Interaction of Pharmaceuticals with Schardinger Dextrins V: Interaction with a Series of Phenyl-Substituted Carboxylic Acids

Abstract

Interactions were observed between beta-cyclodextrin and a series of phenyl-substituted carboxylic acids in aqueous solution. By use of the solubility method of analysis, definite interactions were found to occur with each of the acids. When phase diagrams allowed, stoichiometric ratios were calculated for the complexes and the corresponding Kf and Δ F 0 values determined. Stoichiometries from the analysis of various isolated complexes agreed quite closely with those obtained from the phase diagrams. Several of the inclusion complexes exhibit extremely high formation constants indicative of thermodynamically favorable interactions. Even though a complex mechanism consisting of pure inclusion and other attractive forces is expected for these interactions, the experimental data indicate the relative importance of the separation between the carboxyl and phenyl groups in the net interactions observed. Saturated acids were found to be far more reactive with beta-cyclodextrin than were the corresponding unsaturated acids. This finding could have important pharmacological and biochemical implications, as beta-cyclodextrin has been used as an enzyme model by numerous investigators.