The solubility of naphthalene was recently estimated using a similar methodology, the Extended Einstein Crystal Method , but with additional approximations. Specifically, since naphthalene molecules interact very weakly with each other in the crystal lattice and with water molecules in solution, the differences between the internal partition function of a naphthalene molecule in the solid and in the solution were assumed to be negligible. This allowed the authors to drop some complexities in treatment of the solution-phase part of the calculation. However, that approach is only suitable for compounds that are only very weakly interacting in solution and in the crystal. ASA, in contrast, is a molecule that interacts strongly with other ASA molecules in its crystal lattice and with water molecules in solution via hydrogen bonds. For instance, an important crystalline feature that is not necessarily present in solution is the dimer structure, with two ASA molecules bound together via hydrogen bonds between the carboxylic acid groups. Differences between the internal partition functions of the molecule in the solid (q solid ASA ) and in solution (q solut ion ASA ) would probably not be negligible in this scenario, thus a more general approach is needed for treatment of such cases. Our work here provides one attempt in that direction.