title: Methylated β-cyclodextrins: influence of degree and pattern of substitution on the thermodynamics of complexation with tauro- and glyco-conjugated bile salts.
abstract: The complexation of 6 bile salts with various methylated β-cyclodextrins was studied to elucidate how the degree and pattern of substitution affects the binding. The structures of the CDs were determined by mass spectrometry and NMR techniques, and the structures of the inclusion complexes were characterized from the complexation-induced shifts of (13)C nuclei as well as by 2D ROESY NMR. Thermodynamic data were generated using isothermal titration calorimetry. The structure-properties analysis showed that methylation at O3 hinders complexation by partially blocking the cavity entrance, while methyl groups at O2 promote complexation by extending the hydrophobic cavity. Like in the case of 2-hydroxypropylated cyclodextrins, the methyl substituents cause an increased release of ordered water from the hydration shell of the bile salts, resulting in a strong increase in both the enthalpy and the entropy of complexation with increased number of methyl substituents. Due to enthalpy-entropy compensation the effect on the stability constant is relatively limited. However, when all hydroxyl groups are methylated, the rigid structure of the free cyclodextrin is lost and the complexes are severely destabilized due to very unfavorable entropies.
authors.affiliation: NSM, Research Unit for Functional Biomaterials, Roskilde University, Universitetsvej 1, DK-4000 Roskilde, Denmark.
authors.forename: Christian
authors.initials: C
authors.lastname: Schönbeck
authors.forename: Peter
authors.initials: P
authors.lastname: Westh
authors.forename: Jens Christian
authors.initials: JC
authors.lastname: Madsen
authors.forename: Kim Lambertsen
authors.initials: KL
authors.lastname: Larsen
authors.forename: Lars Wagner
authors.initials: LW
authors.lastname: Städe
authors.forename: René
authors.initials: R
authors.lastname: Holm
mesh_terms: D002151:Calorimetry; D002793:Cholic Acids / Q000737:chemistry*; D019277:Entropy; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D008745:Methylation; D047392:beta-Cyclodextrins / Q000737:chemistry*
chemical_list: D002793:Cholic Acids; D047392:beta-Cyclodextrins; C108732:methyl-beta-cyclodextrin