COSMO‐RS as a Predictive Tool for Lipophilicity
Carsten Wittekindt, Andreas Klamt · QSAR & Combinatorial Science · 2009
Abstract The COSMO‐RS method was applied to predict altogether 4155 experimental available values of 12 different hydrocarbon‐water (logPalk) and 1‐n‐octanol‐water (logPow) partition coefficients. The over all results of the correlation between the predicted and experimental partition coefficients demonstrate that COSMO‐RS is able to a priori predict the values of all systems under investigation for almost all organic compounds. As a showcase, the outliers of the hexadecane‐water system were critically assessed. In two cases the prediction could be improved by correcting the underlying chemical structure. The remaining three outliers are due to known problems of seldom elements (germanium compounds) or of insufficient conformational representation of the molecule (crown‐ethers). Finally, ΔlogP which is the difference between (logPow−logPalk) is correlated with the blood‐brain partition coefficient (logBB). On an external test set of 199 compounds the logBB prediction based on ΔlogP is slightly inferior to our existing QSPR model (RMSE: 0.52 vs. 0.46)