Nitrite Formation at a Diiron Dinitrosyl Complex

Abstract

Pathogenic bacteria employ iron-containing enzymes to detoxify nitric oxide (NO • ) produced by mammals as part of their immune response. Two classes of diiron proteins, flavodiiron nitric oxide reductases (FNORs) and the hemerythrin-like proteins from mycobacteria (HLPs), are upregulated in bacteria in response to an increased local NO • concentration. While FNORs reduce NO • to nitrous oxide (N 2 O), the HLPs have been found to either reduce nitrite to NO • (YtfE), or oxidize NO • to nitrite (Mka-HLP). Various structural and functional models of the diiron site in FNORs have been developed over the years. However, the NO • oxidation reactivity of Mka-HLP has yet to be replicated with a synthetic complex. Compared to the FNORs, the coordination environment of the diiron site in Mka-HLP contains one less carboxylate ligand and, therefore, is expected to be more electron-poor. Herein, we synthesized a new diiron complex that models the electron-poor coordination environment of the Mka-HLP diiron site. The diferrous precursor Fe II Fe II reacts with NO • to form a diiron dinitrosyl species ({FeNO} 72 ), which is in equilibrium with a mononitrosyl diiron species (Fe II {FeNO} 7 ) in solution. Both complexes can be isolated and fully characterized. However, only oxidation of {FeNO} 7 2 produced nitrite in high yield (71%). Our study provides the first model that reproduces the NO • oxidase reactivity of Mka-HLP and suggests intermediacy of an {FeNO} 6 /{FeNO} 7 species.

Exploring second coordination sphere effects in flavodiiron nitric oxide reductase model complexes

“…1, but the mechanism of N 2 O formation by FNORs is still debated due to the numerous contributing factors involved in the process. 38–42…”