Selenium electrophilic center shuttle active electrons to boost mitochondrial electron leakage

Designing drugs based on the high level of redox homeostasis characteristics is a viable approach to reduce the side effects of chemotherapy drugs. Previous strategies mainly focus on increasing oxidative stress or inhibit antioxidant systems, herein, we report a new strategy to design efficient chemotherapeutics by employing electrophilic center to convert antioxidant agents to oxidizing stress. By employing strong polarization selenium atom (Se), we constructed an electrophilic center with "easy in easy out" characteristics to shuttle active electrons from NADH and GSH to boost mitochondrial electron leakage. The experimental results confirmed that the electrophilic center shuttles electrons through Se radical intermediates, and the polarizability strength of the center is critical for electron shuttle efficiency. The strategy of constructing electrophilic centers with strong polarization properties to intelligently regulate active electrons has expanded new avenues to develop chemotherapy drugs and will also have broad applications in the biological and medical fields.