Development and Validation of Liquid Chromatography-Based Methods to Assess the Lipophilicity of Cytotoxic Platinum(IV) Complexes
- Author(s)
- Matthias H. M. Klose, Sarah Theiner, Hristo P. Varbanov, Doris Hoefer, Verena Pichler, Mathea Sophia Galanski, Samuel M. Meier-Menches, Bernhard K. Keppler
- Abstract
Lipophilicity is a crucial parameter for drug discovery, usually determined by the logarithmic partition coefficient (Log P) between octanol and water. However, the available detection methods have restricted the widespread use of the partition coefficient in inorganic medicinal chemistry, and recent investigations have shifted towards chromatographic lipophilicity parameters, frequently without a conversion to derive Log P. As high-performance liquid chromatography (HPLC) instruments are readily available to research groups, a HPLC-based method is presented and validated to derive the partition coefficient of a set of 19 structurally diverse and cytotoxic platinum(IV) complexes exhibiting a dynamic range of at least four orders of magnitude. The chromatographic lipophilicity parameters Φ
0 and Log k
w were experimentally determined for the same set of compounds, and a correlation was obtained that allows interconversion between the two lipophilicity scales, which was applied to an additional set of 34 platinum(IV) drug candidates. Thereby, a Φ
0 = 58 corresponds to Log P = 0. The same approacheswere successfully evaluated to determine the distribution coefficient (Log D) of five ionisable platinum(IV) compounds to sample pH-dependent effects on the lipophilicity. This study provides straight-forward HPLC-based methods to determine the lipophilicity of cytotoxic platinum(IV) complexes in the form of Log P and Φ
0 that can be interconverted and easily expanded to other metal-based compound classes.
- Organisation(s)
- Department of Inorganic Chemistry, Department of Analytical Chemistry, NMR Centre
- External organisation(s)
- Karl-Franzens-Universität Graz, Medizinische Universität Wien
- Volume
- 6
- Pages
- 71-84
- No. of pages
- 14
- DOI
- https://doi.org/10.3390/inorganics6040130
- Publication date
- 12-2018
- Peer reviewed
- Yes
- Austrian Fields of Science 2012
- 104003 Inorganic chemistry, 301904 Cancer research
- Keywords
- ASJC Scopus subject areas
- Inorganic Chemistry
- Sustainable Development Goals
- SDG 3 - Good Health and Well-being
- Portal url
- https://ucrisportal.univie.ac.at/en/publications/d765a33e-d853-4e47-813a-4a596431cc1c