title: Reactivities of substituted α-phenyl-N-tert-butyl nitrones.
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.
authors: Avignon Université , Equipe Chimie Bioorganique et Systèmes Amphiphiles, 33 rue Louis Pasteur, F-84000 Avignon, France.
authors: Marie
authors: M
authors: Rosselin
authors: Fanny
authors: F
authors: Choteau
authors: Kamal
authors: K
authors: Zéamari
authors: Kevin M
authors: KM
authors: Nash
authors: Amlan
authors: A
authors: Das
authors: Robert
authors: R
authors: Lauricella
authors: Elisabeth
authors: E
authors: Lojou
authors: Béatrice
authors: B
authors: Tuccio
authors: Frederick A
authors: FA
authors: Villamena
authors: Grégory
authors: G
authors: Durand
mesh_terms: D008968:Molecular Conformation; D009589:Nitrogen Oxides / Q000138:chemical synthesis* / Q000737:chemistry; D011789:Quantum Theory
chemical_list: D009589:Nitrogen Oxides; C015388:nitrones