Hydration of Cisplatin Studied by an Effective Ab Initio Pair Potential Including Solute-Solvent Polarization.

Abstract

The hydration of cis-[PtCl2(NH3)2] (cisplatin) has been studied by means of classical molecular dynamics simulations using a new interaction potential obtained by fitting about 4000 ab initio interaction energies calculated at the MP2 level. The functional form included several r(-n) terms (n = 4, 6, 8, 12) to achieve an accurate description of the interactions in the different regions around the cisplatin. Bulk solvent effects on the cisplatin-water molecule interactions have been included by means of a continuum model. Radial Distribution Function (RDF) analysis does not provide a clear enough description of the hydration pattern due to the intricate solvent arrangement around the solute. Angle-solved RDFs and spatial distribution functions have been used to provide more detailed pictures of the local hydration structure around the two ligands, chloride and ammine groups, and the axial region. Based on this information, it is shown a more convenient way to compute the running coordination number for the first hydration shell by simultaneously considering angle-solved RDFs centered on the ligand representative atoms of the complex: ammino N, Cl, and Pt atoms. This way, the hydration number is obtained by integrating over an interlocking-sphere volume built by the spheres centered on the cation and the main atoms of each ligand. Compared to previous works dealing with cisplatin hydration, the global hydration number for the first coordination shell is now higher and involves about 27 water molecules. The importance of the structural sampling, the computational level, as well as the functional form adopted for the interaction potential are thoroughly discussed with respect to the previous proposed intermolecular potential.