Structure-Lipophilicity Relationships of Neutral and Protonated β-Blockers,Part I,Intra- and Intermolecular Effects in Isotropic Solvent Systems |
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Authors: | Giulia Caron Guillaume Steyaert Alessandra Pagliara Frdric Reymond Patrizia Crivori Patrick Gaillard Pierre-Alain Carrupt Alex Avdeef John Comer KarlJ Box HubertH Girault Bernard Testa |
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Abstract: | The objectives of this study were to validate new experimental techniques used to measure the log P of protonated drugs, and to investigate the inter- and intramolecular forces influencing the partitioning behavior of β-blockers in isotropic biphasic solvent systems. The lipophilicity parameters of a number of β-blockers were measured by two-phase titration, centrifugal partition chromatography (CPC), and cyclic voltammetry (CV) in one or more of the following solvent systems: octanol/water, 1,2-dichloroethane/water, and dibutyl ether/water. CV proved to be a promising technique for measuring the lipophilicity of protonated β-blockers. Derived parameters such as Δlog P (difference between log P in two different solvent systems, a parameter valid for a given solute in a given electrical form) and diff (difference between log P of two different electrical forms of a given solute, in the same system) yielded insights into inter- and intramolecular interactions characteristic of β-blockers. The relevance of these parameters in structure-permeation relationships is explored. |
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