Facet-Engineered Copper Electrocatalysts Enable Sustainable NADH Regeneration with High Efficiency

Electrochemical regeneration of the nicotinamide cofactor (NADH) provides a sustainable approach to enzymatic reactions. However, the low productivity and selectivity of bioactive 1,4-NADH limit its broad applications. The hydrogenation of NAD⁺ to 1,4-NADH at the electrode surface is strongly coupled to the conformation of adsorbed NAD*, the formation of adsorbed hydrogen (H_ad), and the H_ad transfer to NAD*. Therefore, searching for materials with a suitable NAD* conformation, low H_ad formation energy, and rapid NAD* hydrogenation becomes a key task for the research. In this study, the (111) facet of Cu was found to exhibit a higher 1,4-NADH selectivity of 86.4%, compared to 50.4% and 57.4% for (100) and (110) facets, respectively. Density functional theory (DFT) calculations revealed that the high selectivity of Cu(111) stemmed from the favorable conformation of adsorbed NAD* and the reduced hydrogenation barrier. Subsequently, a Cu nanowire electrode with a (111)-dominant surface and abundant grain boundaries, Cu_gb(111), was constructed. Electrochemical kinetic analysis and DFT calculations demonstrated that the grain boundaries reduce the reaction barrier of H_ad formation. A record-high 1,4-NADH productivity of 73.5 μmol h^-1 cm^-2 was achieved by Cu_gb(111), while the 1,4-NADH selectivity was well-maintained at 84.7%. This study elucidates the effects of crystal facets and grain boundaries on regulating the selectivity and productivity of 1,4-NADH, providing a pathway for renewable energy-powered, high-efficiency green biomanufacturing.