Carbon nanodot-sensitized regeneration of nicotinamide cofactor analogues for biocatalytic C=C bond reduction

Abstract

Ene reductases from the old yellow enzyme (OYE) family can catalyze stereoselective reduction of C=C bond. The provision of stoichiometric NAD(P)H makes their application economically not feasible. Herein, this thesis covers the design of the light-triggered regeneration of the reduced form of nicotinamide analogues (mNADHs) by employing nitrogen-doped carbon nanodots (N-CDs) and rhodium-based electron mediator (M) that was further coupled with OYE-driven catalysis. CDs are emerging nano-sized photocatalysts as they are low-cost, water-soluble, photostable, and biocompatible. Photoexcited electrons were transferred from N-CDs to M that exhibits the excellent regiospecficity for 1,4-mNADHs. Subsequently, mNADHs delivered hydrides to OYE for the conversion of 2-methylcyclohexenone to enantiopure (R)-2-methylcyclohexanone (enantiomeric excess &gt

99%). Furthermore, regeneration of mNADHs outperformed that of NADH in terms of turnover frequencies and total turnover numbers. Our results suggest that the application of the photochemical regeneration of better-than-nature mNADHs to redox enzymatic reactions can synthesize high-valued chemicals in a productive and economical way.