Dr Alison Paul - Research Profile

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 anticancer 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:
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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
dose
drug
place
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.
time
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
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:
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
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.
-1
Figures 1a: NMRD of 5mg ml 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 solidstate 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.
b.
c.
d.
Valorisation of unconventional feedstock like CO2, biomass constituents and coal.
Development of heterogeneous catalysts for various transformations.
Synthesis and characterization of inorganic nanomaterials.
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:
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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
15
N 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,
15
N 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
13
15
1) Aliphatic H, C and N 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
1
13
15
2) H, C and N 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:
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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
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 nanoparticles 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:
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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.
1E13
Gasoline
Diesel
1E12
1E11
20
40
60
80
100
-1
-1
160
140
120
100
80
60
40
20
0
1E14
Mass Emitted (mg km )
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.
Number Emitted (km )
Soot particulate emitted by cars
120
-1
Speed (km hr )
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:
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


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.
P680*
e-
Tyrz
13.6 Å
TyrzH
W
Tyrz
Q165
D170
H2O
E198
w
O
Mn
X
X
X
w
D170
reaction site
W
Mn
O
O
O
Mn D342
Mn
D170
W
Mn
H332
H = histidine
Q = glutamic acid
Ca
E198
w
O
O
Mn
E333
O
Mn D342
Mn
H332
O
E354
H337
Tyrz
D = asparatate
E = glutamate
Mn
O
H337
R = arginine
H332
O
H337
HO
E354
H+
Mn D342
Mn
Tyrz
O
E333
O
E354
Ca
E198
O
Mn
E333
5.1 Å
R357
Ca
O
OH
O
H2O
D170
W
Ca
E198
w
O
Mn
E333
O
Mn
E354
O
Mn D342
Mn
H332
O
H337
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.
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.
60
Nickel
-1
Relative Energy (kJ mol )
Paladium
50
Precious metal catalysts can be used for a
Platinum
variety of hydrogenation reactions. The ease of
40
hydrogenation and the reaction conditions that
30
can be used depend critically on the diffusion
20
of the hydrogen over the surface and through
10
the bulk of the catalyst particles. We have
0
found already that for pure Pt, Pd and Ni the
fcc
hcp
fcc
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).
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 intramolecular 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.
Ligand redistribution equilibria
Our principal aim is to prepare chiral ligands
that are able to suppress these equilibria,
R
R
iPr
iPr
N
N
iPr
affording
well-defined
complexes,
and
N
N
N R
py
N
subsequently using these complexes in a range
2
Ca
Ca
N
N(SiMe3)2
of catalytic transformations. Our recent work in
N R
N
N
iPr
the area has managed to achieve 50% ee in the
N
N
5
iPr
iPr
R
R
calcium-catalysed
hydroamination
of
+
aminoalkenes (see Scheme). Such levels of
[Ca{N(SiMe3)2}2(py)2]
selectivity are unprecedented in calcium
Hydroamination catalysis
chemistry, and the project will utilise new
H
N
ligand architectures to further improve the
R1 R1
selectivity in this, and related, catalytic
NH2
n
R1
n
reactions.
R1
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.
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 lifesupport 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
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
for
 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.
60
Nickel
-1
Relative Energy (kJ mol )
Paladium
50
Precious metal catalysts can be used for a
Platinum
variety of hydrogenation reactions. The ease of
40
hydrogenation and the reaction conditions that
30
can be used depend critically on the diffusion
20
of the hydrogen over the surface and through
10
the bulk of the catalyst particles. We have
0
found already that for pure Pt, Pd and Ni the
fcc
hcp
fcc
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).
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.
2.
3.
4.
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.
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.
L. Kesavan, R. Tiruvalam, M. H. Ab Rahim, M. I. bin Saiman, D. I. Enache, R. L. Jenkins, N. Dimitratos, J. A. LopezSanchez, 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.
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 dand 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 a
b
e
Fe2(MnO4)3 nanoparticles supported
on MnO3 nanorods show better
performance
as
catalysts
for
methanol oxidation to formaldehyde c
d
that bulk Fe2(MnO4)3 catalysts (Fig.
1). This synthetic project is directed
001
010
towards the design and synthesis of
[001]
[010]
high surface area MnO3 that could be
an improved support for the
Figure 1 MoO3 nanorods (a-d) and Fe2(MnO4)3 nanoparticles supported on the
Fe2(MnO4)3
nanoparticles.
The
MnO3 nanorods (e).
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, 5664. (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)
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.
OTBS
N
TBSO
BrCH2Li
H
O
NMe
Lycoposerramine A
H H
TfOH (1 equiv.)
O
OAc
O
CH2Cl2, 0 - 25 °C
89%
3
O
OTBS
H H CHO
O
HO
O
N
H
2
O
N
Me
O
O
1
OH
O
H
H
Cl 7 steps Me
H H
4
HO
H H
7-deacetoxyalcyonin acetate
[O]
R3CCH2OH
R3C B
O
One other area that we have
calculated transition states for
improved yields
become involved in over the various R and
boronic esters
bromomethylation and alkyl group
last
few
years
is
migration
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. Elliott, Keith Smith, D. Heulyn Jones, Ajaz Hussain and Basil 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
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 crosscoupling. 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) Nheterocyclic 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 7membered 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,
In-Situ Solid-State
driven both by fundamental scientific curiosity and by industrial
13C NMR of Glycine
α polymorph
necessity. Several directions of our research are targeted towards
Crystallization
obtaining a deeper fundamental understanding of the phenomenon of
β polymorph
Total time =
16.8
hours
polymorphism and its practical implications, including the discovery of
new polymorphic systems, structural rationalization (in many cases
Time
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,
C Chemical Shift / ppm
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.
13
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.
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.
N
N
..
Z
N
Me Z
L
Z = PR2, NR2, SR, OR, OH
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.
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
XPS and AFM of gold nanoparticles on a
the presence of functional groups such as hydroxides on
graphite surface
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.
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.
2.
3.
4.
Capture and utilization of CO2
Renewable and clean energy
Material design including atomic control manufacturing.
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 abinitio, 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
Ni10/YSZ model
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.
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
multistage, 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.
hydrogen dual catalysis
Figure
1:
Borrowing
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
strategy will be subsequently applied towards the synthesis of important biologically active molecules
natural products.
For a review, see D. W. C. MacMillan et al., Chem. Sci., 2012, 3, 633-658.
this
and
Figure 2: Synergistic catalysis
3) Novel Lewis Acid Organocatalysts. In comparison to other areas of organocatalysis,
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
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
For a selected review on Lewis acid organocatalysis, see O. Sereda et al.,Top. Curr. Chem.,
291, 349-393.
Figure
organocatalysis
Lewis
can
3).
3:
Novel
Lewis
2010,
acid
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 metalorganic 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:
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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 SingleCrystal Transformation: Photocrystallographic Identification of the Metastable [Ni(dppe)(h1-ONO)Cl] Isomer"
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:
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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
intermediates arising from isoprene ozonolysis. The appropriate
interrogated using UV cavity ring-down spectroscopy and their
providing the first insights into their UV spectral signatures. UV
then be used to selectively detect and probe the reaction kinetics
synthetically generated Criegee intermediates with other trace
constituents. The breakdown of these intermediates to form
in the troposphere (an atmospheric chemical 'scrubber', which
leads to the removal of many trace pollutants) could also be
1
route to the production of Criegee
compounds could then be
absorption spectra recorded,
absorption spectroscopy could
of
these
The structure of isoprene and the Criegee
tropospheric
intermediates formed during its tropospheric
hydroxyl radicals
ozonolysis. Only the smallest Criegee intermediate
oxidizes and thus
CH2OO has been directly detected. The large
investigated.
brackets group different conformers of the same
isomeric form.
The synthetic route to carbonyl oxides utilized recently involves
and subsequent photolysis, of a gem-diiodo precursor in the presence of oxygen. For example:
the
production,
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 CH 2OO”, 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).
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:
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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.