Dr Alison Paul - Research Profile

The group is interested in all aspect of soft matter; that is polymers, surfactants and particles, and the

aggregated structures they form in aqueous solutions. Of particular interest are the design, synthesis,

characterisation of polymeric drug delivery systems, and tailoring these to their potential applications as anti-

cancer therapeutics. This has recently broadened to include collaborative work with Drs. Platts and Willock to

develop molecular modelling techniques and evaluate their ability to predict behaviour by comparing with

experiments on model systems.

Research areas include:

Structure property relationships in surfactants

Polymeric drug delivery systems and imaging agents

Emulsions, microemulsions, gels and foams

Particle dispersions

Colloidal systems in unusual solvents

Custom synthesis of molecules for improved functionality and performance

Project Example

(AP1) The importance of molecular structure in optimising drug release

To facilitate the targeted delivery of highly cytotoxic anti-cancer drugs to tumours,

polymers can be used to exploit natural uptake and transport mechanisms within the

body providing enhanced circulation times, localisation to tumour sites, and controlled,

triggered or prolonged release of an encapsulated or covalently linked drug molecule.

The research project will involve the grafting of model drug molecules to clinically

relevant polymers, and the study of the subsequent release of the drug in solution

conditions designed to mimic that encountered in vivo, following the release

kinetics, and relating this to the structure of the polymer-drug conjugate. These

data will be compared with parallel experiments in which there is no covalent

linkage of the drug to the polymer, merely physical association of the drug due to

hydrophobic interactions. These experiments will entail the use of a range of

spectroscopic techniques which may include UV-VIS/fluorescence/circular

dichroism/FT-IR, light scattering and NMR methods.

Selected Publications

1) V Giménez, C James, A Armiñán, R Schweins, A Paul, M-J. Vicent, J. Cont. Rel., 2012, 159(2), 290-2)

2) A Paul, C James, R K Heenan, R Schweins, Biomacromolecules, 2010, 11(8), 1978-1982

3) P C Griffiths, I A Fallis, C James, I R Morgan, G Brett, R K Heenan, R Schweins, I Grillo and A Paul, Soft

Matter, 2010, 6, 1981-1989

4) MJ. Vicent, F Greco, RI. Nicholson, A Paul, PC Griffiths, R Duncan Angewandte Chemie Int. Ed. 2005, 44, 2-6

dose

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place

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Dr Angelo J. Amoroso - Research Profile

The main research themes of the Amoroso group are synthesis and applications of

transition metal complexes. Much of this research is involves synthetic chemistry

involving multi-step organic and inorganic syntheses. The materials are

subsequently analysed by a range of in-house techniques (NMR, FFC relaxometry

and electrochemistry) or by collaboration with other expert groups within the

department or abroad.

Research areas include:

Imaging (MRI/MRS/PET)

Ligand design

Project Example (with IAF)

We are interested in the development of super-paramagnetic iron oxide particles (SPIOs) which may be

developed for dual imaging by MRI and PET. Recently, we synthesised 5nm Fe3O4 particles coated in oleic acid.

These hydrophobic compounds may be solubilised in aqueous solution by a metallosurfactant. Unlike

reported larger SPIOs, which are effective T2 MRI contrast agents, this material is a T1 reagent (34.7 s-1 mg-1 ml

at 10MHz, 25⁰C equating to 4.46 s-1 mM-1 Fe; this appears quite modest until one considers the number of

iron atoms per cluster!) In addition, we were able to dope the Fe3O4 lattice with Ga(III), and observed that

using low doping levels (< 2% Ga(III) : Fe(III)) we still obtained an effective T1 contrast agent but the

relaxivity is somewhat reduced. While this work has been carried out using naturally occurring Ga(III), the PET

isotope, 68Ga(III) may be used to form a dual PET/MRI reagent.

Figures 1a: NMRD of 5mg ml-1

solution of Ni(II), Cu(II) and Zn(II) solubilised SPIO at 25⁰C; Figure 1b. TEM of Cu(II) metallosurfactant

solubilised SPIO; Figure 1c. TEM of Ga(III) doped SPIO.

Our current interests lie in the further functionalisation of the surfactants with specific targeting vectors such

that these imaging agents may be selectively delivered to sites/cells of interest. A typical project would

require the synthesis of Fe3O4 nanoparticles, the synthesis of a novel surfactant, and investigation of the

surfactants solubilising properties and the characterisation of the resulting material. Furthermore, we are

interested in investigating the inductive heating of these SPIOs with regard to pursuing dual imaging and

therapeutic agents (theranostics!).

Selected Publications: Knight JC, Prabaharan, R, Ward BD, Amoroso AJ, Edwards PG, Kariuki BM. A facile one-pot synthesis of

a new cryptand via a Pd(II)-catalysed carbonylation reaction. Dalton Trans. 2010: 10031-10033; Knight JC, Amoroso AJ, Edwards PG,

Prabaharan R, Singh N. The co-ordination chemistry of bis(2,2'-bipyrid-6'-yl) ketone with first row transition metals: The reversible

interconversion of a mononuclear complex and a dinuclear hemiketal containing species. Dalton Trans. 2010: 8925-8936;

Dr Rebecca Melen – Research Profile

Organic/Inorganic

Main Group chemistry has undergone a renaissance in recent years with the realisation that the

reactivity of main group elements often closely resembles that of transition metals, with recent studies

revealing that main group elements can act as homogenous catalysts for a range of transformations.

The development of main group alternatives to conventional transition metal catalysts is an emerging

‘hot topic’.

Research in the Melen group focuses on the use of main group Lewis acids in organic synthesis and

catalysis. The research programme includes:

• Main group catalyst design.

• Applications of main group Lewis acids in organic synthesis and catalytic processes.

• Mechanistic studies to determine reaction pathways.

Project Example

This research program aims to exploit main group Lewis acid compounds in a broad range of Lewis

acid catalysed transformations. This project combines synthetic chemistry, main group chemistry and

catalysis will involve the handling of air-sensitive compounds (using glovebox and Schlenk-line

techniques) and multi-nuclear NMR spectroscopy.

Depletion of the π-electron density in alkenes and alkynes, by Lewis-acid coordination (an

electrophile), is known to activate such groups to nucleophilic attack. In these reactions the Lewis acid

and Lewis base (nucleophile) undergo a 1,2-addition across the π-bond (Scheme 1). To date such

reactions have been typically catalysed by (precious) metals with few examples of main group

promoted transformations. This project will focus on the synthesis of appropriate starting materials

followed by their main group Lewis acid catalysed cyclisation. In all cases the mechanistic pathways

and the role of the Lewis acid will be explored by means of

experimental and theoretical methods. The atom-economic

nature of these cyclisations, coupled with access to a

diverse range of heterocycles has the potential for

substantial exploitation in the pharmaceutical industry, as

well as within the academic community and may change

current perceptions of catalytic processes in which the

chemical dominance of d-block metals is rarely questioned.

Scheme 1

References:

Chem. Commun., 2013, 50, 7243-7245, DOI: 10.1039/C4CC01370K; Chem. Commun., 2014, 50, 1161-1174,

DOI: 10.1039/C3CC48036D; J. Am. Chem. Soc., 2014, 136, 777-782, DOI: 10.1021/ja4110842; Chem. Eur. J.,

2013, 19, 11928-11938, DOI: 10.1002/chem.201301899

Dr Colan Hughes - Research Profile

Within the Harris group, my research focuses on the identification and characterization of new organic

solid materials. We use a range of different experimental methods to produce new forms which we then

subject to a variety of analysis techniques in order to determine their structures and properties. Past projects

have included studies of several amino acids (both biological1 and non-biological2), a number of phosphine

oxides3 and pharmaceuticals, including ibuprofen4. The new forms discovered include both polymorphs

(distinct solid forms with identical chemical compositions) and solvates (including hydrates). Knowledge about

polymorphism and solvate formation is crucial if compounds are to be used in industry or as pharmaceuticals.

Discovering New Crystal Forms

We use a combination of ex-situ and in-situ methods to discover new crystal forms. Our ex-situ

methods employ various crystallization techniques to produce samples which we then identify using solid-

state NMR and powder X-ray diffraction. Our in-situ methods involve performing the crystallization whilst

carrying out analysis at the same time. Of particular importance is the use of solid-state NMR to monitor in

situ the crystallization of organic compounds from solution. We have also used differential scanning

calorimetry and dynamic vapour sorption to discover new forms produced as a consequence of changes in

temperature and humidity. Such methods have allowed us to identify many new forms which we are now

endeavouring to identify and characterize, with the ultimate goal of determining their crystal structures.

Determining Crystal Structures

To find the crystal structure of a newly discovered form, we use the powder X-ray diffraction pattern,

which is characteristic of a particular crystal form. From this pattern, we can determine the crystal structure

using a “direct space” method, in which the diffraction pattern is simulated for different arrangements of the

molecules within the unit cell, to find the arrangement which best fits the experimental pattern. In particular,

our method uses a genetic algorithm during this process. We now have numerous compounds for which we

know new forms exist that are awaiting dedicated study.

Project Example

An example of the full process of discovery through to final structure determination is illustrated in the

figure. We crystallized L-phenylalanine from water and found that, under certain conditions, a form was

produced with a 13C NMR spectrum (a - red) which did not match the spectrum for the known form of

L-phenylalanine (black). This was subjected to

dynamic vapour sorption (b), which showed

that it was a hydrate. These results also

revealed the presence of a new anhydrous

polymorph at zero humidity. We acquired a

powder X-ray diffraction pattern (c) of this new

form and from this determined its crystal

structure (d). This structure allowed us to

understand the relationship between the

anhydrous form and the hydrate, with water

molecules easily entering into channels

(marked with blue circles) to form the hydrate.

1. E. Courvoisier, P. A. Williams, G. K. Lim, C. E. Hughes & K. D. M. Harris, Chem. Commun. 48, 2761-2763 (2012)

2. P. A. Williams, C. E. Hughes, G. K. Lim, B. M. Kariuki & K. D. M. Harris, Cryst. Growth Des. 12, 3104-3113 (2012)

3. C. E. Hughes, P. A. Williams, T. R. Peskett & K. D. M. Harris, J. Phys. Chem. Lett. 3, 3176-3181 (2012)

4. P. A. Williams, C. E. Hughes & K. D. M. Harris, Cryst. Growth Des. 12, 5839-5845 (2012)

Dr M. Sankar - Research Profile

The objective of Sankar’s research group is to develop heterogeneous catalysts for a green and sustainable

future. Key research areas include:

a. Valorisation of unconventional feedstock like CO2, biomass constituents and coal.

b. Development of heterogeneous catalysts for various transformations.

c. Synthesis and characterization of inorganic nanomaterials.

d. Mechanistic investigation of catalytic transformations using kinetic and in-situ spectroscopic methods.

Much of this research involves preparation and catalytic testing of inorganic materials in laboratory,

characterisation of these materials using advanced spectroscopic and microscopic techniques (X-ray

absorption spectroscopy, transmission electron microscopy) through collaborations with experts within the

UK or abroad and finally in-situ spectroscopic (DRIFT-IR, ATR-IR and XAS) studies aiming at unravelling the

mechanisms of catalytic reactions.

Project - Outline

Crude oil has been one of the common feedstock for producing fuels and chemicals (bulk and fine). This is a

fine resource and its availability is decreasing. There is a pressing need to find alternative feedstock to

produce fuels and chemicals which is renewable. Biomass has been identified as one of the viable

alternatives. Heterogeneous catalysts are expected to play a crucial role, similar to their role in petrochemical

conversions, in converting biomass based feedstock to chemicals and fuels. However the difference in the

chemical nature of the biomass based feedstock poses enormous challenge in designing catalysts for their

valorisation. Most of the projects will be aimed at addressing this challenge.

In a typical project, carefully designed inorganic materials (polyoxometalates, mixed-metal oxide

nanoparticles and supported metal nanoparticles/nanoalloys) will be synthesized, appropriately characterized

(XRD, X-ray absorption spectroscopy, electron microscopy) and tested for single step or multi step

transformation(s) (selective oxidation, hydrogenation, C-C coupling, hydrogen auto transfer,

transesterification) aiming at converting bio-derived (from cellulose, hemicellulose and lignin) substrates to

intermediates for making bulk or fine chemicals. A major part of the project will be dedicated to understand

the mechanism of the given catalytic transformation using kinetic and/or in-situ spectroscopic methodologies.

Finally a structure-activity relationship will be arrived and this information will be fed back to the catalyst

development phase of the project. Accordingly, the structural property(ies) of the catalytic material will be

altered by changing the synthesis strategy(ies) to arrive at an active, stable and selective catalyst for these

valorization transformations.

Selected Publications

1. M. Sankar et al., The benzaldehyde oxidation paradox explained by the interception of peroxy radical by

benzyl alcohol, Nature Communications 2014, 5, 3332.

2. M. Sankar et al., Designing Bimetallic Catalysts for a Green and Sustainable Future, ChemSocRev, 2012, 41,

8099.

3. M. Sankar et al., Synthesis of Stable Ligand-free Gold–Palladium Nanoparticles Using a Simple Excess

Anion Method, ACS Nano, 2012, 6, 6600.

4. M. Sankar et al., Effective catalytic system of zinc-substituted polyoxometalate for cycloaddition of CO2 to epoxides, Applied Catalysis A: General, 2004, 276, 217.

5. M. Sankar et al., Transesterification of Cyclic Carbonates to Dimethyl Carbonate Using Solid Oxide Catalyst at Ambient Conditions: Environmentally Benign Synthesis, ChemSusChem, 2010, 3, 575.

Dr David J. Miller - Research Profile

I am interested in the use of synthetic organic chemistry as applied to the solution

of biological problems. The understanding of how Nature’s macromolecules such as

proteins and DNA work and interact with one another can often be probed by use of

small organic molecules. Such molecules are often not available from the natural

pool and so the synthetic chemist is central to solving such problems. Similarly,

synthetic chemistry although well capable of preparing the most complex and

intricate of molecules can often only do so at great expense of time and resources.

Natural systems, if harnessed correctly offer the opportunity to construct molecules

of such complexity much more quickly and efficiently.

Research areas include:

Mechanistic enzymology

Synthetic Chemistry

Medicinal Chemistry

Chemical Biology

Example Projects

Terpenoids are a group of natural products that exhibit a breathtaking array of structure and biological

activity. For example artemisinin is one of the world’s leading anti-malarial drugs and the hydrocarbon

germacrene D is a volatile signaling molecule recognised by aphids as an alarm pheromone. We use terpene

synthases to convert unnatural substrate molecules into analogues of terpenoids and hence produce

bioactive compounds of complex molecular architecture in one step using the enzymes as a synthetic reagent.

Calpains are cysteine proteases that are activated by calcium ions. -Calpain is a member of this family of

enzymes that appears to have a key role in cell-membrane expansion and hence motility of white blood cells

(neutrophils). Development of potent and selective -calpain inhibitors may lead to drugs capable of

preventing neutrophils leaving the blood stream and so aid in the treatment of autoimmune diseases such as

osteoarthritis.

Selected Publications

A 1,6-ring closure mechanism for (+)-δ-cadinene synthase? Juan A. Faraldos, David J. Miller,

Veronica Gonzalez, Zulfa Yoosuf-Aly, Oscar Cascón, Amang Li, Rudolf K. Allemann, J. Am. Chem.

Soc. 2012, 134, 5900–5908.

Chemoenzymatic preparation of germacrene A and germacrene D analogues. Oscar Cascón,

Sabrina Touchet, David J. Miller, Verónica Gonzalez, Juan A. Faraldos and Rudolf K. Allemann,

Chem. Commun. 2012, 9702-9704.

Potent inhibition of Ca2+-dependent activation of calpain-1 by novel mercaptoacrylates Sarah E.

Adams, Christian Parr, David J. Miller, Rudolf K. Allemann, Maurice B. Hallett, Med. Chem.

Commun., 2012, 3, 566-570.

Calpain-1 inhibitors for selective treatment of rheumatoid arthritis- what is the future? David J. Miller,

Sarah E. Adams, Maurice B. Hallett , Rudolf K. Allemann, Future Med. Chem. 2013, accepted.

Dr E. Joel Loveridge – Research Profile

Work in the Loveridge group is mostly focused on the relationship between the structure, dynamics and function of enzymes, as a route to understanding and controlling nature’s chemistry. A particular theme is how binding partners (small molecules, nucleic acids, or other proteins) affect a protein’s dynamics and how the protein affects its binding partners. This work involves multidimensional NMR spectroscopy, mostly using Cardiff’s flagship 600 MHz Bruker NMR spectrometer equipped with a quadruple resonance QCI cryoprobe, in conjunction with other biophysical techniques. Higher-field NMR instruments at national centres (Birmingham, 800 MHz and 900 MHz; Mill Hill, 700 MHz and 800 MHz) are also routinely used.

Research Areas and Project Examples

Biomolecular structure, dynamics and interactions by NMR

NMR is a powerful tool for studying the structure, dynamics and interactions of biomacromolecules such as protein and DNA. These can be related to the biochemical function of the biomacromolecule. Projects include investigation of the structures of small proteins, the binding of metal complexes to amyloid-beta peptides (the causative agents of Alzheimer’s disease), and the binding of small molecules to DNA. Novel 31P-filtered NOESY techniques

15N and 13C edited 3D NOESY spectra of uniformly 15N, 13C labelled proteins are routinely used in biological chemistry to solve the structures of proteins. In these spectra, only NOEs to protons attached to either 15N and 13C are detected, simplifying the information available. Further simplification can be introduced by filtering the spectra: for example, a 13C-edited, 12C filtered NOESY experiment only detects NOEs from protons attached to 12C (unlabelled ligands) to protons attached to 13C (the labelled protein). For proteins whose binding partners contain phosphate groups, our QCI cryoprobe, which allows simultaneous pulsing on 1H, 13C, 15N and 31P, may dramatically simplify 15N and 13C edited NOESY spectra by using 31P filtering. Bulgecin biosynthesis

The bulgecins are a group of sulfated glycopeptides which, despite having no native antibacterial activity, greatly increase the potency of b-lactam antibiotics such as penicillins. Synthesis of these molecules is challenging, and the biosynthetic pathway is not known. Purification and isotopic labelling of the bulgecins, in conjunction with genetic techniques to detect and sequence the gene cluster, will allow the biosynthesis to be elucidated. Understanding the biosynthesis of the bulgecins will ultimately allow analogues to be made through mutasynthesis and mutagenesis techniques.

Selected Publications

1) Aliphatic 1H,

13C and

15N Chemical Shift Assignments of Dihydrofolate Reductase from the Psychropiezophile Moritella

profunda in Complex with NADP+ and Folate, Loveridge, E.J., Matthews, S.M., Williams, C., Whittaker, S.B.-M., Günther, U.L., Evans, R.M., Dawson, W.M., Crump, M.P. and Allemann, R.K., Biomol. NMR Assign. 2013, in press, DOI:10.1007/s12104-012-9378-x 2)

1H,

13C and

15N chemical shift assignments of unliganded Bcl-xL and its complex with a photoresponsive Bak-derived

peptide, Wysoczanski, P., Mart, R.J., Loveridge, E.J., Williams, C., Whittaker, S.B.-M., Crump, M.P. and Allemann, R.K., Biomol. NMR Assign. 2013, in press, DOI: 10.1007/s12104-012-9407-9. 3) NMR Solution Structure of a Photoswitchable Apoptosis Activating Bak Peptide Bound to Bcl-xL, Wysoczanski, P., Mart, R.J., Loveridge, E.J., Williams, C., Whittaker, S.B.-M., Crump, M.P. and Allemann, R.K., J. Am. Chem. Soc. 2012, 134(18), 7644-7647. 4) The Role of Large-Scale Motions in Catalysis by Dihydrofolate Reductase, Loveridge, E.J., Tey, L.-H., Behiry, E.M., Dawson, W.M., Evans, R.M., Whittaker, S.B.-M., Günther, U.L., Williams, C., Crump, M.P. and Allemann, R.K., J. Am. Chem. Soc. 2011, 133(50), 20561-20570. 5) Bulgecin A: A Novel Inhibitor of Binuclear Metallo-β-Lactamases, Simm, A.M., Loveridge, E.J., Crosby, J., Avison, M.B., Walsh, T.R. and Bennett, P.M., Biochem. J., 387, 585-590 (2005)

Dr Simon J.A. Pope - Research Profile

The research of the Pope group is dominated by the design, synthesis and application

of metal complexes to a variety of bio- and materials related disciplines. The research

involves multi-step organic and inorganic synthetic chemistry and the use of a variety

of spectroscopic techniques including time-resolved luminescence measurements.

Specific training will be given all key aspects of advanced synethesis and spectroscopy.

A number of international collaborations are in place to allow detailed assessments of

the various applications.

Research areas include:

ligand design, d- and f-metal coordination chemistry, and synthesis

photophysics

biomedical imaging using luminescence and MRI

luminescent sensors, DNA binding and therapeutics

solar cell devices and OLEDs

Project Example

Prototypical bimodal luminescence/MR agents

The use of d-metal complexes in clinical MRI imaging is currently restricted

to a singular example: this project will address the rational design of next

generation bimodal contrast agents based upon the development of new

anthraquinone MnII and CrIII coordination complexes. The complexes will be

highly coloured, fluorescent and biologically active (including DNA binding

behaviour). Through detailed electronic and paramagnetic spectroscopic

characterization, this study will also elucidate and optimize the key physical

parameters that determine the water relaxivity of such species and their

potential MRI capabilities. This multi-disciplined synthetic, spectroscopic

study will generate key information towards the development of

prototypical contrast agents based upon paramagnetic MnII and CrIII coordination complexes.

Selected Publications from previous undergraduate projects

1) ‘Using substituted cyvclometalated quinoxaline ligands to finely tune the luminescence properties of Iridium(III) complexes’ Inorg. Chem., 2013, 52, 448 2)‘Enhanced photooxidation sensitizers: the first examples of cyclometalated pyrene complexes of Iridium (III)’ Chem. Commun., 2012, 48, 10838 3)‘Tuning the electronics of phosphorescent, amide-functionalized, cyclometalated Ir(III) complexes: syntheses, structures, spectroscopy and theoretical studies’ Eur. J. Inorg. Chem., 2012, 4065. 4) ‘A one-step synthesis towards new ligands based on aryl-functionalized thiazolo[5,4-d]thiazole chromophores’ Tetrahedron Lett., 2010, 51, 5419 5) ‘Rhenium complexes of chromophore-appended dipicolylamine ligands: syntheses, spectroscopic properties, DNA binding and X-ray crystal structure’ New J. Chem., 2008, 32, 2140

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Prof Stan Golunski - Research Profile

All the projects in my research group are in the field of environmental catalysis. They

fall into two categories: (i) reducing the release of pollutants into the atmosphere, and

(ii) purification of water. Although the catalysts are mostly in the form of metal nano-

particles supported on metal oxides, materials such as zeolites and perovskites are

becoming increasingly important. In order to meet the challenge of designing catalysts

with high activity, selectivity and durability, we have to understand how the surface

and bulk structure of these materials influence the catalytic reaction mechanisms.

Research areas include:

On-board H2 generation by fuel reforming

Exhaust gas aftertreatment – destruction of CO, hydrocarbons, NOx and particulate released by petrol and diesel engines

Catalytic wet air oxidation

Control of greenhouse gas emissions

Understanding the interactions between the metal and the support in supported-metal catalysts

Project Example

Fine particles of soot are released by all forms of combustion engines. Currently the best control method

relies on trapping the soot, which can then react with NO2 from the exhaust gas. However, there is not always

enough NO2 available to remove all the soot and regenerate the trap. The ideal solution would be to make

use of the O2 that is present in the exhaust, often in high concentrations. This requires the development of a

catalyst that can be incorporated into a soot trap, where it will activate O2 and deliver reactive oxygen species

to the immobilised soot particles.

In this project, you will prepare alkali-metal catalysts,

which you will study for the combustion of carbon.

You will assess their performance by measuring the

onset temperature and the rate of combustion, using

thermal analysis. As emission control systems have to

be long-lasting (100,000 miles of driving), you will also

need to devise a test to rank the relative durability of

your catalysts.

Selected Publications

1) What is the point of on-board fuel reforming?, S Golunski, Energy Environ. Sci., 3 (2010) 1918

2) Raising the fuel heating value and recovering exhaust heat by on-board oxidative reforming of bioethanol,

P Leung, A Tsolakis, J Rodriguez-Fernandez, S Golunski, Energy Environ. Sci., 3 (2010) 780

3) Promotion of ceria catalysts by precious metals: Changes in nature of the interaction under reducing and

oxidizing conditions, N. Acerbi, S. Golunski, S. C. Tsang, H. Daly, C. Hardacre, R. Smith and P. Collier, J. Phys.

Chem. C, 116 (2012) 13569

Prof Peter J. Knowles - Research Profile

Computation — whether from first principles or through simple models — has in

recent years emerged as an equal partner of experiment in elucidating the structure,

energetics and reactivity of materials. Our research efforts are focused on applying

theory, through computation, to the prediction of the electronic structure of

molecules, which determine molecular properties and the forces between atoms. The

main research themes of the Knowles group are the development of new

approximations and computational methods for calculating molecular electronic

structure, the application of such methods to interesting chemical problems, and the

construction of conceptual models for chemical bonding.

Research in this field combines theory, software design and high-performance computing, and applies them

to give fundamental first-principles understanding of structure and reactivity. Undergraduate projects

typically concentrate on specific chemical applications, but can include other elements according to taste.

Project Examples

1. Ab-initio calculations on small molecule adsorption to Au clusters

Interest in the chemistry of Au was triggered by the discovery around 20 years ago that Au nano-particles are

capable of catalysing difficult oxidation reactions (for example, CO to CO2). In this project we will explore high

level ab initio calculations on small Au clusters with and without adsorbates such as CO and O2, and link to

more approximate computational methods that are applicable to larger clusters.

2. Concepts in chemical bonding

The curly arrow is ubiquitous in discussions of reaction mechanism, yet it is seldom defined precisely what is

meant by the arrow and its movement. In this project, we will develop a rigorous and quantitative analytical

recipe for taking the result of an electronic structure calculation and turning it into a three-dimensional

graphical object that represents the movement of a single important electron, or electron pair, through the

progress of a chemical reaction. The project is suitable for someone with some experience of computer

programming, and an interest in writing software.

Selected Publications

Robinson, J. B. and Knowles, P. J. 2013. Rigorously extensive orbital-invariant renormalized perturbative triples corrections from quasi-variational coupled cluster theory. Journal of Chemical Physics 138(7), article number: 074104. (10.1063/1.4791636)

Werner, H.-J. et al. 2012. Molpro: a general-purpose quantum chemistry program package. Wiley Interdisciplinary Reviews: Computational Molecular Science 2(2), pp. 242-253. (10.1002/wcms.82)

Cooper, B. and Knowles, P. J. 2010. Benchmark studies of variational, unitary and extended coupled cluster methods. The Journal of Chemical Physics 133(23), article number: 234102. (10.1063/1.3520564 )

Izsák, R. et al. 2009. High accuracy ab initio calculations on reactions of OH with 1-alkenes. The case of propene. Journal of Chemical Theory and Computation 5(9), pp. 2313-2321. (10.1021/ct900133v)

Dr James E. Redman - Research Profile

The main research theme of the Redman group is the chemistry and interactions of

peptides and nucleic acids. Much of this research involves synthetic organic chemistry,

particularly preparation of amino acids, peptides and nucleic acid analogues. The

compounds are analysed by a range of techniques, in particular HPLC and mass

spectrometry. Biological properties of the molecules are investigated in collaboration

with colleagues at the School of Medicine.

Research areas include:

Unnatural amino acid synthesis

Immunology of cyclic peptides

Software for sequencing of cyclic peptides by mass spectrometry

Nucleic acid secondary structure

Manipulating gene expression with oligonucleotide analogues

Project Example

Many natural products consist of polyamides of proteinogenic and non-proteinogenic amino acids linked in

cyclic chains. These compounds often have useful activities, such as antibacterial or anti-cancer properties,

which makes desirable their isolation from natural sources and preparation by chemical synthesis. Cyclic

peptides can also be designed to act as small molecule mimics of much larger folded proteins. Cyclisation of

the peptide backbone has the advantage of increasing stability towards proteases which can enhance peptide

half life in vivo. We are currently investigating cyclic peptides for stimulating immune responses of T-cells as a

potential immunotherapy of cancer. This project involves the design, synthesis and analysis of cyclic peptides

which are then tested for their immunological activity in collaboration with groups at the School of Medicine.

Mass spectrometry is used for peptide characterisation and is a valuable

tool for structure determination of small quantities of peptide. The

analytical chemistry aspects of the project involve determination of the

amino acid sequence of cyclic peptides by mass spectrometry using

fragmentation by collision induced dissociation (CID). We have previously

found that computer software can assist in deducing sequences from

fragmentation mass spectra of simple head-to-tail cyclised peptides.

Before we can apply these techniques to more complex peptides, we

need to establish the rules which govern how these compounds fragment

during mass spectrometry. To address this issue, we are also synthesising

and recording CID mass spectra of a variety of cyclic peptides with a view towards making predictions about

fragmentation pathways. There will be the opportunity for synthetic peptide chemistry, hands-on mass

spectrometry, and development/testing of software for computer analysis of spectra.

Selected Publications

1) The human hyaluronan synthase 2 gene and its natural antisense RNA exhibit coordinated expression in the renal proximal tubular epithelial cell, J. Biol. Chem. 2011, 286, 19523-19532. 2) A conserved stem loop motif in the 5'untranslated region regulates Transforming Growth Factor-ß1 translation, PLoS ONE 2010, 5(8), e12283-e12283. 3) Automated mass spectrometric sequence determination of cyclic peptide library members, J. Comb. Chem. 2003, 5, 33-40.

Dr Ian A. Fallis - Research Profile

The main research themes of the Fallis group are synthesis, reactivity and applications

of transition metal complexes. Much of this research is involves synthetic chemistry

involving multi-step organic and inorganic syntheses. The materials are subsequently

analysed by a range of in-house techniques (NMR, ENDOR, X-ray, electrochemistry) or

by collaboration with other expert groups within the department, UK or abroad.

Research areas include:

Sensors

Bioinorganic chemistry and medicine

Biomedical imaging

Ligand chemistry and chirality

Surfactants and liquid crystals

Project Example

Green plants and cyanobacteria use water as a source of reducing power in carbohydrate synthesis with the

concomitant evolution of molecular oxygen. This process of water oxidation is governed by the oxygen

evolving centre of photosystem II (PSII - OEC) which contains a penta-nuclear Mn4Ca cluster as the

catalytically active species. The oxidation of water by PSII is arguably the most important of all chemical

transformations, as it generates the current oxygen in the atmosphere, upon which virtually all life on earth

depends.

This synthetic project is directed towards

the design of ligands and metal complexes

which will mimic the structure and

reactivity of the PSII - OEC. These studies

will not only elucidate the fundamental

processes at work in PSII but also provide

insight into the operation of what is in

essence a high potential biological

oxidation catalyst. The work will involve

the development of multi-step ligand

syntheses and methodologies, and the

use of a range of spectroscopic and

structural techniques including, x-ray

crystallography, NMR, EPR and

electrochemistry.

Selected Publications

1) Structure and pulsed EPR characterization of N,N '-bis(5-tert-butylsalicylidene)-1,2-cyclohexanediamino-vanadium(IV) oxide and its adducts with propylene oxide, Dalton Transactions, 2011, 40, 7454-7462. 2) Evaluation of Electronics, Electrostatics and Hydrogen Bond Cooperativity in the Binding of Cyanide and Fluoride by Lewis Acidic Ferrocenylboranes, Inorg. Chem., 2010, 49, 157-173. 3). Structure-property relationships in metallosurfactants, Soft Matter, 2010, 6, 1981-1989. 4) Locus-Specific Microemulsion Catalysts for Sulfur Mustard (HD) Chemical Warfare Agent Decontamination, J. Am. Chem, Soc., 2009, 131, 9746-9755.

Ca

O

Mn

OO

Mn

O

MnMn

w

W

D170

X

E333

P680*

Tyrz

X

Q165

XR357

D342

H337

E354

H332

E198

13.6 Å

5.1 Å

reaction site

D = asparatate

E = glutamate

H = histidine

Q = glutamic acid

R = arginine

e-

H+

Ca

O

Mn

OO

MnO

MnMnw

W

D170

O

E333

H2O

D342

H337

E354

H332

E198

Ca

O

Mn

OO

MnO

MnMnw

W

D170

O

E333

HO

D342

H337

E354

H332

E198

Ca

O

Mn

OO

MnO

MnMnw

W

D170

O

E333

OH

D342

H337

E354

H332

E198

Tyrz

Tyrz

Tyrz

H2O

TyrzH

Prof Gerald Richter - Research Profile

The main research focus of the Richter group is on light-dependent enzymes and proteins. This includes work on the reaction mechanism as well as applications. Possible projects range from organic synthesis to molecular biology.

Research areas include:

• Mechanism of DNA photolyase: Repair of UV lesions in DNA

• Mechanism of phototropins: Blue-light perception in plants

• Synthesis of organic compounds using multiple enzymes

• Synthesis of flavin analogues

Flavoproteins are ubiquitous proteins and are able to catalyse a wealth of reactions from electron transfer (redox reactions, radical formation) to adduct formation. The relevant biologically active cofactors are FAD and FMN. Most of these reactions are only possible within the protein environment which can for example stabilise a flavin radical for days whereas the free species in aqueous solution has a lifetime of μs. In different flavoproteins the chemically reactive moiety is the isoalloxazine ring system of flavin. The protein environment is therefore directing which reaction will occur. Research in my laboratory is aimed at the elucidation of reaction mechanisms of enzymes, with a particular emphasis on light-dependent flavoproteins. We are investigating two different families of these proteins: the DNA photolyase family and the phototropin protein group.

We could show that the primary process in blue light perception in plants is the formation of a covalent adduct between phototropin (LOV domains) and the cofactor FMN. This process is reversible and all our experimental data are consistent with a radical pair mechanism.

Replacement of the native cofactor FMN with the analogue 5-deazaFMN resulted in a photosensitive protein that forms a stable photoproduct upon irradiation with blue light. The dark state can be regenerated by irradiation with UV light. We have thus created a photo-active nanoswitch. We are using different spectroscopic techniques in order to address the problem from as many directions as possible. Currently we are using NMR, EPR, ENDOR, Raman, and infrared spectroscopy. We have shown that reaction mechanisms could only be addressed reasonably using these techniques by labelling of proteins and co-factors with stable isotopes.

Selected Publications

1) Eisenreich, W. et al. 2009. Tryptophan 13C nuclear-spin polarization generated by intraprotein electron transfer in a LOV2 domain of the blue-light receptor phototropin. Biochemical Society Transactions 37(2), pp. 382-386. 2) Richter, G. et al. 2005. Photochemically induced dynamic nuclear polarization in a C450A mutant of the LOV2 domain of the Avena sativa blue-light receptor phototropin. Journal of the American Chemical Society 127(49), pp. 17245-17252. 3 Kelly, M. et al. 2001. The NMR structure of the 47-kDa dimeric enzyme 3,4-dihydroxy-2-butanone-4-phosphate synthase and ligand binding studies reveal the location of the active site. Proceedings of the National Academy of Sciences 98(23), pp. 13025-13030. 4) Salomon, M. et al. 2001. An optomechanical transducer in the blue light receptor phototropin from Avena sativa. Proceedings of the National Academy of Sciences 98(22), pp. 12357-12361.

Dr David J. Willock - Research Profile

The Willock research group use computational chemistry to investigate surfaces and

molecules with a focus on heterogeneous catalysis. We use quantum chemistry to

understand surface reactivity calculating reaction energetics and the properties of key

intermediates for comparison with experiment. We also develop atomistic codes for

sampling of the conformational space of polymeric materials. This work is often carried

out in collaboration with experimental colleagues so that the computational results can

be validated against measurements on real systems.

Current research areas include:

Oxidation reactions catalysed by supported metal nanoparticles.

The interaction of metal nanoparticles with oxide supports and with carbon.

The vibrational spectra of molecular adsorbates on surfaces.

Alkane oxidation using metal-oxo containing surfaces.

The role of water in metal-complex catalysed reactions.

Project Example

Hydrogen transport on alloy catalysts.

Precious metal catalysts can be used for a

variety of hydrogenation reactions. The ease of

hydrogenation and the reaction conditions that

can be used depend critically on the diffusion

of the hydrogen over the surface and through

the bulk of the catalyst particles. We have

found already that for pure Pt, Pd and Ni the

barriers to diffusion are very different as shown

below, leading to a higher mobility of hydrogen on .Pt than on Ni or Pd. In recent years Au/Pd has been shown

to have some interesting properties in catalysis involving hydrogenation and this project we will explore the

influence of alloying on the mobility of surface adsorbed H.

We will use quantum chemistry calculations to examine the diffusion of hydrogen over a variety of metal

surfaces and through the bulk, including alloy systems.

Selected Publications

1. “Direct Catalytic Conversion of Methane to Methanol in Aqueous Medium by using Copper-Promoted Fe-ZSM-5”, C. Hammond, M. M. Forde, M. H. Ab Rahim, A. Thetford, Q. He, R. L. Jenkins, N. Dimitratos, J. A. Lopez-Sanchez, N. F. Dummer, D. M. Murphy, A. F. Carley, S. H. Taylor, D. J. Willock, E. E. Stangland, J. Kang, H. Hagen, C. J. Kiely and G. J. Hutchings, Angew. Chem., 51, 5129, (2012). DOI: 10.1002/anie.201108706

2. “Bespoke Force Field for Simulating the Molecular Dynamics of Porous Organic Cages”, D. Holden, K. E. Jelfs, A. I. Cooper, A. Trewin, and D. J. Willock, J. Phys. Chem. C, 116 (31), 16639–16651, (2012). DOI: 10.1021/jp305129w

3. “Enantioselective hydrogenation of α-ketoesters: An in situ surface-enhanced Raman spectroscopy (SERS) study.” R. J. Taylor, Y. X. Jiang, N. V. Rees, G. A. Attard, E. L. Jeffery, and D. J. Willock, J. Phys. Chem. C, 115, 21363-21372, (2011).

4. “A periodic DFT study of the activation of O2 by Au nanoparticles on α-Fe2O3.”, K. L. Howard and D. J. Willock, Faraday Disc.152 (1), 135-151, (2011).

0

10

20

30

40

50

60

fcc hcp fcc

Rel

ati

ve

En

ergy (

kJ m

ol

-1)

Nickel

Paladium

Platinum

Prof Damien M. Murphy - Research Profile

The research interests of the EPR/ENDOR Spectroscopy Research Group, led by Prof. Murphy, focus on a number of topics including:

Structure and reactivity of paramagnetic centres and reactive oxygen species in heterogeneous photocatalysis, including the nature and reactivity of surface trapped electrons on oxides.

Structure - function relationships and mechanistic pathways in homogeneous catalysis, as probed by multi-frequency ENDOR spectroscopy.

Role of paramagnetic redox centres in selective oligomerisation catalysis. Orientation selective ENDOR for structure determination in frozen solution

The Group utilises both continuous wave (CW) and Pulsed EPR/ENDOR techniques at both X- and Q-band frequencies, and have strong collaborations with all colleagues in Inorganic Chemistry. Collaborative synthetic/spectroscopic projects are therefore common. For further information see: http://www.cardiff.ac.uk/chemy/epr/

PhD project example – Low valent Cr(I) centres in oligomerisation catalysis

Paramagnetic chromium (I) complexes are important precatalysts for olefin oligomerization. Despite this

importance, very little is known about the structure of the catalysts under real conditions, whilst a

mechanistic understanding of the reaction has remained speculative. In 2011 we reported on the intra-

molecular formation of a Cr(I) bis-arene complex following the addition of triethylaluminum to a

dichloromethane solution of a Cr(I) bis(diarylphosphino)amine complex, highlighting the structural complexity

of the complexes formed in-situ; Organometallics, 2011, 30, 4505; 2013, 32, 1924. Following on from this

work we have now identified the intermediate species involved in the transformation of the parent Cr(I)

complexes into the stable [Cr(1-bis-6-arene)]+ complex, by careful control of the reaction conditions. To

continue this work, in this project we will

prepare a series of PNP ligands to stabilise

the paramagnetic Cr(I) centres, and

subsequently study how the distribution and

stability of the Cr(I) intermediates are

modulated depending on the ligand

structure. Eventually we hope to use high

pressures as a thermodynamic controlling

factor to stabilise other reaction

intermediates of relevance to this important

catalytic reaction.

Recent Publications

1) The benzaldehyde Oxidation Paradox Explained by the Interception of Peroxy Radical by Benzyl Alcohol, M. Sankar, E. Nowicka,

E. Carter, D. M. Murphy,

D.W. Knight, D. Bethell, G.J. Hutchings, Nature Comms, 2014, NCOMMS-13-05032B.

2) A Neutral, Monomeric Germanium(I) Radical, W.D. Woodul, E. Carter, R. Müller, A.F. Richards, A. Stasch, M. Kaupp, D.M. Murphy, M. Driess, C. Jones, J. Am. Chem. Soc., 2011, 133, 10074. 3) The importance of iron(I) in catalytic C-C bond-formation, C.J. Adams, R.B. Bedford, E. Carter, N.J. Gower, M.F. Haddow, J.N. Harvey, M. Huwe, M.A. Cartes, S.M. Mansell, D.M. Murphy, C. Mendoza, E.C. Neeve, J. Nunn, J. Am. Chem. Soc., 2011, 134, 10333. 4) Three-coordinate Nickel(I) complexes stabilised by six, seven and eight membered ring N-hetereocyclic carbenes: synthesis, EPR/DFT studies and catalytic activity, M.J. Page, W.Y. Lu, R. Poulten, E. Carter, A.G. Algarra, B.M. Kariuki, S.A. Macgregor, M.F. Mahon, K.J. Cavell, D.M. Murphy, M.K. Whittlesey, Chem. Eur. J., 2013, 19, 2158. 5) An ENDOR and DFT analysis of hindered methyl group rotations in frozen solutions of bis(acetylacetonato)-copper(II). K. Sharples, E. Carter, C.E. Hughes, K.D.M. Harris, J.A. Platts, D.M. Murphy, Phys.Chem.Chem.Phys., 2013, 15, 15214.

Dr. Benjamin D. Ward - Research Profile

The main research themes of the Ward group are synthesis, reactivity and

catalytic applications of s- and f-block metal complexes. This research involves

synthetic chemistry involving multi-step organic and air sensitive organometallic

syntheses using Schlenk line and glove box techniques. The materials are

subsequently analysed primarily by spectroscopy (NMR, IR) and X-ray

crystallography. We have a number of collaborations within Cardiff and the UK in

order to probe the applications of the metal catalysts in a range of important

chemical processes.

Research areas include:

Asymmetric catalysis

Reaction mechanisms

Environmentally benign catalysis

Organometallic and coordination chemistry

Project Example

Many chemical processes rely heavily on precious metals, such as rhodium, platinum, and palladium. The cost

of these metals, and the cost of recycling, is significant. One alternative approach is to use the Alkaline Earth

(AE) metals, such as magnesium and calcium; these metals are non-toxic, environmentally benign, and since

they are highly abundant elements they are inexpensive (Ca is the 5th most abundant element in the Earth’s

crust). Whilst there have been a number of examples of the AE metals in catalysis in recent years, asymmetric

derivatives, that are able to prepare chiral materials with high enantiomeric excesses, are hard to achieve.

The principal reason for this is their complex coordination chemistry, in which ligands undergo rapid ligand

exchange, thereby affording non-chiral species.

Our principal aim is to prepare chiral ligands

that are able to suppress these equilibria,

affording well-defined complexes, and

subsequently using these complexes in a range

of catalytic transformations. Our recent work in

the area has managed to achieve 50% ee in the

calcium-catalysed hydroamination of

aminoalkenes (see Scheme). Such levels of

selectivity are unprecedented in calcium

chemistry, and the project will utilise new

ligand architectures to further improve the

selectivity in this, and related, catalytic

reactions.

Selected Publications

1) Calcium amido-bisoxazoline complexes in asymmetric hydroamination/cyclisation catalysis, Chem. Commun., 2012, 48, 11790. 2) Chiral calcium catalysts for asymmetric hydroamination/cyclisation, Chem. Commun., 2011, 47, 5449. 3) Modular ligand variation in calcium bisimidazoline complexes: effects on ligand redistribution and hydroamination catalysis, Dalton Trans., 2011, 40, 7693.

HN

R1

R1

NH2

R1 R1

nn

N

N

N

N

iPr

iPr

CaN(SiMe3)2

py

R

R

N

N

N

N

iPr

iPr

Ca

R

R

+

N

N

N

N

iPr

iPr

R

R

2

5

[Ca{N(SiMe3)2}2(py)2]

Ligand redistribution equilibria

Hydroamination catalysis

Dr B. Kariuki - Research Profile

The main research theme is materials chemistry. Most elements and compounds exist

in the solid state at ambient conditions and, with application in areas as diverse as

electronics and pharmaceutical industries, the importance of understanding the solid state is

clear. Solid state chemistry is the study of the synthesis, structure, properties and

applications of solids. In addition to the inherent properties of the isolated atoms, ions or

molecules, the effect of confinement in the solid can be significant and can result in

behaviour substantially different from that observed for isolated atoms, molecules or ions.

Project example

Crystallization is a process of spontaneous gathering of atoms, molecules or ions without an

external force. This self-assembly process often occurs with inclusion of solvent molecules in

solids of many organic salts. It is not unusual for the solvent to be lost on thermal treatment

of the material. An example with water as the solvent is:

The desolvation process can display complex behaviour.

Additionally, re-solvation of the product material may occur in some cases if it is exposed to

the solvent.

The aim of the project would be to understand the process by carrying out a systematic

investigation. The materials would be generated, crystallized and characterized as part of the

study which would include the use of thermal and diffraction techniques.

Dr Stuart Taylor

I have been active in the field of heterogeneous catalysis research since starting my

PhD on selective methane oxidation in 1991. I have worked on many different areas,

but most extensively in the field of oxidation catalysis, focusing on both selective and

total oxidation. My research receives funding from UK funding bodies and also

extensively from a number of industrial companies; examples include Johnson

Matthey, Sabic, Jaguar Land Rover, General Motors, Scania, National Nuclear

Laboratories, Molecular Products, Dow Chemicals and ExxonMobil. I also collaborate

widely with UK and international institutions, and examples are Universities of

Valencia and Alicante (Spain), Carbon Research Institute (Zaragoza, Spain), Lehigh

University (PA, USA) and Victoria University, New Zealand).

My research group is interested in discovering, developing and understanding catalysts for a range of

reactions and applications. There is also a focus on probing new methods for preparing catalysts, as well as

characterizing them using a wide variety of solid state techniques, such as adsorption methods, powder X-ray

diffraction, laser Raman spectroscopy, electron microscopy and temperature programmed techniques.

Catalyst performance is evaluated using laboratory scale microreactors for gas phase reactions and autoclaves

and stirred reactors for liquid phase reactions. Some more specific areas of research interest are:

Investigation of metal oxide and precious-metal-based catalysts for the oxidative destruction of Volatile Organic Compounds (VOCs) for environmental protection.

Mixed metal oxide and supported metal catalysts for low temperature carbon monoxide oxidation for life-support and environmental applications.

Development of new catalysts for selective oxidation reactions, focussing on utilisation of short-chain alkanes, oxygenated compounds, aromatics and bio-renewables.

Improved methodologies for preparing catalysts, including novel processes such as supercritical methods for preparing high activity and greener catalysts.

Previous projects

Some examples of previous project titles are:

The oxidative destruction of volatile organic compounds using supported precious metal catalysts modified by the addition of vanadium oxide.

Preparation, characterisation and activity studies of copper manganese oxide catalysts prepared by solid state grinding for ambient temperature carbon monoxide oxidation.

A surface science and catalytic investigation of bimetallic systems for hydrogenation reactions.

The selective oxidation of propane to propene using supported vanadium oxide catalysts.

Some relevant papers

Gold-palladium core-shell nanocrystals with size and shape control optimized for catalytic performance, Angewandte

Cheemie (Int. Ed.), 52 (5), (2013), 1477-1480. DOI: 10.1002/anie.201207824

Oxidation of methane to methanol with hydrogen peroxide using supported gold-palladium alloy nanoparticles,

Angewandte Chemie (Int. Ed.), 52 (4), (2013), 1280-1284. DOI: 10.1002/anie.201207717

Influence of the preparation method on the activity of ceria zirconia mixed oxides for naphthalene total oxidation, Appl.

Catal. B, 132-133, (2013), 98-106. DOI: 10.1016/j.apcatb.2012.11.036

Total oxidation of naphthalene using palladium nanoparticles supported on BETA, ZSM-5, SAPO-5 and alumina

powders, Appl. Catal. B., 129, (2013), 98-105. DOI: 10.1016/j.apcatb.2012.08.041

Dr David J. Willock - Research Profile

The Willock research group use computational chemistry to investigate surfaces and

molecules with a focus on heterogeneous catalysis. We use quantum chemistry to

understand surface reactivity calculating reaction energetics and the properties of key

intermediates for comparison with experiment. We also develop atomistic codes for

sampling of the conformational space of polymeric materials. This work is often carried

out in collaboration with experimental colleagues so that the computational results can

be validated against measurements on real systems.

Current research areas include:

Oxidation reactions catalysed by supported metal nanoparticles.

The interaction of metal nanoparticles with oxide supports and with carbon.

The vibrational spectra of molecular adsorbates on surfaces.

Alkane oxidation using metal-oxo containing surfaces.

The role of water in metal-complex catalysed reactions.

Project Example

Hydrogen transport on alloy catalysts.

Precious metal catalysts can be used for a

variety of hydrogenation reactions. The ease of

hydrogenation and the reaction conditions that

can be used depend critically on the diffusion

of the hydrogen over the surface and through

the bulk of the catalyst particles. We have

found already that for pure Pt, Pd and Ni the

barriers to diffusion are very different as shown

below, leading to a higher mobility of hydrogen on .Pt than on Ni or Pd. In recent years Au/Pd has been shown

to have some interesting properties in catalysis involving hydrogenation and this project we will explore the

influence of alloying on the mobility of surface adsorbed H.

We will use quantum chemistry calculations to examine the diffusion of hydrogen over a variety of metal

surfaces and through the bulk, including alloy systems.

Selected Publications

1. “Direct Catalytic Conversion of Methane to Methanol in Aqueous Medium by using Copper-Promoted Fe-ZSM-5”, C. Hammond, M. M. Forde, M. H. Ab Rahim, A. Thetford, Q. He, R. L. Jenkins, N. Dimitratos, J. A. Lopez-Sanchez, N. F. Dummer, D. M. Murphy, A. F. Carley, S. H. Taylor, D. J. Willock, E. E. Stangland, J. Kang, H. Hagen, C. J. Kiely and G. J. Hutchings, Angew. Chem., 51, 5129, (2012). DOI: 10.1002/anie.201108706

2. “Bespoke Force Field for Simulating the Molecular Dynamics of Porous Organic Cages”, D. Holden, K. E. Jelfs, A. I. Cooper, A. Trewin, and D. J. Willock, J. Phys. Chem. C, 116 (31), 16639–16651, (2012). DOI: 10.1021/jp305129w

3. “Enantioselective hydrogenation of α-ketoesters: An in situ surface-enhanced Raman spectroscopy (SERS) study.” R. J. Taylor, Y. X. Jiang, N. V. Rees, G. A. Attard, E. L. Jeffery, and D. J. Willock, J. Phys. Chem. C, 115, 21363-21372, (2011).

4. “A periodic DFT study of the activation of O2 by Au nanoparticles on α-Fe2O3.”, K. L. Howard and D. J. Willock, Faraday Disc.152 (1), 135-151, (2011).

0

10

20

30

40

50

60

fcc hcp fcc

Rel

ati

ve

En

ergy (

kJ m

ol

-1)

Nickel

Paladium

Platinum

Professor Graham J. Hutchings FRS - Research Profile

The main research themes of the Hutchings group are the design of

heterogeneous catalysts. The research involves the preparation of novel materials

and their characterisation using a range of techniques including in situ

spectroscopic methods such as DRIFTS, laser Raman and UV-visible spectroscopy

and in situ diffraction methods. There is particular interest in catalysis by gold

which we have designed catalysts for the direct synthesis of hydrogen peroxide,

the oxidation of alcohols and hydrocarbons. We are now designing a new range of

catalysts where we are replacing gold with other less expensive metals as part of a

European Research Council funded project on After the Goldrush

Research areas include:

Selective oxidation

Catalyst design

Catalysis by Gold

Project Example

We have recently shown that AuPt nanoparticles

supported on MgO are very effective catalysts for

the oxidation of glycerol, a biorenewable feedstock,

to glycerate and tartrate (see Brett et al. Angew.

Chem. Int. Ed. 2011, 50, 10136). We consider that

an electronic promotion of the palladium is induced

by alloying with gold (see figure for XEDS mapping

and microscopy of the nanoparticles). We would

now be interested in exploring catalysts where we

can exploit two design strategies (a) replace the Au

with a less expensive metal to determine if improved performance can be obtained, (b) add a third reactive

metal to see if further synergistic effects can be observed. The project will involve the preparation of novel

supported metal catalysts, investigation of their catalytic activity for oxidation reactions and characterisation

of active materials.

Selected Publications

1. Andrew A. Herzing, Christopher J. Kiely, Albert F. Carley, Philip Landon and Graham J. Hutchings “Identification of Active Gold Nanoclusters on Iron Oxide Supports for CO Oxidation” Science 321 (2008) 1331-1335.

2. J. K. Edwards, B. Solsona, Edwin Ntainjua N, A. F. Carley, A. A. Herzing, C. J. Kiely and G. J. Hutchings, “Switching-off Hydrogen Peroxide Hydrogenation in the Direct Synthesis Process” Science, 323 (2009) 1037-1041.

3. L. Kesavan, R. Tiruvalam, M. H. Ab Rahim, M. I. bin Saiman, D. I. Enache, R. L. Jenkins, N. Dimitratos, J. A. Lopez-Sanchez, S. H. Taylor, D. W. Knight, C. J. Kiely, G. J. Hutchings “Solvent-Free Oxidation of Primary Carbon-Hydrogen Bonds in Toluene Using Au-Pd Alloy Nanoparticles” Science, 331 (2011) 195-199.

4. J.A. Lopez-Sanchez, N. Dimitratos, S. White, G. Brett, L. Kesavan, P. Miedziak, R. Tiruvalam, R.L. Jenkins, A.F. Carley, D. Knight, C.J. Kiely and G.J. Hutchings, “Facile removal of stabilizer-ligands from supported gold nanoparticles” Nature Chemistry 3 (2011) 551-556

Dr James E. Redman - Research Profile

The main research theme of the Redman group is the chemistry and interactions of

peptides and nucleic acids. Much of this research involves synthetic organic chemistry,

particularly preparation of amino acids, peptides and nucleic acid analogues. The

compounds are analysed by a range of techniques, in particular HPLC and mass

spectrometry. Biological properties of the molecules are investigated in collaboration

with colleagues at the School of Medicine.

Research areas include:

Unnatural amino acid synthesis

Immunology of cyclic peptides

Software for sequencing of cyclic peptides by mass spectrometry

Nucleic acid secondary structure

Manipulating gene expression with oligonucleotide analogues

Project Example

Many natural products consist of polyamides of proteinogenic and non-proteinogenic amino acids linked in

cyclic chains. These compounds often have useful activities, such as antibacterial or anti-cancer properties,

which makes desirable their isolation from natural sources and preparation by chemical synthesis. Cyclic

peptides can also be designed to act as small molecule mimics of much larger folded proteins. Cyclisation of

the peptide backbone has the advantage of increasing stability towards proteases which can enhance peptide

half life in vivo. We are currently investigating cyclic peptides for stimulating immune responses of T-cells as a

potential immunotherapy of cancer. This project involves the design, synthesis and analysis of cyclic peptides

which are then tested for their immunological activity in collaboration with groups at the School of Medicine.

Mass spectrometry is used for peptide characterisation and is a valuable

tool for structure determination of small quantities of peptide. The

analytical chemistry aspects of the project involve determination of the

amino acid sequence of cyclic peptides by mass spectrometry using

fragmentation by collision induced dissociation (CID). We have previously

found that computer software can assist in deducing sequences from

fragmentation mass spectra of simple head-to-tail cyclised peptides.

Before we can apply these techniques to more complex peptides, we

need to establish the rules which govern how these compounds fragment

during mass spectrometry. To address this issue, we are also synthesising

and recording CID mass spectra of a variety of cyclic peptides with a view towards making predictions about

fragmentation pathways. There will be the opportunity for synthetic peptide chemistry, hands-on mass

spectrometry, and development/testing of software for computer analysis of spectra.

Selected Publications

1) The human hyaluronan synthase 2 gene and its natural antisense RNA exhibit coordinated expression in the renal proximal tubular epithelial cell, J. Biol. Chem. 2011, 286, 19523-19532. 2) A conserved stem loop motif in the 5'untranslated region regulates Transforming Growth Factor-ß1 translation, PLoS ONE 2010, 5(8), e12283-e12283. 3) Automated mass spectrometric sequence determination of cyclic peptide library members, J. Comb. Chem. 2003, 5, 33-40.

Dr Jamie Platts - Research Profile

We employ theoretical and computational methods to study and predict a range of chemically and biologically

important phenomena, with particular emphasis on intermolecular interactions, such as hydrogen bonding,

pi-stacking and molecular recognition, and the properties of inorganic complexes from the p-, d- and f-blocks,

including their bonding and spectroscopy as well as their interactions with biomolecules.

In one strand of research, we use DFT and ab initio methods to explore how hydrogen bonding and pi-stacking

affect how transition-metal complexes bind to DNA. Cisplatin is the archetypal metal-based anti-cancer drug,

but its severe toxicity and limited efficacy mean that alternatives are urgently required. In order to

complement experimental data, theoretical predictions can give valuable insight into the mode of action and

potential activity on varying ligand and/or metal. One such example that we are working on is “kiteplatin”,

currently in clinical trials for treatment of colorectal cancer.

A second area of interest lies in the electronics of inorganic complexes, much of which is in collaboration with

synthetic chemists both in Cardiff and elsewhere. Together with scientists in Australia and Denmark, we

recently demonstrated the first experimental evidence for a “non-nuclear attractor”, i.e. a maximum in the

electron density not associated with a nucleus, in a Mg—Mg bond. We have also used DFT to examine the

extent of back-bonding and the role of d- and f- electrons in several uranium complexes, and from this explain

their observed spectroscopic properties.

Project Example

Theoretical methods, especially DFT, are widely used

to predict and interpret spectroscopic results.

Molecular orbital data is invaluable in understanding

and assigning fluorescence and phosphorescence

spectra, for instance in the metal-to-ligand charge

transfer (MLCT) phosphorescent rhenium complexes

shown on the right. Similarly, DFT calculated spin

densities and hyperfine coupling constants can give

important insight into EPR spectra. Complexes of d-

and f-block metals show interesting spectroscopic

behaviour, but also present challenges to modelling

methods due to the importance of electron correlation

and relativity. This project will involve calibration and

prediction of such spectroscopic properties using

modern theoretical methods, working in close

cooperation with experimentalists wherever possible.

Selected Publications

1) The effect of intermolecular hydrogen bonding on the planarity of amides. PCCP, 2012, 14, 11944 2) Revisiting [PtCl2(cis-1,4-DACH)]: an underestimated antitumor drug with potential application to the treatment of oxaliplatin-refractory colorectal cancer. J.Med. Chem. 2012, 55, 7182 3) Density functional theory studies of interactions of ruthenium arene complexes with base pair steps. J. Phys. Chem. A, 2011, 115, 11293 4) First experimental characterization of a non-nuclear attractor in a dimeric magnesium(I) compound. J. Phys. Chem. A, 2011, 115, 194

Dr Jonathan K. Bartley - Research Profile

Research is focussed on exploring new methods for synthesising materials for use as

catalysts and supports that will give improved catalyst performance. A number of

methodologies for preparing catalysts have been developed such as:

supercritical antisolvent precipitation

the use of structure directing agents

high temperature - high pressure synthesis

nanorods and nanotubes as catalysts and supports

Project Example

The methodology for preparing mixed metal oxide catalysts has changed little over the last 60 years. Typically

metal nitrate solutions are co-precipitated using a base to yield precursors that are then calcined to form the

oxide catalysts. Due to the crude preparation methodology, catalysts prepared in this way are a complex

mixture of mixed oxide and single oxide phases. This leads to a waste of the active metals which can be

present either as inactive phases or as unselective phases which reduce the activity and selectivity of the final

catalyst.

Recently we have found that

Fe2(MnO4)3 nanoparticles supported

on MnO3 nanorods show better

performance as catalysts for

methanol oxidation to formaldehyde

that bulk Fe2(MnO4)3 catalysts (Fig.

1). This synthetic project is directed

towards the design and synthesis of

high surface area MnO3 that could be

an improved support for the

Fe2(MnO4)3 nanoparticles. The

project will involve the synthesis of

MoO3 and supported Fe2(MnO4)3/MoO3 catalysts, characterisation using a range of techniques available in

the CCI including, X-ray diffraction, Raman spectroscopy and SEM.

Selected Publications

1. Fe2(MoO4)3/MoO3 nano-structured catalysts for the oxidation of methanol to formaldehyde. J. Catal., 2012, 296, 56-64. (10.1016/j.jcat.2012.09.001)

2. Oxidation of benzyl alcohol by using gold nanoparticles supported on ceria foam. ChemSusChem, 2012, 5, 125-131. (10.1002/cssc.201100374)

3. Synthesis of high surface area CuMn2O4 by supercritical anti-solvent precipitation for the oxidation of CO at ambient temperature. Catal. Sci. & Tech., 2011, 1, 740-746. (10.1039/c1cy00064k)

4. The synthesis of highly crystalline vanadium phosphate catalysts using a diblock copolymer as a structure directing agent. Catal. Today, 2010, 157, 211-216. (10.1016/j.cattod.2010.03.013)

5. Recovery and reuse of nanoparticles by tuning solvent quality. ChemSusChem 2010 3 339-341. 10.1002/cssc.200900280)

[010]

[001]

c d

b a

001

010

e

Figure 1 MoO3 nanorods (a-d) and Fe2(MnO4)3 nanoparticles supported on the

MnO3 nanorods (e).

Dr Mark C. Elliott - Research Profile

Research in my group focuses on the development of new reactions for organic

synthesis, and the applications of these reactions to important biologically-active

targets. This research is supported by computational investigations to gain a deeper

understanding of the factors affecting reactivity and selectivity.

Research areas include:

Total synthesis (alkaloids, terpenes)

Development of new synthetic methodology

Computational chemistry

Research Areas

Two targets that have been the focus of

attention over the last few years are

lycoposerramine A and

7-deacetoxyalcyonin acetate. Our

approach to these targets is

summarised in the reaction

schemes. Both of these targets

have been the subject of

undergraduate research projects,

and significant discoveries have

been made during the course

of these projects.

One other area that we have

become involved in over the

last few years is

rearrangement reactions of organoboron compounds. As a result of a computational and

experimental investigation, we now understand the factors that allow high yields of products in

which tertiary alkyl groups migrate from boron to carbon, and are applying these reactions to

important new systems.

Selected Publications

Factors Affecting Migration of Tertiary Alkyl Groups in Reactions of Alkylboronic Esters with Bromomethyllithium Mark C. El l iott, Keith Smith, D. Heulyn Jones, Ajaz Hussain and Basi l A. Saleh J. Org. Chem., 2013, in press. doi:10.1021/jo4000459

Studies towards the total synthesis of lycoposerramine A. Synthesis of a model for the tetracyclic core M. C. Elliott and J. S. Paine Org. Biomol. Chem., 2009, 7, 3455. doi:10.1039/b909860g

An improved protocol for the Prins desymmetrisation of cyclohexa-1,4-dienes M. Butters, M. C. Elliott, J. Hill-Cousins, J. S. Paine and A. W. J. Westwood Tetrahedron Lett., 2008, 49, 4446. doi:10.1016/j.tetlet.2008.05.022

NO

NH

H

Me H

NMe

OTBSO

Cl

OTBS

Lycoposerramine A

NO

O

H

Me

OOTBS

7 steps

1 2

O

H

H

H

HCHO

HO

OH

TfOH (1 equiv.)

CH2Cl2, 0 - 25 °C89%

O

O

OOAc

H

HHO

7-deacetoxyalcyonin acetate

H

H

3 4

BR3CO

O BrCH2Li

various R andboronic esters

calculated transition states forbromomethylation and alkyl group

migration

R3CCH2OH[O]

improved yields

Dr Niklaas (Niek) J. Buurma - Research Profile

The main research themes of the Buurma group are reactions and interactions in aqueous

solutions. Much of this research involves synthetic chemistry involving multi-step organic

syntheses. The physical properties of the synthesised compounds are subsequently analysed

by a range of techniques. The focus of MChem projects can be either on the synthetic studies

or on the interaction/kinetic studies, but a successful project involves both aspects. As a

result, both synthetic dexterity and some mathematical ability (for data analysis) are crucial.

Research areas include:

Genosensors

Nucleic acid templated functional assemblies

Biophysical chemistry of small-molecule DNA interactions

Kinetics of racemisation of drug-like molecules

Palladium-catalysed reactions in aqueous solutions

Green chemistry through immobilised catalyst systems

Project Examples

Twinned optoelectronically-active DNA binders – ligand synthesis and interaction studies

DNA-binding cationic conjugated oligoheteroaromatics are of interest because their optoelectronic properties

change upon binding to DNA. Changes in spectroscopic and electronic properties of DNA binders are exploited

for two main technologies, viz. the development of electronic biosensors and the directed assembly of

electronically interesting nanostructures or nanobioelectronics. We synthesise redox-active compounds with

affinity for DNA using approaches including click chemistry, Pd-catalysed coupling reactions (Stille, Suzuki and

Sonogashira), as well as SN2 reactions. Physical studies with these ligand(s) quantify the interactions of the

new compounds with DNA and involve UV-visible, fluorescence, circular dichroism, and NMR spectroscopy

but more specialised techniques such as viscometry and isothermal titration calorimetry.

Racemisation of drug-like molecules

The kinetics of racemisation of substituted hydantoins are studied using circular dichroism and 1H-NMR

spectroscopy. Primary kinetic isotope effects, solvent kinetic isotope effects, isotopic labeling, the observed

general-base catalysis, Brønsted , Hammett plots, and kinetic modelling all suggest a stepwise mechanism

(SE1) as the most likely mechanistic route for base-catalysed racemisation of hydantoins. A recent paper

reporting on racemisation of a thiohydantoin, however, suggests that racemisation of thiohydantoins occurs

via an SE2 mechanism. We study whether the racemisation reactions of hydantoins and thiohydantoins follow

different mechanisms. This project involves the synthesis of substituted thiohydantoins and kinetic studies of

racemisation under varying conditions to establish racemisation mechanism(s).

Catalysis by palladium complexes and palladium nanoparticles

We study the kinetics and mechanism of the oxidative homocoupling reaction of aryl boronic acids as

catalysed by palladium complexes, by palladium nanoparticles and by immobilised palladium nanoparticles.

This process is of significant interest because it is analogous to the rate-determining step of the Suzuki cross-

coupling. This project involves the synthesis of new ligands for palladium and the synthesis of palladium

complexes as well as detailed kinetic studies (and of course a combination of the two). Alternatively, the

project involves kinetic studies using (immobilized) nanoparticles.

Dr Nancy Dervisi - Research Profile

Dr Dervisi’s research interests include the synthesis and coordination of functionalised ligands, such as NHC carbenes and phosphines and their catalytic, biological and optoelectronic applications. Much of our ligand design takes inspiration from the hydrocarbon chiral pool (sugars in particular). Such ligands offer the advantages of predetermined backbone chirality with often rigid structure and high degree of peripheral functionalisation. As an example, chelating diphosphine and N-heterocyclic carbene ligands have been derived from D-isomannide, a mannitol dehydration product. In this case we have taken advantage of the predetermined backbone chirality of a naturally occurring polyol (mannitol) and have prepared highly functional ligands with multiple chiral centres in just two synthetic steps. Another area of interest is the study of the electronic and steric properties of large ring (>5) N-heterocyclic carbene ligands. In this area we have contributed in the understanding of the factors affecting the stability of such NHC ligands and their applications in catalysis. Research areas include:

Catalytic applications of transition metals

Bioinorganic chemistry and medicinal applications

Ligand / Coordination chemistry and chirality

Reactive microemulsions

Project Example

Large ring N-heterocyclic Carbene Ligands The strong π-donating properties of NHCs make them effective stabilizing ligands in organometallic chemistry as well as important ligands in some forms of catalysis. To date research has largely focused on five-membered ring carbenes. Previously, we reported the first examples of novel, saturated, seven-membered diazepanylidene carbenes and their transition metal complexes.

A simple, versatile and high yielding route from amidines has also been devised, leading to 6- and 7- membered carbenes (and saturated 5-membered NHCs). This methodology allows the isolation of a range of carbenes, and hence metal complexes, which are not available via other routes. Six-, and in particular, seven-membered ring carbenes are intriguing from several points of view. They are very basic, somewhat more basic than the saturated 5-membered-ring carbenes, which are in turn more basic than their unsaturated counterparts. Structurally they also offer some unique features. The saturated seven-membered ring is highly twisted providing an opportunity to design new chiral ligand systems and the large heterocyclic rings lead to large N-CNHC-N angles.

Selected Publications 1. P. Marshall, R. L. Jenkins, W. Clegg, R. W. Harrington, S. K. Callear, S. J. Coles, I. A. Fallis and A. Dervisi, Dalton Transactions, 2012, 12839-12846. DOI: 10.1039/C2DT31740K 2. Phillips, N.; Rowles, J.; Kelly, M. J.; Riddlestone, I.; Rees, N. H.; Dervisi, A.; Fallis, I. A.; Aldridge, S., Organometallics 2012, 31 (23), 8075-8078. DOI: 10.1021/om301060h 3. C. Carcedo, J. C. Knight, S. J. A. Pope, I. A. Fallis, A. Dervisi, Organometallics, 2011, 2533-2562. DOI: 10.1021/om200125w 4. Dervisi, A.; Fallis, I. A.; Cavell, K. J.; Iglesias, M.; Beetstra, D.; Stasch, A.; Horton, P.; Coles, S.; Hursthouse, M., Organometallics, 2007, 26 (19), 4800 - 4809.

Professor Kenneth D.M. Harris – Research Profile

The research of the Harris group is focused on understanding fundamentals of solid

materials, with particular interest in organic crystalline solids. Several experimental

techniques are employed in our research, particularly X-ray diffraction and solid-state NMR

spectroscopy. The overall aim is to achieve fundamental insights on challenging problems

within solid-state chemistry.

Research areas of current interest include:

• Fundamentals of crystallization processes and polymorphism.

• New strategies and techniques for structure determination from powder X-ray diffraction data.

• Structural design of organic materials ("crystal engineering").

• Solid-state chemistry of pharmaceutical materials.

• Aperiodic materials (incommensurate materials and quasicrystals).

• Solid-state NMR spectroscopy, particularly the development of new techniques for in-situ studies.

• Chemistry and physics of solid inclusion compounds: incommensurate structures, dynamic properties, crystal growth processes, transport processes.

• Molecular motion, disorder and phase transitions in crystalline solids.

Project Example

Although the phenomenon of polymorphism in crystalline solids (i.e. the existence of materials with identical

chemical composition but different crystal structures) was first discussed in the scientific literature 180 years

ago, recent years have seen an immense upsurge of activity in this field,

driven both by fundamental scientific curiosity and by industrial

necessity. Several directions of our research are targeted towards

obtaining a deeper fundamental understanding of the phenomenon of

polymorphism and its practical implications, including the discovery of

new polymorphic systems, structural rationalization (in many cases

exploiting state-of-the-art methodology for carrying out structure

determination using powder X-ray diffraction), establishing correlations

between crystal structures of polymorphs and their physical properties,

and exploring the evolution of different polymorphic forms in situ

during crystallization processes. Typical undergraduate research projects may encompass research within any

of these themes.

Selected Publications

Publications involving undergraduate project students are marked *

1)* The crystal structure of L-arginine, E. Courvoisier, P.A. Williams, G.K. Lim, C.E. Hughes, K.D.M. Harris, Chemical Communications, 2012, 48, 2761–2763. 2) Discovery of a new system exhibiting abundant polymorphism: m-aminobenzoic acid, P.A. Williams, C.E. Hughes, G.K. Lim, B.M. Kariuki, K.D.M. Harris, Crystal Growth and Design, 2012, 12, 3104–3113. 3)* Exploiting in situ solid-state NMR for the discovery of new polymorphs during crystallization processes, C.E. Hughes, P.A. Williams, T.R. Peskett, K.D.M. Harris, Journal of Physical Chemistry Letters, 2012, 3, 3176–3181. 4) X-ray birefringence: a new strategy for determining molecular orientation in materials, B.A. Palmer, G.R. Edwards-Gau, A. Morte-Ródenas, B.M. Kariuki, G.K. Lim, K.D.M. Harris, I.P Dolbnya, S.P. Collins, Journal of Physical Chemistry Letters, 2012, 3, 3216–3222. 5) New insights into the preparation of the low-melting polymorph of racemic ibuprofen, P.A. Williams, C.E. Hughes, K.D.M. Harris, Crystal Growth and Design, 2012, 12, 5839–5845.

13C Chemical Shift / ppm

Total time =

16.8 hours

Time

In-Situ Solid-State13C NMR of Glycine

Crystallizationα polymorph

β polymorph

13C Chemical Shift / ppm

Total time =

16.8 hours

Time

In-Situ Solid-State13C NMR of Glycine

Crystallizationα polymorph

β polymorph

Dr Paul D. Newman - Research Profile

Dr Newman’s main research interests are in the area of homogeneous catalysis and

the coordination chemistry of asymmetric ligands. The research is heavily synthetic

and involves aspects of organic, inorganic and organometallic syntheses. Typical

analysis is by a range of spectroscopies including NMR, EPR (collaborative), and IR in

combination with X-ray crystallography and electrochemistry. New metal complexes

are assessed as catalysts in a range of useful organic transformations such as

hydrogenation, oxidation and hydrosilylation.

Research areas include:

Chiral-at-metal complexes

Bicyclic and macrocyclic ligands

Asymmetric oxidation

Rigid phosphine ligands

Project Example

Asymmetric catalysis is extremely important for the production of high-end chemicals. A large number of such

processes are metal-catalysed and the stereoselection is controlled by supporting ligands with a predefined

chiral element(s). Even though many of these systems have proved highly successful, there is an inherent

limitation in that the source of the ligand chirality is often remote from the metal. This is something of a

paradox as, while the supporting ligand is crucial, the metal is the catalytic hub that assembles substrates,

enables reaction and expels product. Fundamentally, a catalyst containing a chiral metal centre should exert

greater stereocontrol than one containing solely chiral ligands. Such chiral-at-metal complexes are known for

non-labile metals and some of these have been employed in asymmetric synthesis.1,2 However,

configurationally labile systems, e.g. closed-shell metals (Zn2+, Cu+), are less well explored as their inherent

lability can frustrate their isolation as single enantiomers/diastereomers and subsequent catalytic application.

We have been developing multidentate ligands with rigid chiral frameworks that can ‘lock-out’ certain

configurations upon coordination thus enabling the preparation of chiral-at-metal complexes.3 Examples of

such systems are shown in the figure.

This synthetic project is directed towards the further development of

these ligands and metal complexes with emphasis on Cu(I) and Zn(II) to

establish the limits of the stereocontrol. These studies will be supported

by catalytic investigations on hydrosilylation of ketones, lactide

polymerisation and asymmetric CO2/epoxide copolymerisation. The work

will involve ligand syntheses, complexation chemistry and the use of a

range of spectroscopic and structural techniques including, x-ray

crystallography, NMR spectroscopy, and electrochemistry.

Selected Publications

1) E. B. Bauer, Chem Soc. Rev., 2012, 41, 3153. 2) a) S. J. Meek, R. V. O’Brien,, J. Llaveria, R. R. Schrock, A. H. Hoveyda, Nature, 2011, 471, 461; b) S. J. Malcolson, S. J. Meek, E. S. Sattely, R. R. Schrock, A. H. Hoyveda, Nature, 2008, 456, 933; c) Y.-J. Lee, R. R. Schrock, A. H. Hoveyda, J. Am. Chem. Soc., 2009, 131, 10652. 3) P. D. Newman, K. J. Cavell, B. M. Kariuki, Chem. Commun., 2012, 48, 6511.

N N

NZ

..

Z = PR2, NR

2, SR, OR, OH

MeLZ

Dr Philip R. Davies - Research Profile

Our interests cover a wide variety of topics linked by the role of surface chemistry: these

include catalysis, films and coatings and classic surface science. We use a variety of methods

ranging from x-ray photoelectron spectroscopy, scanning tunnelling microscopy and LEED for

studying structure, intermediates and products on well characterised single crystal surfaces

in ultra high vacuum equipment to infrared microscopy and atomic force microscopy for

studying film morphology and chemistry under ambient conditions.

Project Example

The role of functional groups in stabilising gold nanoparticles on graphite

This project is part of an EPSRC grant investigating gold/carbon catalysts for the hydrochlorination of ethyne,

a topic in which Cardiff has a world leading position. The

EPSRC project is for model studies of gold on graphite

under ultra high vacuum (UHV) conditions and using

theory. What we want to achieve in this project is to

bridge the gap between this idealised research and the

practical catalyst. The latter consists of gold nanoparticles

on activated carbon; crucially we know that catalysts

based on graphite are unsuccessful but we don’t know

why! A key difference between the two types of catalyst is

the presence of functional groups such as hydroxides on

carbon which are absent on graphite, but how these

influence the nature of the adsorbed gold has not been investigated. The UHV model studies must use

graphite so bridging the gap between ideal and real catalysts is critically important – and a great opportunity

for us! If we can discover the difference between the model and actual catalysts we will gain a fundamental

insight into the catalysts mode of action. The project will explore the formation of gold nanoparticles on

graphite surfaces treated to create specific functional groups mimicking those present on the real catalyst.

The effects on the resulting gold particles will be explored using cutting edge surface analysis techniques

including AFM, XPS and SEM.

Selected Publications

1. An investigation into the chemistry of electrodeposited lanthanum hydroxide-polyethylenimine films, Thin Solid Films. 520 (2012) 2735–2738.

2. The oxidation of Fe(111) Surface Science. 605 (2011) 1754–1762.

3. New insights into the mechanism of photocatalytic reforming on Pd/TiO2, J.Catal. B. Environ. 107 (2011) 205–209.

4. Sustainable H2 gas production by photocatalysis, J. Photochem. & Photobiol. A. 216 (2010) 115–118.

5. Transient Oxygen States in Catalysis: Ammonia Oxidation at Ag(111) Langmuir. 26 (2010) 16221–16225.

6. Influence of Thermal Treatment on Nanostructured Gold Model Catalysts Langmuir. 26 (2010) 16261–16266.

XPS and AFM of gold nanoparticles on a

graphite surface

Dr Alberto Roldan – Research Profile

Dr Roldan's research is aimed at understanding the dynamism of surface processes that underlie phenomena such

as catalysis and corrosion. His group employs a range of computational tools to model physical and chemical

properties of these systems regarding the experimental synthetic and working conditions. The use of micro-kinetic

models allows them to approach specific conditions including the optimization of the catalyst structure and

working conditions improving yields, selectivity of the catalyst as well as controlling sintering effects.

The main interest for our work is the optimization of catalytic processes on heterogeneous systems, extended

surfaces or nanoparticles. Particularly we are interested in:

1. Capture and utilization of CO2

2. Renewable and clean energy

3. Material design including atomic control manufacturing.

4. Sintering and coalescence of nanostructures

In the quest to gain understanding of these aspects, we evaluate the balance between kinetics and thermodynamics

relaying on computational technologies to simulate the reactor conditions. These have demonstrably led to

reductions in development costs, shorter time-to-market, and the design and development of more efficient

materials as presented by the Materials Genome Initiative. The application of computer methodologies such as ab-

initio, quantum mechanics/molecular mechanics simulations or polarizable continuum models provides an easy

control of the parameters affecting the processes leading to atomic level understanding of the process.

Project Example

The economic importance of design particles

derives largely from their use as supported

catalysts, where the most important

requirement is a good controllability of their

design and stability under working conditions.

For instance, fuel cells lose their

electrochemical performance through the

agglomeration of the supported nickel, which

works as an electrode. Hence, our key objective

is to use computational tools to develop a

reliable method to simulate the metal clustering in an increasingly realistic model. Specifically, we aim to: investigate

the metal mobility across the supporting surface and evaluate the thermodynamics and kinetics of the sintering

process as a function of the cluster size. We will then unravel the agglomeration mechanism with atomic accuracy

and extrapolate the results to realistic working conditions by developing a micro-kinetic model.

Selected Publications

A. Roldan, N. Hollingsworth, A. Roffey, H.U. Islam, J.B. Goodall, C.R. Catlow, J.A. Darr, W. Bras, G. Sankar, K.B. Holt, G. Hogarth, N.H. de Leeuw, Chem Commun, 51 (2015) 7501-7504. A. Cadi-Essadek, A. Roldan, N.H. de Leeuw, The Journal of Physical Chemistry C, 119 (2015) 6581-6591.

Ni10

/YSZ model

Research Profile – New Frontiers in Organocatalysis

Overview: Research in the Morrill group is focused in the field of Synthetic Organic Chemistry. We are

particularly interested in exploring new frontiers in organocatalysis, employing dual catalytic methods to

rapidly generate molecular complexity, forming densely functionalised molecules in a stereodefined fashion.

The multi-step, one-pot nature of this dual catalysis approach represents progress towards more sustainable

chemistry. The development of novel organocatalysts, especially those that operate via unusual or

previously unknown modes of activation, represents another significant area of interest. The utility and

impact of our developed methodologies will ultimately be exemplified through its application in the total

synthesis of natural products and molecules of biological significance.

Research Areas: Research in the Morrill group will be underway from June 2015 and areas of interest will

include:

The exploration of new frontiers in organocatalysis via the productive merger of organocatalysis with other transition metal, organometallic or biochemical modes of activation.

The development of novel Lewis acid organocatalysts for a variety of organic transformations.

Expanding the utility of neglected, yet readily available and cheap precursors in organocatalytic transformations.Project Examples:

1) Dual Catalysis. The development of novel dual catalysis systems involving

borrowing hydrogen will be investigated (Figure 1). This approach will allow

asymmetric organocatalysis to be performed at a lower oxidation state, utilizing readily

available alcohol substrates to access useful stereodefined building blocks. The multi-

stage, one-pot nature of this dual catalysis reaction design represents progress towards

sustainable chemistry.

For a recently published highlight in this area, see D. Hollmann, ChemSusChem, 2014, 7, 2411–2413. Figure 1: Borrowing

hydrogen dual catalysis

2) Synergistic Catalysis. In 2012, MacMillan defined synergistic catalysis as a synthetic strategy

wherein both the nucleophile and the electrophile are simultaneously activated by two separate and

distinct catalysts to afford a single chemical transformation (Figure 2). We will develop novel

synergistic catalysis systems via the productive merger of organocatalysis with other transition metal,

organometallic or biochemical modes of activation. This synergistic approach will allow access to

various densely functionalised carbo- and heterocyclic species from simple precursors with high

stereocontrol that would be difficult to access via either catalytic method alone. It is envisaged that this

strategy will be subsequently applied towards the synthesis of important biologically active molecules and

natural products.

For a review, see D. W. C. MacMillan et al., Chem. Sci., 2012, 3, 633-658. Figure 2: Synergistic catalysis

3) Novel Lewis Acid Organocatalysts. In comparison to other areas of organocatalysis, Lewis

acid organocatalysis has received less attention, perhaps due to the difficulties in establishing

defined modes of activation in comparison to enamine, iminium etc for Lewis base

organocatalysis. With this in mind, the development of novel Lewis acid organocatalysts that can

accelerate organic reactions, particularly in a highly enantioselective fashion, remains a

significant goal in organic synthesis. We will design a novel class of Lewis acid

organocatalysts that operate by accepting a lone pair of electrons from the substrate (Figure 3).

For a selected review on Lewis acid organocatalysis, see O. Sereda et al.,Top. Curr. Chem., 2010,

291, 349-393. Figure 3: Novel Lewis acid

organocatalysis

Prof Davide Bonifazi

Bonifazi’s group research focuses on the demonstration of key functions through the development

of novel organic supramolecular architectures, aiming at the achievement of interdisciplinary

solutions to current scientific challenges.

Specifically, exploiting the newest organic synthesis and carbon-based nanostructure chemistry, we

design and prepare hierarchized nano-structured organic architectures of interest in materials

science, carbon-based nano-medicine, self-assembly of hybrid architectures at interfaces, and

physical-organic studies.

Current developed topics include:

Supramolecular Organic Nanochemistry

Biomimetic nanostructured surfaces

New emissive heteroatom-doped p-conjugated scaffoldings

Advanced materials based on carbon nanostructures

Prof Angela Casini

The research in my group is in the fields of Bioinorganic and Medicinal Inorganic Chemistry. In

particular the study of the role of metal ions in biological systems and of the mechanisms of action of

metal-based anticancer agents are active topics of our research program. Besides synthetic

chemistry and structural characterization of new metal complexes we strongly focus on an intensive

biological evaluation of the new compounds as possible anticancer agents, and on the investigation

of their mechanisms of action.

Notably, the peculiar chemical properties of metal-based compounds impart innovative

pharmacological profiles to this class of therapeutic and diagnostic agents, most likely in relation to

novel molecular mechanisms still poorly understood. The development of improved metallodrugs

requires clearer understanding of their physiological processing and molecular basis of actions. Our

research in the field constitutes the basis of a systematic and interdisciplinary approach to address

some of the critical issues in the study of the molecular mechanisms of metallodrugs’ action via the

implementation of high-resolution biophysical techniques coupled with more pharmacological

methods. Thus, biophysical techniques such as high-resolution mass spectrometry (both molecular

and elemental sensitive), various spectroscopies and X-ray crystallography, are complemented by

fluorescence microscopy, protein expression and purification, screening of enzyme activity, as well

as in vitro and ex vivo screening of drug toxicity, accumulation and metabolism.

An important task of our research is to discover the unique properties of metal compounds as

modulators (inhibitors or activators) of proteins/enzyme activities, and to exploit them for different

therapeutic and imaging purposes or as molecular biological tools. As an example, we have identified

the aquaporins (AQPs), membrane water channels with crucial roles in normal human physiology

and pathophysiology, as possible target systems for metal compounds. Certainly, there is

considerable potential for translating knowledge of AQP structure, function and physiology to the

clinic, and there is great translational potential in aquaporin-based therapeutics.

Overall, these projects encompass a variety of metal ions and different ligand systems studied by

various techniques, as well as numerous collaborations in the field. Our research is highly

interdisciplinary ranging from Inorganic and Bioinorganic Chemistry to Molecular Biology,

Biochemistry, Toxicology and Molecular Pharmacology.

Dr Timothy L. Easun - Research Profile

The main research objective of the Easun group is to combine nanofluidics and metal-

organic frameworks (MOFs) with photogated control of molecular flow to create a new

platform technology for the development of nanofluidic devices. This research involves

synthesis of organic linkers, supramolecular assembly of extended metal-organic

frameworks, photochemistry and spectroscopic analysis. Along with standard analytical

techniques (NMR, MS X-ray crystallography etc.), time-resolved and spatially-resolved

spectroscopies are exploited to understand and control the motion of molecules on

ultrafast timescales and over nanoscale distances.

Research areas include:

Microporous materials (including MOFs)

Supramolecular photochemistry

Spatiotemporal spectroscopies (IR, Raman, transient absorption, luminescence...)

Microfluidic and nanofluidic devices

Structure-function relationships in photoactive crystals

Project Example

The flow of gases and liquids through very small channels, of the order of a few nanometres across, is known

as nanofluidics. Being able to study and control the movement of molecules on this scale offers exciting

possibilities in the miniaturising of microfluidic devices used for medical diagnostics, sensing, and materials

sorting applications, with one ultimate goal being single-molecule sorting. Metal-organic frameworks (MOFs)

are highly ordered porous materials with extremely well-defined pores and channels that offer a new

platform on which to undertake nanofluidic studies.

This synthetic project will involve the design and synthesis of new MOFs which contain photoactive linkers

that contain photoactive, sterically bulky

molecules based on chromene, spirooxazine and

spiropyran derivatives that undergo a significant

geometry change on UV irradiation. The

photochemical behaviour of the ligands and MOFs will be

studied with IR, Raman, absorption and emission

spectroscopies and the MOF photocrystallographic

behaviour will be characterised by X-ray

crystallography and microscopy techniques to provide

essential insight into the diffusion behaviour of guest species in nanochannels and pores.

Selected Publications

1) Chem. Eur. J., 2014, 20, 7317: "Analysis of High and Selective Uptake of CO2 in an Oxamide-containing {Cu2(OOCR)4} Based Metal Organic Framework" 2) Chemical Science, 2014, 5, 539: "Modification of Coordination Networks Through a Photoinduced Charge Transfer Process" 3) Nature Chemistry, 2010, 2, 688: "Photoreactivity examined through incorporation in metal-organic frameworks" 4) Angewandte Chemie Int. Ed., 2009, 48, 31, 5711: "Reversible 100 % Linkage Isomerization in a Single-Crystal to Single-Crystal Transformation: Photocrystallographic Identification of the Metastable [Ni(dppe)(h1-ONO)Cl] Isomer"

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Dr Joseph M. Beames - Research Profile

The focus of the research in the Beames group is to develop and use spectroscopic tools suitable for probing complex

atmospheric and physical chemistry reactions in a laboratory environment. In particular, the goals of the group are to utilize UV

and IR spectroscopy (CRDS/CEAS) to sensitively detect highly reactive trace gases, and to probe particulate matter (aerosol)

formation and composition.

Key components of this research are:

UV and IR spectrometer development

Probing the chemistry of reactive short-lived intermediates (e.g. Criegee intermediates) for monitoring both indoor and outdoor air quality

The atmospheric implications of chemical complexity

Quantitative trace gas detection for use in explosives detection and medical sensing

Spectroscopic interrogation of particulate matter (aerosol) formation and composition

Sample project:

The last two hundred years have seen new anthropogenic emissions dramatically change the chemical composition and chemistry of the troposphere,

creating an incredibly diverse set of atmospheric conditions based on location and level of human population. Much of what we know about the

changing climate comes from carefully constructed atmospheric models. These models often comprise thousands of competing chemical reactions

which can be used to predict global chemical concentrations. However, such models rely on accurate laboratory studies of the underlying reaction rates

and outcomes.

In 2008 the first unambiguous direct detection of a Criegee intermediate was reported by VUV ionization. Criegee intermediates, or carbonyl oxides,

are important reactive intermediates in the ozonolysis of alkenes, which is the main loss pathway for alkenes in the troposphere. Criegee intermediates

were proposed to be vital in these oxidative reactions over 50 years ago, but their highly reactive and short lived nature meant that they had never

been isolated. In 2012 a novel synthetic route1 to the generation of Criegee intermediates made possible the routine production of several small

Criegee intermediates under laboratory conditions. Since then the UV and IR spectroscopy of several such species have been characterized for use as

an alternative laboratory-based Criegee intermediate detection method. Although some small Criegee intermediates have been synthetically produced

and identified, there are many important moieties yet to be detected and characterized. This includes many Criegee intermediates that arise from the

ozonolysis of isoprene. Isoprene is emitted into the troposphere in greater quantities than any other alkene, and therefore the detection and

characterization of its ozonolysis products is of great importance to the atmospheric chemistry community.

One approach to investigating such topics is to design a synthetic route to the production of Criegee

intermediates arising from isoprene ozonolysis. The appropriate compounds could then be

interrogated using UV cavity ring-down spectroscopy and their absorption spectra recorded,

providing the first insights into their UV spectral signatures. UV absorption spectroscopy could

then be used to selectively detect and probe the reaction kinetics of these

synthetically generated Criegee intermediates with other trace tropospheric

constituents. The breakdown of these intermediates to form hydroxyl radicals

in the troposphere (an atmospheric chemical 'scrubber', which oxidizes and thus

leads to the removal of many trace pollutants) could also be investigated.

1 The synthetic route to carbonyl oxides utilized recently involves the production,

and subsequent photolysis, of a gem-diiodo precursor in the presence of oxygen. For example:

CH2I2 + h (248 nm) → CH2I + I

CH2I + O2 → CH2OO + I

Key references:

O. Welz, J.D. Savee, D.L. Osborn, S.S. Vasu, C.J. Percival, D.E. Shallcross, and C.A. Taatjes, "Direct Kinetic Measurements of Criegee Intermediate

(CH2OO) Formed by Reaction of CH2I with O2," Science 335, 204 (2012).

J.M. Beames, F. Liu, L. Lu, M.I. Lester, “Ultraviolet Spectrum and Photochemistry of the Simplest Criegee Intermediate CH2OO”, J. Am. Chem. Soc.

134(49), 20045 (2012).

C.A. Taatjes, O. Welz, A.J. Eskola, J.D. Savee, A.M. Scheer, D.E. Shallcross, B. Rotavera, E.P.F. Lee, J.M. Dyke, D.K.W. Mok, D.L. Osborn, C.J. Percival

“Direct Measurements of Conformer-Dependent Reactivity of the Criegee Intermediate CH3CHOO” Science, 340, 6129 (2013).

R. Chhantyal-Pun, A. Davey, D.E. Shallcross, C.J. Percival, A.J. Orr-Ewing, “A kinetic study of the CH2OO Criegee intermediate self-reaction, reaction with

SO2 and unimolecular reaction using cavity ring-down spectroscopy” Phys. Chem. Chem. Phys. 17(5), 3617 (2014).

The structure of isoprene and the Criegee intermediates formed during its tropospheric ozonolysis. Only the smallest Criegee intermediate CH2OO has been directly detected. The large brackets group different conformers of the same isomeric form.

Dr Yu-Hsuan Tsai - Research Profile

The Tsai group is interested in functional study of biomolecules using synthetic

molecules. Current research focus on protein glycosylations. The works involve

techniques in synthetic chemistry, biochemistry and molecular biology.

Research areas include:

Synthesis of biological important molecules

Study of protein functions by genetic incorporation of unnatural amino acids

Project Example

Prions are the infectious agents that attack the central nervous system and subsequently invade the brain.

There are a number of prion diseases that affect humans and other mammals, and all of the diseases are

untreatable and fatal.

Glycosylphosphatidylinositol (GPI) is ubiquitous in all eukaryotic cells. GPIs are normally attached to proteins

as a posttranslational modification that may involve in protein sorting, signal transductions and microdomain

formation on cell surface. However, in most cases, the function of GPI anchors is unknown beyond anchoring

protein on extracellular membrane due to the low availability of pure GPI samples.

Prion protein (PrP) is expressed as a cell

surface glycoprotein with a GPI anchor, but

the role of the GPI in prion diseases is still

unclear. In cells, the absence of the GPI

moiety reduces conversion of cellular PrP to

its infectious counterpart, and cells lacking GPI

anchored PrP develop infectious amyloid

disease without clinical symptoms, thus

supporting the theory that the PrP GPI anchor

may play a critical role in the pathogenesis of

prion diseases.

We will synthesize different PrP GPI anchors,

which would be ligated to proteins. The

biophysical properties of GPI anchored PrP

will then be studied, followed by in vivo experiments. The research involves organic synthesis and

biochemistry techniques. Training in both synthetic chemistry and molecular biology will be provided.

Selected Publications

1. A general method for synthesis of GPI anchors illustrated by the total synthesis of the low molecular

weight antigen from Toxoplasma gondii. Y.-H. Tsai, S. Götze, N. Azzouz, H. S. Hahm, P. H. Seeberger, D.

Varon Silva, Angew. Chem. Int. Ed. 2011, 50, 9961-9964;

2. A General and Convergent Synthesis of Diverse Glycosylphosphatidylinositol Glycolipids. Y.-H. Tsai, S. Götze, I. Vilotijevic, M. Grube, D. Varon Silva, P. H. Seeberger, Chem. Sci. 2013, 4, 468-481.