Revisiting the Radical Quenching Activity of Ebselen Analogues in Homogeneous Phase and In Silico Anti‐ferroptotic Activity with Histone Deacetylase

The radical quenching activity of ebselen derivatives was evaluated using kinetic EPR measurements and fluorescence‐based oxygen radical absorbance capacity assays. Reaction rate constants with t ‐BuOO • radicals were estimated by EPR, while their oxidation potentials were measured by square‐wave voltammetry. All derivatives exhibited significant radical quenching activity. The reactivity is depended on the nature and number of substituents, modulating the electron density and steric effects. The high activity with high rate constants is attributed to the formation of a Se‐centered conjugated dipolar transition state, where electron‐donating substituents were found to enhance the radical quenching efficiency. Additionally, in silico studies revealed that all compounds exhibited favorable binding affinities toward the histone deacetylase 8 protein.