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 (O 2./.O 2H) 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-O 2 - and DMPO-O 2H adducts. Using DFT and the PCM solvation method, the pK a of DMPO-O 2H was predicted to be 14.9 ± 0.5. On the basis of free energy considerations, the formation of DMPO-O 2H at neutral pH proceeds via initial addition of O 2. to DMPO to form the DMPO-O 2 - adduct and then subsequent protonation by water (or other acidic sources) to form DMPO-O 2H. Under acidic conditions, the addition of .O 2H to DMPO is predicted to be more exoergic than the addition of O 2. and is consistent with available experimental kinetic data.
ASJC Scopus subject areas
- Physical and Theoretical Chemistry