Interaction of Heptakis (2,3,6-Tri-O-methyl)-β-cyclodextrin with Cholesterol in Aqueous Solution

The interaction of cholesterol with heptakis (2,3,6-tri-O-methyl)-β-cyclodextrin (TOM-β-CyD) was investigated in water using solubility method. It was found that TOM-β-CyD forms two kinds of soluble complexes, with molar ratios of 1：1 and 1：2 (cholesterol：TOM-β-CyD). The thermodynamic parameters for 1：1 and 1：2 complex formation of cholesterol with TOM-β-CyD were：ΔG01：1 = -11.0 kJ/mol at 25 ℃ (K1：1 = 7.70 × 10 M-1) ; ΔH01：1 = -1.28 kJ/mol ; TΔS01：1 = 9.48 kJ/mol ; ΔG01：2 = -27.8 kJ/mol at 25 ℃ (K1：2 = 7.55 × 104M-1) ; ΔH01：2 = -0.57 kJ/mol ; TΔS01：1 = 27.3 kJ/mol. The formation of the 1：2 complex occurred much more easily than that of the 1：1 complex. The driving force for 1：1 and 1：2 complex formation was suggested to be exclusively hydrophobic interaction. Based on the measurements of proton nuclear magnetic resonance spectra and studies with Corey-Pauling-Koltun atomic models, the probable structures of the 1：2 complex were estimated. In addition, the interaction of TOM-β-CyD with cholesterol was compared with that of heptakis (2, 6-di-O-methyl)-β-CyD (DOM-β-CyD). The interaction of TOM-β-CyD is more hydrophobic than that of DOM-β-CyD, and the life time of the complexed TOM-β-CyD is sufficiently long to give separated signals, at the NMR time scale, which differs from that of complexed DOM-β-CyD.