Distortion of the [FeNO]₂ Core in Flavodiiron Nitric Oxide Reductase Models Inhibits N-N Bond Formation and Promotes...

Flavodiiron nitric oxide reductases (FNORs) carry out the reduction of nitric oxide (NO) to nitrous oxide (N₂O), allowing infectious pathogens to mitigate toxic levels of NO generated in the human immune response. We previously reported the model complex [Fe₂(BPMP)(OPr)(NO)₂](OTf)₂ (1, OPr^- = propionate) that contains two coplanar NO ligands and that is capable of quantitative NO reduction to N₂O [White et al. J. Am. Chem. Soc. 2018, 140, 2562-2574]. Here we investigate, for the first time, how a distortion of the active site affects the ability of the diiron core to mediate N₂O formation. For this purpose, we prepared several analogues of 1 that contain two monodentate ligands in place of the bridging carboxylate, [Fe₂(BPMP)(X)₂(NO)₂]^3+/1+ (2-X; X = triflate, 1-methylimidazole, or methanol). Structural data of 2-X show that without the bridging carboxylate, the diiron core expands, leading to elongated (O)N-N(O) distances (from 2.80 Å in 1 to 3.00-3.96 Å in 2-X) and distorted (O)N-Fe-Fe-N(O) dihedral angles (from coplanarity (5.9°) in 1 to 52.9-85.1° in 2-X). Whereas 1 produces quantitative amounts of N₂O upon one-electron reduction, N₂O production is substantially impeded in 2-X, to an initial 5-10% N₂O yield. The main products after reduction are unprecedented hs-Fe^II/{Fe(NO)₂}^9/10 dinitrosyl iron complexes (DNICs). Even though mononuclear DNICs are stable and do not show N-N coupling (since it is a spin-forbidden process), the hs-Fe^II/{Fe(NO)₂}^9/10 DNICs obtained from 2-X show unexpected reactivity and produce up to quantitative N₂O yields after 2 h. The implications of these results for the active site structure of FNORs are discussed.