General method for determining macrodissociation constants of polyprotic, amphoteric compounds from solubility measurements.

Equilibrium solubility and pH measurements can be used to determine macrodissociation constants of weak acids and bases of some highly insoluble substances. Equations are derived extending solubility, pH, and pKa (macroscopic) relationships to polyprotic, amphoteric substances. A general method for estimating pKa values, given a set of solubility and pH measurements, is presented. Included in the estimation procedure is a subroutine for approximating thermodynamic pKa values. The method was tested on two data sets (tyrosine and 2,3-dihydroxyadenine) and rendered pKa (thermodynamic) estimates in close agreement with those using other methods.