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

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.

SUBMITTER: Roque J

PROVIDER: S-EPMC7138741 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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

Roque John J Havrylyuk Dmytro D Barrett Patrick C PC Sainuddin Tariq T McCain Julia J Colón Katsuya K Sparks William T WT Bradner Evan E Monro Susan S Heidary David D Cameron Colin G CG Glazer Edith C EC McFarland Sherri A SA

Photochemistry and photobiology 20191206 2

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 pho ...[more]

PMID: 31691282

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

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

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