Heavy‐Atom‐Free Supramolecular Photosensitizers Derived from Conventional Fluorophores

Abstract Heavy‐atom‐free photosensitizers (PSs) offer advantages such as efficient generation of reactive oxygen species (ROS), low dark cytotoxicity, good photostability, and high biocompatibility. Although the development of new PSs through organic synthesis has been a focus of active research, supramolecular chemistry offers a complementary pathway. This study presents a versatile supramolecular strategy to convert conventional fluorophores into heavy‐atom‐free PSs using a cyclic peptide‐based scaffold that densely assembles fluorophore moieties. Results demonstrate that supramolecular PSs constructed from four synthetic fluorophore types—cyanines, coumarins, rhodamines, and BODIPYs—exhibit a remarkable enhancement in ROS generation efficiency, attributed to the increased intersystem crossing efficiency induced by self‐assembly. Moreover, these supramolecular PSs function as visible‐light photocatalysts, efficiently regenerating NAD + from NADH. The densely packed polymer shell further shields enzymes from ROS‐induced deactivation, thereby facilitating the development of robust photoenzyme catalytic systems. This study not only enriches the design methodology of heavy‐atom‐free PSs, but also paves the way for eco‐friendly photobiocatalytic systems.