Incorporating Heavy Atom Effect onto Molecular Rotors for Realizing Exceptionally Photocatalytic Oxidation Reaction under Low‐Temperature Conditions

ABSTRACT Organic artificial enzymes, renowned for their stability under non‐physiological conditions, have recently attracted attention. In this study, we strategically designed small molecular photo‐activated oxidase mimics by incorporating halogen atoms onto styrene‐based molecular rotors, termed DAPy‐X ^m series (X = Cl, Br, and I), to leverage the heavy atom effect and amplify the generation of reactive oxygen species (ROS). In addition, incorporation of halogen atoms at the meta ‐position of 4‐methyl‐picolinium unit modulates the internal rotational barrier, thereby enhancing the temperature sensitivity of DAPy‐X ^m series. Among them, DAPy‐I ^m exhibited a significant enhancement in generating both superoxide anion (O ₂ ^•− ) and singlet oxygen ( ¹ O ₂ ) species. Taking advantage of its unique photo‐responsive oxidase‐like behavior with cold‐adapted property, DAPy‐I ^m is successfully applied to the visible‐light driven synthesis of ergosterol peroxide (EP), a bioactive compound with notable anti‐tumor and anti‐microbial characteristics. Remarkably, the photo‐oxidase activity of DAPy‐I ^m is significantly improved at low temperatures compared to higher‐temperature conditions, highlighting the potential of heavy atom‐engineered molecular rotors to achieve an exceptionally low‐temperature photocatalytic reaction for synthesizing thermo‐sensitive products.