Reactivities of Substituted 伪-Phenyl-N-tert-butyl Nitrones

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• 作者：Marie Rosselin ; Fanny Choteau ; Kamal Z茅amari ; Kevin M. Nash ; Amlan Das ; Robert Lauricella ; Elisabeth Lojou ; B茅atrice Tuccio ; Frederick A. Villamena ; Gr茅gory Durand
• 刊名：Journal of Organic Chemistry
• 出版年：2014
• 出版时间：July 18, 2014
• 年：2014
• 卷：79
• 期：14
• 页码：6615-6626
• 全文大小：488K
• ISSN：1520-6904

文摘

In this work, a series of 伪-phenyl-N-tert-butyl nitrones bearing one, two, or three substituents on the tert-butyl group was synthesized. Cyclic voltammetry (CV) was used to investigate their electrochemical properties and showed a more pronounced substituent effect for oxidation than for reduction. Rate constants of superoxide radical (O₂^{鈥⑩€?/sup>) reactions with nitrones were determined using a UV鈥搗is stopped-flow method, and phenyl radical (Ph鈥?/sup>) trapping rate constants were measured by EPR spectroscopy. The effect of N-tert-butyl substitution on the charge density and electron density localization of the nitronyl carbon as well as on the free energies of nitrone reactivity with O₂鈥⑩€?/sup> and HO₂鈥?/sup> were computationally rationalized at the PCM/B3LYP/6-31+G**//B3LYP/6-31G* level of theory. Theoretical and experimental data showed that the rates of the reaction correlate with the nitronyl carbon charge density, suggesting a nucleophilic nature of O₂鈥⑩€?/sup> and Ph鈥?/sup> addition to the nitronyl carbon atom. Finally, the substituent effect was investigated in cell cultures exposed to hydrogen peroxide and a correlation between the cell viability and the oxidation potential of the nitrones was observed. Through a combination of computational methodologies and experimental methods, new insights into the reactivity of free radicals with nitrone derivatives have been proposed.}