Solubility of organic compounds in octanol: Improved predictions based on the geometrical fragment approach

Two new models are introduced to predict the solubility of chemicals in octanol (S_oct), taking advantage of the extensive character of log(S_oct) through a decomposition of molecules into so-called geometrical fragments (GF). They are extensively validated and their compliance with regulatory requirements is demonstrated. The first model requires just a molecular formula as input. Despite an extreme simplicity, it performs as well as an advanced random forest model involving 86 descriptors, with a root mean square error (RMSE) of 0.64 log units for an external test set of 100 molecules. For the second one, which requires the melting point T_m as input, introducing GF descriptors reduces the RMSE from about 0.7 to <0.5 log units, a performance that could previously be obtained only through the use of Abraham descriptors. A script is provided for easy application of the models, taking into account the limits of their applicability domains.