Complexation forces in aqueous solution. Calorimetric studies of the association of 2-hydroxypropyl-β-cyclodextrin with monocarboxylic acids or cycloalkanols

The formation of complexes between 2-hydroxypropyl-β-cyclodextrin and monocarboxylic acids or cycloalkanols has been studied calorimetrically at 298 K in phosphate buffer, pH 11.3. The forces involved in the association process are discussed in the light of the signs and values of the thermodynamic parameters obtained: association enthalpy, binding constant, Gibbs free energy, and entropy. From this study it was inferred that (i) for monocarboxylic acids, hydrophobic interactions are the primary force determining complexation, as indicated by the small enthalpies and by the high and positive entropies. For the cycloalkanols, instead, enthalpies are negative and entropies positive or negative, depending on the solvent medium employed, namely water or phosphate buffer; (ii) the most important requirement for the formation of the complex is a good spatial fit between the two interacting molecules. A cavity elongation effect occurs because of the presence of the hydroxypropyl groups on the rim of the macrocycle. The relative contribution of hydrophobic and van der Waals interactions varies with the dimensions of the guest molecules; (iii) a linear correlation exists between enthalpy and entropy of complexation, underlying that inclusion is a process dominated by hydration phenomena and ascribed to the modifications experienced by the solvent in the hydration shells of the interacting substances.