, 80, 225–236. 3. H. P-Monteiro, A. Stern, Free Rad. Bio. Med., 1996, 21, 323–333. 4. H. Ischiropoulos, Arch. Biochem. Biophys., 1998, 356, 1–11.

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SYNTHESIS OF INDOLE AND INDOLINE DERIVATIVES VIA RADICAL CYCLISATION ONTO ARYL AZIDES

François Brucelle and Philippe Renaud

Universität Bern, Departement für Chemie und Biochemie, Freiestrasse 3, CH-3012 Bern, Switzerland Indole and indoline-containing alkaloids have long been the subjects of intense interest because of their biological activities and because of the challenge posed by their complex structures. Intramolecular radical cyclisations onto azide groups to afford N-heterocycles have been pioneered by Kim et al [1] using tributyltin or tris(trimethylsilyl)silyl radicals and iodoalkyl azides. This strategy was then applied by Murphy for the synthesis of the tetracyclic core of Aspidosperma alkaloids involving iodoaryl azides as key intermediates [2]. Hereby we describe a novel approach to prepare indolines via a tandem radical addition/cyclisation using Et3B-air as radical initiator. Ortho-azidoallylbenzene 1 is thus converted to the desired N-heterocycle 2 by addition of an ester substituted radical followed by cyclisation in an open to air process. The corresponding indole 3 can then be obtained by simple oxidation.

[1] S. Kim, G. H. Joe, J. Y. Do, J. Am. Chem. Soc. 1994, 116 (12), 5521-5522. [2] (a) M. Kizil, J. A. Murphy, J. Chem. Soc., Chem. Commun. 1995, 1409. (b) M. Kizil, B. Patro, O. Callaghan, J. A. Murphy, M. B. Hursthouse, D. Hibbs, J. Org. Chem. 1999, 64 (21), 7856-7862. (c) B. Patro, J. A. Murphy, Org. Lett. 2000, 2 (23), 3599-3601. (d) S. Zhou, S. Bommezijn, J. A. Murphy, Org. Lett. 2002, 4 (3), 443-445.

38

HETEROCYCLIC CHEMISTRY TRIGGERED BY ONE-ELECTRON OXIDATION OF GUANINE IN DNA

Cynthia J. Burrows

Department of Chemistry, University of Utah, Salt Lake City, UT 84112-0850, USA

Oxidative stress is thought to underlie many disorders from cancer and aging to neurological and heart diseases. DNA bases, particularly guanine (G), are a key target of reactive oxygen species including 1O2, HO•, ROO•, HONOO– and CO3

•–, as well as transition metals that serve as one-electron oxidants. Depending on the context, nucleosides vs. single-stranded DNA vs. duplex DNA, guanine can be oxidized to 8-oxo-7,8-dihydroguanine (OG) or other heterocycles.

Our laboratory has investigated the facile further oxidation of OG that leads to a family of hydantoin structures, notably spiroiminodihydantoin (Sp) and guanidinohydantoin (Gh), in the presence of nucleophiles such as water or primary amines. Of current interest is the fate of the radical cation OG•+ as a function of its base-pairing and base-stacking contexts which are strong determinants of both the reactivity of OG•+ as well as the partitioning between Sp and Gh-type products. The influence of the helical superstructure of DNA on the purine radical cation chemistry will be discussed as well as mechanistic parallels to flavin redox chemistry.

NHN

NO

NH2NR

NHN

HN O

NH2NR

O

NuNH2+

NH

HN

NH2NR

O

Nu

Nu: G

-2e-

SpGh-2e-

NHN

HN

O

NH2NR

O

OG

+

39

EPR STUDY OF PARAMAGNETIC CENTRES IN GAMMA IRRADIATED HIGH SURFACE PRISTINE AND

ORGANICALLY MODIFIED PRECIPITATED AND MESOMORPHOUS SILICA: FREE VALENCE MIGRATION

AND REACTION MECHANISMS

A.Buttafava, D.Dondi, A.Faucitano1, S.Sozzani2, S.Bracco2

1Dipartimento di Chimica Generale-Universita’ di Pavia; V.le Taramelli 12, 27100 Pavia; 2Dipartimento di Scienza dei Materiali, Universita’ di Milano Bicocca

Silica is widely used as inorganic filler in elastomer based composites. Chemical modification of the silica are required aimed at improving the compatibility of silica with the rubber matrix and favouring the formation of rubber-silica chemical bonds during the vulcanization process. In many specific applications, vulcanization of elastomer-silica composites can be carried out at room temperature by using ionizing radiations. In this way initiating radical and ionic species are generated in the silica and rubber components with relative concentrations which are function of their respective electron densities. Since silica is 30-40% by weight in the mixture, the fraction of initiating centres generated by radiations within the silica particles is important and so are the inherent reactions which are expected to lead to silica-rubber chemical bonds. In this work, the nature and behaviour of the paramagnetic centres generated by gamma radiations in high surface precipitated silica zeosil 1165 (165m2/g) and mesomorphous silica (ca 1000 m2/g) have been investigated by EPR spectroscopy in the temperature range 77 K – 298 K. Two sets of experiments have been carried out using pristine silica and silica modified by impregnation with the polybutadiene olygomer PB-5000 ( Mn= 5000, 25% vinyl bond content). The modified silica can be considered a model for silica particles embedded in a polybutadiene rubber matrix, suited for giving information on silica-rubber reactions. The results are below summarized. The γ irradiation at 77 K of neat SiO2 samples of different morphology and surface area has led to the formation of a variety of reactive paramagnetic species among which H atoms and three Si and O centred species have been tentatively identified

40

with the help of DFT calculations. The paramagnetic centres were found to be highly thermally unstable, their decay being > 50% on warming at 117 K and > 95% at 177 K. Significant differences were observed for the two type of silica part of which are reckoned with impurities present in zeosyl samples. When silica samples impregnated with a 15-18% by weight of PB-5000 were used, the formation of Si bound polybutadiene radicals arising from the addition of the reactive centres at the PB vinyl double bond were detected after the irradiations, with coupling constants 3a(H) = 2.27 mT; 1a(H) =1.53 mT. Such species were indefinitely stable under vacuum at room temperature. The rationale of this result is that silica reactive centres arriving at the surface are captured by the PB substrate through the double bond addition reaction. This spin trapping takes place at the surface in competition with other decay coupling reactions. With Zeosyl 1165 (15-18% by weight of PB distributed over 165 m2/g surface) the onset temperature for this process is very low since the adduct radicals are seen to be the prominent species already after the irradiation at 77 K . Significantly different results were observed with mesomorphous silica which is characterized by a greater specific surface area (15-18 weight % of PB distributed over ca 1000 m2/g surface). The major species detected after the irradiation at 77 K were the silica centres and the reactions leading to the formation of the adduct radicals were observed only after warming at higher temperature ( > 130 K ). The different behaviour in explained in terms of lower surface concentration of the PB chains acting as spin trapping agents; this implies longer surface diffusion pathways for the reactive centres to meet and higher activation energies.

41

EFFICIENT RADICAL ADDITION REACTIONS VIA DESULFONYLATION CHLORINE-ATOM TRANSFER

Lidong Cao, Philippe Renaud

University of Berne, Department of Chemistry and Biochemsitry, Freiestrasse 3, CH-3012 Berne, Switzerland

In the past three decades, we have witnessed significant progress in radical reactions toward organic synthesis. Among various types of radical process, halogen atom-transfer radical addition reactions have received considerable addention because of their atom-economic nature and high efficiency.[1] Due to the strong C-Cl bond dissociation energy, Cl-atom transfer reactions are mostly limited to polychlorinated substrates and often require the use of transition metal catalysts.[1] Recently we found that desulfonylation chlorine-atom transfer radical addition reactions of ethyl chlorosulfonyl acetate 1 to various olefins can be efficiently initiated by lauroyl peroxide (DLP). This reactions shows good compatibility with a broad range of functional groups.

The reaction was successfully extended to weinreb amide 3.

[1] Byers, J. In Radicals in Organic Synthesis; Renaud, P., Sibi, M. B., Eds.;Wiley-

VCH: Weinheim, Germany, 2001; Vol. 1, p 72.

42

THE CHARGE TRANSFER BAND OF AN OXIDIZED WATSON-CRICK GUANOSINE-CYTIDINE COMPLEX

Andrea Peluso, Tonino Caruso, Amedeo Capobianco

Dipartimento di Chimica. Università di Salerno, Via Ponte don Melillo I-84084 Fisciano (SA) Italy

The charge transfer transition of the one-electron oxidized Watson-Crick complex between guanosine (Gs) and cytidine (Cd) derivatives has been observed for the first time in the near IR region, by using spectroelectrochemical measurements in chloroform and dichloromethane solution.[1] The CT band shifts at lower wavenumbers as expected upon methylation of cytosine, see Figure 1. This spectroscopic signal represents an important piece of information for a deeper understanding of long range hole transport in duplex DNA, because it provides the first experimental determination of the relative energy of the electronic state with the positive charge localized on the cytosine site, which in turns determines hole transfer rates via tunneling or superexchange mechanisms.[2-4]

Figure 1. NIR absorption spectra of the Gs:Cd (blue line) and Gs:5mCd (red line) complexes in CH2Cl2, recorded at 0.57 V vs Fc+/Fc.

[1] A. Capobianco, M. Carotenuto, T. Caruso, A. Peluso; Angew. Chem. Int. Ed. 2009, 48, 9526. [2] B. Giese, J. Amaudrut, A.-K. Kohler, M. Spormann, S. Wessely; Nature 2001, 412, 318. [3] S. Kanvah, J. Joseph, G. B. Schuster; Acc. Chem. Res. 2010, 43, 280. [4] J. C. Genereux, J. K. Barton; Chem. Rev. 2010, 110, 1642.

43

NITROXIDE-MEDIATED COPOLYMERIZATION: FROM THEORY AND KINETIC ANALYSIS TOWARD

NEW MATERIALS Bernadette Charleux,1 Ségolène Brusseau,1,2 Julien Nicolas,3 Charlotte Dire,2 Stéphanie Magnet,4 Laurence Couvreur5 1- Université Lyon 1, CPE Lyon, CNRS UMR 5265, Laboratoire de Chimie Catalyse Polymères et Procédés (C2P2), Equipe LCPP, 43 Bd du 11 novembre 1918, 69616 Villeurbanne, France 2- UPMC Univ. Paris 6 and CNRS UMR 7610, Laboratoire de Chimie des Polymères, 4 place Jussieu, 75252 Paris cedex 05, France 3- Univ. Paris-Sud, CNRS UMR CNRS 8612, Laboratoire de Physico-Chimie, Pharmacotechnie et Biopharmacie, Faculté de Pharmacie, 5 rue Jean-Baptiste Clément, 92296 Châtenay-Malabry, France 4- Arkema, Groupement de Recherches de Lacq, RN 117, B.P. n°34, 64170, Lacq, France 5- Arkema, 420, rue d'Estienne d'Orves, 92705, Colombes, France In nitroxide-mediated controlled radical polymerization (NMP), most of the kinetic studies were devoted to homopolymerization and block copolymer formation. In contrast, much less attention has been paid to the random copolymerization mechanism, and reports on the copolymerization kinetics are very scarce. We present here a detailed investigation on the controlled-radical copolymerization kinetics for systems based on reversible termination, in particular NMP (1). A theoretical expression for the average activation-deactivation equilibrium constant was developed, considering both the terminal model and the implicit penultimate unit effect model. It is possible to use this information to give a full theoretical description of the copolymerization kinetics based on the average propagation rate constant and the reversible termination of the propagating radicals. This theoretical description was applied to the copolymerization of methyl methacrylate (MMA) and styrene (Sty) (1-3) or acrylonitrile (4) in the presence of SG1 and helped the development of NMP of methacrylate monomers, which cannot be homopolymerized via NMP in a controlled manner, unless a specific nitroxide is synthesized (5). The presence of the purposely chosen comonomer in small amount leads to a drastic reduction of the irreversible termination reactions and favors the formation of stable alkoxyamines. This gives access to the synthesis of methacrylate-rich

44

macroinitiators and block copolymers (6-10) at low temperature, typically in the 70-90 °C range. As a particular application of the system, SG1-capped poly(sodium methacrylate)-rich macroinitiators were used to initiate the polymerization of methyl methacrylate in an aqueous emulsion system, in the presence of a small percentage of styrene. This led to the in situ formation of amphiphilic diblock copolymers and their simultaneous self-assembly into micelles, via a polymerization-induced micellization approach (8-10).

(1) B. Charleux, J. Nicolas, O. Guerret, Macromolecules 2005, 38, 5485. (2) J. Nicolas, C. Dire, L. Mueller, J. Belleney, B. Charleux, S. Marque, D. Bertin,

S. Magnet, L. Couvreur, Macromolecules 2006, 39, 8274. (3) J. Nicolas, L. Mueller, C. Dire, K. Matyjaszewski, B. Charleux, Macromolecules

2009, 42, 4470. (4) J. Nicolas, S. Brusseau, B. Charleux, J. Polym. Sci.: Part A: Polym. Chem.

2010, 48, 34. (5) Y. Guillaneuf, D. Gigmes, S.R.A. Marque, P. Astolfi, L. Greci, P. Tordo, D.

Bertin Macromolecules, 2007, 40, 3108. (6) C. Dire, B.Charleux, S. Magnet, L. Couvreur Macromolecules 2007, 40, 1897. (7) J. Nicolas, P. Couvreur, B. Charleux, Macromolecules 2008, 41, 3758. (8) S. Brusseau, J. Belleney, S. Magnet, L. Couvreur, B. Charleux, Polym. Chem.,

DOI:10.1039/B9PY00371A (9) C. Dire, S. Magnet, L. Couvreur, B. Charleux, Macromolecules 2009, 42, 95. (10) C. Dire, J. Nicolas, S. Brusseau, B. Charleux, S. Magnet, L. Couvreur, ACS

Symp. Series 2009, 1024, 303.

45

THE COPPER COORDINATION ENVIRONMENT IN ASYMMETRIC DIELS-ALDER REACTIONS CATALYZED BY

t-Bu-bis(OXAZOLINE) Cu(OTf)2 in CH2Cl2

Pawel Ciasa), V. Umamaheswaria), Andreas Pöpplb), Martin Kauppc), Carsten Bolm d) and Georg Gescheidta)

a) Institute of Physical and Theoretical Chemistry, Graz University of Technology, Technikerstrasse 4/I, 8010 Graz, Austria b) Faculty of Physics and Earthscience, University of Leipzig, Linnestrasse 5, 04103 Leipzig, Germany c) Institute of Inorganic Chemistry, University of Würzburg, Am Hubland, 97074 Würzburg, Germany d) Institute of Organic Chemistry, RWTH Aachen, Landoltweg 1, 52056 Aachen, Germany Ab initio density functional theory (DFT) calculations of electron paramagnetic resonance (EPR) parameters for the Cu(II) bis(oxazoline) complexes used in asymmetric Diels-Alder reactions were conducted. The reaction between ethyl glyoxylate and cyclohexadiene in the presence of [Cu(II) t-Bu-box]OTf2 as catalyst in CH2Cl2 was investigated. Geometry optimization, g tensors and hyperfine coupling constants for the paramagnetic Cu (II) center and 14N, 1H and 19F magnetic nuclei were calculated using the B3LYP method. Computational results were compared with experimental data obtained by means of EPR/ENDOR/HYSCORE spectroscopy. It is shown that the structure of primary [Cu(II) t-Bu-box] complex formed at the first stage of the catalytic process is strongly dependent on the counterions and solvent molecules. Calculations employing the model with an axial OTf- counterion and one solvent molecule added to the coordination sphere of the Cu (II) metal center give the best agreement with the experiment. The results demonstrate that DFT calculations combined with the EPR experiments can provide important information on the copper coordination environment within the Cu (II) catalyzed Diels-Alder reactions.

1. “Toward the Mechanism of Enantioselective Diels-Alder Reactions catalyzed by [Cu{(S,S)-t-Bu box}][OTf]2 Complexes: CW- and pulsed- EPR Studies.” V.Umamaheswari, Pawel Cias, Andreas Pöppl, Carsten Bolm and Georg Gescheidt, In preparation. 2. “Pentacoordination During Asymmetric (hetero) Diels-Alder Reactions using t-Bu-bis(oxazoline) Cu(OTf)2 in CH2Cl2.” V.Umamaheswari, Pawel Cias, Andreas Pöppl, Martin Kaupp and Georg Gescheidt, Submitted.

46

ASYMMETRIC RADICAL REACTIONS OF AXIALLY CHIRAL AMIDES

Dennis P. Curran

Department of Chemistry, University of Pittsburgh, Pittsburgh, Pennsylvania, 15260 USA Radical cyclizations (Bu3SnH, Et3B/air, rt) of racemic α-halo-ortho-alkenyl anilides provide 3,4-dihydroquinolin-2-ones in high yield. Cyclizations of enantioenriched precursors occur in similarly high yields and with transfer of axial chirality to the new stereocenter of the products with exceptionally high fidelity (often > 95%).

Single and tandem cyclizations of α-halo-ortho-alkenyl anilides bearing an additional substituent on the α-carbon occur with high chirality transfer and high diastereoselectivity. Straightforward models are proposed to interpret both the chirality transfer and diastereoselectivity aspects.

These first examples of an approach for axial chiral transfer from a reactive species in the amide to an acceptor suggest broad potential for extension both within and beyond radical reactions.

NR'

Me

Me

PMBO

I

NMe

R'H

HR

Me

PMBN

PMB

Me

Me

O

HR'

H

O

Bu3SnH

•

R

HR

high chirality transferand high diastereoselectivity

axially chiral single or tandem cyclizations1–4 new stereocenters

47

ONE ELECTRON OXIDATION OF FERROCENES BY SHORT LIVED AMINOXYL RADICALS

Massimo Bietti,b Claudio D’Alfonso,a Osvaldo Lanzalunga,a Andrea Lapi,a Michela Salamoneb

a Dipartimento di Chimica, Sapienza - Università di Roma, Piazzale A. Moro, 5 00185 Rome, Italy. b Dipartimento di Scienze e Tecnologie Chimiche, Università “Tor Vergata”, Via della Ricerca Scientifica, 00133 Rome Italy.

The reactivity of short lived aminoxyl radicals like phthalimide-N-oxyl radical (PINO) and benzotriazole-N-oxyl radical (BTNO) in hydrogen atom transfer (HAT) processes has been quite intensively investigated.1 Much less information is instead available about their involvement in electron transfer (ET) processes.2 For this reason we have investigated the one electron oxidation of ring substituted ferrocenes (FcX) to the corresponding ferrocenium ions by a series of aminoxyl radicals by laser flash photolysis in CH3CN. Aminoxyl radicals were generated by reaction of N-hydroxy derivatives with the cumyloxyl radical produced by 355 nm laser photolysis of dicumyl peroxide. The rate constants (kET) of the ET reactions have been determined by following the decay of the aminoxyl radicals or the buildup of

48

the ferrocenium ions as a function of the concentration of the electron donor. By applying the Marcus cross relation, from the kET and the self-exchange rate of the ferrocene/ferrocenium couple we have determined the self exchange rate of the the N-O•/N-O− couples. From the latter values it is possible to evaluate the effect of the structure of the substituents of the aminoxyl group on the intrinsic barrier and to identify the aminoxyl radicals which display better oxidizing properties.

1 F. Recupero, C. Punta, Chem. Rev., 107, 3800 (2007); C. Galli, P. Gentili, O. Lanzalunga, Angew. Chem. Int. Ed., 47, 4790 (2008). 2 E. Baciocchi, M. Bietti, M. F. Gerini, O. Lanzalunga, J. Org. Chem., 70, 5144 (2005); E. Baciocchi, M. Bietti, M. Di Fusco, O. Lanzalunga, J. Org. Chem., 72, 8748 (2007); E. Baciocchi, M. Bietti, M. Di Fusco, O. Lanzalunga, D. Raponi J. Org. Chem., 74, 5576 (2009); E. Baciocchi, M. Bietti, O. Lanzalunga, A. Lapi, D. Raponi J. Org. Chem., 75, 1378 (2010).

49

PREVENTION OF BIOLOGICAL DAMAGE INDUCED BY MYELOPEROXIDASE BY INHIBITION OF THE ENZYME

HALOGENATION CYCLE: NEW USES FOR OLD COMPOUNDS

Maud Koelsch1,2, Roger Mallak1,2, Garry G. Graham2, Tracey Kajer1, Marian K. Milligan2, Ly Q. Nguyen3, Dawn W. Newsham2, Anthony J. Kettle4, Kieran F. Scott5, John B. Ziegler3 David I. Pattison1, Shanlin Fu6, Clare L. Hawkins1, Martin D. Rees1* and Michael J. Davies1,7 1Heart Research Institute, Sydney, Australia; 2Dept of Pharmacology, Univ. of NSW and Dept, of Clinical Pharmacology, St Vincent’s Hospital, Sydney; 3School of Paediatrics, Univ. of NSW, Sydney; 4Free Radical Research Group, Dept. of Pathology, Univ. of Otago Christchurch, New Zealand; 5St Vincent’s Hospital Clinical School, Univ. of NSW, St Vincent’s Hospital, Sydney, Australia; 6Dept of Chemistry and Forensic Science, University of Technology, Sydney; 7Faculty of Medicine, Univ. of Sydney, Australia. Myeloperoxidase (MPO) is a cationic heme enzyme released by activated neutrophils, monocytes and some macrophages. MPO utilises H2O2 to generate potent oxidants including hypochlorous (HOCl), hypobromous (HOBr) and hypothiocyanous (HOSCN) acids from chloride, bromide and thiocyanate ions respectively. These oxidants, which are potent bactericidal agents, play a key role in the immune response to invading pathogens.

Inappropriate generation of these oxidants can however result in host tissue damage. This has been implicated in the damage observed in a range of human inflammatory pathologies (e.g. atherosclerosis, kidney disease, asthma, cystic fibrosis, arthritis, some cancers). Inhibition of oxidant formation, or scavenging of the resultant species, is therefore of potential therapeutic importance.

Kinetic studies indicate that HOCl and HOBr react rapidly with biological targets, making inhibition of oxidant formation a more realistic therapeutic target, than scavenging of these species once formed. We show here that the well-established, and well-tolerated, analgesic/antipyretic drug acetaminophen (paracetamol) inhibits HOCl production by isolated MPO in a concentration- and pH-dependent manner, consistent with competitive inhibition of HOCl formation by compound I of the enzyme. The IC50 value (83±6 µM) for inhibition of HOCl formation, at pH 7.4, in within the plasma

50

concentration range of the drug achieved at normal therapeutic doses (4 x 1 g per day, which yields a peak plasma concentration of 60-130 µM). Acetaminophen has also been shown to effectively inhibit neutrophil-derived HOCl production, without affecting superoxide radical generation. Studies with other MPO substrates indicates that acetaminophen also inhibits HOBr and HOSCN formation.

In each system acetaminophen is converted to dimeric and fluorescent products, the yield of which correlates inversely with the yield of oxidant formed. These products arise via one-electron oxidation of the phenol to the corresponding phenoxyl radical, by compound I or compound II of the enzyme, with subsequent oligomerization of the radicals. These species have been characterized by HPLC, LC/MS and NMR. The yield of the dimer provides a useful indicator of the effectiveness of this compound as an inhibitor of enzyme activity, with the dimer detected in human plasma. As oxidant production by MPO in vivo is likely to be localised to materials such as the heparan sulfate proteoglycans of extracellular matrix, as a result of MPO binding to these materials, we have also examined whether acetaminophen inhibits the formation of chloramines, induced by HOCl, on cell-derived matrix; acetaminophen retains its inhibitory activity in such systems. Other readily oxidised materials can also act as MPO inhibitors in an analogous manner.

Overall, these data indicate that acetaminophen may be an important modulator of MPO activity in vivo and prevent oxidant-mediated tissue damage.

51

EVIDENCE OF RADICAL CHAIN REACTIONS IN THE PHOTOREDUCTION OF 3-METHYL-QUINOXALIN-2-ONES

BY N-PHENYLGLYCINE

Julio R. De la Fuente1, Krzysztof Bobrowski2, Karina Corada1, Komal Dadlani1, Alvaro Cañete3, Christian Aliaga1.

1Fac. Cs. Qcas. Y Farm., Universidad de Chile. 2Institute of Nuclear Chemistry and Technology, Warsaw, Poland. 3Depto. Qca., Fac. Química, Pontificia Universidad Católica de Chile

In the last decades, many studies devoted to the pharmacological properties of quinoxalin-2-one derivatives have been published. Several of these works locate the quinoxalin-2-one moiety inside of protein pockets, suggesting interactions with potentially electron donor amino-acid residues. However, as long we have known, there are not reports concerning to the transient species generated by electron transfer from the amino-acids. In this work, we report on the photoreactions of some 7-substituted-3-methyl-quinoxalin-2-one derivatives with N-phenylglycine.

These compounds photoreact efficiently with the appearance of isosbestic points suggesting the formation of single photoproducts. The high quantum yields ranging from 0.1 to 2.5 measured for the derivatives, strongly suggesting radical chain reactions after a photoinduced electron transfer as the first step.

This assumption was tested by generating quinoxalin-2-ones radical-anions by laser flash photolysis in the presence of N-phenylglycine or DABCO and pulse radiolysis in Ar saturated acetonitrile. The transient spectra obtained in these experiments show nearly identical spectral features supporting the formation of the radical anion of quinoxalin-2-ones as the first step of photolysis.

Acknowledgments to FONDECYT grants N° 1070623 and 1100121 for financial support.