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Thermodynamics of partitioning of β-blockers in the n-octanol- buffer and liposome systems

1987; Elsevier BV; Volume: 36; Issue: 2-3 Linguagem: Inglês

10.1016/0378-5173(87)90152-9

1873-3476

G. V. Betageri, James A. Rogers,

Analytical Chemistry and Chromatography

The thermodynamics of partitioning (Km) of 10 β-adrenergic receptor blocking agents have been determined in the n-octanolbuffer and liposome-buffer systems at pH 7.4. Plots of log Km vs 1/T were linear in the n-octanol-buffer system from 30°C to 50 ° C, but some drugs exhibited a lower than expected or a zero Km at lower temperatures. Partitioning was generally greater in dimyristoylphosphatidylcholine liposomes than in the n-octanol-buffer system, but it was less below than above the Tc of the phospholipid. A Km of nadolol in n-octanol-buffer was detected only at 50°C, however, significant values were obtained in liposomes, but only above the Tc. A correlation between log Km(n-octanol) and log Km(liposome) (r = 0.986) was obtained at 30° C for all β-blockers except acebutolol. Enthalpies and entropies of partitioning were positive in the n-octanol-buffer system and in liposomes above the Tc, but negative below the Tc. Hydrophobie substituent constants were 55% greater in liposomes overall and varied depending on the polarity of the substituent and its position on the aromatic ring structure. Enthalpy-entropy compensation was not observed in the n-octanol-buffer system or in liposomes below the Tc, but it was found in liposomes above the Tc. Thus, it is concluded that the liposome system is a more selective partitioning model than the n-octanol-buffer system.