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

Abstract

Countercurrent chromatography was used to determine the octanol-water partition coefficients (P o/w ) of 23 diuretic drugs. The measured P o/w values ranged over 4 orders of magnitude from 0.05 to 550 (-1.3 < log P o/w < +2.7). All the compounds, except spironolactone, were ionizable. The P o/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 case. In each case, hypothetical compounds are graphically studied through log P o/w vs pH curves. The apparent P o/w coefficients of the diuretics were determined at pH 2.58, 5.86, and 7.39 using 0.01 M ammonium phosphate buffers. The results were analyzed using the theoretical model. The P o/w coefficients of the molecular forms agreed with the literature values. The P o/w coefficients of the ionic forms were obtained. The model also allows establishment of the acidity constants of the studied molecules.

Polyphenols in countercurrent chromatography. An example of large scale separation

“…These physico chemical parameters are precious data in hydrophobic studies, in quantitative structureactivity relationships (QSAR) and quantitative structureretention relationships (QSRR) in pharmacological or chromatographic studies, respectively. CCC is a very powerful tool to determine accurately the liquid-liquid partition coefficients of solutes [8,9,15]. Figure 2 also show that CCC compensates easily its low efficiency by a high selectivity power.…”

“…Furthermore, the separation initiated in Step 2 is improved in Step 3 since 4 moves faster than 3 with the organic mobile phase. The advantages of the dual mode use were evidenced in the partition coefficient determination [8,15] and general uses of CCC [7,18].…”

“…The peaks elute in decreasing P aq/org order ( Table V). The P value is calculated as P = V aq /V R [15,17]. The volume of organic phase needed to elute all the hydrophobic tannins out of the CCC machine is 95 mL (Eq.…”

Retention behavior ofo-phthalic, 3-nitrophthalic, and 4-nitrophthalic acids in ion-suppression reversed-phase high performance liquid chromatography using acids instead of buffers as ion-suppressors

“…A small pH change can induce a large variation of K ow of the compound [10]. The integrated form of the coefficients K 9 ow of the dibasic acid is described by…”

“…This cannot be readily explained by the order of K ow of those substances. As the K ow value of the neutral form of an ionizable sample only reveals the lipophilicity of the unionized species, it is inappropriate to ignore the hydrophobicity difference of the molecule and its ion(s) [10]. The separation of many ionizable compounds is well known since Horvath's work of 1977 [11,12].…”