The apparent lipophilicity of quaternary ammonium ions is influenced by Galvani potential difference, not ion-pairing: A cyclic voltammetry study

Purpose. This work examines whether ion-pairing contributes to the apparent lipophilicity of cations, which is seen by a shake-flask or titrimetic met hod to be influenced by the nature and concentration of counter-ions. Methods. To solve this problem, the lipophilicity of several quaternary amm onium drugs was measured by cyclic voltammetry in the 1,2-dichloroethane/wa ter system. The standard ionic partition coefficient values so obtained (lo g P-dce(o.C)) were correlated with log P-oct 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 differ ence at the ITIES (interface between two immiscible electrolyte solutions). Conclusions. The standard lipophilicity values were not influenced by count er-ions. In contrast, simulations showed that the increased apparent lipoph ilicity of cations, as measured by the shake-flask method in the presence o f lipophilic anions, is fully accounted for by the resulting increase in th e Galvani potential difference.