title: Prediction of aqueous solubility of drugs and pesticides with COSMO-RS.
abstract: 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.
authors.affiliation: COSMOlogic GmbH&Co.KG, Leverkusen, Germany. andreas.klamt@cosmologic.de
authors.forename: Andreas
authors.initials: A
authors.lastname: Klamt
authors.forename: Frank
authors.initials: F
authors.lastname: Eckert
authors.forename: Martin
authors.initials: M
authors.lastname: Hornig
authors.forename: Michael E
authors.initials: ME
authors.lastname: Beck
authors.forename: Thorsten
authors.initials: T
authors.lastname: Bürger
mesh_terms: D001185:Artificial Intelligence; D008956:Models, Chemical; D010575:Pesticides / Q000737:chemistry*; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D012995:Solubility; D013816:Thermodynamics; D014867:Water / Q000737:chemistry*
chemical_list: D010575:Pesticides; D004364:Pharmaceutical Preparations; D014867:Water