Effects of Thioether Substituents on the O₂ Reactivity of β-Diketiminate-Cu(I) Complexes: Probing the Role of the Methionine Ligand in Copper Monooxygenases

Aboelella, N. W.; Gherman, B. F.; Hill, L. M.; York, J. T.; Holm, N.; Young, V. G., Jr.; Cramer, C. J.; Tolman, W. B.
J. Am. Chem. Soc. 2006, 128, 3445.

The activation of dioxygen by dopamine β-monooxygenase (DβM) and peptidylglycine α-hydroxylating monooxygenase (PHM) is postulated to occur at a copper site ligated by two histidine imidazoles and a methionine thioether, which is unusual since such thioether ligation is not present in other O₂-activating copper proteins. In order to assess the possible role of the thioether ligand in O₂ activation by DβM and PHM, two new ligands comprising β-diketiminates with thioether substituents were synthesized and Cu(I) and Cu(II) complexes 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 "η²" 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(μ-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(μ-oxo) species is proposed and the possible relevance of this role to that of the methionine in the active sites of DβM and PHM is discussed.

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