Poulsen Bjørn C, Estalayo-Adrián Sandra, Blasco Salvador, Bright Sandra A, Kelly John M, Williams D Clive, Gunnlaugsson Thorfinnur
School of Chemistry and Trinity Biomedical Sciences Institute (TBSI), Trinity College Dublin, The University of Dublin, Dublin 2, Ireland.
School of Biochemistry and Immunology and Trinity Biomedical Sciences Institute (TBSI), Trinity College Dublin, The University of Dublin, Dublin 2, Ireland.
Dalton Trans. 2016 Nov 15;45(45):18208-18220. doi: 10.1039/c6dt03792e.
Four new Ru(ii) polypyridyl complexes that contain an extended aromatic moiety derived from pyrazino[2,3-h]dipyrido[3,2-a:2',3'-c]phenazine and either 1,10-phenanthroline (phen) or 1,4,5,8-tetraazaphenanthrene (TAP) have been synthesized, their solid state X-ray crystal structure determined and their photophysical and biological properties evaluated. Their interactions with DNA have been studied, and they have been tested for their potential as photodynamic therapeutic (PDT) agents in the treatment of cancer. A practical modification of a method by Carter, Rodriguez and Bard has been introduced and used to calculate binding parameters for the complexes which show a strong affinity for DNA with binding constants in the order of 10 M (in 10 mM phosphate buffer). The complexes containing phen as an ancillary ligand become emissive upon binding to DNA ("light switch effect"), but do not show selective cytotoxicity upon light irradiation. On the other hand, the TAP complexes, which show an inverse "light switch effect" (emission quenched upon binding to DNA), are strongly photo-toxic suggesting their use in Photodynamic Therapy (PDT). In HeLa cells the best PDT agent shows an IC value (light) = 4 μM vs. IC value (dark) = 62 μM.
合成了四种新型的钌（II）多吡啶配合物，它们含有衍生自吡嗪并[2,3-h]二吡啶并[3,2-a:2',3'-c]菲嗪的扩展芳香部分，以及1,10-菲咯啉（phen）或1,4,5,8-四氮杂菲咯啉（TAP），测定了它们的固态X射线晶体结构，并评估了它们的光物理和生物学性质。研究了它们与DNA的相互作用，并测试了它们作为光动力治疗（PDT）剂治疗癌症的潜力。引入并使用了Carter、Rodriguez和Bard方法的一种实用改进方法来计算配合物的结合参数，这些配合物对DNA具有很强的亲和力，结合常数约为10 M（在10 mM磷酸盐缓冲液中）。含有phen作为辅助配体的配合物在与DNA结合时会发光（“光开关效应”），但在光照下不显示选择性细胞毒性。另一方面，表现出相反“光开关效应”（与DNA结合时发射淬灭）的TAP配合物具有很强的光毒性，表明它们可用于光动力治疗（PDT）。在HeLa细胞中，最佳的PDT剂显示IC值（光照）= 4 μM，而IC值（黑暗）= 62 μM。
