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Reactivities of substituted α-phenyl-N-tert-butyl nitrones.

Rosselin M, Choteau F, Zéamari K, Nash KM, Das A, Lauricella R, Lojou E, Tuccio B, Villamena FA, Durand G - J. Org. Chem. (2014)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Avignon Université , Equipe Chimie Bioorganique et Systèmes Amphiphiles, 33 rue Louis Pasteur, F-84000 Avignon, France.

ABSTRACT
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.

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Synthesis of Mono-, Di-, and Tri-β-Substituted NitronesReagents and conditions: (a)benzaldehyde, zinc powder, AcOH, 4 Å molecular sieves; ethanol,15 → 60 °C, 10 h; (b) Ac2O/pyr (1/1 v/v), roomtemperature, 12 h; (c) DCI, DMAP, THF, 2 h, room temperature, thenCH3NH2, 18 h, room temperature.
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sch1: Synthesis of Mono-, Di-, and Tri-β-Substituted NitronesReagents and conditions: (a)benzaldehyde, zinc powder, AcOH, 4 Å molecular sieves; ethanol,15 → 60 °C, 10 h; (b) Ac2O/pyr (1/1 v/v), roomtemperature, 12 h; (c) DCI, DMAP, THF, 2 h, room temperature, thenCH3NH2, 18 h, room temperature.


Reactivities of substituted α-phenyl-N-tert-butyl nitrones.

Rosselin M, Choteau F, Zéamari K, Nash KM, Das A, Lauricella R, Lojou E, Tuccio B, Villamena FA, Durand G - J. Org. Chem. (2014)

Synthesis of Mono-, Di-, and Tri-β-Substituted NitronesReagents and conditions: (a)benzaldehyde, zinc powder, AcOH, 4 Å molecular sieves; ethanol,15 → 60 °C, 10 h; (b) Ac2O/pyr (1/1 v/v), roomtemperature, 12 h; (c) DCI, DMAP, THF, 2 h, room temperature, thenCH3NH2, 18 h, room temperature.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4216227&req=5

sch1: Synthesis of Mono-, Di-, and Tri-β-Substituted NitronesReagents and conditions: (a)benzaldehyde, zinc powder, AcOH, 4 Å molecular sieves; ethanol,15 → 60 °C, 10 h; (b) Ac2O/pyr (1/1 v/v), roomtemperature, 12 h; (c) DCI, DMAP, THF, 2 h, room temperature, thenCH3NH2, 18 h, room temperature.
Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Avignon Université , Equipe Chimie Bioorganique et Systèmes Amphiphiles, 33 rue Louis Pasteur, F-84000 Avignon, France.

ABSTRACT
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.

Show MeSH