Pyrgos[ <i>n</i> ]cages: Redefining antibacterial strategy against drug resistance
Y Zhang, M. Luo, Xiangling Shi, Aimin Li, Wei Zhou, Yuyao Yin, Hui Wang, Wing‐Leung Wong, Xinxin Feng, Qing He
Abstract
Amid rising antibiotic resistance, the quest for advanced antibacterial agents to surpass microbial adaptation is paramount. This study introduces Pyrgos[ n ]cages ( n = 1 to 4), pioneering multidecker cationic covalent organic cages engineered to combat drug-resistant bacteria via a dual-targeting approach. Synthesized through successive photocatalytic bromination and cage-forming reactions, these architectures stand out for their dense positive charge distribution, exceptional stability, and substantial rigidity. Pyrgos[ n ]cages exhibit potent bactericidal activity by disrupting bacterial membrane potential and binding to DNA. Notably, these structures show unparalleled success in eradicating both extracellular and intracellular drug-resistant pathogens in diverse infection scenarios, with antibacterial efficiency markedly increasing over 100-fold as the decker number rises from 1 to 3. This study provides an advance in antibacterial tactics and underscores the transformative potential of covalent organic cages in devising enduring countermeasures against antibiotic-resistant microbial threats.