Research interests
Antibiotics Chemistry: The rise and rise of the so-called 'Superbugs' is well documented in the media. Bacteria that are resistant to (i.e. not killed by) most current antibiotics are increasingly widespread, and the need for new drugs and new strategies to combat them grows ever more important. We are widely interested in antibiotics chemistry and antibiotic biosynthesis, and are pursuing a number of approaches to meet the challenges posed by antibiotic resistant bacteria. Current strategies include the synthesis of new cyclobutanone antibiotics and the design of antibiotics with novel 'double-punch' and 'resistance-activated' modes of action.

Hydrocarbon Oxidation and C-H Activation:The conversion of simple hydrocarbons (alkanes, alkenes and aromatic compounds) to functionalised targets is of great interest in synthetic and medicinal chemistry, but many of these key transformations are inaccessible with current synthetic methods. Nature uses highly efficient enzyme systems to oxidise hydrocarbons in high yield with complete selectivity. We are working to develop new catalysts inspired by these biological systems, and to use them for the selective oxidation of hydrocarbon substrates: new reagents for synthesis and for the environment. We have synthesised a series of small-molecule systems that mimic the non-heme iron oxidase (NHIO) active site and are developing these as catalysts for biomimetic hydrocarbon oxidation and iron-mediated C-H activation.

Metal Sensing: Heavy metals like cadmium and mercury form some of the most toxic materials known. Yet some plants and microbes have developed strategies to live in locales prone to high levels of cadmium and mercury pollution, using sulfur-rich proteins to bind and the toxic metal ions and sequester them away from the rest of the cell's machinery. These proteins incorporate high numbers of cysteine residues, which makes them effective agents for heavy metal sequestration: the numerous sulfur atoms bind tightly to mercury, cadmium and other metal ions. Our approach uses thiol- and sulfide-rich peptides as agents for binding and sensing mercury.

Nitrile Hydratase Mimics and Mechanism: Nitrile hydratase is an unusual metalloenzyme that brings about the selective conversion of nitriles to primary amides. Crystal structures of nitrile hydratases show a remarkable ligand environment in the active site. Two nitrogen atoms from main-chain amides bind to the metal (iron(III) or cobalt(III)), along with three sulfur atoms, each in a different oxidation state. And these five metal binding ligands are located in a short section of the primary sequence, spread across only six amino acids in one peptide chain. We are working to develop new peptide-based systems as bio-inspired catalysts for nitrile hydration, to study the unusual sulfur oxidation that occurs at the nitrile hydratase active site, and to elucidate a detailed mechanism for nitrile hydratase catalysis.