In this paper we explore cisplatin interactions with sulfur-containing amino acids in a polarizable continuum model. Two cisplatin hydrated complexes were considered as reactants (chloro complex, cis- [Pt(NH3)2Cl(H2O)] ; hydroxo complex, cis-[Pt(NH3)2(OH)(H2O)] ).
We considered the following reaction mechanism: first step, substitution of the aqua ligand by amino acid; second step, dissociative chelate formation. For the optimized complex (at the B3LYP/6-31 G(d)/COSMO level), the energy profile was determined using the B3LYP/6-311 G(2df,2pd) level and two different PCM modelssCOSMO and UAKS/DPCM methods which were adapted for use on transition metal complexes.
The results show thermodynamic preference for bonding by cysteine sulfur followed by the amino group nitrogen, methionine thioether sulfur, and carboxylgroup oxygen.