Selenium-centered radicals: generation, detection and their relevance in chemistry and biology

A shift in perception of selenium from a metabolic toxin to an essential trace element for humans and animals has a profound implication on various scientific disciplines. Selenium is vital for maintaining cellular redox homeostasis, preserving structural integrity, and regulating immune defense and cancer prevention strategies. These biological impacts are driven by its unique properties including redox sensitivity, high nucleophilicity and multiple oxidation states. Transitions between different oxidation states occur via multi-step electron transfers that often involve transient selenium-centered radicals. These radicals undergo inter- and intra-molecular reactions, achieving stability through the formation of two-center three-electron (2c-3e) hemi-bonds. Crucially, their reactivity and biochemical behaviour are influenced by chemical structure and heteroatom substitution. In biological systems, these radicals function through selenoproteins that manage oxidative stress, various infections, and many other diseases. In organic synthesis, they facilitate the development of organoselenium compounds that act as antioxidants and glutathione peroxidase mimics. Despite their importance, the current literature remains fragmented, with synthetic chemists primarily investigating their utility in radical-mediated selenylation and C-Se bond formation, while biologists focus on their role in ROS scavenging. This review bridges the disciplinary gaps by providing a unified overview of the generation, detection, structure and chemical reactivity and biological relevance of selenium-centered radicals.