The Semireduced Mechanism for Nitric Oxide Reduction by Non-Heme Diiron Complexes: Modeling Flavodiiron Nitric Oxide Reductases

Flavodiiron nitric oxide reductases
(FNORs) are a subclass of flavodiiron
proteins (FDPs) capable of preferential binding and subsequent reduction
of NO to N2O. FNORs are found in certain pathogenic bacteria,
equipping them with resistance to nitrosative stress, generated as
a part of the immune defense in humans, and allowing them to proliferate.
Here, we report the spectroscopic characterization and detailed reactivity
studies of the diiron dinitrosyl model complex [Fe2(BPMP)­(OPr)­(NO)2]­(OTf)2 for the FNOR active site that is capable
of reducing NO to N2O [Zheng et al., J. Am. Chem.
Soc. 2013, 135, 4902–4905].
Using UV–vis spectroscopy, cyclic voltammetry, and spectro-electrochemistry,
we show that one reductive equivalent is in fact sufficient for the
quantitative generation of N2O, following a semireduced
reaction mechanism. This reaction is very efficient and produces N2O with a first-order rate constant k >
102 s–1. Further isotope labeling studies
confirm
an intramolecular N–N coupling mechanism, consistent with the
rapid time scale of the reduction and a very low barrier for N–N
bond formation. Accordingly, the reaction proceeds at −80 °C,
allowing for the direct observation of the mixed-valent product of
the reaction. At higher temperatures, the initial reaction product
is unstable and decays, ultimately generating the diferrous complex
[Fe2(BPMP)­(OPr)2]­(OTf) and an unidentified ferric
product. These results combined offer deep insight into the mechanism
of NO reduction by the relevant model complex [Fe2(BPMP)­(OPr)­(NO)2]2+ and provide direct evidence that the semireduced
mechanism would constitute a highly efficient pathway to accomplish
NO reduction to N2O in FNORs and in synthetic catalysts.