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Flavodiiron nitric oxide reductases (FNORs) protect microbes from nitrosative stress under anaerobic conditions by mediating the reduction of nitric oxide (NO) to nitrous oxide (N 2 O). The proposed mechanism for the catalytic reduction of NO by FNORs involves a dinitrosyldiiron intermediate with a [hs-{FeNO} 7 ] 2 formulation, which produces N 2 O and a diferric species. Moreover, both NO and hydrogen sulfide (H 2 S) have been implicated in several similar physiological functions in biology and are also known to cross paths in cell signaling. Here we report the synthesis, spectroscopic and theoretical characterization, and N 2 O production activity of an unprecedented monohydrosulfidodinitrosyldiiron compound, with a [(HS)hs-{FeNO} 7 /hs-{FeNO} 7 ] formulation, that models the key dinitrosyl intermediate of FNORs. The generation of N 2 O from this unique compound follows a semireduced pathway, where one-electron reduction generates a reactive hs-{FeNO} 8 center via the occupation of an Fe-NO antibonding orbital. In contrast to the well-known reactivity of H 2 S and NO, the coordinated hydrosulfide remains unreactive toward NO and acts only as a spectator ligand during the NO reduction process.

Reaction of [Fe 2 (N-Et-HPTB)(CH 3 COS)](BF 4 ) 2 (1) with (NO)(BF 4 ) produces a nonheme mononitrosyl diiron(II) complex, [Fe 2 (N-Et-HPTB)(NO)(DMF) 3 ](BF 4 ) 3 (2). Complex 2 is the first example of a [Fe II {Fe(NO)} 7 ] species and is also the first example of a mononitrosyl diiron(II) complex that mediates the reduction of NO to N 2 O. This work describes the selective synthesis, detailed characterization and NO reduction activity of 2 and thus provides new insights regarding the mechanism of flavodiiron nitric oxide reductases.

Two non-heme iron-nitrosyl species, [Fe2(N-Et-HPTB)(O2CPh)(NO)2](BF4)2 (1a) and [Fe2(N-Et-HPTB)(DMF)2(NO)(OH)](BF4)3 (2a), are characterized by FTIR and resonance Raman spectroscopy. Binding of NO is reversible in both complexes, which are prone to NO photolysis under visible light illumination. Photoproduction of N2O occurs in high yield for 1a but not 2a. Low-temperature FTIR photolysis experiments with 1a in acetonitrile do not reveal any intermediate species, but in THF at room temperature, a new {FeNO}(7) species quickly forms under illumination and exhibits a ν(NO) vibration indicative of nitroxyl-like character. This metastable species reacts further under illumination to produce N2O. A reaction mechanism is proposed, and implications for NO reduction in flavodiiron proteins are discussed.

Inducible NO synthase in mammals helps to produce up to micromolar concentration of nitric oxide (NO) which acts as a key immune defense agent to kill invading pathogens. In order to counter the toxic effects of NO, the pathogens have expressed flavodiiron nitric oxide reductases (FNORs). The FNORs reduce the toxic NO into much less toxic N 2 O and thus help the pathogens to survive under nitrosative stress. As a consequence, these pathogens proliferate in the human body and cause harmful infections. An appreciable amount of research work has been performed to discover the true mechanism of the FNORs. Different mechanisms involving both mononitrosyl and dinitrosyl diiron complexes as key intermediates are proposed. Evidences for the involvement of new intermediates and more and more experimental evidences for existing ones in the proposed catalytic cycle of FNORs are coming up. These interesting biochemical events have recently boosted the biomimetic chemistry of the FNOR activity as well. This article discusses the importance and the currently understood mechanistic aspects of FNORs. Structural and functional models for the active site of FNORs are discussed along with their success and limitations. Possible future prospects of the modeling chemistry are also suggested. [ABSTRACT FROM AUTHOR]