Mathematical representation of apparent dissociation constants in aqueous-organic solvent mixtures.

Abstract

A mathematical model for calculating apparent acid dissociation constants (pK(a)) in hydroorganic mixtures with respect to the concentration of organic solvent in a binary mixture is proposed. The correlation ability of the proposed model is evaluated by employing pK(a) value of 75 different weak acids in 13 water-cosolvent systems. The results show that the equation is able to correlate the pK(a) values with an overall mean percentage differences (MPD) of 0.52+/-0.43%. In order to test the prediction capability of the model, four experimental pK(a) values for each data set have been employed to train the model, then the pK(a) values at other solvent compositions predicted and the overall MPD obtained is 1.41+/-1.15%. The applicability of the model to correlate/predict pK(a) values of structurally related drugs in a given binary solvent has been shown. The obtained overall MPD for correlation and prediction capabilities are 1.60+/-2.16 and 2.89+/-3.22%, respectively.