Reactivity of Superoxide Radical Anion and Hydroperoxyl Radical with α-Phenyl-N-tert-butylnitrone (PBN) Derivatives
Reactivity of Superoxide Radical Anion and Hydroperoxyl Radical with α-Phenyl-N-tert-butylnitrone (PBN) Derivatives
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DOI：
10.1021/jp804929d
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发表时间：
2008-12-04
影响因子：
2.9
通讯作者：
Villamena, Frederick A.
中科院分区：
文献类型：
--
作者：
Durand, Gregory;Choteau, Fanny;Villamena, Frederick A.
硝酮表现出针对自由基介导的病理生理学状况的药理活性，并作为分析试剂用于通过电子顺磁共振（EPR）光谱法鉴定瞬态自由基种类。在这项工作中，采用竞争性自旋捕获、停流动力学和密度泛函理论（DFT）来评估和预测O-2（中心点-）和HO2中心点与各种对位取代的α-苯基-N-叔丁硝酮（PBN）自旋陷阱的反应性。以酚红（PR）为探针，采用竞争性紫外可见停流法测定硝酮捕获O-2（中心点）的速率常数，并采用EPR光谱法，利用与5,5-二甲基吡咯啉N-氧化物（DMPO）的竞争动力学计算HO2中心点捕获速率常数。对位取代对硝酮碳电荷密度以及硝酮与 O-2（中心点-）和 HO2 中心点反应性自由能的影响在 PCM/B3LYP/6-31+G(d,p)//B3LYP/6-31G(d) 理论水平上进行了计算合理化。理论和实验数据表明，O-2(中心点-)加成到PBN衍生物上的速率不受取代基极性效应的影响。然而，HO2 中心点的反应性遵循哈米特方程，并且随着取代基吸电子性的增强而增加。这支持了HO 2 中心点加成到PBN衍生物上的性质是亲电性的，而O-2(中心点-)加成到PBN型化合物上仅是弱亲电性的结论。
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(center dot-) and HO2 center dot with various para-substituted alpha-phenyl-N-tert-butyinitrone (PBN) spin traps. Rate constants of O-2(center dot-) trapping by nitrones were determined using competitive UV-vis stopped-flow method with phenol red (PR) as probe, while HO2 center dot 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(center dot-) and HO2 center dot 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(center dot-) addition to PBN derivatives is not affected by the polar effect of the substituents. However, the reactivity of HO2 center dot follows the Hammett equation and is increased as the substituent becomes more electron withdrawing. This supports the conclusion that the nature of HO2 center dot addition to PBN derivatives is electrophilic, while the addition Of O-2(center dot-) to PBN-type compounds is only weakly electrophilic.