Methylated beta-Cyclodextrins: Influence of Degree and Pattern of Substitution on the Thermodynamics of Complexation with Tauro- and Glyco-Conjugated Bile Salts

Jens Christian Sidney Schönbeck, Peter Westh, Jens C. Madsen, Kim Lambertsen Larsen, Lars Wagner Städe, Rene Holm

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

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 13C 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.
OriginalsprogEngelsk
TidsskriftLangmuir
Vol/bind27
Udgave nummer10
Sider (fra-til)5832-5841
ISSN0743-7463
DOI
StatusUdgivet - 2011

Citer dette

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title = "Methylated beta-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 13C 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.",
author = "Sch{\"o}nbeck, {Jens Christian Sidney} and Peter Westh and Madsen, {Jens C.} and Larsen, {Kim Lambertsen} and St{\"a}de, {Lars Wagner} and Rene Holm",
year = "2011",
doi = "10.1021/la200381f",
language = "English",
volume = "27",
pages = "5832--5841",
journal = "Langmuir",
issn = "0743-7463",
publisher = "American Chemical Society",
number = "10",

}

Methylated beta-Cyclodextrins: Influence of Degree and Pattern of Substitution on the Thermodynamics of Complexation with Tauro- and Glyco-Conjugated Bile Salts. / Schönbeck, Jens Christian Sidney; Westh, Peter; Madsen, Jens C.; Larsen, Kim Lambertsen; Städe, Lars Wagner; Holm, Rene.

I: Langmuir, Bind 27, Nr. 10, 2011, s. 5832-5841.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Methylated beta-Cyclodextrins: Influence of Degree and Pattern of Substitution on the Thermodynamics of Complexation with Tauro- and Glyco-Conjugated Bile Salts

AU - Schönbeck, Jens Christian Sidney

AU - Westh, Peter

AU - Madsen, Jens C.

AU - Larsen, Kim Lambertsen

AU - Städe, Lars Wagner

AU - Holm, Rene

PY - 2011

Y1 - 2011

N2 - 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 13C 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.

AB - 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 13C 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.

U2 - 10.1021/la200381f

DO - 10.1021/la200381f

M3 - Journal article

VL - 27

SP - 5832

EP - 5841

JO - Langmuir

JF - Langmuir

SN - 0743-7463

IS - 10

ER -