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

The inclusion complexes between fusidate, 3-keto fusidate, 11-keto fusidate and 11-deoxy fusidate and alpha-, beta-, and gamma-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 alpha- and beta-CD the obtained results could be modelled to a simple model assuming 1:1 stoichiometry, revealing, not surprisingly, that beta-CD formed a stronger complex compared to alpha-CD. A model assuming 1:2 (fusidate:CD) stoichiometry could be fitted to the data obtained with gamma-CD. The results showed that the different fusidanes formed very strong 1:1 complexes with gamma-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 gamma-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 gamma-CD. The interaction pattern suggests that fusidate may be fully embedded in the cavity of gamma-CD. No interactions between fusidate and the hydrogen atoms situated at the outside of the CD were found.