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Organometallic ruthenium and iridium phosphorus complexes: Synthesis, cellular imaging, organelle targeting and anticancer applications
Author(s) -
Li JuanJuan,
Tian Zhenzhen,
Zhang Shumiao,
Xu Zhishan,
Mao Xudong,
Zhou Yumin,
Liu Zhe
Publication year - 2019
Publication title -
applied organometallic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.53
H-Index - 71
eISSN - 1099-0739
pISSN - 0268-2605
DOI - 10.1002/aoc.4685
Subject(s) - chemistry , cytotoxicity , cisplatin , mechanism of action , cancer cell , reactive oxygen species , a549 cell , biochemistry , stereochemistry , in vitro , cancer , medicine , surgery , chemotherapy
The use of metal complexes containing phosphorus ligands as anticancer agents has not been well studied. In this work, eight novel half‐sandwich Ir III and Ru II compounds with P^P‐chelating ligands have been synthesized and fully characterized, and alongside two crystal structures were reported. All eight complexes displayed highly potent antiproliferative activity, up to nine times more potent than the clinical anticancer drug cisplatin towards A549 lung cancer cells. Complex Ir1 , which has a simpler structure and highly potent antiproliferative activity, was selected to investigate in further mechanistic studies. No hydrolysis and nucleobase binding occurred for complex Ir1 . In order to elucidate subcellular localization, the self‐luminescence of the complex Ir1 was utilized. Ir1 can specifically target lysosomes and facilitate excessive production of reactive oxygen species, resulting in lysosomal membrane permeabilization in A549 cells. Release of cathepsin B and changes in the mitochondria membrane potential also contributed to the observed cytotoxicity of Ir1 , which demonstrated an anticancer action mechanism that was different from that of cisplatin. The favorable results from biological and chemical research demonstrated that these types of complexes hold significant theranostic potential.