NMR studies of chiral recognition mechanisms: interaction of enantiomers of N-imidazole derivatives with cyclodextrin hosts. Correlation with the CD-EKC studies

The inclusion complexes formed between two chiral N-imidazole derivatives and four cyclodextrins (α-, β-, γ-, and highly sulfated-β-CDs) were investigated by one- and two-dimensional 1H NMR. With the additional results of an ESI-MS study, a 1:1 stoichiometry was proven for all the complexes studied. The complexes were also characterized in terms of binding constants and the results were compared to those obtained by CD-EKC. An identical affinity order for the various CDs was obtained with both techniques. Furthermore, the affinity order for both enantiomers determined by their binding constants values is confirmed by the enantiomer migration orders previously determined by CD-EKC. The structural data obtained by the 2D-ROESY experiments allowed us to understand the interaction mechanisms and to propose, for different analyte structures, theoretical models of inclusion orientation in the CD cavity. These models are in accordance with our previous hypothesis based on the analyte structure–enantioseparation relationships and the thermodynamic parameters determined by CD-EKC.

Graphical abstractComplexation between cyclodextrins and enantiomers of N-imidazole derivatives: determination of the stoichiometry, of the binding constants and study of the structure complexes by 1D and 2D 1H NMR.Figure optionsDownload full-size imageDownload as PowerPoint slide