title: Molecular and statistical modeling of reduction peak potential and lipophilicity of platinum(IV) complexes.
abstract: 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.
authors.affiliation: School of Chemistry, Cardiff University, Park Place, Cardiff, CF10 3AT, UK.
authors.forename: James A
authors.initials: JA
authors.lastname: Platts
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Ermondi
authors.forename: Giulia
authors.initials: G
authors.lastname: Caron
authors.forename: Mauro
authors.initials: M
authors.lastname: Ravera
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Gabano
authors.forename: Luca
authors.initials: L
authors.lastname: Gaviglio
authors.forename: Giorgio
authors.initials: G
authors.lastname: Pelosi
authors.forename: Domenico
authors.initials: D
authors.lastname: Osella
mesh_terms: D002851:Chromatography, High Pressure Liquid; D018360:Crystallography, X-Ray; D004563:Electrochemistry; D017671:Platinum Compounds / Q000138:chemical synthesis / Q000737:chemistry*; D021281:Quantitative Structure-Activity Relationship
chemical_list: D017671:Platinum Compounds