Biological and Organic Chemistry
Enzyme catalysis: Research in this area has the goals of probing enzymatic reaction mechanisms, elucidating the role of protein dynamics and quantum mechanical effects in catalysis, and tailoring substrate selectivity for synthetic chemistry purposes. Current projects include (i) the enzymology of terpenoid biosynthesis and synthetic biology approaches for expansion of the pool of these secondary metabolites to include novel terpenoid-like compounds with applications as drugs and crop protection agents, (ii) investigation of the role of protein motions and hydride tunnelling in enzyme catalysis, using dihydrofolate reductase as a model system, and (iii) development of inhibitors of the enzyme calpain-1, a potential target for anti-inflammatory therapy in diseases such as rheumatoid arthritis.
Manipulating biomolecular interactions: Our research aims to control interactions between biomolecules by inducing conformational switching using small molecules or light. Current projects include (i) photonic control of protein-protein interactions to regulate the apoptotic pathway in cells, (ii) chemical and enzymatic synthesis of flavins and their analogues and application of these cofactors in protein photoswitches, (iii) controlling interactions of RNA molecules in cells using peptides and nucleic acid analogues and (iv) investigation of the immunogenic properties of cyclic peptides with potential applications in anti-cancer vaccines.
Biomolecular NMR Spectroscopy: This work investigates the relationship between the structure, dynamics and function of enzymes, with emphasis on how binding partners (small molecules, nucleic acids or other proteins) affect a protein’s dynamics and how a protein affects its binding partners. This work is performed using our flagship 600 MHz Bruker NMR spectrometer equipped with a quadruple resonance QCI cryoprobe, as well as national high-field NMR facilities. Current projects involve dihydrofolate reductase and phototropin domains.
Organic Synthesis and Medicinal Chemistry: Much attention within the section is focused on the synthesis of natural and non-natural compounds with important biological properties. Target compounds include alkaloids and terpenoids, with a range of methodologies – particularly hypervalent iodine chemistry, electrophile-driven cyclisation, multicomponent coupling and desymmetrisation – being developed and applied. New efficient technologies for chemical synthesis such as flow chemistry and green chemistry are also active areas. Medicinal chemistry, particularly calpain-1 inhibition and production of artemisinin analogues for treatment of inflammatory diseases and malaria respectively, is a strong theme.
Organic Materials Chemistry: Research is centred on the preparation, characterisation and application of new microporous organic polymers. Among a wide range of exciting new applications, these are currently generating promise for their potential in adsorption and separation technologies.
Physical Organic Chemistry: We work on the rational development of functional chemical systems through quantitative understanding of processes. This typically involves the synthesis of designed molecules and subsequent testing of their physical properties. Projects include (i) design and synthesis of compounds for artificial photosynthesis, (ii) quantification of configurational stability of chiral drug-like molecules, (iii) optoelectronically active DNA-binding molecules and nanoparticle-based systems for use in biosensors and directed assembly, and (iv) mechanistic studies of palladium-catalysed coupling reactions.
Theoretical Organic Chemistry: Modern ab initio and DFT methods, along with atomistic and coarse-grained forcefields, are used to model the structure, properties, reactivity and recognition of organic, inorganic and biological molecules. Recent highlights include elucidation of the mechanism of iminium ion catalysis, development of methods for accurate description of non-covalent interactions and their application to biological and drug molecules, modelling of shape and dynamics of polymers for drug delivery and the description of unusual electronic states in inorganic species. Investigation into the origin of non-statistical reaction dynamics caused by the breakdown of traditional kinetic models such as Transition State Theory, and application of such fundamental knowledge to the design of molecular systems for harvesting of solar energy into fuels.