Abstract

Oxidation and reduction reactions are fundamental to all living organisms, which must extract and process energy from different sources. This lecture will begin by outlining the early discovery and subsequent development of enzymes as extremely efficient (virtually reversible in the Nernstian sense) electrocatalysts, suggesting that minimising overpotential (electrochemical activation energy) would have been a driving factor in early evolution. The lecture will continue with the concept of the Electrochemical Leaf (e-Leaf), a unique platform for biocatalysis that involves the nanoconfinement of complex enzyme cascades (to achieve tandem++ catalysis) in mesoporous electrode materials, with interactive energization and control via electrochemically reversible NAD (H) recycling. The tight channelling of cascade intermediates opens up electrochemistry to all classes of enzymes, since cascade intermediates now become current carriers. The e-Leaf can be exploited for lego-style biosensing and production of complex compounds including pharmaceuticals. It enables studies of the collective action of enzymes that are concentrated in enclosures and which, through their high selectivities and activities, can become analogous to the logic gates of electronic circuits. The outcome – ‘cascadetronics’ – has implications for how living cells operate.

Some relevant papers.

Diode-like Behaviour of a Mitochondrial Electron-transport Enzyme. A. Sucheta, B. A. C. Ackrell, B. Cochran and F. A. Armstrong. Nature 356, 361-362 (1992).

Reversibility and Efficiency in Electrocatalytic Energy Conversion and Lessons from Enzymes. F. A. Armstrong and J. Hirst. Proc. Natl. Acad. Sci. USA 108 , 14049-14054 (2011).

Mechanism of Hydrogen Activation by [NiFe]-hydrogenases. R. M. Evans, E. J. Brooke, S. A. M. Wehlin, E. Nomerotskaia, F. Sargent, S. B. Carr, S. E. V. Phillips and F. A. Armstrong. Nature Chem. Biol. 12, 46-50 (2016).

From Protein Film Electrochemistry to Nanoconfined Enzyme Cascades and the Electrochemical Leaf. F. A. Armstrong, B. Cheng, R. A. Herold, C. F. Megarity and Bhavin Siritanaratkul. Chem. Rev. 123, 5421–5458 (2023),

Replacing a Cysteine Ligand by Selenocysteine in a [NiFe]-Hydrogenase Unlocks Hydrogen Production Activity and Addresses the Role of Concerted Proton-Coupled Electron Transfer in Electrocatalytic Reversibility. R. M. Evans, N. Krahn, J. Weiss, K. A. Vincent, D. Söll and F. A. Armstrong. J. Amer. Chem. Soc. 146, 16971-16976 (2024).

Interactive Biocatalysis Achieved by Driving Enzyme Cascades inside a Porous Conducting Material. B. Siritanaratkul, C. F. Megarity, R. A. Herold and F. A. Armstrong. Communications Chemistry, 7: 132 (2024).

Building Localized NADP Recycling Circuits to Advance Enzyme Cascadetronics. R. A. Herold, C. J. Schofield and F. A. Armstrong. Angewandte Chemie. Int. Ed., 64, e202414176 (2025).