Interactions of cholesterol with cyclodextrins in aqueous solution.

Abstract

The interaction of cholesterol with several cyclodextrins (CDs) was investigated in water using solubility method. It was found that heptakis (2,6-di-O-methyl)-beta-CD (DOM-beta-CD) forms two types of soluble complex, with molar ratios of 1 : 1 and 1 : 2 (cholesterol : DOM-beta-CD), and neither a soluble nor insoluble complex is formed between cholesterol and alpha-CD, beta-CD, and gamma-CD, although a minor soluble complex formation was observed between cholesterol and 2-hydroxylpropyl-beta-CD. The thermodynamic parameters for 1 : 1 and 1 : 2 complex formation of cholesterol with DOM-beta-CD obtained from the changes in K with temperature are as follows: DeltaG degrees (1 : 1)=-11.6 kJ/mol at 25 degrees C (K(1 : 1)=1.09x10(2) M(-1)); DeltaH degrees (1 : 1)=-3.38 kJ/mol; TDeltaS degrees (1 : 1)=8.25 kJ/mol; DeltaG degrees (1 : 2)=-27.1 kJ/mol at 25 degrees C (K(1 : 2)=5.68x10(4) M(-1)); DeltaH degrees (1 : 2)=-3.96 kJ/mol; and TDeltaS degrees (1 : 2)=23.2 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 considered to be mainly hydrophobic interaction. Also, based on the measurements of proton nuclear magnetic resonance spectra and studies with Corey-Pauling-Koltun atomic models, the probable structutures of the 1 : 2 complex were estimated.