Carbon-Dipyrromethenes: Bright Cationic Fluorescent Dyes and Potential Application in Revealing Cellular Trafficking of Mitochondrial Glutathione Conjugates.
Carbon-Dipyrromethenes: Bright Cationic Fluorescent Dyes and Potential Application in Revealing Cellular Trafficking of Mitochondrial Glutathione Conjugates.
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DOI：
10.1021/jacs.0c06916
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发表时间：
2020-09
影响因子：
15
通讯作者：
Hongxing Zhang;Jing Liu;Yuanqiang Sun;Mengxing Liu;W. Guo
中科院分区：
文献类型：
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作者：
Hongxing Zhang;Jing Liu;Yuanqiang Sun;Mengxing Liu;W. Guo
硼-二吡咯亚甲基（Bodipys）自1968年首次报道以来，由于其优异的物理化学性质（包括明亮的荧光、窄的发射带宽、抗光漂白和环境不敏感性），在过去的几十年中成为一类引人注目的染料。然而，典型的Bodipys是高度亲脂的，这通常导致在水溶液中的非荧光聚集体，并且也严重限制了它们对细胞和组织的生物利用度。本文基于Bodipy骨架中简单的单原子B → C取代，合成了一类新的碳-二吡咯亚甲基（简称Cardipys）荧光染料，其发射波长可调，覆盖可见光和近红外区域。这些Cardipys不仅保留了传统Bodipys的优异物理性能，而且由于其阳离子特性而显示出改善的水溶性和光稳定性。此外，阳离子特性也使它们非常容易穿透细胞膜并特异性地积聚到线粒体中，而无需求助于任何靶向基团。有趣的是，几个带有活性苯乙烯基的Cardipys可以作为荧光指示剂，用于绘制谷胱甘肽S-转移酶（GST）催化下线粒体内产生的谷胱甘肽结合物的细胞运输，从而显示出探索线粒体GST/GSH系统的解毒机制或评估与GST活性密切相关的癌细胞耐药性的潜力。
Boron-dipyrromethenes (Bodipys), since first reported in 1968, have emerged as a fascinating class of dyes in the past few decades due to their excellent photophysical properties including bright fluorescence, narrow emission bandwidth, resistance to photobleaching, and environment insensitivity. However, typical Bodipys are highly lipophilic, which often results in the nonfluorescent aggregates in aqueous solution, and also severely limits their bioavailability to cells and tissues. In this work, based on a simple one-atom BC replacement in Bodipy scaffold, we present a new class of carbon-dipyrromethenes (Cardipys for short) fluorescent dyes with tunable emission wavelengths covering the visible and near-infrared regions. These Cardipys not only retain excellent photophysical properties of conventional Bodipys, but also show improved water solubility and photostability due to their cationic character. Moreover, the cationic character also makes them extremely easy to penetrate cell membrane and specifically accumulate into mitochondria without resorting to any mitochondria-targeted groups. Interestingly, several Cardipys bearing active styryl groups could serve as fluorescent indicators to map cellular trafficking of the glutathione conjugates produced within mitochondria under the catalysis of glutathione S-transferase (GST), thus showing potentials in either exploring the detoxification mechanism of mitochondrial GST/GSH system or evaluating the drug resistance of cancer cells that is closely related with GST activity.