Department of Biophysical Chemistry, Kobe Pharmaceutical University, 4-19-1 Motoyamakita Machi, Higashinada Ku, Kobe 658-8558, Japan.
Graduate School of Biomedical Sciences, Nagasaki University, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan.
Sensors (Basel). 2019 May 2;19(9):2049. doi: 10.3390/s19092049.
A small extent of endogenous labile zinc is involved in many vital physiological roles in living systems. However, its detailed functions have not been fully elucidated. In this study, we developed a novel biheteroaryl-based low molecular weight fluorescent sensor, 3-(phenylsulfonyl)-pyrazine-pyridone (), and applied it for the detection of endogenous labile zinc ions from lung cancer cells during apoptosis. The electron-withdrawing property of the sulfonyl group between the phenyl ring as an electron donor and the pyridone ring as a fluorophore inhibited the intramolecular charge transfer state, and the background fluorescence of the sensor was decreased in aqueous media. From the structure-fluorescence relationship analysis of the substituent effects with/without Zn, compound acting as a sensor possessed favorable properties, including a longer emission wavelength, a large Stokes shift (over 100 nm), a large fluorescence enhancement in response to Zn under physical conditions, and good cell membrane permeability in living cells. Fluorescence imaging studies of human lung adenocarcinoma cells (A549) undergoing apoptosis revealed that compound could detect endogenous labile zinc ions. These experiments suggested that the low molecular weight compound is a potential fluorescence sensor for Zn toward understanding its functions in living systems.
在生命系统中,少量的内源性不稳定锌参与了许多重要的生理作用。然而,其详细功能尚未完全阐明。在本研究中,我们开发了一种新型的基于双杂芳基的低分子量荧光传感器,3-(苯磺酰基)-吡嗪-吡啶酮(),并将其应用于检测凋亡过程中肺癌细胞内源性不稳定锌离子。苯环和吡啶酮环之间的磺酰基作为电子给体和荧光团的吸电子性质抑制了分子内电荷转移态,传感器在水介质中的背景荧光降低。从取代基效应的结构-荧光关系分析来看,化合物()作为传感器具有良好的性质,包括更长的发射波长、更大的斯托克斯位移(超过 100nm)、在物理条件下对 Zn 的响应具有较大的荧光增强以及在活细胞中有良好的细胞膜通透性。对人肺腺癌细胞(A549)凋亡过程的荧光成像研究表明,化合物()可以检测内源性不稳定锌离子。这些实验表明,这种低分子量化合物()是一种潜在的用于 Zn 的荧光传感器,有助于理解其在生命系统中的功能。