Theoretical study of anticancer drug cis-dichloro(pyridin-2-ylcarboxaldimine)-palladium(II) compounds containing bulky fluorinated aryl groups binding to purine bases: The activity of three isomers

The reaction mechanism for the monofunctional and bifunctional binding of the three isomers of cis-dichloro(pyridin-2-ylcarboxaldimine)-palladium(II) compounds containing bulky fluorinated aryl groups to guanine (G) and adenine (A) were investigated using density functional theory calculations at the B3LYP level. To test the solvent effect, we performed single-point energy calculations for several selected structures by employing the polarizable continuum model (IEF-PCM). The calculations indicate that the hydrogen bonds play an important role in stabilizing the complexes included in the first and second substitution. Particularly, H⋯FTFM hydrogen bond was observed in the reactions. The activation free energies for the monofunctional and bifunctional binding of the three isomers, referred to as d, e and f, to DNA base increases in the order d < f < e (see Scheme 1), respectively, which is in agreement with the experimental result reported by Scales et al. The electronic factors are more dominant than steric factors in the substitution reaction of purine base with water. Additionally, to better understand the interactions between the compounds and binding sites, the natural orbital population analysis (NPA) was adopt for every stationary point to employ the mutative trend of the net charge on the three important atoms which directly related to the reactions.