What does this research mean for the field?

While β-cyclodextrin binds metaclazepam enantiomers most strongly among native cyclodextrins, current quantum-mechanics calculations significantly overestimate the binding energy differences compared to experimental capillary electrophoresis results, indicating a need for further refinement of QM tools for modeling these noncovalent interactions. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

What question did this study set out to answer?

The research aims to explore the enantioselective binding properties of metaclazepam enantiomers with various cyclodextrins.

April 12, 2026Journal of Chromatography Open0 citationsOpen Access

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Enantioselective recognition of metaclazepam enantiomers by cyclodextrins studied using capillary electrophoresis, NMR spectroscopy and molecular modeling

KMKetevan Museridze AGAnn Gogolashvili LCLali Chankvetadze

Key Points

The research aims to explore the enantioselective binding properties of metaclazepam enantiomers with various cyclodextrins.
Used capillary electrophoresis to separate metaclazepam enantiomers.
Applied nuclear magnetic resonance spectroscopy for structural determination of complexes.
Conducted quantum-mechanical calculations to analyze interaction energies.
β-CD showed the strongest but least enantioselective binding to metaclazepam enantiomers.
(R)-MCZ exhibited tighter binding than (S)-MCZ with both α- and β-CDs.
Binding patterns varied significantly with γ-CD and required further investigation into binding strength discrepancies.

Abstract

• Separation of metaclazepam enantiomers in capillary electrophoresis • Assignment of absolute stereochemical configuration of metaclazepam enantiomers • Determination of structure of metaclazepam complexes with cyclodextrins in solution • Explanation of enantiomer affinity pattern based on molecular modeling calculations In the present study, an attempt was made to explain enantioselective noncovalent interactions of metaclazepam (MCZ) enantiomers with three native cyclodextrins (CDs) with different cavity size by combined use of capillary electrophoresis (CE), nuclear magnetic resonance (NMR) spectroscopy and quantum-mechanics (QM) calculations. With CE, it was observed that the medium size β-CD binds the enantiomers of MCZ most strongly although with very low enantioselectivity. The affinity of the MCZ enantiomers was lowest towards α-CD. Both α- and β-CDs bind ( R )-MCZ more tightly than ( S )-MCZ, while the opposite is the case with γ-CD. ROESY experiments in NMR spectroscopy provided an explanation of the affinity strength of MCZ enantiomers towards the studied CDs based on the extent of insertion of the guest molecule into the cavity of CDs. QM calculations indicated the importance of intermolecular hydrogen bonding in selector-selectand interactions, as well as supported experimentally observed enantiomer affinity pattern towards CDs under this study. On the other hand, binding energy values calculated using QM did not always correlate with the binding strengths experimentally observed in CE. In addition, binding energy differences calculated based on QM are at least one order of magnitude higher when compared to the binding energy differences calculated based on the selectivity of enantioseparations in CE. Thus, QM tools need further development (refinement) in order to properly describe fine noncovalent interactions between CDs and their guests.

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Enantioselective recognition of metaclazepam enantiomers by cyclodextrins studied using capillary electrophoresis, NMR spectroscopy and molecular modeling

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