title: Prediction of cyclohexane-water distribution coefficients with COSMO-RS on the SAMPL5 data set.
abstract: The Conductor-Like-Screening-Model for Real Solvents (COSMO-RS) method has been used for the blind prediction of cyclohexane-water distribution coefficients logD within the SAMPL challenge. The partition coefficient logP of the neutral species was calculated first and then corrected for dissociation or protonation, as appropriate for acidic or basic solutes, to obtain the cyclohexane-water logD. Using the latest version of the COSMOtherm implementation, this approach in combination with a rigorous conformational sampling yielded a predictive accuracy of 2.11 log units (RMSD) for the 53 compounds of the blind prediction dataset. By that it was the most accurate of all contest submissions and it also achieved the best rank order. The RMSD mainly arises from a group of outliers in the negative logD range, which at least partly may arise from dimerization or other experimental problems coming up for very polar molecules in very non-polar solvents.
authors.affiliation: COSMOlogic GmbH&CoKG, Imbacher Weg 46, 51379, Leverkusen, Germany. klamt@cosmologic.de.|Institute of Physical and Theoretical Chemistry, University of Regensburg, 93040, Regensburg, Germany. klamt@cosmologic.de.
authors.forename: Andreas
authors.initials: A
authors.lastname: Klamt
authors.affiliation: COSMOlogic GmbH&CoKG, Imbacher Weg 46, 51379, Leverkusen, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Eckert
authors.affiliation: COSMOlogic GmbH&CoKG, Imbacher Weg 46, 51379, Leverkusen, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Reinisch
authors.affiliation: COSMOlogic GmbH&CoKG, Imbacher Weg 46, 51379, Leverkusen, Germany.
authors.forename: Karin
authors.initials: K
authors.lastname: Wichmann
mesh_terms: D003198:Computer Simulation; D003510:Cyclohexanes / Q000737:chemistry*; D055808:Drug Discovery; D008956:Models, Chemical; D008968:Molecular Conformation; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D012995:Solubility; D012997:Solvents / Q000737:chemistry*; D013816:Thermodynamics; D014867:Water / Q000737:chemistry*
chemical_list: D003510:Cyclohexanes; D004364:Pharmaceutical Preparations; D012997:Solvents; D014867:Water; C506365:Cyclohexane
keywords: COSMO-RS; Distribution coefficients; Molecular modeling; Molecular simulation; SAMPL5; Solvation