Energetics of the encapsulation of <i>o</i>-, <i>m</i>-, and <i>p</i>-hydroxybenzoic acids by β-cyclodextrin and its methylated and hydroxypropylated derivatives in aqueous solution

Abstract

A fully computerized potentiometric technique has been used to analyze the energetics of the encapsulation of o-, m-, and p-hydroxybenzoic acids by β-cyclodextrin (β-CD) and (or) two of its most used derivatives: 2,6-di-O-methyl-β-cyclodextrin (DIMEB) and hydroxypropyl-β-cyclodextrin (HPBCD). The study has been carried out by measuring the pH of aqueous solutions of the three hydroxyacids in the absence of cyclodextrin at 25°C, and in the presence of cyclodextrin at several temperatures ranging from 15 to 40°C, keeping constant the concentration of the guest. The dissociation constant of the acids and the binding constants of the inclusion complexes formed have been simultaneously determined at all the temperatures by using a model previously derived by us. The carboxylic forms have been found to bind the CD with higher affinities than the carboxylate partners do, irrespective of the temperature, the cyclodextrin used, and the position of the substituents on the guest molecules. The formation of the inclusion complexes studied in this work has been found to be enthalpy driven, with a favorable enthalpic term dominant over an unfavorable entropic one. The effect of the substituents of both guest and host molecules on the thermodynamics of the inclusion processes has been analyzed. Key words: binding constant, β-cyclodextrin, hydroxybenzoic acid, inclusion complex, substituent effect.