| Abstract
| - The thermodynamics of the spin trapping of various cyclic nitrones with biologically relevant radicals suchas methyl, mercapto, hydroperoxy, superoxide anion, and nitric oxide was investigated using computationalmethods. A density functional theory (DFT) approach was employed in this study at the B3LYP/6-31+G(d,p)//B3LYP/6-31G(d) level. The order of increasing favorability for ΔGrxn (kcal/mol) of the radical reaction withvarious nitrones, in general, follows a trend similar to their respective experimental reduction potentials aswell as their experimental second-order rate constants in aqueous solution: NO (14.57) < O2•- (−7.51)<•O2H (−13.92) < •SH (−16.55) < •CH3 (−32.17) < •OH (−43.66). The same qualitative trend is predictedupon considering the effect of solvation using the polarizable continuum model (PCM): i.e., NO (14.12) <O2•- (9.95)< •O2H (−6.95) < •SH (−13.57) < •CH3 (−32.88) < •OH (−38.91). All radical reactions withthese nitrones are exoergic, except for NO (and O2•- in the aqueous phase), which is endoergic, and the freeenergy of activation (ΔG⧧) for the NO additions ranges from 17.7 to 20.3 kcal/mol. This study also predictsthe favorable formation of certain adducts that exhibit intramolecular H-bonding interactions, nucleophilicaddition, or H-atom transfer reactions. The spin density on the nitronyl N of the superoxide adducts revealsconformational dependences. The failure of nitrones to trap NO at normal conditions was theoreticallyrationalized due to the endoergic reaction parameters.
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