Thermodynamics of hydrogen bond and hydrophobic interactions in cyclodextrin complexes

Values of K, Delta G degrees, Delta H degrees, Delta S degrees and Delta C-p degrees for the binding reaction of small organic ligands forming 1:1 complexes with either alpha- Or beta-cyclodextrin were obtained by titration calorimetry from 15 degrees C to 45 degrees C. A hydrogen bond or hydrophobic interaction was introduced by adding a single functional group to the ligand. The thermodynamics of binding with and without the added group are compared to estimate the contribution of the hydrogen bond or hydrophobic interaction. A change in the environment of a functional group is required to influence the binding thermodynamics, but molecular size-dependent solute-solvent interactions have no effect. For phenolic O-H-O hydrogen bond formation, Delta H degrees Varies from -2 to -1.4 kcal mol(-1) from 15 degrees C to 45 degrees C and Delta C-p degrees is increased by 18 cal K-1 mol(-1). The hydrophobic interaction has an opposite effect: in alpha-cyclodextrin, Delta C-p degrees = -13.3 cal K-1 mol(-1) per ligand -CH2-, identical-to values found for the transfer of a -CH2- group from water to a nonpolar environment. At room temperature, the hydrogen bond and the -CH2- interaction each contribute about -600 cal mol(-1) to the stability (Delta G degrees) of the complex, With increased temperature, the hydrogen bond stability decreases (i.e., hydrogen bonds ''melt''), but the stability of the hydrophobic interaction remains essentially constant.