title: Formation of a cationic gold(I) complex and disulfide by oxidation of the antiarthritic gold drug auranofin.
abstract: The mechanism of action of auranofin, an antiarthritic gold(I) drug, is unknown, but several studies suggest that oxidation may be important for its biochemical effect. Bulk electrolysis studies on auranofin [(Et(3)P)Au(TATG); TATG = 2,3,4,6-tetraacetyl-1-thio-d-glucopyranosato] at +1.2 and +1.6 V versus Ag/AgCl in 0.1 M Bu(4)NBF(4)/CH(2)Cl(2) results in n values of 0.5 and >2 electrons, respectively. Oxidation of auranofin with the mild oxidant, Cp(2)Fe(+), results in formation of disulfide and a digold(I) cation with a bridging thiolate ligand, [(Et(3)PAu)(2)(mu-TATG)](+) (1). The X-ray structure of the PMe(3) analogue, [(Me(3)PAu)(2)(mu-TATG)](NO(3)) (2), is reported. Compound 2 forms a tetranuclear cluster containing an almost perfect square of four gold atoms with Au.Au distances averaging 3.14 A. The complex crystallizes in the tetragonal space group P4(2)2(1)2 with cell constants a = 26.1758(6) A, b = 26.1758(6) A, c = 9.7781(3) A, alpha = beta = gamma = 90 degrees, V = 6699.7(3) A(3), Z = 4, R1 = 0.0644, and wR2 = 0.1152. A mechanism for oxidation of auranofin and possible biological implications are discussed.
authors.affiliation: Department of Chemistry, The University of Maine, Aubert Hall, Orono, Maine 04469-5706, USA.
authors.forename: Ahmed A
authors.initials: AA
authors.lastname: Mohamed
authors.forename: Jinhua
authors.initials: J
authors.lastname: Chen
authors.forename: Alice E
authors.initials: AE
authors.lastname: Bruce
authors.forename: Mitchell R M
authors.initials: MR
authors.lastname: Bruce
authors.forename: Jeanette A
authors.initials: JA
authors.lastname: Krause Bauer
authors.forename: David T
authors.initials: DT
authors.lastname: Hill
mesh_terms: D018501:Antirheumatic Agents / Q000737:chemistry* / Q000494:pharmacology; D001310:Auranofin / Q000737:chemistry* / Q000494:pharmacology; D018360:Crystallography, X-Ray; D004572:Electrolysis; D008968:Molecular Conformation; D009942:Organometallic Compounds / Q000737:chemistry* / Q000494:pharmacology; D016877:Oxidants / Q000737:chemistry; D010084:Oxidation-Reduction; D013440:Sulfides / Q000737:chemistry
chemical_list: D018501:Antirheumatic Agents; D009942:Organometallic Compounds; D016877:Oxidants; D013440:Sulfides; D001310:Auranofin