Highly Efficient Thiol-Michael Addition Post-Modification toward Potent Degradable Antibacterial Polyesters with...

Area of Science:

• Polymer Chemistry
• Materials Science
• Biomedical Engineering

Background:

• Poly(3-methylene-1,5-dioxepan-2-one) (PMDXO) is a versatile degradable polymer.
• Thiol-Michael addition is a key post-modification reaction for polymer synthesis.

Purpose of the Study:

• To investigate the accelerating effect of the γ-oxa group in PMDXO on thiol-Michael addition.
• To synthesize and evaluate guanidinium-functionalized aliphatic polyesters for antibacterial applications.
• To establish the structure-activity relationship for antibacterial performance.

Main Methods:

• Post-modification of PMDXO using thiol-Michael addition.
• Synthesis of guanidinium-functionalized aliphatic polyesters.
• In vitro antibacterial assays against 214 clinically isolated ESKAPE strains.
• In vitro biocompatibility testing (hemolysis and cytotoxicity).
• In vivo efficacy studies in murine models of bacterial infection (peritonitis, abscess, skin wound).

Main Results:

• The γ-oxa in PMDXO significantly accelerates thiol-Michael addition under mild conditions.
• A cationic polyester, P20-2C, was synthesized with low hemolytic activity and moderate cytotoxicity.
• P20-2C exhibited potent broad-spectrum bactericidal activity against ESKAPE strains.
• P20-2C demonstrated significant in vivo efficacy in multiple bacterial infection models.
• A multimodal bactericidal mechanism involving membrane disruption and ROS upregulation was proposed.

Conclusions:

• PMDXO is a promising platform for developing functional aliphatic polyesters.
• P20-2C represents a highly effective and biocompatible antibacterial material.
• The findings support the development of novel polymers for combating antibiotic-resistant bacteria.