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Macrocycle Conformational Flexibility as a Key to Enantioselective Recognition
Tadeu Luiz Gomes Cabral1,2, Matthias Stein1, Claudio F Tormena2
1Molecular Simulations and Design Group, Max Planck Institute for Dynamics of Complex Technical Systems, Sandtorstrasse 1, Magdeburg 39106, Germany.
JACS Au
|July 30, 2026
Summary
This study uses NMR and computational methods to differentiate enantiomers with a chiral macrocycle (MAC). The research reveals that the MAC
Area of Science:
- Chiral chemistry
- Supramolecular chemistry
- Analytical chemistry
Background:
- Enantiomer differentiation is crucial but challenging.
- Diffusion-NMR (DOSY) with chiral resolving agents shows promise.
- Limitations exist in assigning absolute configurations and understanding chiral recognition.
Purpose of the Study:
- Investigate enantiomer differentiation using a specific chiral macrocycle (MAC).
- Combine NMR experiments and computational modeling.
- Elucidate the molecular basis of chiral recognition by the MAC.
Main Methods:
- Utilized diffusion-NMR (DOSY) experiments.
- Employed computational modeling and conformational searches.
- Conducted temperature-dependent 1H and selective ROESY NMR measurements.
Main Results:
- The chiral macrocycle (MAC) showed stereopreference for (S)-enantiomers.
- Computational modeling indicated selectivity arises from a closed MAC conformation.
- NMR data supported an equilibrium between open and closed MAC conformers.
Conclusions:
- The closed MAC-enantiomer complexation explains observed diffusion-NMR and shielding differences.
- Macrocyclic receptor conformational flexibility is key to chiral recognition.
- Findings advance understanding of enantioselective interactions and MAC design.
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