Separation of enilconazole enantiomers in capillary electrophoresis with cyclodextrin‐type chiral selectors and investigation of structure of selector‐selectand complexes by using nuclear magnetic resonance spectroscopy

Abstract

In the present study, the enantiomer migration order (EMO) of enilconazole in the presence of various cyclodextrins (CDs) was investigated by capillary electrophoresis (CE). Opposite EMO of enilconazole were observed when β-CD or the sulfated heptakis(2-O-methyl-3,6-di-O-sulfo)-β-CD (HMDS-β-CD) was used as the chiral selectors. Nuclear magnetic resonance (NMR) spectroscopy was used to study the mechanism of chiral recognition between enilconazole enantiomers and those two cyclodextrins. On the basis of rotating frame nuclear Overhauser (ROESY) experiments, the structure of an inclusion complex between enilconazole and β-CD was derived, in which (+)-enilconazole seemed to form a tighter complex than the (-)-enantiomer. This correlates well with the migration order of enilconazole enantiomers observed in CE. No evidence of complexation between enilconazole and HMDS-β-CD could be gathered due to lack of intermolecular nuclear Overhauser effect (NOE). Most likely the interaction between enilconazole and HMDS-β-CD leads to formation of a shallow external complex that is sufficient for separation of enantiomers in CE but cannot be evidenced based on ROESY experiment. Thus, in this particular case CE documents the presence of intermolecular interactions which are at least very difficult to be evidenced by other instrumental techniques.

Recent studies of docking and molecular dynamics simulation for liquid‐phase enantioseparations

“…Despite the fact that ‘external’ complexes between CD derivatives and guest molecules have been observed , the main complexation mode occurs via inclusion between an apolar part of the guest molecule by hydrophobic interactions in the cavity, and polar interactions at the polar rim of the CD . Several noncovalent interactions underlie recognition processes like HBs, π‐π and hydrophobic interactions, dipole‐dipole stacking, van der Waals and dispersion forces.…”

Separation of brombuterol enantiomers in capillary electrophoresis with cyclodextrin‐type chiral selectors and investigation of structure of selector‐selectand complexes using nuclear magnetic resonance spectroscopy

“…A representative example is heptakis(2‐O‐methyl‐3,6‐di‐O‐sulfo)‐β‐CD (HMDS‐β‐CD), synthesized by Vigh and coworkers in 2000 . This CD provides significant chiral recognition, but in most cases studied until now in detail, no inclusion complex formation can be confirmed by NMR spectroscopy . In the present study, brombuterol (BB) was used as an example of chiral guest molecule interacting with various CD‐hosts having different cavity size and the nature and position of substituents.…”

Chiral separation of lansoprazole and rabeprazole by capillary electrophoresis using dual cyclodextrin systems

“…Their chiral discrimination process usually involves an inclusion of a hydrophobic moiety of the chiral analyte in the CD cavity, along with lateral interactions of the hydroxyl or other polar groups of the CD with polar moieties of the guest molecule . Although this is the general case, several unusual binding modes were also described or proposed . External complex formation of the β‐blocker talinolol was observed in aqueous (with heptakis(2,3‐di‐O‐methyl‐6‐sulfo)‐β‐CD) as well as in non‐aqueous (with heptakis(2,3‐di‐O‐acetyl‐6‐sulfo)‐β‐CD) environments using NMR spectroscopy .…”

“…No evidence of complexation between the topical fungicide enilconazole enantiomers and heptakis(2‐O‐methyl‐3,6‐di‐O‐sulfo)‐β‐CD was established using NMR spectroscopy, although CE experiments evidenced enantioselectivity using this CD as chiral selector. The authors proposed the formation of a shallow external complex between the enantiomers of the analyte and the chiral selector, which is difficult to detect by NMR spectroscopy .…”