Bidentate Ligands on Osmium(VI) Nitrido Complexes Control Intracellular Targeting and Cell Death Pathways
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Lippard_Bidentate ligands.pdf
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Author(s)
Suntharalingam, Kogularamanan
Lin, Wei
Lippard, Stephen J.
Johnstone, Timothy
Bruno, Peter Michael
Hemann, Michael
Date Issued
August 2013
Journal
Journal of the American Chemical Society
Publisher
American Chemical Society (ACS)
Citation
Suntharalingam, Kogularamanan, Timothy C. Johnstone, Peter M. Bruno, Wei Lin, Michael T. Hemann, and Stephen J. Lippard. “Bidentate Ligands on Osmium(VI) Nitrido Complexes Control Intracellular Targeting and Cell Death Pathways.” Journal of the American Chemical Society 135, no. 38 (September 25, 2013): 14060–14063.
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Author's final manuscript
Abstract
The cellular response evoked by antiproliferating osmium(VI) nitrido compounds of general formula OsN(N[superscript N])Cl[subscript 3] (N[superscript N] = 2,2′-bipyridine 1, 1,10-phenanthroline 2, 3,4,7,8-tetramethyl-1,10-phenanthroline 3, or 4,7-diphenyl-1,10-phenanthroline 4) can be tuned by subtle ligand modifications. Complex 2 induces DNA damage, resulting in activation of the p53 pathway, cell cycle arrest at the G2/M phase, and caspase-dependent apoptotic cell death. In contrast, 4 evokes endoplasmic reticulum (ER) stress leading to the upregulation of proteins of the unfolded protein response pathway, increase in ER size, and p53-independent apoptotic cell death. To the best of our knowledge, 4 is the first osmium compound to induce ER stress in cancer cells.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Massachusetts Institute of Technology. Department of Chemistry
Koch Institute for Integrative Cancer Research at MIT
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DOI of Published Version
https://doi.org/10.1021/ja4075375
