Reactivity of superoxide radical anion and hydroperoxyl radical with alpha-phenyl-N-tert-butylnitrone (PBN) derivatives.
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)(*-) and HO(2)(*) with various para-substituted alpha-phenyl-N-tert-butylnitrone (PBN) spin traps. Rate constants of O(2)(*-) trapping by nitrones were determined using competitive UV-vis stopped-flow method with phenol red (PR) as probe, while HO(2)(*) 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)(*-) and HO(2)(*) 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)(*-) addition to PBN derivatives is not affected by the polar effect of the substituents. However, the reactivity of HO(2)(*) follows the Hammett equation and is increased as the substituent becomes more electron withdrawing. This supports the conclusion that the nature of HO(2)(*) addition to PBN derivatives is electrophilic, while the addition of O(2)(*-) to PBN-type compounds is only weakly electrophilic.
Durand
Grégory
G
Laboratoire de Chimie Bioorganique et des Systèmes Moléculaires Vectoriels, Université d'Avignon et des Pays de Vaucluse, Faculté des Sciences, 33 rue Louis Pasteur, 84000 Avignon, France. gregory.durand@univ-avignon.fr
Choteau
Fanny
F
Pucci
Bernard
B
Villamena
Frederick A
FA
D003497:Cyclic N-Oxides / Q000138:chemical synthesis / Q000737:chemistry*; D004578:Electron Spin Resonance Spectroscopy; D004583:Electrons; D007700:Kinetics; D009589:Nitrogen Oxides / Q000737:chemistry; D013481:Superoxides / Q000737:chemistry*; D013816:Thermodynamics
D003497:Cyclic N-Oxides; D009589:Nitrogen Oxides; C015388:nitrones; D013481:Superoxides; C029217:phenyl-N-tert-butylnitrone