Hydrophobicity of Ionizable Compounds. A Theoretical Study and Measurements of Diuretic Octanol−Water Partition Coefficients by Countercurrent Chromatography

Countercurrent chromatography was used to determine the octanol−water partition coefficients (Po/w) of 23 diuretic drugs. The measured Po/w values ranged over 4 orders of magnitude from 0.05 to 550 (−1.3 < log Po/w < +2.7). All the compounds, except spironolactone, were ionizable. The Po/w values were strongly depending on the aqueous-phase pH. A theoretical model linking these values with the pH was derived for four cases:  (i) molecular acid−anionic base, (ii) cationic acid−molecular base, (iii) biprotic systems with two acidic or basic groups showing the same charge sign, and (iv) biprotic systems with ionizable groups showing different charges with special attention to the amino acid ca…