Regulating Peptide Self-Assemblies by Halogen Bonding and Other Halogen Effects.

Area of Science:

• Biomaterials Science
• Supramolecular Chemistry
• Chemical Biology

Background:

• Peptide self-assembly is crucial for developing advanced biomaterials.
• Understanding non-covalent interactions, like hydrogen bonding (HB) and halogen bonding (XB), is key to controlling self-assembly.
• Halogen effects, beyond direct XB, can significantly impact molecular behavior.

Purpose of the Study:

• To investigate the modulation of peptide self-assembly by halogen bonding (XB) and other halogen effects.
• To compare the influence of iodine versus fluorine in functionalized peptides on self-assembly properties.
• To elucidate the interplay between XB, HB, and hydrophobic interactions in peptide self-organization.

Main Methods:

• Synthesis of three functionalized pentapeptides with a common FFK motif.
• Incorporation of a tetrafluoroiodophenyl (TFIP) moiety as an XB donor.
• Characterization of self-assembly, thermal stability, and viscoelastic properties using comprehensive studies.

Main Results:

• Histidine-functionalized peptide showed significant C-I···N XB, while phenylalanine-terminated peptide showed negligible XB.
• Iodine-containing peptides exhibited higher stability and enhanced viscoelastic properties than fluorinated analogues.
• Distinct self-assembly mechanisms (cooperative vs. isodesmic) were observed, attributed to iodine's hydrophobicity and polarizability.

Conclusions:

• Halogen bonding and other halogen effects, in synergy with hydrogen bonding, can modulate peptide self-assembly.
• Iodine's unique properties lead to enhanced stability and different self-assembly behaviors compared to fluorine.
• A delicate balance of XB, HB, and hydrophobic interactions fine-tunes peptide self-organization.