Prior to beginning the process of estimating distribution coefficients, the pKa of each compound was first determined using an optimized HTE workflow. pKa is the acid dissociation constant which is used to estimate the pH at which a compound will be optimally dissolved . The pKa of a compound affects the fraction of molecules being ionized, which in turn affects the solubility of the compound in aqueous media since ionized molecules are more soluble in aqueous media than neutral molecules. Using the Henderson-Hasselbalch equation, a relationship between the solubility and the pKa can be established: