Formation of a cationic gold(I) complex and disulfide by oxidation of the antiarthritic gold drug auranofin

Inorg Chem. 2003 Apr 7;42(7):2203-5. doi: 10.1021/ic026057z.

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.

MeSH terms

  • Antirheumatic Agents / chemistry*
  • Antirheumatic Agents / pharmacology
  • Auranofin / chemistry*
  • Auranofin / pharmacology
  • Crystallography, X-Ray
  • Electrolysis
  • Molecular Conformation
  • Organometallic Compounds / chemistry*
  • Organometallic Compounds / pharmacology
  • Oxidants / chemistry
  • Oxidation-Reduction
  • Sulfides / chemistry

Substances

  • Antirheumatic Agents
  • Organometallic Compounds
  • Oxidants
  • Sulfides
  • Auranofin