Journal of Physical Chemistry A, Vol.111, No.39, 9995-10001, 2007
Rate constants of hydroperoxyl radical addition to cyclic nitrones: A DFT study
Nitrones are potential synthetic antioxidants against the reduction of radical-mediated oxidative damage in cells and as analytical reagents for the identification of HO2 center dot and other such transient species. In this work, the PCM/B3LYP/6-31+G(d,p)HB3LYP/6-31G(d) and PCM/mPWIK/6-31+G(d,p) density functional theory (DFT) methods were employed to predict the reactivity of HO2 center dot 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 I 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 HO2 center dot 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 HO2 center dot addition to nitrones. The presence of intramolecular H-bonding interactions in the transition states were predicted and may play a significant role toward a facile addition of HO2 center dot to nitrones. In general, HO2 center dot 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 HO2 center dot could pave the way toward improved radical detection and antioxidant protection.