Many HNO-scavenging pathways exist to regulate its biological and pharmacological activities. Such reactions often involve ferric heme proteins and form an important basis for HNO probe development. However, mechanisms of HNO reactions with ferric heme proteins are largely unknown. We performed a computational investigation using metmyoglobin and catalase as representative ferric heme proteins with neutral and negatively charged axial ligands to provide the first detailed pathways. The results reproduced experimental barriers well with an average error of 0.11 kcal mol-1 . The rate-limiting step was found to be dissociation of the resting ligand or HNO coordination when there is no resting ligand. For both heme proteins, in contrast to the non-heme case, the reductive nitrosylation step was found to be barrierless proton-coupled electron transfer, which provides the major thermodynamic driving force for the overall reaction. The origin of the difference in reactivity between metmyoglobin and catalase was also revealed.
Keywords: bioinorganic chemistry; computational chemistry; heme proteins; nitrogen oxides; reaction mechanisms.
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