Hao Liang, Li Zhi-Wei, Zhang Dong-Yang, He Liang, Liu Wenting, Yang Jing, Tan Cai-Ping, Ji Liang-Nian, Mao Zong-Wan
MOE Key Laboratory of Bioinorganic and Synthetic Chemistry , School of Chemistry , Sun Yat-Sen University , Guangzhou 510275 , China . Email:
Chem Sci. 2018 Dec 4;10(5):1285-1293. doi: 10.1039/c8sc04242j. eCollection 2019 Feb 7.
Precise quantitative measurement of viscosity at the subcellular level presents great challenges. Two-photon phosphorescence lifetime imaging microscopy (TPPLIM) can reflect micro-environmental changes of a chromophore in a quantitative manner. Phosphorescent iridium complexes are potential TPPLIM probes due to their rich photophysical properties including environment-sensitive long-lifetime emission and high two-photon absorption (TPA) properties. In this work, a series of iridium(iii) complexes containing rotatable groups are developed as mitochondria-targeting anticancer agents and quantitative viscosity probes. Among them, ([Ir(ppy-CHO)(dppe)]PF; ppy-CHO: 4-(2-pyridyl)benzaldehyde; dppe: -1,2-bis(diphenylphosphino)ethene) shows satisfactory TPA properties and long lifetimes (up to 1 μs). The emission intensities and lifetimes of are viscosity-dependent, which is mainly attributed to the configurational changes in the diphosphine ligand as proved by H NMR spectra. displays potent cytotoxicity, and mechanism investigations show that it can accumulate in mitochondria and induce apoptotic cell death. Moreover, can induce mitochondrial dysfunction and monitor the changes in mitochondrial viscosity simultaneously in a real-time and quantitative manner TPPLIM. Upon treatment, a time-dependent increase in viscosity and heterogeneity is observed along with the loss of membrane potential in mitochondria. In summary, our work shows that multifunctional phosphorescent metal complexes can induce and precisely detect microenvironmental changes simultaneously at the subcellular level using TPPLIM, which may deepen the understanding of the cell death mechanisms induced by these metallocompounds.
在亚细胞水平进行粘度的精确定量测量面临巨大挑战。双光子磷光寿命成像显微镜（TPPLIM）能够以定量方式反映发色团的微环境变化。磷光铱配合物因其丰富的光物理性质，包括对环境敏感的长寿命发射和高二光子吸收（TPA）性质，而成为潜在的TPPLIM探针。在这项工作中，一系列含有可旋转基团的铱（III）配合物被开发为靶向线粒体的抗癌剂和定量粘度探针。其中，（[Ir(ppy-CHO)(dppe)]PF；ppy-CHO：4-(2-吡啶基)苯甲醛；dppe：-1,2-双（二苯基膦基）乙烯）表现出令人满意的TPA性质和长寿命（长达1微秒）。其发射强度和寿命与粘度相关，这主要归因于双膦配体的构型变化，1H NMR光谱证明了这一点。该配合物显示出强大的细胞毒性，机制研究表明它可在线粒体中积累并诱导凋亡性细胞死亡。此外，该配合物可诱导线粒体功能障碍，并通过TPPLIM实时定量监测线粒体粘度的变化。在用该配合物处理后，观察到线粒体粘度和异质性随时间增加，同时伴有膜电位丧失。总之，我们的工作表明多功能磷光金属配合物可利用TPPLIM在亚细胞水平同时诱导并精确检测微环境变化，这可能会加深对这些金属化合物诱导的细胞死亡机制的理解。
