Prediction of logP for Pt(II) and Pt(IV) complexes
- Author(s)
- Igor V. Tetko, Hristo P. Varbanov, Mathea Sophia Galanski, Mona Talmaciu, James A. Platts, Mauro Ravera, Elisabetta Gabano
- Abstract
The octanol/water partition coefficient, logP, is one of the most important physico-chemical parameters for the development of new metal-based anticancer drugs with improved pharmacokinetic properties. This study addresses an issue with the absence of publicly available models to predict logP of Pt(IV) complexes. Following data collection and subsequent development of models based on 187 complexes from literature, we validate new and previously published models on a new set of 11 Pt(II) and 35 Pt(IV) complexes, which were kept blind during the model development step. The error of the consensus model, 0.65 for Pt(IV) and 0.37 for Pt(II) complexes, indicates its good accuracy of predictions. The lower accuracy for Pt(IV) complexes was attributed to experimental difficulties with logP measurements for some poorly-soluble compounds. This model was developed using general-purpose descriptors such as extended functional groups, molecular fragments and E-state indices. Surprisingly, models based on quantum-chemistry calculations provided lower prediction accuracy. We also found that all the developed models strongly overestimate logP values for the three complexes measured in the presence of DMSO. Considering that DMSO is frequently used as a solvent to store chemicals, its effect should not be overlooked when logP measurements by means of the shake flask method are performed. The final models are freely available at ochem.eu/article/76903.
- Organisation(s)
- Department of Inorganic Chemistry, NMR Centre
- External organisation(s)
- Helmholtz-Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt, BigChem GmbH, École polytechnique fédérale de Lausanne, Cardiff University, Iuliu Hațieganu University of Medicine and Pharmacy, Università Del Piemonte Orientale
- Journal
- Journal of Inorganic Biochemistry
- Volume
- 156
- Pages
- 1-13
- No. of pages
- 13
- ISSN
- 0162-0134
- DOI
- https://doi.org/10.1016/j.jinorgbio.2015.12.006
- Publication date
- 03-2016
- Peer reviewed
- Yes
- Austrian Fields of Science 2012
- 104003 Inorganic chemistry, 106002 Biochemistry, 106023 Molecular biology
- Keywords
- ASJC Scopus subject areas
- Biochemistry, Inorganic Chemistry
- Portal url
- https://ucrisportal.univie.ac.at/en/publications/ab4e049d-44fa-41d2-a513-be3f46ca582e