Computational assessment of the platinum (II) complex of imidazolidine dioximes substituted with methoxydiglycol units: from activation to DNA binding

Abstract

To overcome the issue of toxicity inherent in the approved anticancer agents, many cisplatin derivatives continue to be designed and tested today. Recently, we have proposed a new series of platinum complexes with highly potent imidazolidine dioxime ligands, a combination of two active ligands targeting DNA, substituted with aliphatic carbon chains or aromatic moiety. Quantum mechanical calculations have revealed their potential activity, particularly highlighting the potentially enhanced activity of complexes with aliphatic substituents in DNA platination. Here, we extend our previous study with the inclusion of methoxydiglycol unit (2-(2-methoxyethoxy)ethyl substituents) into the imidazolidine dioxime ligands of our previously proposed complexes to possibly enhance the solubility and bioavailability. Our current investigation focuses on modeling the aquation and DNA binding reactions to assess the potential of this modification and the results are compared to cisplatin.