Noncovalent interactions within a synthetic receptor can reinforce guest binding

Area of Science:

• Supramolecular Chemistry
• Host-Guest Chemistry
• Chemical Biology

Background:

• Anion recognition is crucial in biological processes and chemical sensing.
• Cyclic peptides are versatile scaffolds for designing anion receptors.
• Understanding binding mechanisms is key to developing high-affinity receptors.

Purpose of the Study:

• To investigate the binding properties of biscyclopeptide anion receptors.
• To elucidate the role of intra-receptor interactions in anion complex stability.
• To explore strategies for enhancing host-guest affinities.

Main Methods:

• X-ray crystallography for structural determination of anion complexes.
• Microcalorimetry to analyze thermodynamic binding parameters and solvent effects.
• Comparative studies with monomeric cyclopeptides in different solvents.

Main Results:

• Biscyclopeptide receptors bind sulfate and iodide with micromolar affinity in water.
• Crystal structures reveal anions bound between peptide rings, stabilized by hydrophobic interactions.
• Microcalorimetry indicates hydrophobic interactions compensate for desolvation costs.

Conclusions:

• Intra-receptor noncovalent interactions significantly contribute to anion complex stability.
• Reinforcing molecular recognition through internal interactions is a promising strategy for host-guest chemistry.
• This work provides insights into designing advanced anion receptors with enhanced affinities.