Abstract Lehnert

Nitric oxide (NO) is biosynthesized in mammals as a signaling molecule, and as an immune defense agent (by macrophages) to fight off invading pathogens. However, pathogenic bacteria use flavodiiron NO reductases (FNORs) as a protection against exogenous NO. These enzymes reduce two molecules of NO to non-toxic N2O and water. FNORs are therefore implicated in bacterial pathogenesis as these enzymes equip these microbes with resistance against the mammalian immune defense agent NO. Despite this biomedical significance, the mechanism of these enzymes is not well understood. FNORs contain a typical non-heme diiron active site, which is in close proximity (~4 Å) of the flavin (FMN) binding domain of an adjacent subunit. We have prepared the diiron dinitrosyl model complex [Fe2(BPMP)(OPr)(NO)2]X2 (X = BPh4, OTf, BF4) and characterized it using a number of spectroscopic techniques, and studied its reactivity towards N2O formation. The crystal structure of this complex shows two end-on coordinated {FeNO}7 units in a coplanar arrangement. Importantly, reduction of this complex leads to the clean formation of N2O in quantitative yield, as previously reported. This complex therefore represents the first example of a functional model system for FNORs. More recent investigations have shown that this complex undergoes quantitative N-N bond formation and N2O release in the presence of 1 equivalent of reductant, via a semireduced {FeNO}7-{FeNO}8 intermediate. Spectroscopic studies on the stable, mononuclear {FeNO}8 complex [Fe(TMG3tren)(NO)]+ show that reduction of a high-spin {FeNO}7 complex results in a weakening of the Fe-NO bond and an increase of radical character on the bound NO ligand, leading to the observed increase in reactivity. More recent efforts are now directed toward investigating whether a direct NO reduction from a diferrous model complex can be accomplished.