4.5 Article

16-Electron Half-Sandwich Rhodium(III), Iridium(III), and Ruthenium(II) Complexes as Lysosome-Targeted Anticancer Agents

期刊

ORGANOMETALLICS
卷 40, 期 23, 页码 3999-4010

出版社

AMER CHEMICAL SOC
DOI: 10.1021/acs.organomet.1c00572

关键词

-

资金

  1. Young Talents Invitation Program of Shandong Provincial Colleges and Universities, Shandong Provincial Natural Science Foundation [ZR2018MB023]
  2. Key Laboratory of Polymeric Composite & Functional Materials of Ministry of Education [PCFM-2021A01]
  3. Taishan Scholars Program

向作者/读者索取更多资源

The 16-electron piano-stool rhodium, iridium, and ruthenium complexes were successfully synthesized and characterized through rearranged coordination reactions, demonstrating stability and fluorescence in solution. These complexes showed promising activity against cancer cells, with cytotoxicity comparable to or even better than cisplatin, and exhibited structure-activity relationships that influenced their potency. Furthermore, the mechanism of action studies revealed that the cytotoxicity of the complex Rh5 was associated with perturbations in the cell cycle and induction of apoptosis, as well as disruption of lysosomal integrity.
The 18-electron half-sandwich platinum group (Rh, Ru, Ir, and Os) metal anticancer complexes have been largely reported due to their easy tunable structure, high potency toward cancer cells, and specific mechanism of actions. However, the 16-electron (without the leaving group Cl-) half-sandwich complexes and their biological evaluation are rarely investigated. With an easy access to the required alpha-keto-beta-diimine ligands using m-CPBA as oxidant, we herein reported the synthesis and characterization of a panel of structurally related 16-electron piano-stool rhodium, iridium, and ruthenium complexes through the rearranged coordination reaction. These complexes have been well-established by NMR spectroscopy, mass spectrometry, single-crystal X-ray crystallography, and elemental analysis. Each of these complexes was stable and exhibited fluorescence in solution. Although no reaction with nucleobase (9-EtG and 9-MeA) was observed, the representative Rh5 showed affinity toward CT-DNA. These 16-electron complexes showed promising activity toward A549 and HeLa cancer cells with the values of IC50 in the range 7.1-32.3 mu M, which was comparable to or even better than cisplatin. In addition, the structure-activity relationships were observed that the change of the metal center from iridium(III) and ruthenium(II) to rhodium(III) could enhance the cytotoxicity of these unsaturated complexes. The investigation of mechanism of actions (MoAs) using flow cytometry displayed that the cytotoxicity of the complex Rh5 was associated with the perturbation of the cell cycle and the induction of cell apoptosis. Moreover, microscopic analysis by confocal microscopy suggested that the representative 16-electron complex Rh5 entered A549 cells via energy-dependent pathway and predominantly accumulated in lysosomes, thus resulting in the disruption of lysosomal integrity.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.5
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据