Cis-diaminedichloroplatinum (II) (CACP) is one of the most important drugs for cancer treatment. The primary cytotoxic mechanism of tumor killing by CACP was postulated to involve an initial displacement of one of the chlorine atoms by a water molecule inside the cell. In addition, there is a suggestion that, the ligand substitutions in square planar metal complexes proceeds from associative mechanism. Solvent is one of the factors affecting the reactivity of these types of complexes. The ligand substitution usually takes place via an associative mechanism by changing the geometry or electronic structure of the complex. Since the lowest unoccupied molecular orbital (LUMO) of the molecule is usually considered as a reactivity index toward a nucleophile. Therefore it can be used for prediction of reaction medium effects on the changing the tendency of the complex in a nuclophilic attack. There are only few limited theoretical studies on cisplatin and its derivatives with and without the solvent molecules. To investigate the effects of solvent on the reactivity of CACP in a nuclephilic reaction, the SCRF, PCM solvent models have been selected and molecular orbital analysis was carried out. The specific solutesolvent interactions were considered using Monte Carlo (MC) method.
