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• W3213505311 abstract "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 α-keto-β-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 μM, 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." @default.
• W3213505311 created "2021-11-22" @default.
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• W3213505311 date "2021-11-17" @default.
• W3213505311 modified "2023-10-16" @default.
• W3213505311 title "16-Electron Half-Sandwich Rhodium(III), Iridium(III), and Ruthenium(II) Complexes as Lysosome-Targeted Anticancer Agents" @default.
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• W3213505311 doi "https://doi.org/10.1021/acs.organomet.1c00572" @default.
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