d'Ischia M, Costantini C
Department of Organic and Biological Chemistry, University of Naples Federico II, Italy.
Bioorg Med Chem. 1995 Jul;3(7):923-7. doi: 10.1016/0968-0896(95)00083-s.
Exposure of the neurotransmitters dopamine (1a) and norepinephrine (1b), as well as of other catechol compounds (1c-e), to nitric oxide (NO) in aerated phosphate buffer at room temperature leads to the corresponding 6-nitroderivatives (2a-e) in yields higher than 80%. Formation of nitration products depends on the presence of oxygen and is inhibited by excess ascorbic acid, whereas sulfhydryl compounds, e.g. cysteine, and scavengers of reactive oxygen species, such as catalase and superoxide dismutase, exert no significant inhibitory effect. O-Methylated catechols are poorly or not reactive toward NO. These and other observations are consistent with a mechanism involving coupling of a semiquinone radical with NO or a higher oxide, e.g. nitrogen dioxide (NO2). The observed formation of potentially toxic 6-nitrocatecholamines under physiologically relevant conditions may open new perspectives to an understanding of the biochemical processes underlying NO-induced toxicity and neuronal degeneration.
在室温下，将神经递质多巴胺（1a）、去甲肾上腺素（1b）以及其他儿茶酚化合物（1c - e）置于通有空气的磷酸盐缓冲液中，并使其与一氧化氮（NO）接触，会生成相应的6 - 硝基衍生物（2a - e），产率高于80%。硝化产物的形成取决于氧气的存在，且会受到过量抗坏血酸的抑制，而巯基化合物（如半胱氨酸）以及活性氧清除剂（如过氧化氢酶和超氧化物歧化酶）则没有显著的抑制作用。邻甲基化儿茶酚对NO的反应性较差或无反应。这些以及其他观察结果与一种涉及半醌自由基与NO或更高氧化物（如二氧化氮（NO₂））偶联的机制相一致。在生理相关条件下观察到的潜在有毒6 - 硝基儿茶酚胺的形成，可能为理解NO诱导的毒性和神经元变性背后的生化过程开辟新的视角。
