Resolving Conformational Chirality in a Stereolabile Macrocycle
Haiying Wang1,2,3, Cai-Hong Zhan4, Kim K Baldridge3
1College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, Fujian61005, P. R. China.
Journal of the American Chemical Society
|July 23, 2026
Summary
This study demonstrates how a dynamically racemic macrocycle spontaneously resolves into enantiomers upon crystallization. This allows for the characterization and sorting of chiral molecules based on their solid-state properties and crystal shape.
Area of Science:
- Supramolecular Chemistry
- Crystallography
- Chiroptical Spectroscopy
Background:
- Conformational chirality is often difficult to study due to rapid stereochemical averaging.
- Enantiomeric resolution and chiroptical characterization are frequently hindered by dynamic processes in solution.
Purpose of the Study:
- To investigate the spontaneous resolution of a stereolabile macrocycle upon crystallization.
- To link molecular structure, solid-state chiroptical response, and crystal morphology in a dynamically racemic system.
Main Methods:
- Single-crystal X-ray diffraction to determine crystal structure.
- Solid-state electronic and vibrational circular dichroism for chiroptical analysis.
- Density functional theory calculations to support absolute configuration assignment.
Main Results:
- A pillar[5]arene-based macrocycle, racemic in solution, forms a conglomerate upon crystallization, with individual crystals containing single enantiomers.
- Absolute configurations were established using chiroptical spectroscopy and computational methods.
- Crystal morphology (hemihedral facets) correlated with absolute configuration, enabling visual sorting.
- Conglomerate packing was retained in solvomorphs, and chiral guests influenced crystallization outcomes.
Conclusions:
- Crystallization can overcome dynamic averaging to enable the resolution and characterization of conformational chirality.
- This work establishes a direct link between molecular chirality, solid-state properties, and macroscopic features like crystal morphology.
- The findings offer a method for making averaged conformational chirality structurally, spectroscopically, and visually legible.
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