Effects of thioether substituents on the O2 reactivity of beta-diketiminate-Cu(I) complexes: probing the role of the methionine ligand in copper monooxygenases.
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.
Aboelella
Nermeen W
NW
Department of Chemistry, Center for Metals in Biocatalysis, and Minnesota Supercomputer Institute, University of Minnesota, 207 Pleasant Street SE, Minneapolis, Minnesota 55455, USA.
Gherman
Benjamin F
BF
Hill
Lyndal M R
LM
York
John T
JT
Holm
Nicole
N
Young
Victor G
VG
Cramer
Christopher J
CJ
Tolman
William B
WB
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
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