Direct O 2 mediated oxidation of a Ni(II)N 3 O structural model complex for the active site of nickel acireductone dioxygenase (Ni-ARD): characterization, biomimetic reactivity, and enzymatic implications.

A new biomimetic model complex of the active site of acireductone dioxygenase (ARD) was synthesized and crystallographically characterized ( [Ni( ii )( N -(ethyl- N 'Me ₂ )(Py)(2- t -ButPhOH))(OTf)]- 1). 1 displays carbon-carbon oxidative cleavage activity in the presence of O ₂ towards the substrate 2-hydroxyacetophenone. This reactivity was monitored via UV-Visible and NMR spectroscopy. We postulate that the reactivity of 1 with O ₂ leads to the formation of a putative Ni(III)-superoxo transient species resulting from the direct activation of O ₂ via the nickel center during the oxidative reaction. This proposed intermediate and reaction mechanism were studied in detail using DFT calculations. 1 and its substrate bound derivatives display reactivity toward mild outer sphere oxidants, suggesting ease of access to high valent Ni coordination complexes, consistent with our calculations. If confirmed, the direct activation of O ₂ at a nickel center could have implications for the mechanism of action of ARD and other nickel-based dioxygenases and their respective non-traditional, enzymatic moonlighting functions, as well as contribute to a general understanding of direct oxidation of nickel(II) coordination complexes by O ₂ .