Intramolecular force field for carboxylate Pt(II)-complexes

Force-field parameters are required for classical molecular dynamics (MD) simulations. Generally, these force fields are well described for organic molecules but are missing for transition metal complexes, especially those with heavy metals. In the present study, the structure and force constants of important carboxylate Pt(II)-complexes were obtained from a systematic benchmarking including 70 quantum mechanics computational protocols. The best protocol was selected based on the structure and vibrational spectrum for carboplatin, namely LC-omega PBE/LANL2TZ(f)/6-31+G(2df)/IEF-PCM(UFF). The resulting force field was used for MD simulation of carboplatin, oxaliplatin and nedaplatin in an aqueous solution. The MD trajectories were analyzed and discussed regarding the solute structure and solute-solvent interaction. For carboplatin, some solute-solvent clusters with 2-16 water molecules were selected and used to calculate the Pt-195 NMR chemical shift. The results clearly show the primary role of the explicit solute-solvent interaction on the Pt-195 chemical shift, with the agreement with the experiment being improved systematically with the inclusion of water molecules up to 16, which error was only 20 ppm (1.1%). Overall, the force-field parameters for carboxylate Pt(II)-complexes provided here are very useful to study the interaction of these molecules with proteins, DNA, etc., using classical MD simulations.

Automated summary

This study obtained force-field parameters for carboxylate Pt(II)-complexes through systematic benchmarking, which are valuable for simulating the interactions between these molecules and solvents.