Modifying Charge and Hydrophilicity of Simple Ru(II) Polypyridyl Complexes Radically Alters Biological Activities: Old Complexes, Surprising New Tricks

Compounds capable of light-triggered cytotoxicity are appealing potential therapeutics, because they can provide spatial and temporal control over cell killing to reduce side effects in cancer therapy. Two simple homoleptic Ru­(II) polypyridyl complexes with almost-identical photophysical properties...

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Bibliographic Details
Published in:Inorganic chemistry 2014-10, Vol.53 (19), p.10370-10377
Main Authors: Dickerson, Matthew, Sun, Yang, Howerton, Brock, Glazer, Edith C
Format: Article
Language:English
Subjects:
Cell Death - drug effects
Cell Line, Tumor
Cell Survival - drug effects
DNA - drug effects
DNA Damage
Dose-Response Relationship, Drug
HL-60 Cells
Humans
Hydrophobic and Hydrophilic Interactions
Jurkat Cells
Ligands
Molecular Structure
Organometallic Compounds - chemical synthesis
Organometallic Compounds - chemistry
Organometallic Compounds - pharmacology
Plasmids
Polymers - chemistry
Pyridines - chemistry
Ruthenium - chemistry
Structure-Activity Relationship
Sulfonic Acids - chemistry
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Summary:Compounds capable of light-triggered cytotoxicity are appealing potential therapeutics, because they can provide spatial and temporal control over cell killing to reduce side effects in cancer therapy. Two simple homoleptic Ru­(II) polypyridyl complexes with almost-identical photophysical properties but radically different physiochemical properties were investigated as agents for photodynamic therapy (PDT). The two complexes were identical, except for the incorporation of six sulfonic acids into the ligands of one complex, resulting in a compound carrying an overall −4 charge. The negatively charged compound exhibited significant light-mediated cytotoxicity, and, importantly, the negative charges resulted in radical alterations of the biological activity, compared to the positively charged analogue, including complete abrogation of toxicity in the dark. The charges also altered the subcellular localization properties, mechanism of action, and even the mechanism of cell death. The incorporation of negative charged ligands provides a simple chemical approach to modify the biological properties of light-activated Ru­(II) cytotoxic agents.
ISSN:0020-1669
1520-510X
DOI:10.1021/ic5013796