Highly Selective Electrocatalytic 1,4‐NADH Regeneration Based on Host–Guest Recognition Mediated by Cucurbit[8]uril on NiO

Efficient regeneration of nicotinamide adenine dinucleotide (NADH) cofactors, particularly 1,4-NADH, is crucial for advancing oxidoreductase catalysis. Electrocatalysis provides a promising route for 1,4-NADH regeneration, but an expensive catalyst, typically a rhodium organometallic complex, is frequently required to guarantee the high selectivity of 1,4-NADH, significantly limiting its large-scale application. Herein, inspired by the catalytic pocket and enzyme-substrate interaction in nature, a direct electrochemical 1,4-NADH regeneration route was designed by modification of the surface of nickel oxide (NiO) with cucurbit[8]uril (CB[8]) (denoted as CB[8]-NiO). The host-guest interaction between CB[8] and NAD⁺ was proved, which is similar in principle to substrate-enzyme-specific recognition. CB[8] acted as a catalytic pocket for NAD⁺, providing a suitable cavity volume to accommodate the positively charged nicotinamide part of NAD⁺. NAD⁺ entered the CB[8] cavity and approached the surface-adsorbed hydrogen atoms on NiO in a reaction-ready configuration to achieve the regioselective 1,4-NADH regeneration. Remarkably higher 1,4-NADH selectivity of 97.8% on CB[8]-NiO was obtained at -0.47 V versus reversible hydrogen electrode (RHE) than that of bare NiO (77.4%).