Theoretical DFT study of solvent effects on platinum complexes interactions with cysteine and methionine


T. Zimmermann, J. V. Burda


Department of Chemical Physics and Optics, Faculty of Mathematics and Physics,Charles University, Ke Karlovu 3, 121 16 Prague 2, Czech Republic


Interactions of two cisplatin hydrated forms cis‑[Pt(NH3)2ClH2O]+ and cis‑[Pt(NH3)2(OH)H2O]+ with cysteine and methionine in vacuum and with implicit solvent were simulated. In the first step, reaction mechanism involves formation of monodentate intermediates where aqua ligand is replaced with the amino acid. In the next stage, another platinum ligand is replaced by one of the remaining donor atoms of the amino acid creating a chelate structure.

Structures were optimized using DFT method with splitted valence double-zeta basis set extended by polarization and diffuse functions on heavy atoms. Solvent effects were described utilizing SCRF/COSMO solvation model in both optimization and single point calculations. Core electrons of platinum, sulfur and chlorine atoms were described by quasirelativistic pseudopotentials. Energy decomposition together with the NPA population and MO analysis were performed using 6-311++G(2df,2pd) basis set. Reaction energies were determined in the so-called supermolecular approach as well as in the model of isolated molecules.

Bond dissociation energies were calculated with counterpoise correction. In solvent, a modified protocol for basis set superposition corrections was applied to take into account interaction with solvent.

Estimation of pKa values of all investigated complexes was done. Several implicit solvent methods were used and the best results were obtained for the B3LYP/6-311++G(2df,2pd) method with DPCM solvation scheme and UAHF cavities. Spheres around platinum ligands were constructed following UAHF rules using atomic charges obtained from NPA analysis within the single point CPCM calculations.