Sulfonium-based polymethacrylamides for antimicrobial use: influence of the structure and composition

Area of Science:

• Polymer Chemistry
• Antimicrobial Agents
• Drug Discovery

Background:

• Growing antibiotic resistance necessitates novel therapeutic strategies.
• Antimicrobial polymers (AMPs) offer a promising alternative to conventional antibiotics.
• Sulfonium cations are an emerging class of AMPs with potential therapeutic applications.

Purpose of the Study:

• To investigate structure-activity relationships of side-chain sulfonium-based AMPs.
• To explore the impact of hydrophobic and hydrophilic groups on antimicrobial activity.
• To compare the efficacy of same-center versus different-center polymer structures.

Main Methods:

• Synthesized a library of side-chain sulfonium polymers with varying hydrophobic (aliphatic/aromatic) and hydrophilic (PEG) groups.
• Systematically varied the positioning of cationic and hydrophobic groups (same-center vs. different-center).
• Evaluated bactericidal activity against Gram-positive and Gram-negative bacteria.

Main Results:

• Side-chain sulfonium polymers exhibited significant antimicrobial activity.
• Polymers with same-center cationic and hydrophobic groups were more potent than different-center structures.
• Sulfonium-based AMPs demonstrated superior activity and selectivity over quaternary ammonium analogues.

Conclusions:

• Side-chain sulfonium polymers represent a promising class of antimicrobial agents.
• Optimizing the arrangement of functional groups is crucial for enhancing AMP efficacy.
• Sulfonium-based AMPs offer a viable alternative to combat antibiotic-resistant bacteria.