Complexation of natural and methylated β-cyclodextrins with long-chain Carboxylic acids in aqueous solutions. Calorimetric studies at 298 K

The formation of complexes between β-cyclodextrin or methyl-β-cyclodextrin and monocarboxylic acids from C5 to C12 has been studied calorimetrically at 298 K in aqueous buffer phosphate, pH 11.3. When a complex forms, calorimetry enables the calculation of both the enthalpy and the association constant, from which the Gibbs free energy and the entropy of the process can be obtained. The forces involved in the association process are then discussed in the light of the signs and values of the thermodynamic parameters obtained. For β-cyclodextrin, 1:1 inclusion complexes form, characterized by an irregular variation in the values of enthalpies, entropies and association constants at increasing alkyl chain length. A model is proposed to explain this unusual behaviour for acids longer than ten carbon atoms. The association involving methyl-β-cyclodextrin shows, instead, a regular variation of the thermodynamic parameters up to the C12 term. An elongation of the cavity effect is discussed: the cavity behaves as it were deeper than that of the natural cyclodextrins. Association is characterized prevailingly by hydrophobic interactions; for the longer terms, the high and almost invariant entropic contribution determines the large association constants, notwithstanding the positive, unfavorable enthalpic contribution. This is an indication that the relaxation of water molecules from the hydrophobic hydration shells of the external methyl groups is the contribution that mainly determines the association process.