Exploration and exploitation of alloelectronic catalysis

The kinetic and thermodynamic rules that govern synthetic chemistry should be considered limitations to overcome. Thermodynamically, spontaneous chemical reactions must proceed energetically downhill. Kinetically, the rate of a reaction is constrained by the slowest chemical step, which limits the extent to which a reaction can accelerated by catalysis. Biology overcomes these limitations by expending energy, coupling the reactions of ‘energy carrier’ molecules to thermodynamically or kinetically unfavourable processes, enabling nitrogen fixation under mild conditions (driven catalysis), ‘uphill’ adenosine triphosphate (ATP) synthesis (endergonic synthesis), and high-fidelity sequence-specific polymerization (programmable synthesis) by the ribosome. Replicating this strategy would be transformative in synthetic chemistry, changing the way that chemists think about and perform synthesis. Crucial to biology’s driven reactivity is allostery, where ligand binding adjacent to an enzyme active site induces a conformational change that modulates catalytic activity. When these conformational changes are driven by the reaction of ‘energy carrier’ molecules at the allosteric site, energy can be transduced to the catalysed reaction to permit nonequilibrium control. Instead of complex conformational changes, the aim of this proposal is to develop and explore alloelectronic catalysis. AlloElectro aims to exploit simple and controlled electronic changes in the ligand field (i.e. at an ‘alloelectronic’ site) of common metal catalysts. Reversible changes in the electronic environment of the ‘active site’ will enable a metal catalyst to adapt to individual elementary steps and overcome them, with the energy input capable of being transduced to drive the catalysed reaction uphill. The alloelectronic effect therefore results in new opportunities for ‘contra-thermodynamic’ reactivity, driven catalysis and programmable synthesis using established catalysts, ligands and methods.