Semmelweis University, Department of Pharmaceutical Chemistry, Hőgyes E. u. 9, 1092, Budapest, Hungary.
University of Medicine, Pharmacy, Sciences and Technology of Târgu Mureş, Faculty of Pharmacy, Department of Toxicology and Biopharmacy, Str. Marinescu Gheorghe 38, 540142, Târgu Mures, Romania.
Chem Biodivers. 2019 Sep;16(9):e1900358. doi: 10.1002/cbdv.201900358. Epub 2019 Aug 20.
The complete macro- and microequilibrium analyses of 3-nitrotyrosine, a biomarker of oxidative stress damage, are presented for the first time. The protonation macroconstants were determined by H-NMR-pH titration, while microconstants were elucidated by a combination of deductive and NMR methods, in which properties of the methyl ester derivative as an auxiliary compound were also studied. Combination of the NMR-pH characterization of the title and auxiliary compounds and the pair-interactivity parameters of 3-iodotyrosine provided the sufficient system to evaluate all the microconstants. NMR-pH profiles, macroscopic and microscopic protonation schemes, and species-specific distribution diagrams are included. The phenolate basicity of 3-nitrotyrosine is 500 times below that of tyrosine, and it is even lower than that of 3-iodotyrosine. This phenomenon can be explained by the stronger electron withdrawing and the negative mesomeric effect of the nitro group. Based on our results, 89 % of the phenolic OH groups are deprotonated in 3-NT molecules at the pH of the blood plasma.
首次完整地对 3-硝基酪氨酸（氧化应激损伤的生物标志物）进行宏观和微观平衡分析。通过 H-NMR-pH 滴定法确定质子化宏观常数，而微观常数则通过演绎和 NMR 方法的组合来阐明，其中还研究了甲酯衍生物作为辅助化合物的性质。标题和辅助化合物的 NMR-pH 特性以及 3-碘酪氨酸的对相互作用参数的组合提供了评估所有微观常数的充分系统。包括 NMR-pH 曲线、宏观和微观质子化方案以及特定于物种的分布图。3-硝基酪氨酸的酚盐碱性比酪氨酸低 500 倍，甚至比 3-碘酪氨酸还低。这种现象可以用硝基的更强的吸电子性和负的共轭效应来解释。根据我们的结果，在血浆 pH 值下，3-NT 分子中 89%的酚羟基被去质子化。
