A study on the reactivity of edaravone towards oxidative radicals by pulse radiolysis

Abstract

Edaravone or RadiCut®, 3-methyl-1-phenyl-2-pyrazolin-5-one, is a newly developed free radical scavenger which has been approved in Japan as a neuroprotective drug since 2001. In the present work, the transient intermediates and the reactivity of edaravone towards ^·OH, N3^·, Br₂^·-, SO₄^·-, and CCl₃O₂^·- are investigated by pulse radiolysis techniques. The oxidation of edaravone by N3^·, Br₂^·-, SO₄^·-, and CCl₃O₂^·- results in an absorption band with λ_max = 345 nm (ε_345nm = 2600 M^-1cm^-1), which is assigned to the edaravone radical formed by H-abstraction or electron transfer. However, the transient species produced by the reaction of edaravone with ^·OH shows an absorption band with λ_max = 320 nm (ε_320nm = 4900 M^-1cm^-1). Accordingly, the main transient species by the reaction of edaravone with ^·OH in the absence of O₂ is attributed to OH-adducts. The rate constants of edaravone reacting with ^·OH, N3^·, SO₄^·-, and CCl₃O₂^·- are estimated to be 8.5×10⁹, 5.4×10⁹, 6×10⁸, and 5.1×10⁸ M^-1s^-1, respectively.