Ionization constants by curve fitting: application to the determination of partition coefficients.

A multiparametric curve-fitting technique for pKa calculation has been adapted for use with a programmable calculator or microcomputer. This method provides for the convenient and accurate determination of the ionization constant in aqueous solution and of the apparent ionization constant in the presence of octanol. From these parameters, partition coefficients and apparent partition coefficients are easily calculated and agree with data reported using the shaker technique or HPLC. The curve-fitting method has been applied to the differential titration technique in which the solvent curve is subtracted from the solution curve before calculations are begun. This method has been applied to the potentiometric titration of aqueous solutions of the salts of bases with a very low solubility in water.