Defect‐Induced Electron Localization Promotes D₂O Dissociation and Nitrile Adsorption for Deuterated Amines.

Electrochemical reductive deuteration of nitriles is a promising strategy for synthesizing deuterated amines with D2O as the deuterated source. However, this reaction suffers from high overpotentials owing to the sluggish D2O dissociation kinetics and high thermodynamic stability of the C≡N triple bond. Here, low‐coordinated copper (LC−Cu) is designed to decrease the overpotential for the electrosynthesis of the precursor of Melatonin‐d4, 5‐methoxytryptamine‐d4, by 100 mV with a 68 % yield (Faradaic efficiency), which is 4 times greater than that of high‐coordinated copper (HC−Cu). The low coordinated sites induced an enrichment of electrons to concentrate K+ ions hydrated deuterium water (K⋅D2O) and decrease the energy of the Volmer step via the polarization effect, leading to a continuous supplementation of *D for the reductive deuteration of nitriles. Moreover, the enhanced local electric field changes the adsorption configuration of nitriles from a semibridge model to a flat model, leading to faster reduction kinetics of nitriles with a high reaction rate at lower potentials. High deuterium incorporation, a wide substrate scope, and easy gram‐scale synthesis over LC−Cu at 300 mA rationalize the design concept. Furthermore, the enhanced antitumor and antioxidation effects of Melatonin‐d4 highlight the great promise of deuterated drugs. [ABSTRACT FROM AUTHOR]