Reengineered Vitamin B12 for Selective Aqueous Nitrate-to-Ammonium Electrocatalysis via Axial-Ligand Gating

Vitamin B12 (cobalamin) is an evolutionarily optimized Co-corrin redox cofactor capable of accessing low-valent cobalt states to mediate challenging biological transformations. Here, we reengineer this biological redox platform into an electrode-addressable catalyst for aqueous nitrate-to-ammonium electrocatalysis and demonstrate that catalytic selectivity is governed by the cooperative interplay between axial-ligand electronic tuning and local proton management. An isostructural series of lower-axial variants (C1-C4) was prepared by systematically modifying the native dimethylbenzimidazole environment, culminating in an l-histidine-ligated derivative (C4) bearing proximal -COOH/-NH₂ functionality. In mildly acidic MOPS buffer (pH 5.81), C4 exhibited the highest performance, achieving ∼90% NH₄ ⁺ Faradaic efficiency at -1.1 V vs SCE while effectively suppressing H₂ and hydroxylamine formation compared with the other derivatives. Electrochemical studies reveal that axial-ligand engineering modulates the Co-(III)/Co-(I) redox manifold, facilitating access to the catalytically active Co-(I) state and promoting nitrate activation. Mechanistic investigations support a pathway in which electrochemical reduction induces Co-CN bond dissociation and solvent coordination to generate a Co-(I)-solvent intermediate, followed by nitrate binding and proton-coupled electron transfer through nitrite and hydroxylamine intermediates to ammonium. ¹⁵N isotopic labeling and in situ spectroelectrochemical measurements confirm the formation of nitrate-derived NH₄ ⁺ and validate the proposed catalytic intermediates. To evaluate the transferability of this molecular design, the catalysts were immobilized on graphene oxide. The heterogeneous systems preserved the activity trend observed in solution, with C4@GO exhibiting the highest NH₄ ⁺ selectivity, demonstrating that the electronic effects imparted by lower axial-ligand engineering remain operative after immobilization. Together, these results establish vitamin B12 as a versatile Co-corrin platform and identify axial-ligand-controlled electronic tuning coupled with spatially programmed proton delivery as a general strategy for designing efficient molecular and hybrid electrocatalysts for selective multiproton, multielectron nitrate reduction in water.