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 °C (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 °C (K1 : 2=7.55×104 M−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.