Perspectives in Inorganic and Bioinorganic Gold Sulfur Chemistry

A detailed picture of the chemical and electrochemical oxidation of a series of mononuclear and dinuclear phosphine Au(I) thiolates is presented. The medicinal implications of the results are illustrated by redox studies on the anti-rheumatoid drug, auranofin, [(2,3,4,6-tetra-acetyl-1-thio- g -D-glucopyranosato)(triethylphosphine) gold(I)]. The phosphine Au(I) thiolate complexes undergo a broad irreversible oxidation in the range, +0.6 to +1.1 V, and a second irreversible oxidation at more positive potentials from +1.2 to +1.6 V (vs. SCE). Chemical oxidation of the Au(I) thiolate complexes with (Cp 2 Fe)(PF 6 ) results in disulfide and tetragold(I) clusters with bridging thiolate ligands, except for the unusual nine Au(I) atoms cluster obtained by oxidation of [(dppm)Au 2 (p-SC 6 H 4 CH 3 ) 2 ]. Chemical oxidation of auranofin with (Cp 2 Fe)(PF 6 ) results in disulfide and a cationic Au(I) cluster with bridging thiolate ligands, [(Et 3 PAu) 2 ( w -SATg)] 2 2+ , typical of mononuclear gold(I) thiolates. The Au(I) clusters react with disulfide to undergo thiolate/disulfide exchange. Comparative rates show clusters react much faster than the mononuclear complex, Ph 3 PAu(SC 6 H 4 CH 3 ). A mechanism for the oxidation of auranofin and related complexes, and possible biological implications are discussed.