Glutathionato-S-Gold(III) complexes formed as intermediates in the reduction of auricyanide by glutathione

Abstract

The reduction of auricyanide ([Au(CN) 4] −, a potential gold(III) metabolite of antiarthritic gold(I) compounds), by glutathione (G −SH, an anionic biological reductant) proceeds through two intermediates (I 230 and I 290) which have previously been identified by their UV–vis spectra, but not isolated. Negative-ion electrospray ionization-mass spectroscopy (ESI-MS) has unambiguously identified them as [Au(CN) 3(SG)] 2− and [Au(CN) 2(SG) 2] 3−, respectively, and allowed their formation and decay to be monitored. The spectra also confirm that the products are aurocyanide ([Au(CN) 2] −, a known metabolite of chrysotherapy agents) and oxidized glutathione (GSSG 2−). The reactions are dependent on the presence or absence of buffering agents and the pH of the reaction media. The reaction can be driven to the first intermediate by using an excess of auricyanide or by running the reaction at low pH which prevents further reaction. At neutral pH and/or with excess of glutathione present, the reaction proceeds to the second intermediate, which is then reduced to aurocyanide. The monoanions, [Au(CN) 3(SGH)] − at m/z = 581.2 and [Au(CN) 2(SGH) 2] − at m/z = 861.5 generate more intense signals than their respective dianions, [Au(CN) 3(SG)] 2− at m/2 = 290.2 and [Au(CN) 2(SG)(SGH)] 2− m/2 = 430.9, respectively, whereas the trianion [Au(CN) 2(SG) 2] 3− ( m/3 = 281.2) was not observed. These studies demonstrate the value of ESI-MS methods for characterizing reactions of metallopharmaceuticals under biomimetic conditions and suggest that they will be useful for other systems which give strong ESI-MS signals.