Auranofin is a phosphine gold(I) thiolate drug, approved by the FDA in 1985 for the treatment of rheumatoid arthritis, with subsequent investigations showing a wide spectrum of medicinal activity that offers significant promise for treatment of other diseases. While some mechanistic data are available, the full details by which gold(I) interacts with sulfur or selenium-containing enzymes and how these interactions may alter cellular redox homeostasis, are not known. Several <i>in vitro</i> electrochemical studies on auranofin demonstrate that oxidation is sulfur-based and occurs at relatively high potentials (+ 1.1 V vs Ag/AgCl) with slow electron transfer characteristics. These studies suggest that the barrier for oxidation of gold(I)-thiolate is high, rendering auranofin relatively redox inert. We have been investigating whether it is possible to lower this barrier with a redox mediator and whether gold(I)-thiolates can influence the redox properties of other redox couples. We report electrochemical and spectroscopic studies, which demonstrate both effects. Preliminary results from cyclic voltammetry, UV-vis and <sup>1</sup>H NMR studies suggest that the redox mediators, ferrocene and 4-nitrophenylferrocene can mediate the oxidation of auranofin and lower the energy barrier for electron transfer. However experimental results for the interaction of auranofin with a third mediator, 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) are consistent with the formation of a charge transfer complex that influences the potential of the DDQ/DDQ- couple, but does not result in electron transfer between auranofin and DDQ.

Electrochemical and spectroscopic investigations of the interaction of auranofin with redox mediators

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