Revisiting the Reaction Mechanism of Electrochemical 1,4‐NADH Regeneration on Carbon Electrodes

The direct electrochemical regeneration of 1,4‐NADH, an essential cofactor in many enzymatic reactions, has emerged as a promising approach due to its compatibility with renewable electricity, reduced CO 2 emissions, and significantly lower environmental impact (E‐factor). However, its application is challenged by low selectivity and high overpotentials. This process is primarily studied on metal electrodes, where it often overlaps with the hydrogen evolution reaction (HER). The occurrence of HER is considered important, as most proposed mechanisms for NAD + reduction reaction (NADRR) suggest that adsorbed hydrogen is a necessary step for 1,4‐NADH formation. However, on carbon materials, appears to be a region where NADRR and HER do not overlap. According to current understanding, this would lead only to dimer formation on carbon, contrary to experimental findings from our research and other literature. In this study, we propose a new mechanism for 1,4‐NADH formation at low overpotentials with proton donation occurring directly from the buffer, bypassing the formation of adsorbed hydrogen (H ads ). We identified optimal conditions for achieving high selectivity of 1,4‐NADH regeneration, resulting in 91% selectivity at 77% conversion, with no HER occurrence and low E‐factor. These conditions include low catalyst loadings, low initial NAD⁺ concentrations, and low overpotentials.