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

Abstract

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 , [( TMG N 3 S)Cu I ] + ([1] + ), and its O 2 -bound analog [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(C 6 F 5 ) 4 (−135 °C, 2-methyltetrahydrofuran (2-MeTHF)) reversibly forms [1•O 2 ]B(C 6 F 5 ) 4 (UV/vis spectroscopy: λ max 442, 642, 742 nm). Resonance Raman studies (413 nm) using 16 O 2 [ 18 O 2 ] corroborated the identity of [1•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 Å. HAA reactivity between [1•O 2 ] + 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 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., N 3 S vs N 4 ), are presented.

Thioether‐Containing Copper Complexes as PHM, DβM, and TβM Model Systems

“…In con-trast, oxygenation in 2-MeTHF at À 135 °C permitted access to the end-on cupric-superoxo [{(TMG et ) 2 N et SEt}Cu II (η 1 -O 2 )] + , based on UV-vis spectroscopy. [37] Features at λ max = 442 (3700), 642 (1525) and 742 nm (1675) match well those of its all-nitrogen analog [{(TMG et ) 3 N}Cu II (η 1 -O 2 )] + , which was structurally authenticated. [39] Confirmation of the assignment by rR was obtained with 413 nm laser excitation affording enhanced isotope-sensitive bands at 446 and 1105 cm À 1 that shifted to 425 and 1042 cm À 1 upon 18 O 2 labeling.…”

“…Although the compounds with tetradentate N 3 S-type ligands in Scheme 4 deviate from the His 2 Met active site of monooxygenases by the presence of an additional N-donor, [25][26][27][28][29][30][31][32][33][34][35][36][37][38] they give rise to copper-oxygen species that are the closest analogs to the ones proposed and/or observed in biological systems. Therefore, these ligands have afforded the closest electronic and functional analogs of PHM, DβM, and TβM, as described below.…”

“…À allowed reactivity studies that will be discussed below (CCDC 2057574). [37] The CuÀ S distance was determined at 2.2709(5), Figure 5.…”

“…[35] from simulation at g zz = 2.23 (A zz = 123 × 10 À 4 cm À 1 ), g yy = 2.11 (A yy = 56 × 10 À 4 cm À 1 ), g xx = 2.02 (A xx = 51 × 10 À 4 cm À 1 ). [37]…”

“…Finally, for the guanidine-based system [{(TMG et ) 2 N et SEt}Cu] 2 + / + its redox potential was determined at 150 mV vs Fc + /Fc as reference. [37]…”