title: Molecular interaction fields vs. quantum-mechanical-based descriptors in the modelling of lipophilicity of platinum(IV) complexes.
abstract: We report QSAR calculations using VolSurf descriptors to model the lipophilicity of 53 Pt(iv) complexes with a diverse range of axial and equatorial ligands. Lipophilicity is measured using an efficient HPLC method. Previous models based on a subset of these data are shown to be inadequate, due to incompatibility of whole molecule descriptors between carboxylato and hydroxido ligands. Instead, the interaction surfaces of complexes with various probes are used as independent descriptors. Partial least squares modelling using three latent variables results in an accurate (R(2) = 0.92) and robust model (Q(2) = 0.87) of lipophilicity, that moreover highlights the importance of size and hydrophobicity terms and the modest relevance of hydrogen bonding.
authors.affiliation: CASMedChem Research Group at the Centre for Innovation, Dipartimento di Biotecnologie Molecolari e Scienza della Salute, Università di Torino, Via Quarello 11, 10135 Torino, Italy.
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: Sabrina
authors.initials: S
authors.lastname: Bianco
authors.forename: James A
authors.initials: JA
authors.lastname: Platts
authors.forename: Domenico
authors.initials: D
authors.lastname: Osella
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry*; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000737:chemistry*; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D007700:Kinetics; D008958:Models, Molecular; D010984:Platinum / Q000737:chemistry*; D025341:Principal Component Analysis; D021281:Quantitative Structure-Activity Relationship; D011789:Quantum Theory
chemical_list: D000970:Antineoplastic Agents; D056831:Coordination Complexes; D010984:Platinum