Mechanistic studies of metal mediated thiol-disulfide exchange were carried out at the B3LYP level of theory using Gaussian 03. The exchange reaction has been modeled using the disulfide, dithiothreitol, with zinc (II) and gold(I) thiolates. The LANL2DZ basis set was used for gold with an effective core potential (ECP), while all other atoms were treated with the 6-31G(d) basis set. Gas phase results suggest that Zn(II) and Au(I) thiol disulfide exchange reactions occur via four-membered transition states involving one metal and 3 sulfur atoms. The theoretical results are consistent with experimental data, indicating that in metal-mediated thiol-disulfide exchange, free thiolate does not form at any point along the reaction coordinate. The energy barrier for the Au(I) mediated thiol-disulfide exchange is 3.5 kcal/mol lower than Zn(II), predicting faster rates for Au(I)-mediated thiol-disulfide exchange.