Structured Electrodes Enable High‐Rate and Selective Electrochemical Nicotinamide Adenine Dinucleotide Regeneration for Biocatalysis

Direct electrochemical regeneration of nicotinamide adenine dinucleotide (NADH) presents a cost-effective and sustainable alternative to enzymatic recycling approaches, yet its industrial application has been hampered by low reaction rates and insufficient selectivity. In this study, we demonstrate the integration of electrochemical NADH regeneration into a zero-gap electrolyzer and systematically evaluate copper, silver, and titanium electrodes with respect to activity and selectivity toward 1,4-NADH. Titanium felt exhibits 100% selectivity for this reaction at a rate of 194 µmol h^-1 under mild conditions (10 mA cm^-2). Increasing the current density to 100 mA cm^-2 significantly enhances the activity, maintaining high selectivity, with titanium and copper electrodes achieving 459 and 258 µmol h^-1, respectively. Notably, coarser copper meshes further boost 1,4-NADH formation, reaching 791 µmol h^-1 at 75% selectivity, underlining the critical role of electrode morphology. This work underscores the potential of scalable, efficient, and selective electrochemical cofactor regeneration, and provides a proof of concept for its application in enzymatic hydrogenation, exemplified by the reduction of acetophenone. We pioneer direct electrochemical NADH regeneration in a zero-gap electrolyzer, optimizing catalysts for high reaction rates and selectivities. Porous titanium cathodes achieve a selectivity of 100% at reaction rates surpassing the state of the art by a factor of over 3.4. Our findings highlight the scalability of this method for industrial enzymatic catalysis, demonstrated through acetophenone hydrogenation.