Cyclomaltoheptaose (β-cyclodextrin) and hydroxyethyl-substituted β-cyclodextrin inclusion complex formation with chlorogenic acid: solvent effects on inclusion complex stability

The inclusion complexes of cyclomaltoheptaose (β-CD) and β-CDʹs 50% hydroxyethyl-substituted derivative (HE-β-CD) with chlorogenic acid (CA) were studied with regard to temperature and water activity (aH2O ≈ mole fraction = XH2O = 0.8–0.99; 0.1 M Na phosphate buffer) utilizing first-derivative spectrophotometric analyses of bathochromic shifts (Δλ) in CAʹs UV absorbance as a function of variable [CD]. From the dependence of the apparent stability constant, K, on XH2O (K = K‡XH2Oz) we estimated that the β-CD · CA complexʹs apparent stoichiometric coefficient, z, for water was ca. 7 ± 1 (K‡ = 1032 ± 54 M−1); this value agrees with recently published literature concerning the minimum number of waters needed to stabilize a similar β-CD adduct. However, we determined that z was significantly lower (4 ± 0.3; K‡ = 809 ± 31 M−) for the HE-β-CD · CA complex. These results argue that a unique species of bound water is involved in β-CD · CA stability since a 50% substitution resulted in an equivalent loss in z as well as substantial decrease in K‡. This hypothesis was supported by NMR inversion recovery experiments whereupon the most significant perturbation to spin-lattice relaxation (ΔT1 = T1β-CD − T1β-CD · CA) was associated with β-CDʹs 1H at position 3 (H−3; ΔT1 = 585 ms). Small ΔT1s were also observed for H-2 (160 ms) and H-6,6′ (83 ms). β-CDʹs ΔT1s were dependent not only upon the adductʹs concentration but also diminished at a high ionic strength. These data indicate that ΔT1 was related to changes in [D2O] at or near β-CDʹs hydroxyl groups and that these D2O molecules were bound with a relatively long residence time. Thermochemical measurements of ΔH and ΔS at various XH2Os display typically linear enthalpy-entropy compensation (ΔH−ΔS) relationships but with a slope (Tc = ∂ΔH/∂ΔS = 272 K) significantly less than standard aqueous thermodynamic measurements (Tc = 305 K) of a similar system. This unequivocal XH2O effect on Tc argues that the chemical part process of CD · guest adduct formation involves changes in relative solvation, presumably desolvation, of β-CDʹs binding site. This interpretation was supported by the dependency of Δλmax on CD binding site dimension and XH2OMeOH.