DFT-based reactivity and QSPR studies of platinum (IV) anticancer drugs

In the present work the influence of different axial ligands on reactivity of some selected Pt(IV) complexes with anticancer activities are investigated in both gas and solvent phases using Density Functional Theory (DFT) calculations. Calculated geometries of the complexes are in good agreement with their available X-ray data. The reactivity descriptors such as hardness, chemical potential and electrophilicity are calculated to measure stability and reactive nature of the complexes. It has been interesting to observe that the increase in the number of carbon chain of carboxylato axial ligand has no influence on reactivity of Pt(IV) complexes. Multiple linear regression analyses are performed to build Quantitative Structure Property Relationship (QSPR) models using DFT and molecular mechanics (MM+) based descriptors in gas and solvent phases. Chemical potential is found to be the most significant single descriptor to measure reduction potential of Pt(IV) complexes giving 87% correlation with experimental data. While gas phase derived descriptors are not statistically significant, inclusion of solvent medium increases the correlation of each descriptor with reduction potential and hydrophobicity of the complexes.