Comparative Enantioseparation of Ketoprofen with Trimethylated α‐, β‐, and γ‐Cyclodextrins in Capillary Electrophoresis and Study of Related Selector–Selectand Interactions Using Nuclear Magnetic Resonance Spectroscopy

Abstract

The enantiomers of ketoprofen were separated by capillary electrophoresis using the (2,3,6-tri-O-methyl)-derivatives of α-, β-, and γ-cyclodextrin (CyD) as chiral selectors. The affinity pattern of the ketoprofen enantiomers toward these CyDs changed depending on their cavity size. Thus, with hexakis (2,3,6-tri-O-methyl)-α-CyD and heptakis (2,3,6-tri-O-methyl)-β-CyD, the R enantiomer of the drug migrated first, whereas the enantiomer migration order was reversed in the presence of octakis(2,3,6-tri-O-methyl)-γ-CyD. The change in the migration order was rationalized on the basis of changes in the structure of the complexes between the ketoprofen enantiomers and the chiral selectors as derived from nuclear magnetic resonance spectroscopy experiments.

Enantioresolution in electrokinetic chromatography-complete filling technique using sulfated gamma-cyclodextrin. Software-free topological anticipation

“…The approaches used in this field are mainly nuclear magnetic resonance (NMR) spectroscopy [9][10][11], molecular modelling [12][13][14], and computer simulations [8]. The combination of chiral CE with molecular modelling and NMR experiments or other supporting techniques (e.g.…”

Cyclodextrin‐mediated enantioseparation of phenylalanine amide derivatives and amino alcohols by capillary electrophoresis—Role of complexation constants and complex mobilities

“…). Opposite migration order of the enantiomers as a function of the size of the cavity of various CDs has been reported, for example, for ketamine , ketoprofen , or norephedrine . It is interesting to note that this behavior was observed for phenylalanine amide ( 1 ) but not for its methyl derivatives 2–4 .…”

Application of cyclodextrins in chiral capillary electrophoresis

“…They explicitly mentioned a possible influence of differences in electrophoretic mobilities of the complexes of the individual enantiomers with a given selector (vide supra) . The mentioned phenomena have been further studied within the same scientific group using several different analytes and CDs . The authors have concluded that (i) changes in the chemical structure of CDs can lead to a reversal of enantiomer affinity pattern in aqueous and nonaqueous electrolytes; (ii) changes of the geometry of analyte–CD complexes do not always result in a substantial change in the chiral recognition ability or chiral recognition pattern; (iii) the degree of chiral recognition, and the efficiency of enantiomer separations, which rely on the formation of external complexes between the analyte and the CD molecules, can be as good as the efficiency of separations where analyte/CD inclusion complexes are formed.…”

“…Nevertheless, these randomly substituted CDs can be very useful in enantioseparations because their separation ability is different from single isomers . Sometimes, the migration order of enantiomers can be reversed as a consequence of the change of the degree of substitution .…”