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.