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Inclusion complexes of fusidic acid and three structurally related compounds with cyclodextrins

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Abstract

The inclusion complexes between fusidate, 3-keto fusidate, 11-keto fusidate and 11-deoxy fusidate and α-, β-, and γ-cyclodextrin (CD) were studied using capillary electrophoresis. By monitoring the changes in mobility of the negatively charged compounds in the presence of varying amount of CD the stability constants of the complexes formed could be obtained. In the case of α- and β-CD the obtained results could be modelled to a simple model assuming 1:1 stoichiometry, revealing, not surprisingly, that β-CD formed a stronger complex compared to α-CD. A model assuming 1:2 (fusidate:CD) stoichiometry could be fitted to the data obtained with γ-CD. The results showed that the different fusidanes formed very strong 1:1 complexes with γ-CD as well as a quite weak 1:2 complex. 3-keto-, 11-keto- and 11-deoxy-fusidate formed stronger complexes compared to fusidate, probably due to an decrease in hydrophilicity caused by the reduced number of hydroxyl groups. The complex between γ-CD and fusidate was studied by use of 2D-NMR spectroscopy. The results showed that most of the hydrogen atoms of fusidate show interactions with the hydrogen atoms in the cavity of γ-CD. The interaction pattern suggests that fusidate may be fully embedded in the cavity of γ-CD. No interactions between fusidate and the hydrogen atoms situated at the outside of the CD were found.

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Abbreviations

CD:

Cyclodextrin

COSY:

Correlation spectroscopy

DQF:

Double Quantum Filtered

ROESY:

Rotating Overhauser Effect Spectroscopy

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Authors and Affiliations

  1. Department of Biotechnology, Chemistry and Environmental Engineering, Aalborg University, Sohngaardsholmsvej 49/57, 9000, Aalborg, Denmark

    Kim Lambertsen Larsen, Stig Bruse Andersen & Reinhard Wimmer

  2. Department of Clinical Biochemistry, AS, Aarhus University Hospital, Aarhus, Denmark

    Anne Louise Mørkbak

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  1. Kim Lambertsen Larsen
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  2. Stig Bruse Andersen
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  3. Anne Louise Mørkbak
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  4. Reinhard Wimmer
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Correspondence to Kim Lambertsen Larsen.

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Larsen, K.L., Andersen, S.B., Mørkbak, A.L. et al. Inclusion complexes of fusidic acid and three structurally related compounds with cyclodextrins. J Incl Phenom Macrocycl Chem 57, 185–190 (2007). https://doi.org/10.1007/s10847-006-9198-7

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  • DOI: https://doi.org/10.1007/s10847-006-9198-7

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