Dramatic Enhancement of Binding Affinities Between Foldamer-Based Receptors and Anions by Intra-Receptor π-Stacking

Area of Science:

• Supramolecular Chemistry
• Chemical Biology
• Organic Chemistry

Background:

• Understanding intra-protein interactions is crucial for designing effective molecular binders.
• Foldamer-based receptors offer a synthetic platform to study binding and folding dynamics.
• Aryl appendages can influence receptor structure and ligand binding through non-covalent interactions.

Purpose of the Study:

• To investigate the energetic interplay between binding and folding in synthetic receptors.
• To design foldamer-based receptors with tunable π-stacking interactions for enhanced anion binding.
• To elucidate the role of aryl appendages in stabilizing helical structures and reinforcing binding affinities.

Main Methods:

• Design and synthesis of foldamer-based receptors with identical hydrogen-bonding sites and varied aryl appendages.
• Utilizing π-stacking interactions within helical backbones for structural stabilization.
• Quantifying binding affinities using association constants for chloride and nitrate ions.

Main Results:

• Receptors with electron-deficient aryl appendages demonstrated significantly enhanced binding affinities.
• Association constants increased by up to three orders of magnitude for chloride and nitrate ions.
• Extended π-stacking interactions within the receptor backbone stabilized the overall complex structure.

Conclusions:

• The energetic interplay of binding and folding is a key factor in molecular recognition.
• Strategic design of aryl appendages in foldamer receptors can dramatically enhance anion binding.
• Stabilization of the folded structure through extended π-stacking is critical for reinforcing binding affinities.