Photobiological Activity of Ru(II) Dyads Based on (Pyren-1-yl)ethynyl Derivatives of 1,10-Phenanthroline

Abstract

Several mononuclear Ru(II) dyads possessing 1,10-phenanthroline-appended pyrenylethynylene ligands were synthesized, characterized, and evaluated for their potential in photobiological applications such as photodynamic therapy (PDT). These complexes interact with DNA via intercalation and photocleave DNA in vitro at submicromolar concentrations when irradiated with visible light (λ irr g 400 nm). Such properties are remarkably sensitive to the position of the ethynylpyrenyl substituent on the 1,10-phenanthroline ring, with 3-substitution showing the strongest binding under all conditions and causing the most deleterious DNA damage. Both dyads photocleave DNA under hypoxic conditions, and this photoactivity translates well to cytotoxicity and photocytotoxicity models using human leukemia cells, where the 5-and 3-substituted dyads show photocytotoxicity at 5-10 μM and 10-20 μM, respectively, with minimal, or essentially no, dark toxicity at these concentrations. This lack of dark cytotoxicity at concentrations where significant photoactivity is observed emphasizes that agents with strong intercalating units, previously thought to be too toxic for phototherapeutic applications, should not be excluded from the arsenal of potential photochemotherapeutic agents under investigation.

The development of anticancer ruthenium(ii) complexes: from single molecule compounds to nanomaterials

“…designed and tested the PDT efficiency of Ru(II) polypyridyl complexes that had the lowest-lying 3 IL-based excited states, with remarkably long lifetimes (from 22 to 270 μs), by linking pyrenylethynylene derivatives ligands, 257–259 which made the complexes hold higher 1 O 2 quantum yields compared to [Ru(bpy) 3 ] 2+ . These complexes interacted with DNA via intercalation and produced photocleavage of DNA in vitro at submicromolar concentrations when irradiated with visible light.…”

Control and utilization of ruthenium and rhodium metal complex excited states for photoactivated cancer therapy

“…The photocytotoxicity of the complexes toward human leukemia cell lines (HL-60) and metastatic melanoma cell line Malme-3M was also investigated as a function of the placement of the pyrenylethynylene substituent on the phen ligand [76,77]. The [Ru(bpy) 2 (3-pyr-phen)] 2+ , [Ru(bpy) 2 (4-pyrphen)] 2+ , and [Ru(bpy) 2 (5-pyr-phen)] 2+ complexes (Fig.…”

Synthesis, Characterization, DNA Binding, and Photocleavage Activity of Oxorhenium (V) Complexes with α‐Diimine and Quinoxaline Ligands

“…It has been demonstrated that inorganic complexes can be used in footprinting studies, as sequence specific DNA binding agents, as diagnostic agents in medicinal applications, and for genomic research. Among different modes of DNA cleavage, oxidative cleavage of DNA upon irradiation with visible light is of main interest due to the potential applications of such compounds in photodynamic therapy of cancer [3, 15] and references therein.…”