A Highly Selective Artificial Coenzyme: 1,1′‐Ethylene‐2,2′‐bipyridinium Dibromide for Bioelectrocatalytic Reduction of CO ₂ to Formate by Formate Dehydrogenase

Abstract The inherent instability and suboptimal electron transfer efficiency of natural coenzymes like NADH pose fundamental challenges in enzymatic CO 2 electroreduction. We address this critical limitation through an electrochemical‐enzymatic hybrid system employing 1,1′‐ethylene‐2,2′‐bipyridinium (DB ∙+ ) as an artificial coenzyme for Candida boidinii formate dehydrogenase ( Cb FDH). This synthetic mediator demonstrates superior electrochemical regeneration at −0.65 V versus Ag/AgCl, maintaining unidirectional redox activity that exclusively drives CO 2 ‐to‐formate conversion while eliminating parasitic reverse reactions. Our engineered three‐compartment electrolyzer achieves spatial decoupling of DB ∙+ regeneration from enzymatic catalysis, delivering six distinct current response cycles within 60 min and sustaining a formate production rate of 0.158 mM/min. System optimization at pH 6.3 yields a maximum formate concentration of 9.5 mM with 75.5% Faradaic efficiency. Mechanistic investigations reveal pH‐dependent substrate specificity: HCO 3 − acts as a competitive inhibitor under alkaline conditions (pH 7.4), while CO 2 /H 2 CO 3 serves as the exclusive enzymatic substrate at optimal pH 6.3. This work pioneers a paradigm for substituting biological cofactors with synthetic analogues, proposing a scalable architecture that harmonizes electrochemical potential regulation with enzymatic stereoselectivity for sustainable carbon utilization. Future research may prioritize depositing high‐specific‐surface‐area conductive materials on electrodes to boost active sites or genetically modifying formate dehydrogenase to optimize enzyme–coenzyme interactions and enhance catalytic efficiency.