American Chemical Society
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A Thioether-Ligated Cupric Superoxide Model with Hydrogen Atom Abstraction Reactivity

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journal contribution
posted on 2021-03-08, 22:29 authored by Mayukh Bhadra, Wesley J. Transue, Hyeongtaek Lim, Ryan E. Cowley, Jung Yoon C. Lee, Maxime A. Siegler, Patrick Josephs, Gerald Henkel, Markus Lerch, Siegfried Schindler, Adam Neuba, Keith O. Hodgson, Britt Hedman, Edward I. Solomon, Kenneth D. Karlin
The central role of cupric superoxide intermediates proposed in hormone and neurotransmitter biosynthesis by noncoupled binuclear copper monooxygenases like dopamine-β-monooxygenase has drawn significant attention to the unusual methionine ligation of the CuM (“CuB”) active site characteristic of this class of enzymes. The copper–sulfur interaction has proven critical for turnover, raising still-unresolved questions concerning Nature’s selection of an oxidizable Met residue to facilitate C–H oxygenation. We describe herein a model for CuM, [(TMGN3S)­CuI]+ ([1]+), and its O2-bound analog [(TMGN3S)­CuII(O2•–)]+ ([1·O2]+). The latter is the first reported cupric superoxide with an experimentally proven Cu–S bond which also possesses demonstrated hydrogen atom abstraction (HAA) reactivity. Introduction of O2 to a precooled solution of the cuprous precursor [1]­B­(C6F5)4 (−135 °C, 2-methyltetra­hydrofuran (2-MeTHF)) reversibly forms [1·O2]­B­(C6F5)4 (UV/vis spectroscopy: λmax 442, 642, 742 nm). Resonance Raman studies (413 nm) using 16O2 [18O2] corroborated the identity of [1·O2]+ by revealing Cu–O (446 [425] cm–1) and O–O (1105 [1042] cm–1) stretches, and extended X-ray absorption fine structure (EXAFS) spectroscopy showed a Cu–S interatomic distance of 2.55 Å. HAA reactivity between [1·O2]+ and TEMPO–H proceeds rapidly (1.28 × 10–1 M–1 s–1, −135 °C, 2-MeTHF) with a primary kinetic isotope effect of kH/kD = 5.4. Comparisons of the O2-binding behavior and redox activity of [1]+ vs [2]+, the latter a close analog of [1]+ but with all N atom ligation (i.e., N3S vs N4), are presented.