Anisotropy in Antimicrobial Bottle Brush Copolymers and Its Influence on Biological Activity

Antimicrobial polymers are a promising alternative to conventional antibiotics in the fight against antimicrobial resistance. Cationic bottle brush copolymers have shown to be superior to linear topologies in previous studies. Herein, the aspect ratio of such polymers is varied creating differently shaped confined unimolecular structures with varying degrees of side chain mobility. Using reversible addition‐fragmentation chain‐transfer (RAFT) polymerization, bottle brushes are produced in a one‐pot procedure. The morphology is confirmed by atomic force microscopy. The hydrophobicity, as determined via high performance‐liquid chromatography (HPLC) analysis, is drastically influenced by the topology. Using Fourier‐transform infrared (FTIR) spectroscopy, it is found that polymers with a high side chain mobility and increased global hydrophilicity, are less hydrated, and have stronger intramolecular hydrogen bonds. A phase segregated morphology leading to unimolecular micellization is assumed. Biological tests reveal increased antimicrobial activity for such segregated polymers. Their excellent hemocompatibility results in highly selective antimicrobial polymers whose adaptability seems to be a key feature in their excellent performance. This study highlights the tremendous importance of structural control in antimicrobial polymers. The anisotropy in antimicrobial bottle brush copolymers is correlated with their physicochemical behavior and biological activity. The results show that long grafts with a high degree of freedom lead to an adaptability and phase‐segregation that is beneficial for selective antimicrobial activity. The study highlights the paramount importance of the aspect ratio in such macromolecules.