Strained,Photoejecting Ru(II) Complexes that are Cytotoxic Under Hypoxic Conditions |
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| Authors: | John Roque III 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 |
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| Institution: | 1. Department of Chemistry and Biochemistry, The University of North Carolina at Greensboro, Greensboro, NC;2. Department of Chemistry, University of Kentucky, Lexington, KY;3. Department of Chemistry, Acadia University, Wolfville, Canada |
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| 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 imidizo4,5-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. |
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