P. A. Jupp, D. Trew, C. H. Turner, Wyeth Research
The measurement of pKa by NMR gives a specific approach to both the determination and the assignment of pKa values to ionisable centres in a molecule. The traditional approach for the measurement of pKa by potentiometric titrations can give the value for the ionisable centre but cannot show where the protons actually resides. Also at low concentrations the influence of the water as a media can distort the values as well as causing determination difficulties if the compound has low solubility. NMR, however can precisely determine the pKa in aqueous as well as mixed solvent systems. Work has been carried out to assess the impact on measuring pKa in organic/aqueous mixtures and clearly demonstrates that protonation is dependant of the nature of the media in which the measurement is made.