CP-2569

Photoredox catalysis, which enables both electron and hydrogen atom transfer, has become a powerful tool for activating chemical bonds and synthesizing complex molecules under mild conditions. Typically, photocatalysts are optimized either for oxidative or reductive reactions within a limited redox window (less than 3.1 V) and for hydrogen atom transfer (HAT) reactions, with few frameworks capable of mediating both pathways for high redox‐demanding reactions (covering more than a 5 V redox window) without requiring special conditions. Herein, we report the use of quinones as multifunctional scaffolds in light‐driven redox transformations, offering access to a redox window of approximately 5 V using visible light. The quinone scaffold's versatility facilitates a wide range of radical and ionic processes under both oxidative and reductive conditions, in addition to enabling HAT reactions. By keeping the parameters, i. e. the reaction partners, constant, such transformations can be carried out under just two reaction conditions. Oxidative transformations and HAT reactions occur under ambient air, while activation of the chromophore for reductive transformations can be achieved using an inorganic base (Cs2CO3) via a simple acid‐base deprotonation event. This dual capability highlights the potential of quinones as scaffolds to extend their utility in photoredox catalysis.

While apoptosis activation has traditionally been considered as an anti-cancer mechanism, current research points to ferroptosis stimulation as a potentially effective cancer therapy. Glutathione peroxidase 4 (GPX4), an essential antioxidant enzyme, serves as a negative regulator of ferroptosis, and its targeted inhibition or degradation can efficiently induce this process. In this study, a potent ferroptosis inducer III-4 that bearing a benzo[b]thiophene moiety was developed by employing a sequential structure optimization process based on RSL-3 to inhibit cancer cells proliferation. At the same time, this cytotoxic activity could be reversed by ferroptosis inducer Fer-1, suggesting that III-4 functions as a ferroptosis inducer. The structure-activity relationship (SAR) of these compounds was also explored. At the cellular level, compound III-4 could block the generation of GSH, cause the accumulation of ROS and MDA, down-regulate GPX4 level, and finally trigger the Fe²⁺-mediated ferroptosis in HT1080 cell lines. Further biological investigation revealed that III-4 arrested the cell cycle at the S phase and inhibited HT1080 cell lines migration. These results indicated that compound III-4 is a candidate for the identification of novel ferroptosis inducer for fibrosarcoma cells.