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Bio-based methacrylates yield selective antimicrobial polymers
Researchers have developed 15 amphiphilic random copolymers from amino acid-derived and terpene-based methacrylates, demonstrating that lysine-rich compositions deliver the highest antimicrobial activity and selectivity. The findings open new pathways for sustainable alternatives to conventional antibiotics.
With antibiotic resistance posing an escalating global health threat, researchers are exploring synthetic alternatives inspired by naturally occurring antimicrobial peptides (AMPs). These peptides are structurally characterised as cationic amphiphilic copolymers, providing a blueprint for the design of new antimicrobial materials. In this study, the team synthesised 15 amphiphilic random copolymers from bio-based building blocks using Reversible Addition–Fragmentation chain Transfer (RAFT) polymerisation.
The copolymers combined amino acid-derived methacrylates with varying side chains, namely alanine, phenylalanine and lysine, as the cationic components, with bio-based tetrahydrogeranyl methacrylate (THGA) serving as the hydrophobic counterpart. This approach yielded a library of polymers with systematically varied cationic-to-hydrophobic ratios, enabling a detailed structure–activity investigation.
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Lysine-based systems deliver highest activity and selectivity
The antimicrobial performance was evaluated against E. coli and S. aureus, while cytotoxicity was assessed using mouse fibroblasts (L929). Copolymers based on lysine with higher cationic content demonstrated the strongest antimicrobial activity and the most favourable selectivity profile. Activity against S. aureus followed a non-linear trend, indicating that the balance between hydrophilic and hydrophobic segments plays a critical role in performance. However, cytotoxicity also increased in parallel with rising cationic content, highlighting the importance of compositional fine-tuning.
Membrane disruption confirmed as primary mechanism
Live/dead staining, scanning electron microscopy (SEM) and calcein leakage assays confirmed that the lysine-containing copolymers act primarily by disrupting bacterial membranes. Leakage was observed in liposomes mimicking bacterial membranes at concentrations below the minimum inhibitory concentration (MIC), supporting the proposed mode of action. The results underline the potential of bio-based amphiphilic copolymers as selective antimicrobial agents and point towards more sustainable design strategies for next-generation pharmaceutical and coating-relevant antimicrobial products.
Source: Cheng, Z. et al., Antimicrobial amphiphilic random copolymers from bio-based methacrylates: effect of chemical composition on activity and selectivity. Polymer Chemistry (2026).
