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-β-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 Cu_M, [(^TMGN₃S)Cu^I]⁺ ([1]⁺), and its O₂-bound analog [(^TMGN₃S)Cu^II(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: λ_max 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 k_H/k_D = 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.