LipE relates the binding affinity and lipophilicity of a compound, which creates a significant parameter for estimating druglikeness. 102 A proper interval of lipophilicity at physiological pH (logD7.4), usually between 1 and 3, underpins the desired ADME properties and dose; therefore, improving potency without excessively increasing lipophilicity is of vital importance in drug discovery optimization programs. To summarize, it can be noted that the inclusion of apparent ionic partitions can improve metrics in the modeling of various metrics where lipophilicity is crucial to simulate biological or artificial environments of higher complexity. Of special interest, we demonstrated that these formalisms can be applied to systems beyond the classical n-octanol/water system. The improvements studied ranged from 4 to 54 % in terms of RMSE (logD units) and depended mainly on the pH at which the system was being simulated, pKa, and hydrophobicity of the molecules.