Energetics of the encapsulation of o-, m-, and p-hydroxybenzoic acids by beta-cyclodextrin and its methylated and hydroxypropylated derivatives in aqueous solution

A fully computerized potentiometric technique has been used to analyze the energetics of the encapsulation of o-, m-, and p-hydroxybenzoic acids by be ta-cyclodextrin (beta-CD) and (or) two of its most used derivatives: 2,6-di -beta-methyl-beta-cyclodextrin (DIMEB) and hydroxypropyl-beta-cyclodextrin (HPBCD). The study has been carried out by measuring the pH of aqueous solu tions of the three hydroxyacids in the absence of cyclodextrin at 25 degree s C, and in the presence of cyclodextrin at several temperatures ranging fr om 15 to 40 degrees C, keeping constant the concentration of the guest. The dissociation constant of the acids and the binding constants of the inclus ion complexes formed have been simultaneously determined at all the tempera tures by using a model previously derived by us. The carboxylic forms have been found to bind the CD with higher affinities than the carboxylate partn ers do, irrespective of the temperature, the cyclodextrin used, and the pos ition of the substituents on the guest molecules. The formation of the incl usion 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 ther modynamics of the inclusion processes has been analyzed.