Department of Chemistry, Acadia University, Wolfville, NS B4P 2R6, Canada.
Inorg Chem. 2010 Mar 15;49(6):2889-900. doi: 10.1021/ic902427r.
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 (lambda(irr) > or = 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 microM and 10-20 microM, 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.
几种单核钌（II）二聚体具有 1,10-菲啰啉取代的芘基乙炔配体，它们被合成、表征，并评估其在光生物学应用中的潜力，如光动力疗法（PDT）。这些配合物通过嵌入与 DNA 相互作用，并在亚微米浓度下在可见光（lambda(irr) >或= 400nm）照射下体外光解 DNA。这种性质对 1,10-菲啰啉环上乙炔基芘基取代基的位置非常敏感，在所有条件下，3-取代基显示出最强的结合，并导致最有害的 DNA 损伤。这两个二聚体在缺氧条件下光解 DNA，这种光活性在使用人白血病细胞的细胞毒性和光细胞毒性模型中得到很好的转化，其中 5-和 3-取代的二聚体在 5-10 microM 和 10-20 microM 时分别显示出光细胞毒性，在这些浓度下，暗毒性最小或基本上没有。在观察到显著光活性的浓度下没有暗细胞毒性，这强调了以前认为对于光治疗应用过于毒性的具有强嵌入单元的试剂不应该被排除在正在研究的潜在光化学治疗剂的武器库之外。
