title: Effects of thioether substituents on the O2 reactivity of beta-diketiminate-Cu(I) complexes: probing the role of the methionine ligand in copper monooxygenases.
abstract: The activation of dioxygen by dopamine beta-monooxygenase (DbetaM) and peptidylglycine alpha-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 DbetaM and PHM, two new ligands comprising beta-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 "eta(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(mu-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(mu-oxo) species is proposed, and the possible relevance of this role to that of the methionine in the active sites of DbetaM and PHM is discussed.
authors.affiliation: Department of Chemistry, Center for Metals in Biocatalysis, and Minnesota Supercomputer Institute, University of Minnesota, 207 Pleasant Street SE, Minneapolis, Minnesota 55455, USA.
authors.forename: Nermeen W
authors.initials: NW
authors.lastname: Aboelella
authors.forename: Benjamin F
authors.initials: BF
authors.lastname: Gherman
authors.forename: Lyndal M R
authors.initials: LM
authors.lastname: Hill
authors.forename: John T
authors.initials: JT
authors.lastname: York
authors.forename: Nicole
authors.initials: N
authors.lastname: Holm
authors.forename: Victor G
authors.initials: VG
authors.lastname: Young
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Cramer
authors.forename: William B
authors.initials: WB
authors.lastname: Tolman
mesh_terms: D003300:Copper / Q000737:chemistry / Q000378:metabolism; D018360:Crystallography, X-Ray; D004299:Dopamine beta-Hydroxylase / Q000737:chemistry* / Q000378:metabolism; D006639:Histidine / Q000031:analogs & derivatives / Q000378:metabolism; D007093:Imidazoles / Q000737:chemistry / Q000378:metabolism; D008024:Ligands; D008715:Methionine / Q000737:chemistry* / Q000378:metabolism; D006899:Mixed Function Oxygenases / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D009097:Multienzyme Complexes / Q000737:chemistry* / Q000378:metabolism; D019906:Nuclear Magnetic Resonance, Biomolecular; D010100:Oxygen / Q000737:chemistry* / Q000378:metabolism; D013056:Spectrophotometry, Ultraviolet; D013059:Spectrum Analysis, Raman; D013440:Sulfides / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D013816:Thermodynamics
chemical_list: D007093:Imidazoles; D008024:Ligands; D009097:Multienzyme Complexes; D013440:Sulfides; D006639:Histidine; D003300:Copper; D008715:Methionine; D006899:Mixed Function Oxygenases; D004299:Dopamine beta-Hydroxylase; C035189:peptidylglycine monooxygenase; D010100:Oxygen