Inverted metal-free active template synthesis of rotaxanes via axle‑mediated macrocyclization
Jiankang Zhong1, Axel Troncossi1, Enzo Olivieri1
1Department of Chemistry, University of Manchester, Manchester, UK.
Nature Chemistry
|June 29, 2026
Summary
Flexible oligo(ethylene glycol) axles enable metal-free rotaxane synthesis by templating macrocycle formation. This novel approach simplifies the creation of complex mechanically interlocked molecules from basic components.
Area of Science:
- Supramolecular Chemistry
- Organic Synthesis
- Materials Science
Background:
- Traditional rotaxane synthesis necessitates specific recognition sites on macrocycles for axle components.
- Existing methods often rely on metal templates or complex precursors.
Purpose of the Study:
- To develop an inverted, metal-free synthetic route to rotaxanes.
- To utilize flexible oligo(ethylene glycol) chains as active templates for macrocycle formation.
Main Methods:
- Employing flexible oligo(ethylene glycol) axles to template amide-bond-forming macrocyclization.
- Iterative assembly of higher-order rotaxanes using progressively longer axles.
- Structural characterization using X-ray crystallography.
- Post-synthetic modification to yield minimalist rotaxanes.
Main Results:
- Achieved [2]rotaxane synthesis with yields up to 70% via axle-templated macrocyclization.
- Demonstrated iterative assembly of [n]rotaxanes, including a [5]rotaxane with four macrocycles on an octa(ethylene glycol) chain.
- X-ray structure revealed helical stacking of macrocycles stabilized by aromatic and hydrogen bonding.
- Successful synthesis of minimalist rotaxanes by removing amide linkages.
Conclusions:
- Flexible axles can actively template macrocycle formation, reversing traditional synthetic strategies.
- This method offers a versatile, metal-free route to diverse rotaxanes and mechanically interlocked molecules.
- The findings expand the structural possibilities for mechanically interlocked molecules by removing functional group constraints.
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