Fakultät für Chemie und Biochemie, Ruhr-Universität-Bochum, Bochum, Germany.
Dalton Trans. 2012 May 14;41(18):5587-98. doi: 10.1039/c2dt00011c. Epub 2012 Mar 14.
The DNA binding modes and cleavage properties of novel dinuclear Ir(III) polypyridyl (pp) complexes {(η(5)-C(5)Me(5))Ir(pp)}(2)(μ-B)(4) depend on the lengths of their rigid bridging dipyridinyl ligands B. Mono-intercalation and strong DNA cleavage properties were observed for the dipyrido[2,3-a:2',3'-c]phenazine (dppz) complexes 1 (B = 4-[(E)-2-(4-pyridinyl)ethenyl]pyridine) and 3 (B = 4-(2-pyridin-4-ylethynyl)pyridine), whose intracationic Ir···Ir' distances are about 13.1 and 13.3 Å, respectively. In contrast, UV/Vis and CD spectra were in accordance with a stable intertwined bis-intercalation mode for pairs of cations of 5 (B = 1,4-di(2-pyridin-4-ylethynyl)benzene), whose much longer Ir···Ir' distance of 20.6 Å allows a stack of five aromatic chromophores to be sandwiched between its effectively parallel dppz ligands. Whereas both 1 and 3 cleaved DNA in the dark, complex 5 exhibited only photoinduced nuclease activity. A significantly higher antiproliferative activity towards MCF-7 breast carcinoma cells was observed for the nucleases 1 and 3, whose IC(50) values of 0.61 and 0.49 were much lower than that of 2.2 μM for bis-intercalator 5. Values of 3.8 μM, only slightly higher than that of 5, were recorded for the 5,6-dimethylphenanthroline complexes 4 and 6, whose bridging ligands are identical to those of 3 and 5, respectively. Marked antileukemic activity (IC(50) = 6-7 μM) associated with increased levels of reactive oxygen species and apoptosis induction was recorded for both 3 and 5 towards Jurkat cells at concentrations of 5 μM and above. Online studies with a sensor chip system indicated that 5 μM solutions of these complexes invoke a rapid and massive reduction in MCF-7 cell respiration.
新型双核 Ir(III) 多吡啶（pp）配合物{(η(5)-C(5)Me(5))Ir(pp)}(2)(μ-B)(4)的 DNA 结合模式和切割性质取决于其刚性桥联二吡啶配体 B 的长度。二吡啶并[2,3-a:2',3'-c]吩嗪（dppz）配合物 1（B = 4-[(E)-2-(4-吡啶基)乙烯基]吡啶）和 3（B = 4-(2-吡啶-4-基乙炔基)吡啶）观察到单核插入和强 DNA 切割性质，其腔内 Ir···Ir'距离分别约为 13.1 和 13.3 Å。相比之下，紫外/可见和 CD 光谱与阳离子对 5（B = 1,4-二(2-吡啶-4-基乙炔基)苯）的稳定交织双插入模式一致，其 Ir···Ir'距离长 20.6 Å，可在其有效平行 dppz 配体之间夹入五个芳香发色团。虽然 1 和 3 在黑暗中均可切割 DNA，但配合物 5 仅表现出光诱导核酸酶活性。对 MCF-7 乳腺癌细胞的增殖活性具有显著抑制作用，1 和 3 的 IC(50)值分别为 0.61 和 0.49，远低于双插入剂 5 的 2.2 μM。对于桥联配体与 3 和 5 相同的 5,6-二甲基菲咯啉配合物 4 和 6，记录到稍高的 3.8 μM 的 IC(50)值，仅略高于 5。在 5 μM 及以上浓度下，Jurkat 细胞对 3 和 5 均表现出明显的抗白血病活性（IC(50) = 6-7 μM），并伴随着活性氧物种和细胞凋亡诱导水平的增加。在线传感器芯片系统研究表明，这些配合物的 5 μM 溶液可迅速大量降低 MCF-7 细胞的呼吸作用。
