Necroptosis-inducing rhenium(V) oxo complexes

Kogularamanan Suntharalingam, Samuel G. Awuah, Peter M. Bruno, Timothy C. Johnstone, Fang Wang, Wei Lin, Yao Rong Zheng, Julia E. Page, Michael T. Hemann, Stephen J. Lippard

Research output: Contribution to journalArticlepeer-review

62 Scopus citations

Abstract

Rhenium(V) oxo complexes of general formula [ReO(OMe)(N^N)Cl2], where N^N = 4,7-diphenyl-1,10-phenanthroline, 1, or 3,4,7,8-tetramethyl-1,10-phenanthroline, 2, effectively kill cancer cells by triggering necroptosis, a non-apoptotic form of cell death. Both complexes evoke necrosome (RIP1-RIP3)-dependent intracellular reactive oxygen species (ROS) production and propidium iodide uptake. The complexes also induce mitochondrial membrane potential depletion, a possible downstream effect of ROS production. Apparently, 1 and 2 are the first rhenium complexes to evoke cellular events consistent with programmed necrosis in cancer cells. Furthermore, 1 and 2 display low acute toxicity in C57BL/6 mice and reasonable stability in fresh human blood.

Original languageEnglish
Pages (from-to)2967-2974
Number of pages8
JournalJournal of the American Chemical Society
Volume137
Issue number8
DOIs
StatePublished - Mar 4 2015

Bibliographical note

Publisher Copyright:
© 2015 American Chemical Society.

ASJC Scopus subject areas

  • Catalysis
  • Chemistry (all)
  • Biochemistry
  • Colloid and Surface Chemistry

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