Monte Carlo simulation of cisplatin molecule in aqueous solution.

The Lennard-Jones (12-6) parameters were obtained for all atoms of cisplatin molecule using the ab initio quantum mechanical potential energy surface for the water-cisplatin interaction as reference data. The parameters found were (epsilon/kcal.mol(-1) and sigma/angstroms) 1.0550, 3.6590 (Pt); 0.0381, 4.6272 (Cl); 0.0455, 3.3783 (N); and 0.0185, 0.0936 (H) and provided very good results for the description of the aqueous solution of cisplatin through Monte Carlo simulation. From statistical analysis of solute-solvent interactions, we observed that the NH3 groups are involved in 53% of the calculated hydrogen bonds with a significant contribution from chlorides (41%) and only 6% involving the Pt center. This is in agreement with the expected behavior for such molecules. Two hydration shells with 22 and 81 water molecules, respectively, centered around 4.6 and 7.3 angstroms were found from the center of mass pair correlation function analysis. The cisplatin atomic Lennard-Jones parameters are reported for the first time, and they might be useful for studying the structure, properties, and processes of cisplatin-like molecules in aqueous solution, including explicitly the solvent effect.