TY - JOUR
T1 - Rate constants of hydroperoxyl radical addition to cyclic nitrones
T2 - A DFT study
AU - Villamena, Frederick A.
AU - Merle, John K.
AU - Hadad, Christopher M.
AU - Zweier, Jay L.
PY - 2007/10/4
Y1 - 2007/10/4
N2 - Nitrones are potential synthetic antioxidants against the reduction of radical-mediated oxidative damage in cells and as analytical reagents for the identification of HO 2 and other such transient species. In this work, the PCM/B3LYP/6-31+G(d,p)//B3LYP/6-31G(d) and PCM/mPWJK/6-31+G(d,p) density functional theory (DFT) methods were employed to predict the reactivity of HO 2 with various functionalized nitrones as spin traps. The calculated second-order rate constants and free energies of reaction at both levels of theory were in the range of 10 0-10 3 M -1 s _1 and 1 to -12 kcal mol -1, respectively, and the rate constants for some nitrones are on the same order of magnitude as those observed experimentally. The trend in HO 2 reactivity to nitrones could not be explained solely on the basis of the relationship of the theoretical positive charge densities on the nitronyl-C, with their respective ionization potentials, electron affinities, rate constants, or free energies of reaction. However, various modes of intramolecular H-bonding interaction were observed at the transition state (TS) structures of HO 2 addition to nitrones0 The presence of intramolecular H-bonding interactions in the transition states were predicted and may play a significant role toward a facile addition of HO 2 to nitrones. In general, HO 2 addition to ethoxycarbonyl- and spirolactam-substituted nitrones, as well as those nitrones without electron-withdrawing substituents,- such as 5,5-dimethyl-pyrroline N-oxide (DMPO) and 5-spirocyclopentyl-pyrroline N-oxide (CPPO), are most preferred compared to the methylcarbamoyl-substituted nitrones. This study suggests that the use of specific spin traps for efficient trapping of HO 2 could pave the way toward improved radical detection and antioxidant protection.
AB - Nitrones are potential synthetic antioxidants against the reduction of radical-mediated oxidative damage in cells and as analytical reagents for the identification of HO 2 and other such transient species. In this work, the PCM/B3LYP/6-31+G(d,p)//B3LYP/6-31G(d) and PCM/mPWJK/6-31+G(d,p) density functional theory (DFT) methods were employed to predict the reactivity of HO 2 with various functionalized nitrones as spin traps. The calculated second-order rate constants and free energies of reaction at both levels of theory were in the range of 10 0-10 3 M -1 s _1 and 1 to -12 kcal mol -1, respectively, and the rate constants for some nitrones are on the same order of magnitude as those observed experimentally. The trend in HO 2 reactivity to nitrones could not be explained solely on the basis of the relationship of the theoretical positive charge densities on the nitronyl-C, with their respective ionization potentials, electron affinities, rate constants, or free energies of reaction. However, various modes of intramolecular H-bonding interaction were observed at the transition state (TS) structures of HO 2 addition to nitrones0 The presence of intramolecular H-bonding interactions in the transition states were predicted and may play a significant role toward a facile addition of HO 2 to nitrones. In general, HO 2 addition to ethoxycarbonyl- and spirolactam-substituted nitrones, as well as those nitrones without electron-withdrawing substituents,- such as 5,5-dimethyl-pyrroline N-oxide (DMPO) and 5-spirocyclopentyl-pyrroline N-oxide (CPPO), are most preferred compared to the methylcarbamoyl-substituted nitrones. This study suggests that the use of specific spin traps for efficient trapping of HO 2 could pave the way toward improved radical detection and antioxidant protection.
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U2 - 10.1021/jp073615s
DO - 10.1021/jp073615s
M3 - Article
C2 - 17845014
AN - SCOPUS:35348981353
SN - 1089-5639
VL - 111
SP - 9995
EP - 10001
JO - Journal of Physical Chemistry A
JF - Journal of Physical Chemistry A
IS - 39
ER -