Nitric oxide (NO) is an endogenously generated molecule that has gained significant interest over the past 30 years. In humans, NO acts as a signaling molecule at low (nM) concentrations in nerve signal transduction, and also acts as an anti-inflammatory agent and vasodilator. On the other hand, NO can be generated in high (uM) concentrations by inducible nitric oxide synthase (iNOS) as an immune defense agent, toxic to most invasive pathogens. However, some pathogens have evolved flavodiiron nitric oxide reductases (FNORs) that can detoxify NO via the two electron reduction of 2NO to N2O, resulting in pathogen proliferation. The active site of FNORs consists of a non-heme diiron core with His and carboxylate ligation, and a redox-active FMN cofactor sitting within ~4Å of the active site. Despite the significance of these enzymes in bacterial pathogenesis, the mechanism of NO reduction is not unambiguously defined. The complex [Fe2(BPMP)(OPr)(NO)2](OTf)2 was synthesized as a model for FNORs, and its reduction of NO to N2O in the presence of reductant was spectroscopically characterized. Importantly, upon addition of one equivalent of cobaltocene, the complex produces N2O rapidly and quantitatively. This supports a “semi-reduced” mechanism, whereby one reducing equivalent is required to activate the diferrous dinitrosyl active site for N-N coupling, while the second reducing equivalent is provided by the diiron core.

Synthesis, characterization, and reactivity studies of a flavodiiron nitric oxide reductase model complex

254th National Meeting (2017)

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