Zinc Photocages with Improved Photophysical Properties and Cell Permeability Imparted by Ternary Complex Formation
Zinc Photocages with Improved Photophysical Properties and Cell Permeability Imparted by Ternary Complex Formation
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DOI：
10.1021/jacs.9b05504
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发表时间：
2019-07-31
影响因子：
15
通讯作者：
Burdette, Shawn C.
中科院分区：
文献类型：
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作者：
Basa, Prem N.;Barr, Chelsea A.;Burdette, Shawn C.
光笼复合物可以控制金属离子的可用性，以询问细胞信号传导途径。我们描述了一种新的光笼，{双[（2-吡啶基）甲基]氨基}（9-氧代-2-咕吨基）乙酸（XDPAdeCage，1），它利用2-咕吨酮乙酸基团介导的光脱羧反应。XDPAdeCage以27%的量子产率光解，并以4.6 pM的亲和力结合Zn 2+，其在光解后降低超过4个数量级。为了与我们先前通过光脱羧释放Zn 2+的方法进行比较，还制备并表征了类似的光笼{双[（2-吡啶基）甲基]氨基}（间硝基苯基）乙酸（DPAdeCage，2），其使用间硝基苄基发色团。2-氧杂蒽酮乙酸发色团的优点包括在优选的解除掩蔽波长下的红移激发和较高的消光系数。[Zn（XDPAdeCage）]（+）与阴离子配体嘧啶的中性三元络合物是膜可渗透的，这避免了利用侵入性技术引入细胞内Zn 2+波动的需要。使用荧光成像，我们已经证实了运输的Zn 2+跨膜，此外，RT-PCR实验表明在光解后的Zn 2+响应蛋白的表达的变化。
Photocaged complexes can control the availability of metal ions to interrogate cellular signaling pathways. We describe a new photocage, {bis[(2-pyridyl)methyl]amino}(9-oxo-2-xanthenyl)acetic acid (XDPAdeCage, 1), which utilizes a 2-xanthone acetic acid group to mediate a photodecarboxylation reaction. XDPAdeCage photolyzes with a quantum yield of 27%, and binds Zn2+ with 4.6 pM affinity, which decreases by over 4 orders of magnitude after photolysis. For comparison to our previous approach to Zn2+ release via photodecarboxylation, the analogous photocage {bis[(2-pyridyl)methyl]amino}(m-nitrophenyl)acetic acid (DPAdeCage, 2), which uses a m-nitrobenzyl chromophore, was also prepared and characterized. The advantages of the 2-xanthone acetic acid chromophore include red-shifted excitation and a higher extinction coefficient at the preferred uncaging wavelength. The neutral ternary complex of [Zn(XDPAdeCage)](+) with the anionic ligand pyrithione is membrane permeable, which circumvents the need to utilize invasive techniques to introduce intracellular Zn2+ fluctuations. Using fluorescent imaging, we have confirmed transport of Zn2+ across membranes; in addition, RT-PCR experiments demonstrate changes in expression of Zn2+-responsive proteins after photolysis.