Cyclomaltoheptaose (β-cyclodextrin) inclusion complex formation with chlorogenic acid: hydration enthalpy, the solvent entropy (hydrophobic) effect, and enthalpy–entropy compensation

Direct isothermal titration calorimetric measurement of ΔH and ΔS for the inclusion of chlorogenic acid (CA) by epichlorohydrin-polymerized cyclomaltoheptaose (β-cyclodextrin, β-CDn), β-CD, and hydroxypropyl-β-CD (HP-β-CD) was performed at various temperatures (T=10, 25, 40, and 55 °C) in 0.1 M Na phosphate buffer (pH 6.7). β-CDn and HP-β-CD, but not soluble β-CD, binding reactions with CA exhibited a significant variation in ΔH as a function of T (ΔCp=−228±51, −145±32, and −10±38 J mol−1 deg−1, respectively). These CD–CA systems exhibited normal enthalpy–entropy compensation (TΔS versus ΔH) behavior with a slope close to unity (α=1.05±0.1) and small intercept (TΔS0=18 kJ mol−1). Thus, as ΔG was fairly uniform (−17±2 kJ mol−1) across T, mutually compensating adjustments in solvent-associated perturbations in both ΔS and ΔH for binding occurred. Relatively large unfavorable changes in ΔS (e.g., ΔSsolv decreased with T) mainly occurred in the substituted β-CD–CA systems and were compensated for by commensurate changes in ΔH. This thermodynamically favorable enthalpic deficit (negative values increasing with T) was negatively correlated with T-dependent alterations in the number of water molecules bound by the β-CDn–CA complexes. This interpretation agrees with previous work [Carbohydr. Res., 282 (1996) 65–79], whereupon the convex curvature in the partitioning of CA by β-CDn as a function of T, implying a non-vanishing ΔCp, was eliminated with low water activity.