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Structure‐Lipophilicity Relationships of Neutral and Protonated β ‐Blockers, Part I, Intra‐ and Intermolecular Effects in Isotropic Solvent Systems
Author(s) -
Caron Giulia,
Steyaert Guillaume,
Pagliara Alessandra,
Reymond Frédéric,
Crivori Patrizia,
Gaillard Patrick,
Carrupt PierreAlain,
Avdeef Alex,
Comer John,
Box Karl J.,
Girault Hubert H.,
Testa Bernard
Publication year - 1999
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/(sici)1522-2675(19990804)82:8<1211::aid-hlca1211>3.0.co;2-k
Subject(s) - lipophilicity , chemistry , partition coefficient , protonation , solvent , intramolecular force , octanol , intermolecular force , computational chemistry , stereochemistry , organic chemistry , molecule , ion
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 Δ log 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.