Reactions of Cycloaurated Au(III) Compounds with Thiols
Bin Song, Beth R Cameron, Renato T Skerlj,
Cycloaurated Au(III) compounds have been shown to have inhibitory activity against cysteine protease enzymes. To aid in the elucidation of the mechanism of the reaction with cysteine residues, cycloaurated compounds 3 - 5 were prepared, all containing a thiolate ligand. The preparations involved ligand substitution reactions of the corresponding dichloride adduct 1 or 2 with thiosalicylic acid, N-acetyl cysteine or 1,2-benzenedithiol in DMF in the presence of Ag2O. No oxidation reaction of the thiol by the Au(III) center was observed, and this result is consistent with the cyclic voltammetric measurement on compound 2 (Ecp = -0.90 V vs Ag/AgCl). Although Ag2O-mediated reaction of compound 1 with N-acetyl cysteine resulted in the formation of compound 4 exclusively, the interaction of the dichloride adduct with cysteine in aqueous medium is very complicated involving multiple reactions. Kinetic studies on the reaction of compounds 3 and 5 with cysteine in aqueous medium showed complicated reactions for 3; however, only a one-step reaction is involved between compound 5 and cysteine. This indicated that both of the Au-N and Au-O bonds are labile to cysteine. Supporting evidence for this Au-N lability is the fact that the Au-N bond in compound 5 reacts reversibly with triphenylphosphine in CH2Cl2 solution.
cycloauration, cysteine, cysteine protease, thiolate, substitution reaction, lability, Kinetics