Spin trapping by 5-carbamoyl-5-methyl-1-pyrroline N-oxide (AMPO): theoretical and experimental studies.
The nitrone 5-carbamoyl-5-methyl-1-pyrroline N-oxide (AMPO) was synthesized and characterized. Spin trapping of various radicals by AMPO was demonstrated for the first time by electron paramagnetic resonance (EPR) spectroscopy. The resulting spin adducts for each of these radicals gave unique spectral profiles. The hyperfine splitting constants for the superoxide adduct are as follows: isomer I (80%), a(nitronyl)(-)(N) = 13.0 G and a(beta)(-)(H) = 10.8 G; isomer II (20%), a(nitronyl)(-)(N) = 13.1 G, a(beta)(-)(H) = 12.5 G, and a(gamma)(-)(H) = 1.75 G. The half-life of the AMPO-O(2)H was about 8 min, similar to that observed for EMPO but significantly shorter than that of the DEPMPO-O(2)H with t(1/2) approximately 16 min. However, the spectral profile of AMPO-O(2)H at high S/N ratio is distinguishable from the spectrum of the (*)OH adduct. Theoretical analyses using density functional theory calculations at the B3LYP/6-31+G//B3LYP/6-31G level were performed on AMPO and its corresponding superoxide adduct. Calculations predicted the presence of intramolecular H-bonding in both AMPO and its superoxide adduct. The H-bonding interaction was further confirmed by an X-ray structure of AMPO, and of the novel and analogous amido nitrone 2-amino-5-carbamoyl-5-methyl-1-pyrroline N-oxide (NH(2)-AMPO). The thermodynamic quantities for superoxide radical trapping by various nitrones have been found to predict favorable formation of certain isomers. The measured partition coefficient in an n-octanol/buffer system of AMPO was similar to those of DMPO and DEPMPO. This study demonstrates the suitability of the AMPO nitrone for use as a spin trap to study radical production in aqueous systems.
Villamena
Frederick A
FA
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
Rockenbauer
Antal
A
Gallucci
Judith
J
Velayutham
Murugesan
M
Hadad
Christopher M
CM
Zweier
Jay L
JL
D018360:Crystallography, X-Ray; D003497:Cyclic N-Oxides / Q000138:chemical synthesis* / Q000737:chemistry; D004578:Electron Spin Resonance Spectroscopy; D008962:Models, Theoretical; D008968:Molecular Conformation; D015394:Molecular Structure; D011758:Pyrroles / Q000138:chemical synthesis* / Q000737:chemistry; D019097:Spin Trapping; D013816:Thermodynamics
C494111:5-carbamoyl-5-methyl-1-pyrroline N-oxide; D003497:Cyclic N-Oxides; D011758:Pyrroles