Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming 650500, P. R. China.
Dalton Trans. 2022 May 24;51(20):7907-7917. doi: 10.1039/d2dt00719c.
The reasonable design of binuclear or multinuclear metal complexes has demonstrated their potential advantages in the anticancer field. Herein, three heterobimetallic Ir(III)-Re(I) complexes, Ir(C^N)LRe(CO)DIP (C^N = 2-phenylpyridine (ppy, in IrRe-1), 2-(2-thienyl)pyridine (thpy, in IrRe-2) and 2-(2,4-difluorophenyl)pyridine (dfppy, in IrRe-3); L = pyridylimidazo[4,5-][1,10]phenanthroline; DIP = 4,7-diphenyl-1,10-phenanthroline), were designed and synthesized. The heterobimetallic IrRe-1-3 complexes show pH-sensitive emission properties, which can be used for specific imaging of lysosomes. Additionally, IrRe-1-3 display higher cytotoxicity against tested tumor cell lines than the clinical chemotherapeutic drug cisplatin. Further mechanisms indicate that IrRe-1-3 can induce apoptosis and autophagy, increase intracellular reactive oxygen species (ROS), depolarize the mitochondrial membrane (MMP), block the cell cycle at the G0/G1 phase and inhibit cell migration. To the best of our knowledge, this is the first example of the synthesis of heterobimetallic Ir(III)-Re(I) complexes with superior anticancer activities and evaluation of their anticancer mechanisms.
双核或多核金属配合物的合理设计已经证明了它们在抗癌领域的潜在优势。在此，我们设计并合成了三种异双核 Ir(III)-Re(I)配合物Ir(C^N)LRe(CO)DIP（C^N = 2-苯基吡啶（ppy，在 IrRe-1 中）、2-(2-噻吩基)吡啶（thpy，在 IrRe-2 中）和 2-(2,4-二氟苯基)吡啶（dfppy，在 IrRe-3 中）；L = 吡啶基咪唑并[4,5-][1,10]菲咯啉；DIP = 4,7-二苯基-1,10-菲咯啉）。这些异双核 IrRe-1-3 配合物具有 pH 敏感性的发光性质，可用于溶酶体的特异性成像。此外，与临床化疗药物顺铂相比，IrRe-1-3 对测试的肿瘤细胞系具有更高的细胞毒性。进一步的机制表明，IrRe-1-3 可以诱导细胞凋亡和自噬，增加细胞内活性氧物种（ROS），使线粒体膜去极化（MMP），阻滞细胞周期于 G0/G1 期，并抑制细胞迁移。据我们所知，这是首例具有优异抗癌活性的异双核 Ir(III)-Re(I)配合物的合成及其抗癌机制的评估。
