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Prediction of aqueous solubility of drugs and pesticides with COSMO‐RS
Author(s) -
Klamt Andreas,
Eckert Frank,
Hornig Martin,
Beck Michael E.,
Bürger Thorsten
Publication year - 2001
Publication title -
journal of computational chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.907
H-Index - 188
eISSN - 1096-987X
pISSN - 0192-8651
DOI - 10.1002/jcc.1168
Subject(s) - cosmo rs , aqueous solution , gibbs free energy , solubility , chemistry , thermodynamics , pesticide , heuristic , quantum chemical , quantum chemistry , set (abstract data type) , activity coefficient , biological system , mathematics , computer science , organic chemistry , molecule , physics , mathematical optimization , ionic liquid , supramolecular chemistry , biology , agronomy , programming language , catalysis
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. © 2002 Wiley Periodicals, Inc. J Comput Chem 23: 275–281, 2002