Villamena Frederick A, Rockenbauer Antal, Gallucci Judith, Velayutham Murugesan, Hadad Christopher M, Zweier Jay L
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.
J Org Chem. 2004 Nov 12;69(23):7994-8004. doi: 10.1021/jo049244i.
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.
合成并表征了硝酮5-氨基甲酰基-5-甲基-1-吡咯啉N-氧化物（AMPO）。首次通过电子顺磁共振（EPR）光谱证明了AMPO对各种自由基的自旋捕获。这些自由基各自产生的自旋加合物给出了独特的光谱轮廓。超氧加合物的超精细分裂常数如下：异构体I（80%），a（硝酰基）（-）（N） = 13.0 G，a（β）（-）（H） = 10.8 G；异构体II（20%），a（硝酰基）（-）（N） = 13.1 G，a（β）（-）（H） = 12.5 G，a（γ）（-）（H） = 1.75 G。AMPO-O₂H的半衰期约为8分钟，与EMPO观察到的半衰期相似，但明显短于DEPMPO-O₂H的半衰期，t₁/₂约为16分钟。然而，高信噪比下AMPO-O₂H的光谱轮廓与（*）OH加合物的光谱不同。在B3LYP/6-31+G//B3LYP/6-31G水平上使用密度泛函理论计算对AMPO及其相应的超氧加合物进行了理论分析。计算预测AMPO及其超氧加合物中均存在分子内氢键。通过AMPO以及新型类似物氨基硝酮2-氨基-5-氨基甲酰基-5-甲基-1-吡咯啉N-氧化物（NH₂-AMPO）的X射线结构进一步证实了氢键相互作用。已发现各种硝酮捕获超氧自由基的热力学量可预测某些异构体的有利形成。AMPO在正辛醇/缓冲液系统中的测得分配系数与DMPO和DEPMPO的相似。本研究证明了AMPO硝酮适用于作为自旋捕获剂来研究水体系中的自由基产生。
