Green light-induced apoptosis in cancer cells by a tetrapyridyl ruthenium prodrug offering two trans coordination sites

Chemical Science
V H S van RixelSylvestre Bonnet

Abstract

In this work, two new photopharmacological ruthenium prodrugs are described that can be activated by green light. They are based on the tetrapyridyl biqbpy ligand (6,6'-bis[N-(isoquinolyl)-1-amino]-2,2'-bipyridine), which coordinates to the basal plane of the metal centre and leaves two trans coordination sites for the binding of monodentate sulphur ligands. Due to the distortion of the coordination sphere these trans ligands are photosubstituted by water upon green light irradiation. In vitro cytotoxicity data on A431 and A549 cancer cell lines shows an up to 22-fold increase in cytotoxicity after green light irradiation (520 nm, 75 J cm-2), compared to the dark control. Optical microscopy cell imaging and flow cytometry indicate that the cancer cells die via apoptosis. Meanwhile, very low singlet oxygen quantum yields (∼1-2%) and cell-free DNA binding studies conclude that light-induced cell death is not caused by a photodynamic effect, but instead by the changes induced in the coordination sphere of the metal by light, which modifies how the metal complexes bind to biomolecules.

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Citations

Jun 28, 2018·Chemistry : a European Journal·Maria FumanalChantal Daniel
Apr 4, 2019·Chemical Communications : Chem Comm·Xue-Quan ZhouSylvestre Bonnet
Apr 18, 2019·Dalton Transactions : an International Journal of Inorganic Chemistry·Na TianQianxiong Zhou
Mar 29, 2019·Gels·Pankaj BharmoriaNobuo Kimizuka
Jul 7, 2018·Dalton Transactions : an International Journal of Inorganic Chemistry·Sylvestre Bonnet
Apr 19, 2019·Chemical Science·Stuart A ArcherJames A Thomas
Jun 1, 2017·Chemistry : a European Journal·Wen SunSi Wu
Dec 13, 2017·Dalton Transactions : an International Journal of Inorganic Chemistry·Vincent H S van RixelSylvestre Bonnet
May 5, 2017·Dalton Transactions : an International Journal of Inorganic Chemistry·Sofia KajoujCécile Moucheron
Jun 10, 2017·Chemical Communications : Chem Comm·Jordi-Amat Cuello-GariboSylvestre Bonnet
Feb 17, 2018·Dalton Transactions : an International Journal of Inorganic Chemistry·Avia TzuberyEdit Y Tshuva
May 26, 2021·Dalton Transactions : an International Journal of Inorganic Chemistry·Priyaranjan KumarAshis K Patra
Aug 12, 2021·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·Anja BusemannSylvestre Bonnet
Aug 8, 2019·Langmuir : the ACS Journal of Surfaces and Colloids·Michael S MeijerSylvestre Bonnet
Jul 28, 2018·Journal of the American Chemical Society·Pankaj BharmoriaNobuo Kimizuka
Oct 10, 2018·Chemical Reviews·Xiaohui WangZijian Guo
Oct 27, 2020·Inorganic Chemistry·Ana C CarrascoAna M Pizarro
Sep 3, 2021·Journal of Photochemistry and Photobiology. B, Biology·Maria SuciuCrina Socaci

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Methods Mentioned

BETA
X-ray
size exclusion chromatography
flow cytometry
confocal microscopy

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