No abstract

No abstract

The enantiomer migration order of the chiral anaesthetic drug ketamine [RS‐2‐(2‐chlorophenyl)‐2‐(methylamino)cyclohexanone] was studied by capillary electrophoresis using various cyclodextrins as chiral selectors. The opposite migration order of the enantiomers of ketamine was observed when native α‐ and β‐cyclodextrins were used as chiral selectors in capillary electrophoresis. The possible mechanisms of the opposite enantiomer migration order were investigated by employing electrospray ionization mass spectrometry, 1H‐NMR spectrometry, one dimensional rotating frame nuclear Overhauser and exchange spectroscopy, X‐ray crystallography, and molecular modeling techniques. As this study indicates, capillary electrophoresis can be used as a reliable experimental technique for examination of the correctness of the results of molecular modeling calculations. In addition, based on X‐ray crystallographic analysis it was confirmed that (–)‐ketamine as a free base possesses S configuration.

Twenty-three cationic chiral analytes were resolved in capillary electrophoresis using native beta-cyclodextrin and single isomer heptakis-(2-O-methyl-3,6-di-O-sulfo)-beta-cyclodextrin as chiral selectors. For 12 of 16 chiral analytes resolved with both chiral selectors the enantiomer migration order was opposite. In selected cases the structure of cyclodextrin-analyte complexes in aqueous solution was investigated using one-dimensional transverse rotating frame nuclear Overhauser and exchange spectroscopy. It was found that in contrast to mainly inclusion-type complexes between chiral analytes and beta-cyclodextrin, external complexes are formed between the chiral analytes and structurally crowded, highly charged heptakis-(2-O-methyl-3,6-di-O-sulfo)-beta-cyclodextrin.