Solvation Thermodynamics in Different Solvents: Water–Chloroform Partition Coefficients from Grid Inhomogeneous Solvation Theory
| Autor: | Michael Schauperl, Anna S. Kamenik, Ursula Kahler, Franz Waibl, Florian Hofer, Johannes Kraml, Klaus R. Liedl |
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| Rok vydání: | 2020 |
| Předmět: |
Chloroform
010304 chemical physics General Chemical Engineering Solvation Water Thermodynamics Context (language use) General Chemistry Library and Information Sciences Grid 01 natural sciences Article 0104 chemical sciences Computer Science Applications Partition coefficient 010404 medicinal & biomolecular chemistry chemistry.chemical_compound Solubility chemistry 0103 physical sciences Solvents |
| Zdroj: | Journal of Chemical Information and Modeling |
| ISSN: | 1549-960X 1549-9596 |
| DOI: | 10.1021/acs.jcim.0c00289 |
| Popis: | Reliable information on partition coefficients plays a key role in drug development, as solubility decisively affects bioavailability. In a physicochemical context, the partition coefficient of a solute between two different solvents can be described as a function of solvation free energies. Hence, substantial scientific efforts have been made toward accurate predictions of solvation free energies in various solvents. The grid inhomogeneous solvation theory (GIST) facilitates the calculation of solvation free energies. In this study, we introduce an extended version of the GIST algorithm, which enables the calculation for chloroform in addition to water. Furthermore, GIST allows localization of enthalpic and entropic contributions. We test our approach by calculating partition coefficients between water and chloroform for a set of eight small molecules. We report a Pearson correlation coefficient of 0.96 between experimentally determined and calculated partition coefficients. The capability to reliably predict partition coefficients between water and chloroform and the possibility to localize their contributions allow the optimization of a compound’s partition coefficient. Therefore, we presume that this methodology will be of great benefit for the efficient development of pharmaceuticals. |
| Databáze: | OpenAIRE |
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