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Updated: Jun 16, 2025
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Self-assembling Morphologies Obtained from Helical Polycarbodiimide Copolymers and Their Triazole Derivatives
Published on: February 7, 2017
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Stabilization of 310-Helices in Macrocycles Using Dominant Rotor Methodology
Martynas J Širvinskas1, George J Saunders1, Monica Mitrache1
1Davenport Research Laboratories, University of Toronto, 80 St. George St., Toronto, Ontario M5S 3H6, Canada.
Journal of the American Chemical Society
|August 19, 2024
Summary
Atropisomeric rotors stabilize rare 310-helices in macrocycles, a normally metastable state. These helical structures remain stable even after prolonged heating and can be selectively enriched.
Area of Science:
- Chemical synthesis and structural biology
- Supramolecular chemistry and peptide science
Background:
- Stabilizing biologically relevant structural motifs is a significant challenge in chemistry.
- Rare 310-helices are typically metastable and difficult to maintain in macrocyclic structures.
Purpose of the Study:
- To investigate the stabilization of 310-helices in macrocycles using atropisomeric dominant rotors.
- To explore the potential of these stabilized helices for applications requiring robust structural motifs.
Main Methods:
- Solid-phase peptide synthesis for macrocycle preparation.
- Extensive structural analysis and molecular dynamics (MD) simulations for solution structure determination.
- Thermal stability assays to assess helicity retention.
Main Results:
- Atropisomeric dominant rotors successfully stabilized 310-helices in macrocycles.
- MD simulations provided evidence for stable 310-helix formation, overcoming the usual metastability.
- The 310-helices demonstrated remarkable thermal stability, retaining helicity after heating to 100 °C for 72 hours.
- Thermal enrichment of crude atropisomeric mixtures yielded 310-helical macrocycles with high selectivity (>20:1).
Conclusions:
- Atropisomeric rotors are effective tools for stabilizing otherwise metastable 310-helical structures in macrocycles.
- The demonstrated thermal stability and selective enrichment offer promising avenues for designing robust macrocyclic compounds.
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