Cyclodextrin and Bile Salt Interactions Using Isothermal Titration Calorimetry

Thomas Allan Rayner, Aiga Mackevica & Paula Melo Paulon Hansen

Studenteropgave: Semesterprojekt


Background: the capability of cyclodextrins of forming complexes with different substrates in aqueous solution, improving consequently the solubility of such compounds, has aroused the attention from the pharmaceutical industry. Cyclodextrins are cyclic oligosaccharides, mainly made up of 6 to 8 glycopyranose units and they can be found in nature or can be artificially synthesized. Purpose: the aim of this project is to investigate the interaction between 2 kinds of cyclodextrins -β-cyclodextrin and hydroxypropyl-0.6-β-cyclodextrin- with 3 kinds of bile salts - glycocholate (GC), glycodeoxycholate (GDC) and glycochenodeoxycholate (GCDC), using isothermal titration calorimetry (ITC) and determine the binding constants and thermodynamics parameters for each different cyclodextrin and bile salt combination under different temperatures: 25, 30, 40 and 50°C. The lowest temperature was chosen based on what has been previously cited in the literature, while the highest temperatures were meant to test the interaction of cyclodextrins and bile salts in the highest temperature range possible using ITC. Results: The interaction of cyclodextrins and bile salts presented a 1:1 binding relation. The binding constant for GCDC and both cyclodextrins were highest when compared to the other bile salts. The entropy and enthalpy changes for all the interactions between bile salts and cyclodextrins decreased with increased temperature. The standard Gibbs free energy has not changed significantly when going from 25°C to 50°C for each interaction, which indicates enthalpy-entropy compensation. Conclusions: Our data and analysis suggest that β-cyclodextrin binds stronger to GC and GCDC than hydroxypropyl-0.6-β-cyclodextrin does. GCDC binds strongest and this may be due to the absence of a hydroxyl group on C12 (C-ring of the bile salt) which makes the bile salt more hydrophobic and thus increases the binding constant (K) and decreases the heat capacity change (ΔCp) of the interaction and therefore also the change in the accessible surface area (ΔASA). Hydrophobic hydration may be the reason for the entropy-enthalpy compensation that has been observed when temperature increases.

UddannelserBasis - International Naturvidenskabelig Bacheloruddannelse, (Bachelor uddannelse) Basis
Udgivelsesdato20 jan. 2010
VejledereChristian Schonbeck & Peter Westh


  • Cyclodextrin
  • Bile Salts
  • Enthalpy
  • Heat Capacity
  • Enthalpy-Entropy Compensation
  • ITC
  • Entropy
  • Accessible Surface Area
  • Hydrophobic Hydration