Hydrophobicity of ionisable compounds studied by countercurrent chromatography.
Countercurrent chromatography (CCC) is a liquid chromatography technique in which the stationary phase is also a liquid. The main chemical process involved in solute separation is partitioning between the two immiscible liquid phases: the mobile phase and the support-free liquid stationary phase. The octanol-water partition coefficients (P(o/w)) is the accepted parameter measuring the hydrophobicity of molecules. It is considered to estimate active principle partitioning over a biomembrane. It was related to the substance biological activity. CCC is able to work with an octanol stationary phase and an aqueous mobile phase. In this configuration, CCC is a useful and easy alternative to measure directly the P(o/w) of the molecules compared to other methods including the classical and tedious shake-flask method. Three ketones are used as model compounds to illustrate the CCC protocol of P(o/w) measurement. The focus of this work is put on ionisable molecules whose apparent P(o/w) is completely changed by ionization. β-Blockers, diuretics and sulfonamides are compound classes that were studied. Some of the experimentally determined P(o/w) coefficients of the molecular forms disagreed with calculated and experimental values available in the literature. The P(o/w) coefficients of the ionic forms and the acidity constants were also calculated using a theoretical model. Relationships between biological properties and hydrophobicity are also discussed.
Departament de Química Analítica, Universitat de València, Burjassot, Spain.
M J
MJ
Ruiz-Ángel
S
S
Carda-Broch
A
A
Levet
A
A
Berthod
D000319:Adrenergic beta-Antagonists / Q000737:chemistry*; D003377:Countercurrent Distribution / Q000379:methods*; D004232:Diuretics / Q000737:chemistry*; D057927:Hydrophobic and Hydrophilic Interactions; D004364:Pharmaceutical Preparations / Q000737:chemistry*
D000319:Adrenergic beta-Antagonists; D004232:Diuretics; D004364:Pharmaceutical Preparations