Molecular and statistical modeling of reduction peak potential and lipophilicity of platinum(IV) complexes
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We report the results of the quantitative structure–property relationship analysis of 31 Pt(IV) complexes, for three of which the synthesis is reported for the first time. The X-ray structural analysis of one complex of the series was performed to demonstrate that the PM6 semiempirical method satisfactorily reproduces key features of the geometry of the complexes investigated. Molecular properties extracted from such calculations were then used to construct models of experimental data such as electrochemical peak potentials (evaluated by cyclic voltammetry) and the octanol–water partition coefficient (evaluated by a reversed-phase high performance liquid chromatography method), which are key aspects in the design of such Pt(IV) complexes as potential anticancer prodrugs. Statistically accurate models for both properties were found using combinations of surface areas, orbital energies, dipole moments, and atomic partial charges. These models could form the basis of virtual screening of potential drug molecules, allowing the prediction of properties, closely related to the antiproliferative activity of Pt(IV) complexes, directly from calculated data.
KeywordsPlatinum complexes Anticancer drug Lipophilicity Quantitative structure–property relationship analysis
Financial support for this work was from the Regione Piemonte (CIPE 2006 project-code A 370 and Ricerca Sanitaria Finalizzata 2009) and the ATF Association (Alessandria, Italy). The research was carried out within the framework of the European Cooperation COST D39 (Metallo-Drug Design and Action) and Consorzio Interuniversitario di Ricerca in Chimica dei Metalli nei Sistemi Biologici (CIRCMSB, Bari, Italy).
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