title: Organometallic Ru(II) Photosensitizers Derived from π-Expansive Cyclometalating Ligands: Surprising Theranostic PDT Effects.
abstract: The purpose of the present study was to investigate the influence of π-expansive cyclometalating ligands on the photophysical and photobiological properties of organometallic Ru(II) compounds. Four compounds with increasing π conjugation on the cyclometalating ligand were prepared, and their structures were confirmed by HPLC, 1D and 2D (1)H NMR, and mass spectrometry. The properties of these compounds differed substantially from their Ru(II) polypyridyl counterparts. Namely, they were characterized by red-shifted absorption, very weak to no room temperature phosphorescence, extremely short phosphorescence state lifetimes (<10 ns), low singlet oxygen quantum yields (0.5-8%), and efficient ligand-centered fluorescence. Three of the metal complexes were very cytotoxic to cancer cells in the dark (EC50 values = 1-2 μM), in agreement with what has traditionally been observed for Ru(II) compounds derived from small C^N ligands. Surprisingly, the complex derived from the most π-expansive cyclometalating ligand exhibited no cytotoxicity in the dark (EC50 > 300 μM) but was phototoxic to cells in the nanomolar regime. Exceptionally large phototherapeutic margins, exceeding 3 orders of magnitude in some cases, were accompanied by bright ligand-centered intracellular fluorescence in cancer cells. Thus, Ru(II) organometallic systems derived from π-expansive cyclometalating ligands, such 4,9,16-triazadibenzo[a,c]napthacene (pbpn), represent the first class of potent light-responsive Ru(II) cyclometalating agents with theranostic potential.
authors.affiliation: Department of Chemistry, Acadia University , Wolfville, Nova Scotia B4P 2R6, Canada.
authors.forename: Tariq
authors.initials: T
authors.lastname: Sainuddin
authors.affiliation: Department of Chemistry, Acadia University , Wolfville, Nova Scotia B4P 2R6, Canada.
authors.forename: Julia
authors.initials: J
authors.lastname: McCain
authors.affiliation: Department of Chemistry, Acadia University , Wolfville, Nova Scotia B4P 2R6, Canada.
authors.forename: Mitch
authors.initials: M
authors.lastname: Pinto
authors.affiliation: Department of Chemistry, Acadia University , Wolfville, Nova Scotia B4P 2R6, Canada.
authors.forename: Huimin
authors.initials: H
authors.lastname: Yin
authors.affiliation: Department of Chemistry, Acadia University , Wolfville, Nova Scotia B4P 2R6, Canada.
authors.forename: Jordan
authors.initials: J
authors.lastname: Gibson
authors.affiliation: Department of Chemistry, Acadia University , Wolfville, Nova Scotia B4P 2R6, Canada.
authors.forename: Marc
authors.initials: M
authors.lastname: Hetu
authors.affiliation: Department of Chemistry, Acadia University , Wolfville, Nova Scotia B4P 2R6, Canada.
authors.forename: Sherri A
authors.initials: SA
authors.lastname: McFarland
mesh_terms: D008024:Ligands; D009942:Organometallic Compounds / Q000737:chemistry* / Q000494:pharmacology; D017319:Photosensitizing Agents / Q000737:chemistry* / Q000494:pharmacology; D066244:Proton Magnetic Resonance Spectroscopy; D017975:Ruthenium Compounds / Q000737:chemistry* / Q000494:pharmacology; D021241:Spectrometry, Mass, Electrospray Ionization; D000068936:Theranostic Nanomedicine
chemical_list: D008024:Ligands; D009942:Organometallic Compounds; D017319:Photosensitizing Agents; D017975:Ruthenium Compounds