Mechanism of N-N Bond Formation by Transition Metal-Nitrosyl Complexes: Modeling Flavodiiron Nitric Oxide Reductases.

Abstract

Nitric oxide (NO) has a number of important biological functions, including nerve signaling transduction, blood pressure control, and, at higher concentrations, immune defense. A number of pathogenic bacteria have developed methods of degrading this toxic molecule through the use of flavodiiron nitric oxide reductases (FNORs), which utilize a nonheme diiron active site to reduce NO → N2O. The well-characterized diiron model complex [Fe2(BPMP)(OPr)(NO)2]2+ (BPMP- = 2,6-bis[(bis(2- pyridylmethyl)amino)methyl]-4-methylphenolate), which mimics both the active site structure and reactivity of these enzymes, offers key insight into the mechanism of FNORs. Presently, we have used computational methods to elucidate a coherent reaction mechanism that shows how one and two-electron reduction of this complex induces N-N bond formation and N2O generation, while the parent complex remains stable. The initial formation of a N-N bond to generate hyponitrite (N2O22-) follows a radical-type coupling mechanism, which requires strong Fe-NO π-interactions to be overcome to effectively oxidize the iron centers. Hyponitrite formation provides the largest activation barrier with Δ G‡ = 7-8 kcal/mol (average of several functionals) in the two-electron, super-reduced mechanism. This is followed by the formation of a N2O22- complex with a novel binding mode for nonheme diiron systems, allowing for the facile release of N2O with the assistance of a carboxylate shift. This provides sufficient thermodynamic driving force for the reaction to proceed via N2O formation alone. Surprisingly, the one-electron "semireduced" mechanism is predicted to be competitive with the super-reduced mechanism. This is due to the asymmetry imparted by the BPMP- ligand, allowing a one-electron reduction to overcome one of the primary Fe-NO π-interactions. Generally, mediation of N2O formation by high-spin [{M-NO-}]2 cores depends on the ease of oxidizing the M centers and breaking of the M-NO π-bonds to formally generate a "full" 3NO- unit, allowing for the critical step of N-N bond formation to proceed (via a radical-type coupling mechanism).