pKa
Acid Dissociation constant, the key to understanding Ionization
Over 1000 publications since 1989 have mentioned pKa, ionization constants or related properties in connection with drugs. The most popular topics include drug receptor binding, ionization and absorption, macromolecules and NMR, drug binding with membranes, membrane analogs and proteins, transport and disposition of drugs in organs and biological fluids, and its general effects in analytical chemistry, for example on chromatography.
pKa is also important because of its effect on other physicochemical properties, notably on lipophilicity, solubility and permeability.
Definition of pKa:
pKa is is defined in mathematical terms as -log10 of Ka, where Ka is the association constant obtained from (in the case of an Acid):
Since pH = −log10[H+], the relationship between pKa and pH can be expressed as follows,
From this equation, it is clear that in a practical sense a pKa value refers to the pH at which you have exactly the same proportion of Neutral and Ionized species present in solution (for a simple monoprotic compound).
The relationship between pKa and pH is most clearly expressed via a Distribution of Species Plot:
This example shows the Distribution of Species that one might expect for a monoprotic acid with a pKa of 6.27 (for example: Flumequine). At high pH, above the pKa, it exists mostly in its ionized form [A-]. At low pH, below the pKa, it exists mostly in its neutral form [AH]. Where the pH is exactly 6.27, there is exactly 50% of both forms present in solution.
Sirius Analytical are renowned experts in the measurement of pKa, we offer measurements by pH-metric, pH-UV and high throughput methods and we can fully resolve even the most complex cases of ionic equilibria.
Our SiriusT3 titration system automatically measures pKas of organic molecules and can create full distribution of species profiles in just minutes.
