A theoretical investigation on DPPH radical-scavenging mechanism of edaravone

• Published in: Bioorganic & medicinal chemistry letters Vol. 13; no. 21; pp. 3789 - 3792
• Main Authors: WANG, Lan-Fen, ZHANG, Hong-Yu
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier 03.11.2003
• Subjects: Antipyrine - analogs & derivatives; Antipyrine - chemistry; Biological and medical sciences; Biphenyl Compounds; Chemical Phenomena; Chemistry, Physical; Edaravone; Electron Transport; Free Radical Scavengers - chemistry; Free Radicals - chemistry; Hydrogen - chemistry; Medical sciences; Miscellaneous; Models, Molecular; Neuropharmacology; Neuroprotective agent; Pharmacology. Drug treatments; Picrates - chemistry; Structure-Activity Relationship; Thermodynamics; Vitamin E - chemistry; DPPH; Nitrogen heterocycle; Theoretical study; Density functional method; Pyrazole derivatives; Neuroprotective agent; Edaravone; Antioxidant; Mechanism of action; Radical scavenger; Biological activity
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2003.07.016

The mechanism of edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one) to scavenge DPPH radical is clarified by density functional theory (DFT) calculations. It is revealed that H-atom-abstraction rather than electron-transfer reaction is involved in the radical-scavenging process of edaravone, and H-atom at position 4 is readily to be abstracted. The C-H bond dissociation enthalpy (BDE) of edaravone is higher than the O-H BDE of alpha-tocopherol, accounting for the activity difference between the two antioxidants. As substituents have little influence on the C-H BDE, 2-pyrazolin-5-one is recognized as the active center for edaravone.