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

Abstract

The major goal of this study was to determine the affinity pattern of brombuterol (BB) enantiomers toward various cyclodextrins (CD) and to evaluate the potential of NMR spectroscopy for understanding fine mechanisms of interactions between CDs and BB enantiomers. Separation of BB enantiomers was performed in a fused‐silica capillary using a phosphate buffer, pH 2.5, at the room temperature in the normal polarity mode. It was shown once again that CE in combination with NMR spectroscopy represents a very sensitive tool for studies of affinity patterns and structure of CD complexes with chiral guests. Although opposite affinity patterns of BB enantiomers were observed toward native β‐ and γ‐CDs, no significant differences between the structures of the complexes of these two CDs with BB were detected by NMR spectroscopy. In contrary to this, the opposite affinity pattern of BB enantiomers toward β‐CD and its two sulfated derivatives, heptakis (2,3‐O‐diacetyl‐6‐sulfo)‐β‐CD (HDAS‐β‐CD) and heptakis (2‐O‐methyl‐3,6‐di‐O‐sulfo)‐β‐CD (HMDS‐β‐CD) was associated with major differences in the structure of the complexes. In addition, it was shown again that HMDS‐β‐CD provides separation of enantiomers without formation of inclusion‐type complex with the chiral analyte.

Recent developments in capillary and microchip electroseparations of peptides (2019–mid 2021)

“…Electric conductivity, electrochemical, NMR, and some other detection modes are less suitable and, thus, much less employed for detection of peptides separated by CE and CEC methods than the above UV-absorption, fluorescence, and MS detection schemes. For that reason, only some recent reviews and articles are cited here, which are dealing with general developments and applications of these detectors in separation methods such as contactless capacitively coupled conductivity detection (C 4 D) [187,188], electrochemical detection [189], chemiluminiscence [190], electrochemiluminiscence [191], infrared and nuclear magnetic resonance spectroscopy [192][193][194]. In these reviews and articles, few applications of these detectors for CE and CEC separations of peptides as model analytes are presented.…”

Challenging Bioanalyses with Capillary Electrophoresis

“…72,73 Cyclodextrins are cyclic sugar molecules with a cavity that enables enantioselective separations of chiral drugs. Beta-cyclodextrin [74][75][76] and β-cyclodextrin derivatives 65,73,[77][78][79][80][81][82][83][84] are the most common additives used for chiral separations, although α-cyclodextrins 74 and γ-cyclodextrin derivatives 85,86 have also been reported. Cyclodextrins modified with different functional groups were used to resolve different drug enantiomers including methylated β-cyclodextrin for psychoactive drugs in under 4 minutes.…”

Recognition in the Domain of Molecular Chirality: From Noncovalent Interactions to Separation of Enantiomers

“…NMR spectroscopy provided the very first confirmation of inclusion complex formation between CDs and guest molecules in solution in 1970 as well as very useful information on the stoichiometry, binding constants, structure, free energy, enthalpy, entropy, and dynamics of CD guest complexes in the last 50 years. ,,, The first article on the structure of an analyte–CD complex determined using NMR spectroscopy in relation to enantioselective CE was published by Yamashoji et al in 1992 . Later, other studies included a correlation between the signal splitting pattern and extent in 1 H, − , 13 C, and 19 F-NMR, ,, spectra, on the one hand, and enantioseparations in CE, on the other hand, as well as stoichiometry, ,,− , binding constants, ,,,,− structure, ,,,,,,,,,− and dynamics of CD–guest complexes , related to CE enantioseparations.…”