Design of Bis-spiropyran Ligands as Dipolar Molecule Receptors and Application to in Vivo Glutathione Fluorescent Probes
Design of Bis-spiropyran Ligands as Dipolar Molecule Receptors and Application to in Vivo Glutathione Fluorescent Probes
复制标题
双螺吡喃偶极分子受体配体的设计及其在体内谷胱甘肽荧光探针中的应用
DOI：
10.1021/ja908215t
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发表时间：
2010-01-20
影响因子：
15
通讯作者：
Abliz, Zeper
中科院分区：
文献类型：
--
作者：
Shao, Na;Jin, Jianyu;Abliz, Zeper
尽管大量的研究致力于开发各种复杂的螺吡喃类化合物用于金属离子传感，但对有机分子传感的关注较少。使用螺吡喃检测有机分子的主要困难之一是螺吡喃与靶标之间的弱且非特异性的相互作用。在这里，我们报告了两个双螺吡喃偶极分子的合成和分子识别特性及其在体内谷胱甘肽（GSH）荧光探针的应用。与单螺吡喃不同，新设计的双螺吡喃分子具有严格保持的分子裂缝和两个螺吡喃单元作为结合模块。分子识别是基于多点静电相互作用和结构互补性之间的开放mercury形式的螺吡喃和分析物。观察到螺吡喃1a在水溶液中以高亲和力（K =（7.52 +/- 1.83）× 10（4）M-1）结合GSH，并在结合时显示出强荧光发射。值得注意的是，Ia的荧光输出不受其他氨基酸和肽的显著影响，特别是结构相似的化合物，如半胱氨酸和高半胱氨酸。此外，荧光各向异性和共聚焦荧光显微镜证实，螺吡喃1a是一个比较好的候选细胞内交付，并可以集中在细胞内积累。因此，1a可在体内用作GSH探针或用作显示细胞内GSH水平的标记物。
Despite considerable efforts toward the development of various sophisticated spiropyrans for metal ion sensing, less attention has been paid to organic molecule sensing. One of the major difficulties for detection of organic molecules using a spiropyran is the weak and nonspecific interaction between the spiropyran and the target. Here, we report the synthesis and molecular recognition characterization of two bis-spiropyrans for dipolar molecules and their application to in vivo glutathione (GSH) fluorescent probes. Unlike the mono-spiropyrans, the newly designed bis-spiropyran molecules feature a rigidly maintained molecular cleft and two spiropyran units as binding modules. The molecular recognition is based on multipoint electrostatic interactions and structure complementarity between the opened merocyanine form of the spiropyran and the analyte. It was observed that the spiropyran 1a binds GSH in aqueous solution with high affinity (K = (7.52 +/- 1.83) x 10(4) M-1) and shows strong fluorescence emission upon binding. Remarkably, fluorescence output of la is not significantly affected by other amino acids and peptides, especially, structurally similar compounds, such as cysteine and homocysteine. Furthermore, fluorescence anisotropy and confocal fluorescent microscopy confirmed that spiropyran 1a is a comparatively good candidate for intracellular delivery and can be accumulated intensively into cells. Thus, 1a can be utilized in vivo as a GSH probe or as a marker to show the level of intracellular GSH.