Investigation of the Structure and Thermodynamics of Inclusion Complexes between γ-Cyclodextrins and Glycoconjugated Bile Salts

Jonatan Køhler

Studenteropgave: Speciale


The thermodynamics and structure of inclusion complexes between seven different γ-cyclodextrins (γCDs) and three biologically relevant bile salts (BSs) were investigated. The six modified γCDs (two methyl-γCDs (Me-γCD), one sulfobutylether-γCD (SBE-γCD), and three 2-hydroxypropyl-γCDs (HP-γCD) were characterized by 1H NMR, 13C NMR, and mass spectrometry. The structural analysis was carried out by use of 2D ROESY NMR. The thermodynamics of complexation was investigated with isothermal titration calorimetry. The structural analysis showed that the structure of all but the fully methylated γCD complexes were similar to what has previously been observed for γ-CD-BS complexes. Isothermal titration calorimetry carried out at temperature interval 5-55 °C yielded stoichiometries and the thermodynamic parameters ΔH°, ΔS°, K, ΔCp° for all but the fully methylated γCD complexes which did not form any stable complexes. Complexation with five of the modified γCDs was athermal at approximately 25 °C, which made a thermodynamic analysis impossible around this temperature. Stability constants decreased with degree of substitution (DS), with methyl substituents having less effect on K than SBE and HP. Enthalpy-entropy compensation was seen as both enthalpy and entropy increased with DS, which is believed to be caused by dehydration of hydrophobic BS surface area. Calculations based on ΔCp° data showed that each of the substituents dehydrated 10-20 Å2 (HP), 22-33 Å2 (SBE), and 10-15 Å2 (methyl) of BS surface area.

UddannelserKemi, (Bachelor/kandidatuddannelse) Kandidat
Udgivelsesdato29 jun. 2015
VejlederePeter Westh & René Holm


  • Complexation
  • Bile Salts
  • NMR
  • Inclusion compounds
  • Cyclodextrins
  • Isothermal titration calorimetry