Interaction of heptakis (2,3,6-tri-O-methyl)-beta-cyclodextrin with cholesterol in aqueous solution

摘要

The interaction of cholesterol with heptakis (2,3,6-tri-O-methyl)-beta-cyclodextrin (TOM-beta-CyD) was investigated in water using solubility method. It was found that TOM-beta-CyD forms two kinds of soluble complexes, with molar ratios of 1: 1 and 1: 2 (cholesterol: TOM-beta-CyD). The thermodynamic parameters for 1:1 and 1:2 complex formation of cholesterol with TOM-beta-CyD were: DeltaG(1:1)(0) = -11.0 kJ/mol at 25degreesC (K-1:1 = 7.70 x 10(M)(4)(-1)); DeltaH(1:1)(0) = 1.28 kJ/mol; TDeltaS(1:1)(0) = 9.48 kJ/mol; DeltaG(1:2)(0) = -27.8 kJ/mol at 25degreesC (K-1:2 = 7.55 x 10(M)(4)(-1)); DeltaH(1:2)(0) = -0.57 kJ/mol; TDeltaS(1:1)(0) = 27.3 kJ/mol. The formation of the 1:2 complex occurred much more easily than that of the I : I 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-beta-CyD with cholesterol was compared with that of heptakis (2,6-di-O-methyl)-beta-CyD (DOM-beta-CyD). The interaction of TOM-beta-CyD is more hydrophobic than that of DOM-beta-CyD, and the life time of the complexed TOM-beta-CyD is sufficiently long to give separated signals, at the NMR time scale, which differs from that of complexed DOM-beta-CyD.