Highly Selective, Red Emitting BODIPY-Based Fluorescent Indicators for Intracellular Mg2+ Imaging.
Highly Selective, Red Emitting BODIPY-Based Fluorescent Indicators for Intracellular Mg2+ Imaging.
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DOI：
10.1039/c8tb01599f
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发表时间：
2018-11
期刊：
影响因子：
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通讯作者：
Qitian Lin;D. Buccella
中科院分区：
文献类型：
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作者：
Qitian Lin;D. Buccella
大多数镁离子的荧光指示剂对其他二价阳离子，特别是钙离子的选择性很差，因此不能提供涉及这些金属的过程中细胞内镁离子浓度的可靠信息。我们报道了一组新的基于烷氧基苯乙烯基功能化的BODIPY荧光团与4-氧代-4H-喹啉-3-羧酸金属结合部分修饰的高选择性荧光指示剂。新型传感器MAGQ1和MAGQ2的最大吸收和发射波长均在600 nm以上，在缓冲溶液中与镁离子配位，荧光增强29倍，量子产率高(Φ>0.3)。对镁离子的荧光响应不受细胞环境中通常存在的竞争二价阳离子存在的影响，并且在生理相关范围内表现出最小的pH依赖性。苯乙烯基BODIPY核心的烷氧基的选择不会影响化合物的基本光物理和金属结合性能，但会显著影响它们在细胞内的保留，从而影响它们在荧光成像中检测细胞内镁离子的适用性。特别是，我们证明了三甘醇(TEG)功能化策略的实用性，该策略通过减少有机阴离子转运体的主动排泄，使MagQ2在活细胞中具有卓越的细胞保留力，而有机阴离子转运体被认为会导致典型阴离子染料的快速渗出。由于具有增强的保留力和优异的光物理性质，MagQ2可以用于检测细胞内镁离子的内流，而不会受到类似于信号转导的高浓度钙离子的干扰。
Most fluorescent indicators for Mg2+ suffer from poor selectivity against other divalent cations, especially Ca2+, thus do not provide reliable information on cellular Mg2+ concentrations in processes in which such metals are involved. We report a new set of highly selective fluorescent indicators based on alkoxystyryl-functionalized BODIPY fluorophores decorated with a 4-oxo-4H-quinolizine-3-carboxylic acid metal binding moiety. The new sensors, MagQ1 and MagQ2, display absorption and emission maxima above 600 nm, with a 29-fold fluorescence enhancement and good quantum yields (Φ > 0.3) upon coordination of Mg2+ in aqueous buffer. Fluorescence response to Mg2+ is not affected by the presence of competing divalent cations typically present in the cellular milieu, and displays minimal pH dependence in the physiologically relevant range. The choice of alkoxy groups decorating the styryl BODIPY core does not influence the basic photophysical and metal binding properties of the compounds, but has a marked effect on their intracellular retention and thus in their applicability for detection of cellular Mg2+ by fluorescence imaging. In particular, we demonstrate the utility of a triethyleneglycol (TEG) functionalization tactic that endows MagQ2 with superior cellular retention in live cells by reducing active extrusion through organic anion transporters, which are thought to cause fast leakage of typical anionic dyes. With enhanced retention and excellent photophysical properties, MagQ2 can be applied in the detection of cellular Mg2+ influx without interference of high concentrations of Ca2+ akin to those involved in signaling.