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

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 ΔG‡ = 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).