title: Calculation of lipophilicity for Pt(II) complexes: experimental comparison of several methods.
abstract: Platinum containing compounds are promising antitumor agents, but must enter cells before reaching their main biological target, namely DNA. Their distribution within the body, and hence their activity is to a large extent determined by their lipophilicity, thus there is a strong interest to develop computational methods to predict this important property. This study analyses accuracy of five methods, namely ALOGPS, KOWWIN, CLOGP and two quantum chemical approaches, to predict octanol/water partition coefficients (logP) for sets of 43 and 12 Pt(II) complexes, collected from the literature and measured by the authors, respectively. All methods gave generally poor results with mean absolute error (MAE) of between 0.8 and 3 log units for prediction of new compounds. Extension of the ALOGPS program with data from the literature set resulted in the best prediction ability, MAE=0.46, for the measured molecules. The program was also able to correctly predict errors in calculated logP values. It is freely available for interactive use at http://www.vcclab.org.
authors.affiliation: Helmholtz Zentrum München-German Research Center for Environmental Health (GmbH), Institute of Bioinformatics and Systems Biology, Ingolstädter Landstrasse 1, 85764 Neuherberg, Germany. itetko@vcclab.org
authors.forename: Igor V
authors.initials: IV
authors.lastname: Tetko
authors.forename: Iwona
authors.initials: I
authors.lastname: Jaroszewicz
authors.forename: James A
authors.initials: JA
authors.lastname: Platts
authors.forename: Janina
authors.initials: J
authors.lastname: Kuduk-Jaworska
mesh_terms: D000465:Algorithms; D057927:Hydrophobic and Hydrophilic Interactions; D008722:Methods; D008956:Models, Chemical; D017671:Platinum Compounds / Q000737:chemistry*; D011789:Quantum Theory; D012984:Software; D012995:Solubility
chemical_list: D017671:Platinum Compounds