TY - JOUR
T1 - Strained, Photoejecting Ru(II) Complexes that are Cytotoxic Under Hypoxic Conditions
AU - Roque, John
AU - Havrylyuk, Dmytro
AU - Barrett, Patrick C.
AU - Sainuddin, Tariq
AU - McCain, Julia
AU - Colón, Katsuya
AU - Sparks, William T.
AU - Bradner, Evan
AU - Monro, Susan
AU - Heidary, David
AU - Cameron, Colin G.
AU - Glazer, Edith C.
AU - McFarland, Sherri A.
N1 - Publisher Copyright:
© 2019 American Society for Photobiology
PY - 2020/3/1
Y1 - 2020/3/1
N2 - 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.
AB - 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.
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U2 - 10.1111/php.13174
DO - 10.1111/php.13174
M3 - Article
C2 - 31691282
AN - SCOPUS:85076379000
SN - 0031-8655
VL - 96
SP - 327
EP - 339
JO - Photochemistry and Photobiology
JF - Photochemistry and Photobiology
IS - 2
ER -