Fine-Feature Modifications to Strained Ruthenium Complexes Radically Alter Their Hypoxic Anticancer Activity

Houston D. Cole, John A. Roque, Liubov M. Lifshits, Rachel Hodges, Patrick C. Barrett, Dmytro Havrylyuk, David Heidary, Elamparuthi Ramasamy, Colin G. Cameron, Edith C. Glazer, Sherri A. McFarland

Research output: Contribution to journalArticlepeer-review

19 Scopus citations


In an earlier study of π-expansive ruthenium complexes for photodynamic and photochemo-therapies, it was shown that a pair of structural isomers differing only in the connection point of a naphthalene residue exhibited vastly different biological activity. These isomers are further explored in this paper through the activity of their functionalized derivatives. In normoxia, the inactive 2-NIP isomer (5) can be made as photocytotoxic as the active 1-NIP isomer (1) by functionalizing with methyl or methoxy groups, while methoxy variants of the 1-NIP isomer became inactive. In all cases, the singlet oxygen sensitization quantum yield was below 1%. Hypoxic photocytotoxicity was attenuated, with only three of the series showing any activity, notwithstanding the photodissociative ligands. The results here are consistent with the earlier findings in that seemingly minor structural modifications on the non-strained ligand can dramatically modulate the normoxic and hypoxic activity of these strained compounds and that these changes appear to exert a greater influence on photocytotoxicity than singlet oxygen sensitization or rates of photosubstitution in cell-free conditions would suggest.

Original languageEnglish
Pages (from-to)73-84
Number of pages12
JournalPhotochemistry and Photobiology
Issue number1
StatePublished - Jan 1 2022

Bibliographical note

Funding Information:
S.A.M. and C.G.C. thank the National Cancer Institute (NCI) of the National Institutes of Health (NIH) (Award R01CA222227) and E.C.G. thanks the National Institute of General Medical Sciences (NIGMS) of the NIH (Award R01GM107586) for support. The content in this review is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. S.A.M. also acknowledges the Canadian Institutes of Health Research (CIHR), the Natural Sciences and Engineering Council of Canada (NSERC), the Canadian Foundation for Innovation (CFI), and the Nova Scotia Research and Innovation Trust (NSRIT) for support. S.A.M. also thanks Dr. Daniel Todd as UNCG’s Triad Mass Spectrometry Facility manager and his assistants Jennifer Simpson and Diane Wallace. We thank Dr. Franklin Moy for his experimental support and instrument maintenance as UNCG’s NMR facility manager.

Publisher Copyright:
© 2021 American Society for Photobiology

ASJC Scopus subject areas

  • Radiation
  • Biochemistry
  • Physical and Theoretical Chemistry


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