Macrocycle formation-mediated augmentation in reactive oxygen species production

While the synthesis of methylene-bridged fluorescent macrocycles has attracted significant research interest, their ability to generate reactive oxygen species (ROS) remains relatively unexplored. Herein, we present a strategy for constructing multifunctional macrocycles through backbone functionalization and successfully synthesize a new class of [2]terphenyl-extended pillar[6]arenes. Upon incorporating benzothiadiazole, highly fluorescent macrocycles with aggregation-induced emission enhancement characteristics, <i>i.e.</i>, [2]terphenyl-benzothiadiazole-extended pillar[6]arenes, were obtained. Subsequent studies on modulating side-chain modifications have revealed distinct singlet oxygen (¹O₂) generation capabilities. Notably, quaternary ammonium-functionalized macrocycles show lower quantum yields yet superior ¹O₂ generation efficiency under light irradiation compared to their ethoxy-modified counterparts and the acyclic building block, while retaining targeted fluorescence imaging capabilities. Significantly, the supramolecular synergy between photodynamic action and ceftizoxime sodium drug complexation drastically enhances antibacterial efficacy compared to individual modalities. This study highlights the potential of quaternary ammonium-functionalized fluorescent macrocycles in ¹O₂ generation and offers promising new avenues for developing antibacterial drugs for biomedical applications.