CYCLOMALTOHEPTAOSE (BETA-CYCLODEXTRIN) AND HYDROXYETHYL-SUBSTITUTED BETA-CYCLODEXTRIN INCLUSION COMPLEX-FORMATION WITH CHLOROGENIC ACID - SOLVENT EFFECTS ON INCLUSION COMPLEX STABILITY

The inclusion complexes of cyclomaltoheptaose (beta-CD) and beta-CD's 50% hydroxyethyl-substituted derivative (HE-beta-CD) with chlorogenic acid (CA) were studied with regard to temperature and water activity (a(H2O) approximate to mole fraction = X(H2O) = 0.8-0.99; 0.1 M Na phosphate buffer) utilizing first-derivative spectrophotometric analyses of bathochromic shifts (Delta lambda) in CA's UV absorbance as a function of variable [CD]. From the dependence of the apparent stability constant, K, on X(H2O) (K=K(double dagger)X(H2O)(z)) we estimated that the beta-CD . CA complex's apparent stoichiometric coefficient, z, for water was ca. 7 +/- 1 (K-double dagger = 1032 +/- 54 M(-1)); this value agrees with recently published literature concerning the minimum number of waters needed to stabilize a similar beta-CD adduct. However, we determined that z was significantly lower (4 +/- 0.3; K-double dagger = 809 +/- 31 M(-1)) for the HE-beta-CD . CA complex. These results argue that a unique species of bound water is involved in beta-CD . CA stability since a 50% substitution resulted in an equivalent loss in z as well as a substantial decrease in K-double dagger. This hypothesis was supported by NMR inversion recovery experiments whereupon the most significant perturbation to spin-lattice relaxation (Delta T-1 = T-1 beta-CD - T-1 beta-CD . CA) was associated with beta-CD's H-1 at position 3 (H-3; Delta T-1 = 585 ms). Small Delta T(1)s were observed for H-2 (160 ms) and H-6,6' (83 ms). beta-CD's H-3 Delta T(1)s were dependent not only upon the adduct's concentration but also diminished at a high ionic strength. These data indicate that Delta T-1 was related to changes in [D2O] at or near beta-CD's hydroxyl groups and that these D2O molecules were bound with a relatively long residence time. Thermochemical measurements of Delta H and Delta S at various X(H2O)s display typically linear enthalpy-entropy compensation (Delta H-Delta S) relationships but with a slope (T-c = partial derivative Delta H/partial derivative Delta S = 272 K) significantly less than standard aqueous thermodynamic measurements (T-c = 305 K) of a similar system. This unequivocal X(H2O) effect on T-c argues that the chemical part process of CD . guest adduct formation involves changes in relative solvation, presumably desolvation, of beta-CD's binding site. This interpretation was supported by the dependency of Delta lambda(max) on CD binding site dimension and X(H2O)(MeoOH).