Sequence-Controlled Stimuli-Responsive Single-Double Helix Conversion between 1:1 and 2:2 Chloride-Foldamer Complexes

Area of Science:

• Supramolecular chemistry
• Polymer science
• Organic chemistry

Background:

• Biopolymers encode crucial information in their primary sequence for structure, stability, and function.
• Encoding similar information into nonbiological polymers remains a significant challenge.

Purpose of the Study:

• To design and characterize a novel foldamer capable of forming a chloride-templated double helix.
• To investigate the factors controlling the interconversion between single and double helical structures.
• To understand how primary sequence modifications influence foldamer stability and structure.

Main Methods:

• Synthesis of a C2-symmetric aryl-triazole foldamer.
• Analysis of foldamer self-assembly into single (1:1) and double (2:2) helices.
• Investigation of structural transitions induced by solvent, temperature, and concentration.
• Site-directed mutagenesis to probe the role of specific residues in helix stabilization.

Main Results:

• A C2-symmetric aryl-triazole foldamer was synthesized and shown to form a chloride-templated 2:2 double helix.
• The foldamer's structure interconverts between single and double helices, controllable by environmental factors.
• Single-site substitutions revealed that anion binding affinity and residue location significantly impact double helix stability.
• Placing stabilizing CH···Cl- hydrogen bonds at the termini strongly favors double helix formation.

Conclusions:

• The primary sequence of abiological foldamers can be programmed to control secondary structure and stability.
• Anion binding interactions, particularly at the termini, are critical for stabilizing double helical structures.
• This work provides a powerful framework for designing synthetic polymers with predictable structures and functions.