Thioether sulfur oxygenation from O₂ or H₂O ₂ reactivity of copper complexes with tridentate N₂S _thioether ligands

To model thioether-copper coordination chemistry including oxidative reactivity, such as occurs in the copper monooxygenases peptidylglycine α-hydroxylating monooxygenase (PHM) and dopamine β-hydroxylase (DβH), we have synthesized new tridentate N₂S ligands L ^SEP and L^SBz [L^SEP = methyl(2- phenethylsulfanylpropyl)(2-pyridin-2-ylethyl)amine; L^SBz = (2-benzylsulfanylpropyl)methyl(2-pyridin-2-ylethyl)amine)]. Both copper(I) and copper(II) complexes have been prepared, and their respective O₂ and H₂O₂ chemistry has been studied. Under mild conditions, oxygenation of [(L^SEP)Cu^I]⁺ (1a) and [(L ^SBz)Cu^I]⁺ (2a) leads to ligand sulfoxidation, thus exhibiting copper monooxygenase activity. A copper(II) complex of this sulfoxide ligand product, [(L^SOEP)Cu^II(CH ₃OH)(OClO₃)₂], has been structurally characterized, demonstrating Cu-O_sulfoXide ligation. The X-ray structure of [(L^SEP)Cu^II(H₂O)(OClO ₃)]⁺ (1b) and its solution UV-visible spectral properties [S-Cu^II LMCT band at 365 nm (MeCN solvent); ε = 4205 M ^-1 cm^-1] indicate the thioether sulfur atom is bound to the cupric ion in both the solid (Cu^II-S distance: 2.31 Å) and solution states. Reaction of 1b with H₂O₂ leads to sulfonation via the sulfoxide; excess hydrogen peroxide gives mostly sulfone product. These results may provide some insight into recent reports concerning protein methionine oxidation, showing the potential importance of copper-mediated oxidation processes in certain biological settings.