What Is the Right Level of Activation of a High-Spin {FeNO} 7 Complex to Enable Direct N-N Coupling? Mechanistic Insight into Flavodiiron NO Reductases.

Flavodiiron nitric oxide reductases (FNORs), found in pathogenic bacteria, are capable of reducing nitric oxide (NO) to nitrous oxide (N ₂ O) to detoxify NO released by the human immune system. Previously, we reported the first FNOR model system that mediates direct NO reduction (Dong, H. T.; J. Am. Chem. Soc. 2018, 140, 13429-13440), but no intermediate of the reaction could be characterized. Here, we present a new set of model complexes that, depending on the ligand substitution, can either mediate direct NO reduction or stabilize a highly activated high-spin (hs) {FeNO} ⁷ complex, the first intermediate of the reaction. The precursors, [{Fe ^II (MPA-(RPhO) ₂ )} ₂ ] ( 1 , R = H and 2 , R = ^t Bu, Me), were prepared first and fully characterized. Complex 1 (without steric protection) directly reduces NO to N ₂ O almost quantitatively, which constitutes only the second example of this reaction in model systems. Contrarily, the reaction of sterically protected 2 with NO forms the stable mononitrosyl complex 3 , which shows one of the lowest N-O stretching frequencies (1689 cm ^-1 ) observed so far for a mononuclear hs-{FeNO} ⁷ complex. This study confirms that an N-O stretch ≤1700 cm ^-1 represents the appropriate level of activation of the FeNO unit to enable direct NO reduction. The higher activation level of these hs-{FeNO} ⁷ complexes required for NO reduction compared to those formed in FNORs emphasizes the importance of hydrogen bonding residues in the active sites of FNORs to activate the bound NO ligands for direct N-N coupling and N ₂ O formation. The implications of these results for FNORs are further discussed.