Aqueous Solubility Prediction

The aqueous solubility of a compound significantly affects its absorption and distribution characteristics. Typically, a low solubility goes along with a bad absorption and therefore the general aim is to avoid poorly soluble compounds. Our estimated logS value is a unit stripped logarithm (base 10) of a compound's solubility measured in mol/liter.

The diagram below shows that more than 80% of the drugs on the market have an (estimated) logS value greater than -4.

Similar to our in-house logP calculation we assess the solubility via an increment system by adding atom contributions depending on their atom types. The atom types employed here differ slightly from the ones used for the cLogP estimation in that respect that the ring membership is not considered. Still there are 271 distinguishable atom types describing the atom and its near surrounding. More than 2000 compounds with experimentally determined solubility values (25 degrees, pH=7.5) were used as training set to optimize the contribution values associated with the atom types.
The correlation plot below shows calculated versus experimentally determined logS. The precision of the logS estimation is not as reliable as the one for logP, because the solubility of a substance depends to a certain extend on how effectively the molecules are arranged in the crystall and these topological aspects cannot be predicted via atom types nor substructure fragments.