Effect of Explicit Hydration on the Cisplatin Reaction Mechanism with Adenine and Guanine

Abstract

Cisplatin is still a first-line agent in cancer treatment due to its effectiveness. Despite the large body of research concerning this drug, the role of explicit water molecules in its mechanism remains uncertain. We addressed the addition of cisplatin with the nitrogenous DNA bases adenine and guanine, with an emphasis on the impact of explicit microsolvation on every step of the action pathway of this pharmaceutical. We used electronic structure calculations to explore the energetics of the key reactions of this mechanism. We also exploited state-of-the-art methods of wave function analyses, namely the Quantum Theory of Atoms in Molecules and the Interacting Quantum Atoms partition, to explore the chemical bonding throughout such steps. Our results reveal that microsolvation significantly affects electronic and Gibbs free activation energies differently as previously reported (F.P. Cossio et. al. ChemPhysChem, 17, 3932, 2016). The changes in activation energies are consistent with Ha

Evelio Francisco Miguélez

Associate Professor

Associate Professor of Physical Chemistry at the University of Oviedo. Expert in the development and application of quantum chemical topology methods, IQA analysis, and electron correlation descriptors.