Strained, Photoejecting Ru(II) Complexes that are Cytotoxic Under Hypoxic Conditions

John Roque, Dmytro Havrylyuk, Patrick C. Barrett, Tariq Sainuddin, Julia McCain, Katsuya Colón, William T. Sparks, Evan Bradner, Susan Monro, David Heidary, Colin G. Cameron, Edith C. Glazer, Sherri A. McFarland

Research output: Contribution to journalArticlepeer-review

39 Scopus citations

Abstract

A series of strained Ru(II) complexes were studied for potential anticancer activity in hypoxic tissues. The complexes were constructed with methylated ligands that were photolabile and an imidizo[4,5-f][1,10]phenanthroline ligand that contained an appended aromatic group to potentially allow for contributions of ligand-centered excited states. A systematic variation of the size and energy of the aromatic group was performed using systems containing 1–4 fused rings, and the photochemical and photobiological behaviors of all complexes were assessed. The structure and nature of the aromatic group had a subtle impact on photochemistry, altering environmental sensitivity, and had a significant impact on cellular cytotoxicity and photobiology. Up to 5-fold differences in cytotoxicity were observed in the absence of light activation; this rose to 50-fold differences upon exposure to 453 nm light. Most significantly, one complex retained activity under conditions with 1% O2, which is used to induce hypoxic changes. This system exhibited a photocytotoxicity index (PI) of 15, which is in marked contrast to most other Ru(II) complexes, including those designed for O2-independent mechanisms of action.

Original languageEnglish
Pages (from-to)327-339
Number of pages13
JournalPhotochemistry and Photobiology
Volume96
Issue number2
DOIs
StatePublished - Mar 1 2020

Bibliographical note

Publisher Copyright:
© 2019 American Society for Photobiology

ASJC Scopus subject areas

  • Biochemistry
  • Physical and Theoretical Chemistry

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