Reactivity of Superoxide Radical Anion and Hydroperoxyl Radical with alpha-Phenyl-N-tert-butylnitrone(PBN)Derivatives

摘要

Nitrones have exhibited pharmacological activity against radical-mediated pathophysiological conditions and as analytical reagents for the identification of transient radical species by electron paramagnetic resonance(EPR)spectroscopy.In this work,competitive spin trapping,stopped-flow kinetics,and density functional theory(DFT)were employed to assess and predict the reactivity of O_2~(·-)and HO_2~· with various para-substituted alpha-phenyl-N-tert-butylnitrone(PBN)spin traps.Rate constants of O_2~(·-)trapping by nitrones were determined using competitive UV-vis stopped-flow method with phenol red(PR)as probe,while HO_2~· trapping rate constants were calculated using competition kinetics with 5,5-dimethylpyrroline N-oxide(DMPO)by employing EPR spectroscopy.The effects of the para substitution on the charge density of the nitronyl-carbon and on the free energies of nitrone reactivity with O_2~(·-)and HO_2~(·-)were computationally rationalized at the PCM/ B3LYP/6-31+G(d,p)//B3LYP/6-31G(d)level of theory.Theoretical and experimental data show that the rate of O_2~(·-)addition to PBN derivatives is not affected by the polar effect of the substituents.However,the reactivity of HO_2~· follows the Hammett equation and is increased as the substituent becomes more electron withdrawing.This supports the conclusion that the nature of HO_2~· addition to PBN derivatives is electrophilic,while the addition of O_2~(·-)to PBN-type compounds is only weakly electrophilic.