Formation of a Cationic Gold(I) Complex and Disulfide by Oxidation of the Antiarthritic Gold Drug Auranofin

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 [(Et3P)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
Bu4NBF4/CH2Cl2 results in n values of 0.5 and >2 electrons,
respectively. Oxidation of auranofin with the mild oxidant, Cp2Fe+,
results in formation of disulfide and a digold(I) cation with a bridging
thiolate ligand, [(Et3PAu)2(μ-TATG)]+ (1). The X-ray structure of
the PMe3 analogue, [(Me3PAu)2(μ-TATG)](NO3) (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 Å. The complex crystallizes in the tetragonal space group
P42212 with cell constants a = 26.1758(6) Å, b = 26.1758(6) Å,
c = 9.7781(3) Å, α = β = γ = 90°, V = 6699.7(3) Å3, Z = 4,
R1 = 0.0644, and wR2 = 0.1152. A mechanism for oxidation of
auranofin and possible biological implications are discussed.