Prediction of aqueous solubility of drugs and pesticides with COSMO-RS.
The COSMO-RS method, originally developed for the prediction of liquid-liquid and liquid-vapor equilibrium constants based on quantum chemical calculations, has been extended to solid compounds by addition of a heuristic expression for the Gibbs free energy of fusion. By this addition, COSMO-RS is now capable of a priori prediction of aqueous solubilities of a wide range of typical neutral drug and pesticide compounds. Only three parameters in the heuristic expression have been fitted on a data set of 150 drug-like compounds. On these data an rms deviation of 0.66 log-units was achieved. Later, the model was tested on a set of 107 pesticides, which have been critically selected based on two experimental data sources and by a crosscheck with an independent HQSAR model. On this data set an rms of 0.61 log-units was achieved, without any adjustments to the structurally extremely diverse pesticides. This result verifies the ability of this extended COSMO-RS to predict aqueous solubilities of drugs and pesticides of almost arbitrary structural classes. The new method is COSMO-RSol.
Klamt
Andreas
A
COSMOlogic GmbH&Co.KG, Leverkusen, Germany. andreas.klamt@cosmologic.de
Eckert
Frank
F
Hornig
Martin
M
Beck
Michael E
ME
Bürger
Thorsten
T
D001185:Artificial Intelligence; D008956:Models, Chemical; D010575:Pesticides / Q000737:chemistry*; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D012995:Solubility; D013816:Thermodynamics; D014867:Water / Q000737:chemistry*
D010575:Pesticides; D004364:Pharmaceutical Preparations; D014867:Water