Estimation of aqueous solubility of organic molecules by the group contribution approach. Application to the study of...

A reliable and generally applicable aqueous solubility estimation method for organic compounds based on a group contribution approach has been developed. Two models have been established based on two different sets of parameters. One has a higher accuracy, while the other has a more general applicability. The prediction potentials of these two models have been evaluated through cross-validation experiments. For model I, the mean cross-validated r2 and SD for 10 such cross-validation experiments were 0.946 and 0.503 log units, respectively. While for model II, they were 0.953 and 0.546 log units, respectively. Applying our models to estimate the water solubility values for the compounds in an independent test set, we found that model I can be applied to 13 out of 21 compounds with a SD equal to 0.58 log unit and model II can be applied to all the 21 compounds with a SD equal to 1.25 log units. Our models compare favorably to all the current available water estimation methods. A program based on this approach has been written in FORTRAN77 and is currently running on a VAX/VMS system. The program can be applied to estimate the water solubility of the water solubility of any organic chemical with a good or fairly good accuracy except for except for electrolytes. Applying our aqueous solubility estimation models to biodegradation studies, we found that although the water solubility was not the sole factor controlling the rate of biodegradation, ring compounds with greater solubilities were more likely to biodegrade at a faster rate. The significance of the relationship between water solubility and biodegradation activity has been illustrated by predicting the biodegradation activity of 27 new chemicals based solely on their estimated solubility values.