My research group is interested in developing novel biophysical tools for studying catalysis at metal centres within proteins. Of particular importance are enzymes that catalyse activation of small molecules such as dihydrogen (H2), carbon monoxide, carbon dioxide, and dinitrogen (N2). The chemistry that occurs at enzyme active sites is inspirational for production and use of future sustainable fuels. Active sites are often based around ‘inorganic’ cores similar to naturally-occurring minerals, and can be studied using a range of spectroscopic techniques. In combination with electrochemistry, it is possible to use spectroscopy to build up 'snapshots' of enzyme reactivity in situ during catalysis. At present we are involved in developing novel room-temperature methods for X-ray absorption spectroscopy, and time-resolved infrared spectroscopy. A deeper mechanistic understanding of how nature has developed efficient enzymes will provide inspiration for the next generation of biomimetic catalysts for green energy and synthesis.
My research is supported by the Royal Society, Royal Society of Chemistry, Science and Technology Funding Council, Diamond Light Source, BBSRC, and EPSRC.
Research group: Metalloenzyme mechanism with sub-turnover frequency time resolution
The activation and redox chemistry of small molecules such as CO, CO2, H2, formate, O2, NO, N2, and NH3 by metalloenzymes play important roles in vital processes such as the global carbon and nitrogen cycles, and as sources of energy or low-potential reducing equivalents in cellular environments (for example certain bacteria have evolved to use CO2 as their sole carbon source and H2 as their sole energy source). Despite the current urgent need for sustainable fuels and greener routes to chemical synthesis, detailed mechanistic understanding of how these small molecule activation reactions are carried out in nature is often lacking. In part this is due to the high turnover frequencies achieved by metalloenzymes, which are often capable of activating small molecules at rates of several thousand reactions every second. New methods are therefore required that are capable of probing metalloenzyme mechanism on fast timescales, or else the native reaction must be retarded to allow kinetic study by more conventional methods.
The image above shows molecular models of two metalloproteins in surface representation showing their metal-containing active sites, buried within the protein matrix.
The image above shows a round metal plate with the words electrochemistry and e-, into which electrons can be fed, changing the redox states of the metalloenzymes shown on there as small spheres. This will change their behaviour following triggers shown above by the word trigger and measured by probes. Electrochemistry can be used to poise metalloenzymes in specific redox states, and this control can be combined with external triggers and spectroscopic probes to study enzyme mechanism in solution.
The graph above shows a typical infrared difference spectrum of a flavin. The y-axis is the difference between IR measured at oxidised and reduced conditions (induced by electrochemically triggered reduction). The x-axis is the wavenumber, expressed in cm-1 with a sharp peak at 1530 cm-1.
The active sites of redox metalloenzymes are often based around an inorganic core and share compositional and structural similarities with naturally-occurring minerals. As such they are well-suited to study using ‘standard’ spectroscopic methods such as infrared, Raman, and X-ray spectroscopies. Electrochemistry provides convenient control over redox state, and makes it possible to ‘trap’ metalloenzymes in inactive or ‘resting’ states ready for spectroscopic study. I am developing methods that combine this electrochemical control with fast experimental triggers to initiate reactivity, and fast spectroscopic methods to allow investigation of metalloenzyme mechanism with sub-turnover frequency time resolution. A deeper mechanistic understanding of how nature has developed efficient metalloenzymes should provide inspiration for the next generation of biomimetic catalysts for ‘green’ energy and synthesis.
I supervise research students on projects involving bioinorganic chemistry, biocatalysis, biomimetic catalysis, and biophysical method development. A particular focus is on redox enzymes involved in small molecule activation. I am always interested in hearing from potential research students, PDRAs, or collaborators.
I am actively involved in teaching on all degrees offered by the School of Chemistry, undertaking a range of laboratory demonstration, tutorials, problem classes, and lectures. I also supervise undergraduate (BSc and MChem) and postgraduate research project students. I am module convenor of CH3202 (Advanced Inorganic Chemistry) and lecture on CH4208 (Bioinorganic Chemistry). I am a Fellow of the Higher Education Academy (FHEA).
I am happy to provide opinion on research at large national facilities, enzyme chemistry, bioinspired chemistry, electrocatalysis, green energy, hydrogen production, and related topics. I have collated a range of short videos detailing research within Leicester that are available via the School of Chemistry.