title: Comparative DFT study of the spin trapping of methyl, mercapto, hydroperoxy, superoxide, and nitric oxide radicals by various substituted cyclic nitrones.
abstract: The thermodynamics of the spin trapping of various cyclic nitrones with biologically relevant radicals such as methyl, mercapto, hydroperoxy, superoxide anion, and nitric oxide was investigated using computational methods. 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 Delta G(rxn) (kcal/mol) of the radical reaction with various nitrones, in general, follows a trend similar to their respective experimental reduction potentials as well 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 predicted upon 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 with these nitrones are exoergic, except for NO (and O2*- in the aqueous phase), which is endoergic, and the free energy of activation (Delta G) for the NO additions ranges from 17.7 to 20.3 kcal/mol. This study also predicts the favorable formation of certain adducts that exhibit intramolecular H-bonding interactions, nucleophilic addition, or H-atom transfer reactions. The spin density on the nitronyl N of the superoxide adducts reveals conformational dependences. The failure of nitrones to trap NO at normal conditions was theoretically rationalized due to the endoergic reaction parameters.
authors.affiliation: The Davis Heart and Lung Research Institute, and the Division of Cardiovascular Medicine, Department of Internal Medicine, College of Medicine, The Ohio State University, Columbus, Ohio 43210, USA. villamena-1@medctr.osu-edu
authors.forename: Frederick A
authors.initials: FA
authors.lastname: Villamena
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Hadad
authors.forename: Jay L
authors.initials: JL
authors.lastname: Zweier
mesh_terms: D000473:Alkanes / Q000737:chemistry*; D003497:Cyclic N-Oxides / Q000737:chemistry*; D003500:Cyclization; D005609:Free Radicals / Q000737:chemistry; D006861:Hydrogen Peroxide / Q000737:chemistry*; D008958:Models, Molecular; D015394:Molecular Structure; D009569:Nitric Oxide / Q000737:chemistry*; D009589:Nitrogen Oxides / Q000737:chemistry*; D011789:Quantum Theory; D019097:Spin Trapping; D013438:Sulfhydryl Compounds / Q000737:chemistry*; D013481:Superoxides / Q000737:chemistry*; D013816:Thermodynamics
chemical_list: D000473:Alkanes; D003497:Cyclic N-Oxides; D005609:Free Radicals; D009589:Nitrogen Oxides; D013438:Sulfhydryl Compounds; C015388:nitrones; D013481:Superoxides; D009569:Nitric Oxide; D006861:Hydrogen Peroxide