Effects of thioether substituents on the O2 reactivity of β-diketiminate-Cu(I) complexes: Probing the role of the methionine ligand in copper monooxygenases

Nermeen W. Aboelella, Benjamin F. Gherman, Lyndal M.R. Hill, John T. York, Nicole Holm, Victor G. Young, Christopher J. Cramer, William B. Tolman

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Abstract

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 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 DβM and PHM, two new ligands comprising β-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 "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.

Original languageEnglish (US)
Pages (from-to)3445-3458
Number of pages14
JournalJournal of the American Chemical Society
Volume128
Issue number10
DOIs
StatePublished - Mar 15 2006

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