A Rh complex anchored cathode for cofactor regeneration and asymmetric reduction coupled with immobilized enzymes

Chiral compounds have a huge market demand in the fields of pharmaceuticals, pesticides, and fine chemicals. Enzymatic electrosynthesis can couple enzyme catalysis, possessing high product purity, high efficiency, and mild conditions, with electrochemical regeneration of expensive cofactor nicotinamide adenine dinucleotide (NADH), possessing easy process monitoring and simple operation for efficient chiral synthesis. In this study, hydrophobic covalent organic framework (COF) was synthesized as the immobilized carrier, which not only enhanced the enzyme catalysis through enriching substrate but also enhanced the stability and reuse of the enzyme. Besides, Rh complex was anchored on hydrophilically-modified electrode to promote the regeneration of NADH, where the anchor of Rh complex can effectively avoid the mutual deactivation from the interference between electron mediator and enzyme, and simplify the separation of products. The immobilized enzyme catalysis and the electrochemical cofactor regeneration were coupled to construct an enzymatic electrosynthesis system for the efficient asymmetric reduction to obtain chiral alcohols, with a maximum turnover frequency (TOF) of 101.1 h⁻¹. Furthermore, the relevant parameters of the system were optimized, and the substrate scope was expanded.