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

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.