A cupric superoxo species has been proposed as the most reactive intermediate in peptidylglycine-α-hydroxylating monooxygenase (PHM) and dopamine-β-monooxygenase (DβM), which can activate the C–H bond of the peptide pro-hormone and dopamine, respectively. These enzymes possess a “noncoupled” dicopper active site and the methionine S-ligated CuM center known to bind O2 and substrate. A crystal structure reveals dioxygen bound to CuM in an end-on superoxo fashion. Although the thioether ligand must play a critical role in determining the electronic structure and functions of CuM site leading to C-H bond activation, the precise role of Met coordination has yet to be fully understood. Thus, to elucidate the fundamental CuI/O2 chemistry and role of sulfurMet ligation in copper monooxygenases, we have generated a new synthetic mononuclear CuII superoxide species, (DMAN3S)CuII(O2•–), mimicking the initial CuI/O2 adduct at the PHM active site. The characterization comes from UV-vis and resonance Raman spectroscopic evidence. The influence of Sthioether-atom ligation in the CuII superoxo complex have been examined through CuI/O2 adducts possessing analog ligands without sulfur. Enhanced reactivity towards both O-H and C-H substrates will be also discussed and can be attributed to the S-ligation, in comparison to close analogues [(L)CuII(O2•–)]+, where L contains only nitrogen donor atoms. This study will contribute significantly to the elucidation of the fundamental CuI/O2 chemistry and role of sulfurMet ligation in copper monooxygenases.

Evolution of thioether S-ligated primary CuI/O2 adducts: The 1st example of CuII-superoxo species with enhanced reactivity

249th National Meeting (2015)

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