Department of Chemistry, Colorado State University, Fort Collins, CO 80523, United States.
Department of Chemistry, Colorado State University, Fort Collins, CO 80523, United States; School of Biomedical Engineering, Colorado State University, Fort Collins, CO 80523, United States; Department of Chemical & Biological Engineering, Colorado State University, Fort Collins, CO 80523, United States.
J Inorg Biochem. 2019 Oct;199:110760. doi: 10.1016/j.jinorgbio.2019.110760. Epub 2019 Jul 16.
Copper containing compounds catalyze decomposition of S-Nitrosoglutathione (GSNO) in the presence of glutathione (GSH) yielding glutathione disulfide (GSSG) and nitric oxide (NO). Extended NO generation from an endogenous source is medically desirable to achieve vasodilation, reduction in biofilms on medical devices, and antibacterial activity. Homogeneous and heterogeneous copper species catalyze release of NO from endogenous GSNO. One heterogeneous catalyst used for GSNO decomposition in blood plasma is the metal-organic framework (MOF), H[(CuCl)-(BTTri), HBTTri = 1,3,5-tris(H-1,2,3-triazol-5-yl) benzene] (CuBTTri). Fundamental questions about these systems remain unanswered, despite their use in biomedical applications, in part because no method previously existed for simultaneous tracking of [GSNO], [GSH], and [GSSG] in water. Tracking these reactions in water is a necessary step towards study in biological media (blood is approximately 80% water) where NO release systems must operate. Even the balanced stoichiometry remains unknown for copper-ion and CuBTTri catalyzed GSNO decomposition. Herein, we report a direct H NMR method which: simultaneously monitors [GSNO], [GSH], and [GSSG] in water; provides the experimentally determined stoichiometry for copper-ion vs CuBTTri catalyzed GSNO decomposition; reveals that the CuBTTri-catalyzed reaction reaches 10% GSNO decomposition (16 h) without added GSH, yet the copper-ion catalyzed reaction reaches 100% GSNO decomposition (16 h) without added GSH; and shows 100% GSNO decomposition upon addition of stoichiometric GSH to the CuBTTri catalyzed reaction. These observations provide evidence that copper-ion and CuBTTri catalyzed GSNO decomposition in water operate through different reaction mechanisms, the details of which can now be probed by H NMR kinetics and other needed studies.
含铜化合物在谷胱甘肽 (GSH) 的存在下催化 S-亚硝基谷胱甘肽 (GSNO) 的分解，生成谷胱甘肽二硫化物 (GSSG) 和一氧化氮 (NO)。从内源性来源扩展 NO 的产生在医学上是理想的，以实现血管扩张、减少医疗器械上的生物膜和抗菌活性。均相和多相铜物种均能催化内源性 GSNO 释放 NO。一种用于在血浆中分解 GSNO 的多相催化剂是金属有机骨架 (MOF)，H[(CuCl)-(BTTri)，HBTTri=1,3,5-三(1H-1,2,3-三唑-5-基)苯] (CuBTTri)。尽管这些系统已在生物医学应用中使用，但仍有一些基本问题尚未得到解答，部分原因是以前没有用于同时跟踪水中 [GSNO]、[GSH] 和 [GSSG] 的方法。在生物介质（血液约 80%为水）中研究这些反应是必需的，因为在这些介质中必须运行 NO 释放系统。甚至对于铜离子和 CuBTTri 催化的 GSNO 分解，平衡化学计量也仍然未知。在此，我们报告了一种直接的 H NMR 方法，该方法：同时监测水中的 [GSNO]、[GSH] 和 [GSSG]；提供了实验确定的铜离子与 CuBTTri 催化的 GSNO 分解的化学计量比；表明 CuBTTri 催化的反应在没有添加 GSH 的情况下达到 10% GSNO 分解（16 小时），而铜离子催化的反应在没有添加 GSH 的情况下达到 100% GSNO 分解（16 小时）；并且在向 CuBTTri 催化的反应中添加化学计量的 GSH 后，GSNO 完全分解。这些观察结果提供了证据，表明铜离子和 CuBTTri 催化的水中 GSNO 分解通过不同的反应机制进行，现在可以通过 H NMR 动力学和其他必要的研究来探究这些机制的细节。
