Thioether sulfur oxygenation from O-2 or H2O2 reactivity of copper complexes with tridentate N2Sthioether ligands

Abstract

To model thioether-copper coordination chemistry including oxidative reactivity, such as occurs in the copper monooxygenases peptidylglycine alpha-hydroxylating monooxygenase (PHM) and dopamine beta-hydroxylase (D beta H), we have synthesized new tridentate N2S ligands L-SEP and L-SBz [L-SEP = methyl(2-phenethylsulfanylpropyl)(2-pyridin-2-ylethyl) amine; LSBz) (2-benzylsulfanylpropyl)methyl(2-pyridin-2-ylethyl)amine)]. Both copper(I) and copper(II) complexes have been prepared, and their respective O-2 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(CH3OH)(OClO3)(2)], has been structurally characterized, demonstrating Cu-O-sulfoxide ligation. The X-ray structure of [(L-SEP)Cu-II(H2O)(OClO3)](+) (1b) and its solution UV-visible spectral properties [S-Cu-II LMCT band at 365 nm (MeCN solvent); epsilon = 4285 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 angstrom) 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.