The central role of cupric superoxide intermediates proposed in hormone and neurotransmitter biosynthesis by non-coupled binuclear copper monooxygenases like dopamine-β-monooxygenase has drawn significant attention to the unusual methionine ligation of the CuM (“CuB”) active site that processes (formally reduces) dioxygen. The active site of this class of enzymes is characterized by two distant (11–14 Å) magnetically “non-coupled” copper centers CuH (CuA) and CuM (CuB). While the His3-ligated CuH center participates in electron relay, the subsequently reduced CuM site with a MetHis2 chelation plays the major role in O2 activation and substrate-binding. The copper–sulfur interaction at this practically mononuclear CuM site has proven critical for turnover, raising still-unresolved questions concerning the enzyme’s selection of an easy to oxidize Met residue to facilitate C–H oxygenation. Here, we describe 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 a demonstrated hydrogen atom abstraction (HAA) reactivity. Introduction of O2 to a pre-cooled 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. N4 vs N3S), are presented. The structure and activity of [1–O2]+ suggests that future studies can provide insights into the role of a sulfur-based ligand in CuI/O2 oxidative reactivity including in this family of monooxygenases.

Characterization of a thioether-ligated cupric superoxide model complex with hydrogen atom abstraction reactivity

ACS Spring Meeting 2021

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