Folding-controlled assembly of ortho-phenylene-based macrocycles

Area of Science:

• Supramolecular Chemistry
• Organic Chemistry
• Materials Science

Background:

• Foldamers are synthetic molecules that mimic biological structures.
• Self-assembly of foldamers into higher-order structures like macrocycles is a key area in supramolecular chemistry.
• Previous studies showed interplay between foldamer folding and self-assembly, leading to emergent behaviors.

Purpose of the Study:

• To demonstrate active control over foldamer self-assembly into macrocycles.
• To investigate how manipulating foldamers' conformational energy surfaces influences macrocycle formation.
• To explore structure-property relationships in foldamer-based macrocycle synthesis.

Main Methods:

• Synthesis of ortho-phenylene foldamers (decamers and octamers) with varying substituents (alkoxy, hydrogen, fluoro).
• Macrocycle formation via imine condensation.
• Analysis of product distribution using gel-permeation chromatography.
• Determination of molecular geometries via NMR spectroscopy and computational chemistry.

Main Results:

• Ortho-phenylene decamers with alkoxy or hydrogen substituents yielded a mixture of [2+2] and [3+3] macrocycles, controlled by entropic and enthalpic factors.
• Introduction of fluoro substituents shifted the assembly quantitatively towards [3+3] macrocycles by favoring foldamer folding.
• Ortho-phenylene octamers showed quantitative misfolding into small macrocycles irrespective of substituents, as they do not fit when perfectly folded.

Conclusions:

• Achieved high-level structural control in complex foldamer systems by manipulating conformational energy.
• Demonstrated that small structural modifications can induce large-amplitude architectural changes in self-assembled structures.
• Established a method to precisely control macrocycle formation by tuning foldamer folding preferences.