Exploiting Bidirectional Electrocatalysis by a Nanoconfined Enzyme Cascade to Drive and Control Enantioselective Reactions

The ability to drive and observe rapid enzyme catalysis in both directions is an important and natural consequence of immobilizing cascade components within electrode nanopores and coupling reactions to the fast, quasi-reversible NADP+/NADPH electrochemistry mediated by bound ferredoxin-NADP+ reductase. This approach has been exploited to investigate and control the redox interconversions between a ketone and secondary alcohol enantiomers catalyzed by enantioselective alcohol dehydrogenase variants. An anticipated advantage of the bidirectionality, in allowing a single cascade to be cycled back and forth while exploiting kinetic selectivity, was the ability to achieve a simple one-electrode de-racemizer; significantly, this was overturned because the nanoconfined enzyme system strongly directs racemization, the thermodynamic outcome. By modifying the concept, it was easily demonstrated that efficient one-pot de-racemizers can be achieved by using two electrodes in sequence, each containing an alcohol dehydrogenase that is enantioselective for one of the half-cycles.