Synthetic Modeling of Nitric Oxide (NO) and Nitroxyl (HNO) Reactivity at Copper Sites
Williams, Kamille D.
Warren, Timothy H.
The N-O functionality is ubiquitous endogenously. The wide range of oxidation states of the nitrogen atom, (+5 to -3), is attributed to the various biologically relevant congeners containing the NO functionality. The simplest form of the N-O moiety is nitric oxide (NO), a stable free radical, which plays an important role in several biological processes such as neurotransmission, immune function, and oxidative stress. The one electron reduced form of nitric oxide is nitroxyl (HNO). Nitroxyl functionality is similar to but distinct from nitric oxide and some report the endogenous formation of NO via nitric oxide synthase (NOS) actually produces a nitric oxide precursor, presumably HNO. The actual production of nitric oxide requires co-factor copper-zinc superoxide dismutase (CuZnSOD), which has been shown to react with HNO to produce NO at a rate of k = 9 × 104 M-1s-1 in the same manner as superoxide dismutases convert O2- to O2.This work seeks to study the interaction between copper and nitroxyl and the formation of a copper-nitroxyl ([Cu](HNO) complex via computational studies and utilization of analogous nitrosobenzene (PhNO). Three binding modes (κ1-N, κ1-O, and η2-ON) were identified for both copper β-diketiminate nitroxyl ([Cu](HNO)) and nitrosobenzene ([Cu](PhNO) complexes. The two viable binding modes (κ1-N and η2-ON) were relatively close in energy and are in exchange at room temperature. The binding of nitrosobenzene to copper results in changes to the copper oxidation state as suggested by x-ray crystallography, cyclic voltammetry, and x-ray absorption studies. All of these studies suggest copper-nitrosobenzene complexes may be best classified as copper(II) compounds bound to nitrosobenzene where the ON bond order is 1.5.The β-diketiminate copper nitrosobenzene complexes can be synthesized via (a) the addition of nitrosobenzene to corresponding copper(I) acetonitriles (b) the double deprotonation of N-phenylhydroxylamine by copper(II) hydroxides and (c) via the disproportionation of N-phenylhydroxylamine via corresponding copper(I) acetonitriles. This work proposes a mechanism for the disproportionation of N-phenylhydroxylamine and investigates the requisite copper(II) nitroxide intermediates. The mechanistic insights and isolated intermediates put forth in this work will add potential inferences for larger related systems and can give insights into how to effect these biological NO processesing.
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