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.