Study on the chiral recognition of the enantiomers of ephedrine derivatives with neutral and sulfated heptakis(2,3-O-diacetyl)-β-cyclodextrins using capillary electrophoresis, UV, nuclear magnetic resonance spectroscopy and mass spectrometry

The enantiomers of methylephedrine, pseudoephedrine and ephedrine showed a different migration behavior in capillary electrophoresis in the presence of β-cyclodextrin (β-CD), heptakis(2,3-O-diacetyl)-β-cyclodextrin and heptakis(2,3-O-diacetyl-6-sulfato)-β-cyclodextrin (HDAS). Utilizing UV, MS and NMR spectroscopy, in particular rotating frame Overhauser experiments, an attempt was made to elucidate the chiral recognition mechanism. In the case of the neutral CDs 1:1 complexes were formed with ephedrine and methylephedrine characterized by the inclusion of the phenyl ring in the cavity and the side chain pointing out of the wider rim. In contrast, manifold complexes were formed with HDAS, which on average are characterized by an upside down inclusion of the phenyl ring in the cavity and the side chain pointing out of the narrow rim. This complex geometry is likely be stabilized by an ion–ion interaction between the positively charged nitrogens of the ephedrine derivatives and the negative charges of HDAS. In addition, an attachment of the ligand to the outside of HDAS and other complex stoichiometries are also possible.