The apparent lipophilicity of quaternary ammonium ions is influenced by galvani potential difference, not ion-pairing: a cyclic voltammetry study.
OBJECTIVE
This work examines whether ion-pairing contributes to the apparent lipophilicity of cations, which is seen by a shake-flask or titrimetic method to be influenced by the nature and concentration of counter-ions.


METHODS
To solve this problem, the lipophilicity of several quaternary ammonium drugs was measured by cyclic voltammetry in the 1,2-dichloroethane/water system. The standard ionic partition coefficient values so obtained (log Pdce(o,C)) were correlated with log Poct values calculated by the CLOGP algorithm for the respective neutral molecules.


RESULTS
The standard (i.e., intrinsic) lipophilicity values are shown to depend on a, the structure of the ion (nature, volume, charge), and b, on the Galvani potential difference at the ITIES (interface between two immiscible electrolyte solutions).


CONCLUSIONS
The standard lipophilicity values were not influenced by counter-ions. In contrast, simulations showed that the increased apparent lipophilicity of cations, as measured by the shake-flask method in the presence of lipophilic anions, is fully accounted for by the resulting increase in the Galvani potential difference.
Bouchard
G
G
Institut de Chimie Thérapeutique, Section de Pharmacie, Université de Lausanne, Switzerland.
Carrupt
P A
PA
Testa
B
B
Gobry
V
V
Girault
H H
HH
D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004563:Electrochemistry; D005025:Ethylene Dichlorides / Q000737:chemistry; D007202:Indicators and Reagents; D008055:Lipids / Q000737:chemistry; D000644:Quaternary Ammonium Compounds / Q000737:chemistry*; D014867:Water / Q000737:chemistry
D005025:Ethylene Dichlorides; D007202:Indicators and Reagents; D008055:Lipids; D000644:Quaternary Ammonium Compounds; D014867:Water