通过 NMR 光谱和 X 射线衍射研究苯胂酸-DMPS 的氧化还原反应和结合。

Phenylarsonic acid-DMPS redox reaction and conjugation investigated by NMR spectroscopy and X-ray diffraction.

机构信息

Institute of Analytical Chemistry, TU Bergakademie Freiberg, 09599 Freiberg, Germany.

出版信息

Environ Toxicol Pharmacol. 2022 May;92:103837. doi: 10.1016/j.etap.2022.103837. Epub 2022 Mar 3.

DOI:10.1016/j.etap.2022.103837

Abstract

The reaction between 2,3-dimercaptopropane-1-sulfonate (DMPS, unithiol) and four phenylarsonic(V) acids, i.e. phenylarsonic acid (PAA), 4-hydroxy-3-nitrophenylarsonic acid (HNPAA), 2-aminophenylarsonic acid (o-APAA) and 4-aminophenylarsonic acid (p-APAA), is investigated in aqueous solution. The pentavalent arsenic compounds are reduced by DMPS to their trivalent analogs and instantly chelated by the vicinal dithiol, forming covalent As-S bonds within a five-membered chelate ring. The different types and positions of polar substituents at the aromatic ring of the arsonic acids influence the reaction rates in the same way as observed for reaction with glutathione (GSH), as well as the syn/anti molar ratio of the diastereomeric products, which was analyzed using time- and temperature-dependent nuclear magnetic resonance (NMR) spectroscopy. Addition of DMPS to the conjugate formed by a phenylarsonic(V) acid and the biologically relevant tripeptide GSH showed the immediate replacement of GSH by chelating DMPS, underlining the importance of dithiols as detoxifying agent.

摘要

2,3-二巯基丙烷-1-磺酸（DMPS，通用硫醇）与四种苯胂酸（V），即苯胂酸（PAA）、4-羟基-3-硝基苯胂酸（HNPAA）、2-氨基苯胂酸（o-APAA）和 4-氨基苯胂酸（p-APAA），在水溶液中的反应进行了研究。五价砷化合物被 DMPS 还原为其三价类似物，并立即被邻二巯基螯合，在五元螯合环内形成共价 As-S 键。芳基胂酸的芳环上不同类型和位置的极性取代基对反应速率的影响与与谷胱甘肽（GSH）的反应相同，以及非对映异构体产物的顺/反摩尔比也通过时间和温度依赖的核磁共振（NMR）光谱进行了分析。向苯胂酸（V）和生物相关的三肽 GSH 形成的共轭物中添加 DMPS，表明 DMPS 立即取代 GSH 进行螯合，这突出了二硫醇作为解毒剂的重要性。