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

Abstract 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%).