Generalizing the Aromatic δ-Amino Acid Foldamer Helix

Area of Science:

• * Organic Chemistry
• * Polymer Science
• * Supramolecular Chemistry

Background:

• * Foldamers are synthetic oligomers mimicking protein secondary structures.
• * Aromatic foldamers offer unique structural and functional properties.
• * Understanding foldamer folding is crucial for designing novel materials.

Purpose of the Study:

• * To synthesize and characterize aromatic oligoamide foldamers with varying flexibility.
• * To investigate the factors influencing the helical stability and structure of these foldamers.
• * To explore the potential for fine-tuning foldamer properties through monomer selection and arrangement.

Main Methods:

• * Synthesis of aromatic oligoamide foldamer sequences using quinoline, pyridine, and benzene-derived δ-amino acids.
• * Structural analysis using X-ray crystallography for key sequences.
• * Spectroscopic characterization including 1H NMR in aqueous solutions.

Main Results:

• * A canonical aromatic helix fold was observed in most synthesized sequences.
• * Helix stability was found to be critically dependent on the ratio of rigid to flexible units.
• * Variations in curvature and tolerance for sp3 centers were noted, demonstrating the general nature of the aromatic δ-peptide helix.
• * Canonical helical folding was achieved by alternating specific monomers, even when they did not fold independently.

Conclusions:

• * Aromatic δ-peptide helices are general and adaptable structures.
• * The stability, curvature, and kinetics of foldamers can be precisely controlled by adjusting the proportion of rigid and flexible units.
• * Systematic combination of compatible δ-amino acids allows for fine-tuning of foldamer properties, including helix handedness and side chain positioning.