| Autor: |
Rosselin M; Avignon Université , Equipe Chimie Bioorganique et Systèmes Amphiphiles, 33 rue Louis Pasteur, F-84000 Avignon, France., Choteau F, Zéamari K, Nash KM, Das A, Lauricella R, Lojou E, Tuccio B, Villamena FA, Durand G |
| Jazyk: |
angličtina |
| Zdroj: |
The Journal of organic chemistry [J Org Chem] 2014 Jul 18; Vol. 79 (14), pp. 6615-26. Date of Electronic Publication: 2014 Jul 03. |
| DOI: |
10.1021/jo501121g |
| Abstrakt: |
In this work, a series of α-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(•-)) reactions with nitrones were determined using a UV-vis stopped-flow method, and phenyl radical (Ph(•)) 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(•-) and HO2(•) 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(•-) and Ph(•) 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. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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