Positional Fluorination of Fmoc-Phenylalanine Modulates Hydrogel Structure and Antibacterial Activity

Area of Science:

• Biomaterials Science
• Nanotechnology
• Medicinal Chemistry

Background:

• Antibiotic resistance necessitates novel therapeutic approaches.
• Self-assembling nanostructures, like Fmoc-F5-Phe, show antibacterial potential.
• The impact of fluorine position on these materials' properties is unclear.

Purpose of the Study:

• To investigate how fluorine position affects Fmoc-phenylalanine derivative hydrogels.
• To evaluate the physical, mechanical, and antibacterial properties of single-fluorinated analogues.
• To identify optimal structures for next-generation antimicrobial biomaterials.

Main Methods:

• Synthesized and characterized three single-fluorinated Fmoc-phenylalanine derivatives.
• Assessed self-assembly kinetics, nanostructure morphology, and mechanical properties.
• Evaluated antibacterial activity against Streptococcus mutans, including ROS generation, morphology disruption, and biofilm inhibition.

Main Results:

• Single-fluorinated Fmoc-phenylalanine hydrogels demonstrated improved stability and mechanical properties over Fmoc-F5-Phe.
• Fmoc-4-F-Phe exhibited the most significant antibacterial activity, inhibiting S. mutans growth at low concentrations.
• Fmoc-4-F-Phe treatment increased reactive oxygen species (ROS) levels and disrupted bacterial morphology and biofilm formation.

Conclusions:

• Fluorine's aromatic position critically influences hydrogel self-assembly and antibacterial efficacy.
• Fmoc-4-F-Phe hydrogels represent a promising, biocompatible platform for antimicrobial applications.
• These materials hold potential for use in surface coatings and other next-generation antibacterial strategies.