pH dependence of the hydrophobicity of β-blocker amine compounds measured by counter-current chromatography

The octanol-water partition coefficients (P-oct) of 17 antiadrenergic beta-blocker compounds were determined by countercurrent chromatography (CCC). Since CCC uses a biphasic liquid system, the octanol-water liquid system was used with essentially an octanol stationary phase and aqueous buffer mobile phase. The P-oct coefficients were obtained directly without any extrapolation. The measured P-oct values were in the 0.0015-4070 range ( -2.8 < log P-oct < 3.6). Since the beta-blocking agents are ionizable compounds, the P-oct values obtained were strongly dependent on the aqueous-phase pH. The apparent P-oct coefficients of the beta-blockers were determined at three different pH values (similar to3, 7 and 11) using 0.01 M ammonium phosphate buffers saturated with octanol. A model allowed us to obtain the molecular and ionic P-oct value using the solute pK(a) with these three experimental octanol-water coefficients. Often, the P-oct coefficients of the molecular forms obtained with the CCC method differ significantly from computed literature values and/or experimental values obtained by extrapolation. Relationships between biological properties and hydrophobicity were also examined. (C) 2003 Elsevier Science B.V. All rights reserved.