Molecular Interactions in Lipophilic Environments Studied by Electrochemistry at Interfaces between Immiscible Electrolyte Solutions

Abstract

The description and understanding of absorption and distribution of potential new drug compounds in the organism is of paramount importance for the successful development of new drugs. However, the currently used physical chemical parameters such as oil-water distribution coefficients and ionization constants frequently fall short when it comes to a detailed description of the highly heterogeneous environments of both lipophilic and hydrophilic characters through which the drug compound passes. In this work, a new procedure based on electrochemistry at the interface between immiscible electrolyte solutions for addressing drug compound-ligand interactions in lipophilic environments as well as nonspecific ligand effects on distribution behavior has been developed. An attractive feature of the method is that it can simultaneously provide data for oil-water partition coefficients and ionization constants. The new procedure is demonstrated using five drug compounds with different physical chemical parameters and cholesterol as the oil-phase ligand. The use of ligand shift ion partition diagrams in the data presentation allows a quick visualization and comparison of a series of related drug compounds.

Liquid/Liquid Interfaces, Electrochemistry atUpdate based on the original article by Frédéric Reymond, Hubert H. Girault,Encyclopedia of Analytical Chemistry, © 2000, John Wiley & Sons, Ltd

“…These ligand shift partition diagrams help to understand noncovalent interactions of functional groups of the drug molecules. (227,228) The use of a commercial 96-well microfilter plate was shown to present a rapid and efficient way to determine partition diagrams of ionized drugs, (229) and the methodology was further improved by the use of a commercial pH gradient gel. (230) Electrochemical extraction of cationic drugs from artificial urine has also been demonstrated, indicating that partition diagrams could also be useful for selective extraction of drugs.…”

Ion transfer voltammetry of tryptamine, serotonin, and tryptophan at the nitrobenzene/water interface

“…Ion transfer voltammetry of aromatic amines, including amino acids, dipeptides, neurotransmitters, and anesthetics, at the organic solvent (O)|water (W) interface has been studied by many authors [7][8][9][10][11][12][13][14][15][16][17][18]. Much attention has been paid to the hydrophobicity of protonated cations of the aromatic amines, as determined by the reversible half-wave potentials of the voltammograms, and to the relationship to their biological or pharmacological activities.…”

Effect of α-Cyclodextrin on Drug Distribution Studied by Electrochemistry at Interfaces between Immiscible Electrolyte Solutions

“…[8][9][10][11][12][13] For example, cyclic voltammetry at ITIES performed at different pH levels of the water phase can provide two-phase partition diagrams. [14][15][16][17][18][19][20] These diagrams allow an accurate determination of transfer potentials corresponding to drug compound transfer from one liquid phase to another and provide the standard partition coefficient of the ionic species.…”

“…The present study focuses on the interactions of five drug compounds ( Figure 1) with R-CD in water by using a special type of ion partition diagram termed the ligand-shift partition diagram. 20 From the observed electrochemical behavior of the studied drug compounds, it was possible to discriminate between drug/R-CD complexation and solvation effects due to the presence of R-CD in the aqueous phase.…”