Interactions of cholesterol with cyclodextrins in aqueous solution

Area of Science:

• Supramolecular Chemistry
• Physical Chemistry
• Drug Delivery Systems

Background:

• Cholesterol is a vital biomolecule with limited aqueous solubility.
• Cyclodextrins (CDs) are widely used to enhance the solubility of poorly soluble compounds.
• Understanding host-guest interactions is crucial for developing effective drug delivery systems.

Purpose of the Study:

• To investigate the interaction between cholesterol and various cyclodextrins in aqueous solutions.
• To characterize the stoichiometry and thermodynamic parameters of cholesterol-CD complex formation.
• To elucidate the structural aspects of the formed complexes.

Main Methods:

• Solubility method to determine complex formation and stoichiometry.
• Thermodynamic analysis (ΔG°, ΔH°, TΔS°) to evaluate complex stability.
• Proton nuclear magnetic resonance (1H NMR) spectroscopy.
• Corey-Pauling-Koltun (CPK) atomic models for structural estimation.

Main Results:

• Heptakis (2,6-di-O-methyl)-beta-cyclodextrin (DOM-beta-CD) formed soluble 1:1 and 1:2 complexes with cholesterol.
• No significant complexation was observed with alpha-CD, beta-CD, and gamma-CD.
• A minor soluble complex formed between cholesterol and 2-hydroxylpropyl-beta-CD.
• The 1:2 DOM-beta-CD:cholesterol complex exhibited favorable thermodynamics (ΔG° = -27.1 kJ/mol) and was driven by hydrophobic interactions.
• Proton NMR and CPK models suggested probable structures for the 1:2 complex.

Conclusions:

• DOM-beta-CD is an effective cyclodextrin for forming soluble cholesterol complexes.
• The 1:2 complex formation is thermodynamically favored and primarily driven by hydrophobic forces.
• The study provides insights into the molecular interactions and structures relevant for cholesterol solubilization.