title: Modifying charge and hydrophilicity of simple Ru(II) polypyridyl complexes radically alters biological activities: old complexes, surprising new tricks.
abstract: 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.
authors.affiliation: Department of Chemistry, University of Kentucky , Lexington, Kentucky 40506, United States.
authors.forename: Matthew
authors.initials: M
authors.lastname: Dickerson
authors.forename: Yang
authors.initials: Y
authors.lastname: Sun
authors.forename: Brock
authors.initials: B
authors.lastname: Howerton
authors.forename: Edith C
authors.initials: EC
authors.lastname: Glazer
mesh_terms: D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000187:drug effects*; D004249:DNA Damage; D004305:Dose-Response Relationship, Drug; D018922:HL-60 Cells; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D019169:Jurkat Cells; D008024:Ligands; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D010957:Plasmids; D011108:Polymers / Q000737:chemistry*; D011725:Pyridines / Q000737:chemistry*; D012428:Ruthenium / Q000737:chemistry*; D013329:Structure-Activity Relationship; D013451:Sulfonic Acids / Q000737:chemistry
chemical_list: D008024:Ligands; D009942:Organometallic Compounds; D011108:Polymers; D011725:Pyridines; D013451:Sulfonic Acids; D012428:Ruthenium; D004247:DNA