TY - JOUR
T1 - Spin trapping by 5-carbamoyl-5-methyl-1-pyrroline N-oxide (AMPO)
T2 - Theoretical and experimental studies
AU - Villamena, Frederick A.
AU - Rockenbauer, Antal
AU - Gallucci, Judith
AU - Velayutham, Murugesan
AU - Hadad, Christopher M.
AU - Zweier, Jay L.
PY - 2004/11/12
Y1 - 2004/11/12
N2 - 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%), αnitronyl-N = 13.0 G and α β-H = 10.8 G; isomer II (20%), αnitronyl-N = 13.1 G, αβ-H = 12.5 G, and αγ-H = 1.75 G. The half-life of the AMPO-O2H was about 8 min, similar to that observed for EMPO but significantly shorter than that of the DEPMPO-O 2H with t1/2 ∼16 min. However, the spectral profile of AMPO-O2H 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 (NH2-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.
AB - 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%), αnitronyl-N = 13.0 G and α β-H = 10.8 G; isomer II (20%), αnitronyl-N = 13.1 G, αβ-H = 12.5 G, and αγ-H = 1.75 G. The half-life of the AMPO-O2H was about 8 min, similar to that observed for EMPO but significantly shorter than that of the DEPMPO-O 2H with t1/2 ∼16 min. However, the spectral profile of AMPO-O2H 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 (NH2-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.
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U2 - 10.1021/jo049244i
DO - 10.1021/jo049244i
M3 - Article
C2 - 15527282
AN - SCOPUS:8644255064
VL - 69
SP - 7994
EP - 8004
JO - Journal of Organic Chemistry
JF - Journal of Organic Chemistry
SN - 0022-3263
IS - 23
ER -