Polymerized cyclomaltoheptaose (β-cyclodextrin, β-CDn) inclusion complex formation with chlorogenic acid: solvent effects on thermochemistry and enthalpy-entropy compensation

The inclusion of chlorogenic acid (CA) by epichlorohydrin-polymerized cyclomaltoheptaose (β-cyclodextrin, β-CDn) was studied with regard to temperature, solvent, and water activity (aH2O ∼ mole fraction = XH2O = 0.8−1 using MeOH as the diluent; 0.1 M sodium phosphate buffer). We discovered that the extreme convex curvature in K (the apparent stability constant) as a function of temperature was nearly eliminated at the lowest XH2O. The latter finding argues that this unusual CD behavior in aqueous media was due to perturbations in β-CDʹs spatial organization in the polymeric matrix with temperature. Related to this we found, from the dependence of K on XH2O (K = K′ XH2Oz), that the β-CDn · CA complexʹs stoichiometric coefficient, z, for water, varied between 5 and 8, depending on the temperature of the solution (K′ = 400–800 M−1; T ∼ 295–315 K). Our determinations of z were similar to those reported previously for β-CD · (+)-limonene (z ∼ 7), soluble β-CD · CA (z ∼ 6) or obtained by molecular dynamics calculations for β-CD · CA reported herein (z ∼ 5). However, β-CDn · CAʹs z values did show a significant positive correlation with temperature not evident in equivalent solution experiments. Calculations of ΔH and ΔS at various XH2O values show linear enthalpy-entropy compensation (ΔH plotted against ΔS) but with a slope (Tc = ∂ΔH∂ΔS ∼ 228 K) significantly less than Tc values determined from either standard aqueous thermodynamic experiments (Tc ∼ 305 K on either β-CD or β-CDn) or variable XH2O (Tc ∼ 272 K) experiments. To the best of our knowledge, this is the smallest Tc value detected in a multitude of CD · guest studies. This evident solvent effect on Tc strongly argues that the chemical part process of inclusion complex formation involves changes in the solvation of the β-CDnʹs binding site.