A theoretical investigation on DPPH radical-scavenging mechanism of edaravone

被引:85
作者
Wang, LF
Zhang, HY [1 ]
机构
[1] Shandong Univ Technol, Shandong Prov Res Ctr Bioinformat Engn & Tech, Lab Computat Biol, Zibo 255049, Peoples R China
[2] Shandong Teachers Univ, Dept Chem, Jinan 250014, Peoples R China
基金
中国国家自然科学基金;
关键词
D O I
10.1016/j.bmcl.2003.07.016
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
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. (C) 2003 Elsevier Ltd. All rights reserved.
引用
收藏
页码:3789 / 3792
页数:4
相关论文
共 32 条
[1]   Ab initio and density functional theory studies for the explanation of the antioxidant activity of certain phenolic acids [J].
Bakalbassis, EG ;
Chatzopoulou, A ;
Melissas, VS ;
Tsimidou, M ;
Tsolaki, M ;
Vafiadis, A .
LIPIDS, 2001, 36 (02) :181-190
[2]   A NEW MIXING OF HARTREE-FOCK AND LOCAL DENSITY-FUNCTIONAL THEORIES [J].
BECKE, AD .
JOURNAL OF CHEMICAL PHYSICS, 1993, 98 (02) :1372-1377
[3]   Poly methoxy phenols in solution: O-H bond dissociation enthalpies, structures, and hydrogen bonding [J].
de Heer, MI ;
Korth, HG ;
Mulder, P .
JOURNAL OF ORGANIC CHEMISTRY, 1999, 64 (19) :6969-6975
[4]   THE DEVELOPMENT AND USE OF QUANTUM-MECHANICAL MOLECULAR-MODELS .76. AM1 - A NEW GENERAL-PURPOSE QUANTUM-MECHANICAL MOLECULAR-MODEL [J].
DEWAR, MJS ;
ZOEBISCH, EG ;
HEALY, EF ;
STEWART, JJP .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1985, 107 (13) :3902-3909
[5]   Theoretical calculation of gas-phase ionization potentials for mono- and polysubstituted benzenes [J].
DiLabio, GA ;
Pratt, DA ;
Wright, JS .
CHEMICAL PHYSICS LETTERS, 1999, 311 (3-4) :215-220
[6]   Theoretical calculation of ionization potentials for disubstituted benzenes: Additivity vs non-additivity of substituent effects [J].
DiLabio, GA ;
Pratt, DA ;
Wright, JS .
JOURNAL OF ORGANIC CHEMISTRY, 2000, 65 (07) :2195-2203
[7]  
FRISCH MJ, 2001, GAUSSIAN 98 REVISION
[8]  
Gajewski J. J., 1990, ADV MOL MODELLING, P65
[9]   Protective effect of edaravone against streptomycin-induced vestibulotoxicity in the guinea pig [J].
Horiike, O ;
Shimogori, H ;
Ikeda, T ;
Yamashita, H .
EUROPEAN JOURNAL OF PHARMACOLOGY, 2003, 464 (01) :75-78
[10]   DEVELOPMENT OF THE COLLE-SALVETTI CORRELATION-ENERGY FORMULA INTO A FUNCTIONAL OF THE ELECTRON-DENSITY [J].
LEE, CT ;
YANG, WT ;
PARR, RG .
PHYSICAL REVIEW B, 1988, 37 (02) :785-789