The action mechanism of anticancer gold(III) complexes is a multi-step process and depends on their redox stability. First, the gold(III) complex undergoes a ligand exchange reaction in the presence of cellular thiols, such as those available in the active site of the enzyme TrxR, and then, the Au-III -> Au-I reduction occurs. Most experimental and theoretical studies describe these processes under chemical conditions without considering the enzyme structure effect. In the present study, molecular models are proposed for the [Au-III(C<^>N<^>C)(SHCysR)](+) adduct, with the [Au-III(C<^>N<^>C)](+) moiety bonded to the Cys498 residue in the C-terminal arm of the TrxR. This one represents the product of the first ligand exchange reaction. Overall, our results suggest that the exchange of the auxiliary ligand (for instance, Cl- to S-R) plays a primary role in increasing the reduction potential, with the enzyme structure having a small effect. The parent compound [Au-III(C<^>N<^>C)Cl] has E degrees = -1.20 V, which enlarges to -0.72 V for [Au-III(C<^>N<^>C)CH3SH](+) and to -0.65 V for the largest model studied, Au-trx. In addition to the effect of the enzyme structure on the redox stability, we also analyze the Au transfer to the enzyme using a small peptide model (a tetramer). This reaction is dependent on the Cys497 protonation state. Thermodynamics and kinetic analysis suggests that the C<^>N<^>C ligand substitution by Cys497 is an exergonic process, with an energy barrier estimated at 20.2 kcal mol(-1). The complete transfer of the Au ion to the enzyme's active site would lead to a total loss of enzyme activity, generating oxidative damage and, consequently, cancer cell death.