Received November 23, 2005

Abstract:

The activation of dioxygen by dopamine -monooxygenase (DM) and peptidylglycine -hydroxylating monooxygenase (PHM) is postulated to occur at a copper site ligated by two histidine imidazoles and a methionine thioether, which is unusual because such thioether ligation is not present in other O₂-activating copper proteins. To assess the possible role of the thioether ligand in O₂ activation by DM and PHM, two new ligands comprising -diketiminates with thioether substituents were synthesized and Cu(I) and Cu(II) complexes were isolated. The Cu(II) compounds are monomeric and exhibit intramolecular thioether coordination. While the Cu(I) complexes exhibit a multinuclear topology in the solid state, variable-temperature ¹H NMR studies implicate equilibria in solution, possibly including monomers with intramolecular thioether coordination that are structurally defined by DFT calculations. Low-temperature oxygenation of solutions of the Cu(I) complexes generates stable 1:1 Cu/O₂ adducts, which on the basis of combined experimental and theoretical studies adopt side-on "²" structures with negligible Cu-thioether bonding and significant peroxo-Cu(III) character. In contrast to previously reported findings with related ligands lacking the thioether group, however (cf., Aboelella; et al. J. Am. Chem. Soc. 2004, 126, 16896), purging the solutions of the thioether-containing adducts with argon results in conversion to bis(-oxo)dicopper(III) species. A role for the thioether in promoting loss of O₂ from the 1:1 Cu/O₂ adduct and facilitating trapping of the resulting Cu(I) complex to yield the bis(-oxo) species is proposed, and the possible relevance of this role to that of the methionine in the active sites of DM and PHM is discussed.

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