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

The central role of cupric superoxide intermediates proposed in hormone and neurotransmitter biosynthesis by noncoupled binuclear copper monooxygenases like dopamine-beta-monooxygenase has drawn significant attention to the unusual methionine ligation of the Cu-M ("Cu-B") 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 C-M, [((N3S)-N-TMG)Cu-I](+)([1](+)), and its O-2-bound analog [((N3S)-N-TMG)Cu-II(O-2(center dot-))](+) O-2](+)). 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 O-2 to a precooled solution of the cuprous precursor [1]B(C6F5)(4) (135 degrees C, 2-methyltetrahydrofuran (2-MeTHF)) reversibly forms [1 center dot O-2]B(C6F5)(4) (UV/vis spectroscopy: lambda(max) 442, 642, 742 nm). Resonance Raman studies (413 nm) using O-16(2) [O-18(2)] corroborated the identity of [1 center dot O-2](+) 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 angstrom. HAA reactivity between [1 center dot O-2](+) and TEMPO-H proceeds rapidly (1.28 X 10(-1) -135 degrees C, 2-MeTHF) with a primary kinetic isotope effect of k(H)/k(D) = 5.4. Comparisons of the O-2-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 N-4), are presented.