Stoichiometry dependent modifications in synthetic heme peroxo reactivity with nitrosonium: a new paradigm for understanding heme mediated nitration chemistry.

Reactivity studies of synthetic heme-peroxo complexes with excess NO+ uncover an unprecedented reaction pathway that diverges sharply from the canonical nitric oxide dioxygenase (NOD) chemistry observed with 1 equiv. of NO+. When exposed to excess NO+, heme-peroxo adducts generate two stoichiometric equivalents of ˙NO2 radicals and concurrently yield "naked" ferric heme products. Comprehensive spectroscopic and computational analyses support this distinctive interconversion, and the resulting ˙NO2 radicals are shown to drive the nitration and oxidation of a series of bioinspired substrates. This stoichiometry-dependent reactivity shift highlights a long-proposed, but experimentally elusive principle governing interactions between heme-oxygen intermediates and nitrogen oxides, providing new mechanistic insight into nitrosative stress pathways relevant to analogous biological systems.