Comparative insights into transition metal mediated nitrite to nitric oxide conversion

Nitrite (NO₂^-) is a widespread environmental pollutant that contributes to eutrophication, nitrosative stress, and N-nitrosamine formation. The chemical factors that make copper optimal for nitrite to NO conversion remain central to understanding copper nitrite reductase activity. Here, we compare ascorbate-driven nitrite reduction using transition-metal salts and synthesized ligand-supported Cu(II) complexes under identical aqueous conditions. CuCl₂ shows the highest activity, producing NO quantitatively within 8 s with an initial NO-generation rate of 15.6 cm³ s^-1 and a TOF of 45 000 h^-1. The synthesized copper complexes, (en)CuCl₂, DMEDACuCl₂, and TMEDACuCl₂, also demonstrate rapid NO formation, confirming that Cu(II)/Cu(I) cycling is the key catalytic platform. Importantly, the NO generation rate of the copper series generally follows the Cu(II)/Cu(I) reduction potential: complexes with more positive potentials show faster NO release, consistent with easier Cu(II) reduction and more efficient electron transfer to HNO₂. TMEDACuCl₂ deviates positively from this trend, suggesting additional ligand effects such as Cu(I) stabilization, altered coordination geometry, or improved substrate access. UV-vis spectroscopy, cyclic voltammetry, ¹⁵N-labeling FTIR, and (TPP)CoNO trapping support a Cu-centered proton-coupled electron-transfer pathway. In contrast, iron forms iron-nitrosyl species that decrease freely detectable NO and limit the effective turnover. These results establish copper as the optimal redox platform for fast nitrite-to-NO conversion.