Stoichiometry Dependent Modifications in Synthetic Heme Peroxo Reactivity with Nitrosonium: A New Paradigm for Understanding Heme Mediated Nitration Chemistry

Abstract

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 under 1 equiv of NO⁺. When exposed to excess NO⁺ (4 equiv), 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 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.