Key Laboratory of Advanced Materials of Tropical Island Resources of Ministry of Education and School of Chemical Engineering and Technology, Hainan University, Haikou, Hainan 570228, China.
College of Life Sciences, Nankai University, Tianjin 300071, China.
Spectrochim Acta A Mol Biomol Spectrosc. 2024 Aug 5;316:124317. doi: 10.1016/j.saa.2024.124317. Epub 2024 Apr 20.
Nitroxyl (HNO), the single-electron reduction product of nitric oxide (NO), has attracted great interest in the treatment of congestive heart failure in clinical trials. In this paper, we describe the first coumarin-based compound N-hydroxy-2-oxo-2H-chromene-6-sulfonamide (CD1) as a dualfunctional HNO donor, which can release both an HNO signaling molecule and a fluorescent reporter. Under physiological conditions (pH 7.4 and 37 °C), the CD1 HNO donor can readily decompose with a half-life of ∼90 min. The corresponding stoichiometry HNO from the CD1 donor was confirmed using both Vitamin B and phosphine compound traps. In addition to HNO releasing, specifically, the degradation product 2-oxo-2H-chromene-6-sulfinate (CS1) was generated as a fluorescent marker during the decomposition. Therefore, the HNO amount released in situ can be accurately monitored through fluorescence generation. As compared to the CD1 donor, the fluorescence intensity increased by about 4.9-fold. The concentration limit of detection of HNO releasing was determined to be ∼0.13 μM according to the fluorescence generation of CS1 at physiological conditions. Moreover, the bioimaging of the CD1 donor was demonstrated in the cell culture of HeLa cells, where the intracellular fluorescence signals were observed, inferring the site of HNO release. Finally, we anticipate that this novel coumarin-based CD1 donor opens a new platform for exploring the biology of HNO.
硝酰（HNO）是一氧化氮（NO）的单电子还原产物，在充血性心力衰竭的临床试验中引起了极大的关注。在本文中，我们描述了第一个香豆素基化合物 N-羟基-2-氧代-2H-色烯-6-磺酰胺（CD1）作为双功能 HNO 供体，它可以同时释放 HNO 信号分子和荧光报告分子。在生理条件下（pH 7.4 和 37°C），CD1 HNO 供体可以很容易地分解，半衰期约为 90 分钟。使用维生素 B 和膦化合物陷阱证实了来自 CD1 供体的相应化学计量 HNO。除了释放 HNO 之外，在分解过程中还生成了特定的降解产物 2-氧代-2H-色烯-6-亚磺酸盐（CS1）作为荧光标记物。因此，可以通过荧光产生来准确监测原位释放的 HNO 量。与 CD1 供体相比，荧光强度增加了约 4.9 倍。根据 CS1 在生理条件下的荧光产生，确定 HNO 释放的浓度检测限约为 0.13 μM。此外，在 HeLa 细胞的细胞培养中证明了 CD1 供体的生物成像，观察到细胞内荧光信号，推断出 HNO 释放的部位。最后，我们预计这种新型香豆素基 CD1 供体为探索 HNO 的生物学打开了一个新的平台。
