Dr Philip Ash

I am a graduate of Wadham College, University of Oxford (MChem). I completed my PhD research in the group of Professor Colin Bain (Durham University) where I used a range of physical methods to study phase transitions in mixed monolayers of surfactant and alkane. My PhD research involved collaborative work at the Royal Institute of Technology (KTH Stockholm) supported by a Rideal Travel Bursary. I carried out postdoctoral research at the University of Oxford with Professor Kylie Vincent, where I received support from the John Fell Fund and a Researcher Mobility Grant (Royal Society of Chemistry) to undertake collaborative work developing spectroscopic-electrochemical methods for studying crystalline heme proteins with Dr. Hans-Petter Hersleth at the University of Oslo. In 2019 I took up a lectureship in the School of Chemistry at the University of Leicester, where I am also a Principal Investigator within the Leicester Institute for Structural and Chemical Biology.

I am a regular user of major national and international research infrastructure, including Diamond Light Source (UK), MAX IV (Sweden), and the Central Laser Facility (UK). As a result of this wide-ranging facility use, I am an inaugural member of the Science and Technology Funding Council’s Multidisciplinary Facility User Advisory Panel (having previously served on the Life Sciences and Soft Materials Advisory Panel), a Peer Review Panel member at Diamond Light Source, a member of the User Working Group for the BERRIES beamline project, and a committee member of the Inorganic Biochemistry Discussion Group (IBDG, Royal Society of Chemistry).

My research group is interested in developing novel biophysical tools for studying the vital chemistry enabled by metal centres within proteins. Of particular importance are enzymes that catalyse the activation of small molecules such as dihydrogen (H₂), carbon monoxide, carbon dioxide, and dinitrogen (N₂), in addition to medicinally-important enzymes that carry out chemistry related to O₂ metabolism. The chemistry that occurs at enzyme active sites is inspirational for a wide range of technologically-relevant applications, including the production and use of future sustainable fuels, CO₂ sequestration and incorporation into value-added products, and the development of novel therapeutic methodology.

Time-resolved structural biology

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 drug production, 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.

Electrochemistry provides convenient control over oxidation state and reactivity, and makes it possible to ‘trap’ metalloenzymes in inactive or ‘resting’ states ready for spectroscopic study. We are developing methods that combine this electrochemical control with ultrafast experimental triggers to initiate reactivity, and ultrafast spectroscopic and structural methods to allow investigation of metalloenzyme mechanism with time resolution on the order of nanoseconds or faster. In collaboration with a range of national and international partners, we are developing novel room-temperature approaches to structural biology, including methods for X-ray absorption spectroscopy, and time-resolved infrared and Raman spectroscopy. A deeper mechanistic understanding of how nature has developed efficient metalloenzymes will provide inspiration for the next generation of biomimetic catalysts for ‘green’ energy and drug development.

New approaches to biomimetic chemistry

The active sites of redox metalloenzymes are often based around an 'inorganic' core, and share compositional and structural similarities with naturally-occurring minerals. These evolutionary features raise questions about the primordial origins of life (what came first, the enzymes or their catalytic cores?), and provide the tantalising possibility of novel approaches to biomimetic chemistry, engineering protein-like functionality into natural and synthetic minerals to produce a new generation of (photo)catalytic materials. Using knowledge gained from our mechanistic studies, we aim to address the question of exactly how much of the enzyme scaffold is needed to sustain catalysis, and incorporate these features into new synthetic materials for a diverse range of applications, from battery technology, solar energy harvesting and photovoltaic devices, to waste water remediation and atmospheric CO₂ valorisation.

Research funding

We are grateful for financial support from the Royal Society, Royal Society of Chemistry, Science and Technology Funding Council, Diamond Light Source, MAX IV, BBSRC, and EPSRC.

Selected Publications:

1. S.B. Carr, W. Li, K. L. Wong, R. M. Evans, S. E. T. Kendall-Price, K. A. Vincent, P. A. Ash, Glutamate “flick” enables proton tunneling during fast redox biocatalysis, Nature Catalysis 2025 (under revision).
2. Z. Duan et al., Cyanophenylalanine as an Infrared Probe for Iron–Sulfur Cluster Redox State in Multicenter Metalloenzymes, ChemBioChem 2025, 26, e202500251. DOI: 10.1002/cbic.202500251
3. R. M. Evans et al., Comprehensive structural, infrared spectroscopic and kinetic investigations of the roles of the active-site arginine in bidirectional hydrogen activation by the [NiFe]-hydrogenase ‘Hyd-2’ from Escherichia coli, Chem. Sci. 2023, 14, 8531-8551. DOI: 10.1039/D2SC05641K
4. T. Chen, P. A. Ash, L. C. Seefeldt, K. A. Vincent, Electrochemical experiments define potentials associated with binding of substrates and inhibitors to nitrogenase MoFe protein, Faraday Discuss. 2023, 243, 270-286. DOI: 10.1039/D2FD00170E
5. P. A. Ash, S. E. T. Kendall-Price, R. M. Evans, S. B. Carr, A. R. Brasnett, S. Morra, J. S. Rowbotham, R. Hidalgo, A. J. Healy, G. Cinque, M. D. Frogley, F. A. Armstrong, K. A. Vincent, The crystalline state as a dynamic system: IR microspectroscopy under electrochemical control for a [NiFe] hydrogenase, Chem. Sci. 2021, 12, 12959-12970.
6. S. Morra et al., Electrochemical control of [FeFe]-hydrogenase single crystals reveals complex redox populations at the catalytic site, Dalton Trans. 2021, 50, 12655-12663.
7. S. P. Best, V. A. Streltsov, C. T. Chantler, W. Li, P. A. Ash, S. Diaz-Moreno, Redox state and photoreduction control using X-ray spectroelectrochemical techniques - advances in design and fabrication through additive engineering, J. Synchrotron Rad. 2021, 28, 472-479.
8. P. A. Ash, S. E. T. Kendall-Price, K. A. Vincent, Unifying activity, structure and spectroscopy of [NiFe] hydrogenases: combining techniques to clarify mechanistic understanding, Acc. Chem. Res. 2019, 52, 3120-3131.
9. D. B. Grabarczyk. P. A. Ash, W. K. Myers, E. L. Dodd, K. A. Vincent, Dioxygen controls the nitrosylation reactions of a protein-bound [4Fe4S] cluster, Dalton Trans. 2019, 48, 13960-13970.
10. R. M. Evans, P. A. Ash, S. E. Beaton, E. K. Brooke, K. A. Vincent, S. B. Carr, F. A. Armstrong, Mechanistic exploitation of a self-repairing, blocked proton transfer pathway in an O₂-tolerant [NiFe]-hydrogenase, J. Am. Chem. Soc. 2018, 140, 10208-10220.
11. P. A. Ash, R. Hidalgo, K. A. Vincent, Protein Film Infrared Electrochemistry Demonstrated for Study of H₂ Oxidation by a [NiFe] Hydrogenase, J. Vis. Exp. 2017, 130, e855858.
12. P. A. Ash, S. B. Carr, H. A. Reeve, A Skorupskaitė, J. S. Rowbotham, R. Shutt, M. D. Frogley, G. Cinque, F. A. Armstrong, K. A. Vincent, A method for generating single metalloprotein crystals in well-defined redox states: combined electrochemical control and infrared microspectroscopic imaging of a NiFe hydrogenase crystal, Chem. Commun. 2017, 53, 5858-5861.
13. P. A. Ash et al., Proton transfer in the catalytic cycle of NiFe hydrogenases: insight from vibrational spectroscopy, ACS Catal. 2017, 7, 2471-2485.
14. Ash, P. A., Vincent, K. A., 'Vibrational Spectroscopic Techniques for Probing Bioelectrochemical Systems' in 'Biophotoelectrochemistry: From Bioelectrochemistry to Biophotovoltaics', Volume 158 of the series 'Advances in Biochemical Engineering / Biotechnology', pp 75-110, Springer, 2016.
15. Philip A. Ash, Holly A. Reeve, Jonathan Quinson, Ricardo Hidalgo, Tianze Zhu, Ian J. McPherson, Min-Wen Chung, Adam J. Healy, Simantini Nayak, Thomas H. Lonsdale, Katia Wehbe, Chris S. Kelley, Mark D. Frogley, Gianfelice Cinque, and Kylie A. Vincent, Synchrotron-Based Infrared Microanalysis of Biological Redox Processes under Electrochemical Control, Analytical Chemistry 2016 88 (13), 6666-6671, DOI: 10.1021/acs.analchem.6b00898
16. Ricardo Hidalgo, Dr. Philip A. Ash, Dr. Adam J. Healy, Professor Kylie A. Vincent, Infrared Spectroscopy During Electrocatalytic Turnover Reveals the Ni-L Active Site State During H2 Oxidation by a NiFe Hydrogenase, Angewandte Chemie 2015 54 (24), 7110-7113, DOI: 10.1002/anie.201502338

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, and novel materials synthesis and characterisation. 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), Dalian lead for CH1203 (Introductory Physical Chemistry), and additionally lecture on CH4208 (Bioinorganic Chemistry) and CH1207/11 (Chemistry of the Real World). 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.

Recent conference presentations include:

• International Conference on Biological Inorganic Chemistry (ICBIC), Long Beach California, 2025
• Tiselius Symposium, Uppsala University, 2025
• European Biological Inorganic Chemistry Conference (EuroBIC), Münster, Germany, 2024
• International Conference on Hydrogenase and Other Redox Metalloenzymes, Walla Walla, USA, 2023

Conference organisation:

• International Conference on Hydrogenase and Other Redox Metalloenzymes, Leicester, 2026
• Royal Society of Chemistry Dalton Conference, Warwick, 2025
• MICRA, Leicester, 2024