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Charge and Delocalisation Effects on the Lipophilicity of Protonable Drugs
Author(s) -
Reymond Frédéric,
Carrupt PierreAlain,
Testa Bernard,
Girault Hubert H.
Publication year - 1999
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/(sici)1521-3765(19990104)5:1<39::aid-chem39>3.0.co;2-3
Subject(s) - lipophilicity , chemistry , ionic bonding , partition coefficient , solvation , ion , ionic potential , aqueous solution , molecule , chemical physics , partition (number theory) , computational chemistry , phase diagram , phase (matter) , stereochemistry , organic chemistry , mathematics , combinatorics
The pH‐lipophilicity profiles of ionisable drugs in water/1,2‐dichloroethane have been determined in order to establish their ionic partition diagrams (diagram shown for N ‐methylephedrine). The results show how neutral species can alter the aqueous pH and how the ionic species can transfer into the organic phase. The difference between the partition coefficients of the ionic and neutral forms of a compound affords valuable information about the effect of the charge on lipophilicity and on the solvation properties of ions in different media. This study also shows that ion partitioning is determined by both the electrostatic field around the molecule and by the possibility of delocalising the charge over several atoms.