Strained, Photoejecting Ru(II) Complexes that are Cytotoxic Under Hypoxic Conditions
| Autor: | Julia McCain, William T. Sparks, Dmytro Havrylyuk, Colin G. Cameron, John Roque, Susan Monro, Sherri A. McFarland, Katsuya L. Colón, Tariq Sainuddin, Edith C. Glazer, Patrick C. Barrett, Evan Bradner, David K. Heidary |
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| Rok vydání: | 2020 |
| Předmět: |
010405 organic chemistry
Ligand Stereochemistry Spectrum Analysis Phenanthroline Antineoplastic Agents General Medicine 010402 general chemistry 01 natural sciences Biochemistry Cell Hypoxia Article 0104 chemical sciences Oxygen chemistry.chemical_compound chemistry Photobiology Coordination Complexes Excited state Pi Ruthenium Compounds Cytotoxic T cell Physical and Theoretical Chemistry Cell-mediated cytotoxicity Cytotoxicity |
| Zdroj: | Photochem Photobiol |
| ISSN: | 1751-1097 0031-8655 |
| Popis: | 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 behavior 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% O(2), 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 O(2)-independent mechanisms of action. |
| Databáze: | OpenAIRE |
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