title: Superoxide radical anion adduct of 5,5-dimethyl-1-pyrroline n-oxide (DMPO). 1. The thermodynamics of formation and its acidity.
abstract: The nitrone 5,5-dimethyl-1-pyrroline N-oxide (DMPO) has been the most widely used spin trap for the detection of transient free radicals in chemical, biological, and biomedical research using electron paramagnetic resonance (EPR) spectroscopy. A density functional theory (DFT) approach was used to predict the thermodynamics of formation of the superoxide anion/hydroperoxyl radical (O2*-/*O2H) adduct of DMPO as well as its pK(a) in aqueous systems. At the B3LYP/6-31+G(d,p)//B3LYP/6-31G(d) level, we predicted (in the gas phase and with a polarizable continuum model (PCM) for water) three conformational minima for both the DMPO-O2- and DMPO-O2H adducts. Using DFT and the PCM solvation method, the pK(a) of DMPO-O2H was predicted to be 14.9 +/- 0.5. On the basis of free energy considerations, the formation of DMPO-O2H at neutral pH proceeds via initial addition of O2*- to DMPO to form the DMPO-O2- adduct and then subsequent protonation by water (or other acidic sources) to form DMPO-O2H. Under acidic conditions, the addition of *O2H to DMPO is predicted to be more exoergic than the addition of O2*- and is consistent with available experimental kinetic data.
authors.affiliation: Center for Biomedical EPR Spectroscopy and Imaging, The Davis Heart and Lung Research Institute, 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: John K
authors.initials: JK
authors.lastname: Merle
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Hadad
authors.forename: Jay L
authors.initials: JL
authors.lastname: Zweier
mesh_terms: D000838:Anions / Q000737:chemistry; D003497:Cyclic N-Oxides / Q000737:chemistry*; D004578:Electron Spin Resonance Spectroscopy; D004583:Electrons; D017665:Hydroxyl Radical / Q000737:chemistry; D007700:Kinetics; D008958:Models, Molecular; D015394:Molecular Structure; D010084:Oxidation-Reduction; D013113:Spin Labels; D019097:Spin Trapping; D013481:Superoxides / Q000737:chemistry*; D013816:Thermodynamics
chemical_list: D000838:Anions; D003497:Cyclic N-Oxides; D013113:Spin Labels; D013481:Superoxides; D017665:Hydroxyl Radical; C017245:5,5-dimethyl-1-pyrroline-1-oxide