Nitric oxide (NO) is involved in many important biological processes in humans, but the overproduction of NO has detrimental consequences for human health. In contrast, denitrifying organisms efficiently detoxify NO. Fungi produce NO during anaerobic respiration, and detoxify NO by reduction to nitrous oxide (N2O) using a Cytochrome P450-type nitric oxide reductase (P450nor). The active site of this enzyme contains a ferric heme coordinated to a proximal cysteinate ligand. In the proposed mechanism, the ferric heme binds NO and is reduced to a ferrous HNO complex. It is speculated that this intermediate is protonated to a formally iron(IV)-NHOH- species as the critical intermediate for NO reduction. This intermediate then reacts with a second equivalent of NO to produce N2O, H2O, and the ferric heme resting state to complete the catalytic cycle. Since the mechanism of NO reduction is unknown, it is insightful to use synthetic models to elucidate the mechanism of this enzyme, in particular the electronic structure and reactivity of the central intermediate for catalysis. The work presented here focuses on the synthesis and characterization of a formally iron(IV)-hydroxylamide intermediate using synthetic heme models. In order to accomplish this, a bis-picket fence porphyrin is employed to prevent degradation of reactive intermediates by sterically shielding iron-bound axial ligands. The reactivity of our iron(IV)-hydroxylamide model towards NO is investigated to determine whether the iron(IV)-NHOH-intermediate is catalytically competent for NO reduction. Figure 1. <img src='https://acs-archive-assets2.s3.amazonaws.com/241nm/uploads/62272_figure1.jpg' alt='' />

Modeling the key intermediate in cytochrome P450 nitric oxide reductase: Electronic structure and reactivity

248th National Meeting (2014)

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