Prediction of aqueous solubility of drugs and pesticides with COSMO-RS

J Comput Chem. 2002 Jan 30;23(2):275-81. doi: 10.1002/jcc.1168.


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.

Publication types

  • Validation Study

MeSH terms

  • Artificial Intelligence
  • Models, Chemical*
  • Pesticides / chemistry*
  • Pharmaceutical Preparations / chemistry*
  • Solubility
  • Thermodynamics
  • Water / chemistry*


  • Pesticides
  • Pharmaceutical Preparations
  • Water