A new family of ten dinuclear Ru(II) complexes based on the bis[pyrrolyl Ru(II)] triad scaffold, where two Ru(bpy)₂centers are separated by a variety of organic linkers, was prepared to evaluate the influence of the organic chromophore on the spectroscopic and in vitro photodynamic therapy (PDT) properties of the compounds. The bis[pyrrolyl Ru(II)] triads absorbed strongly throughout the visible region, with several members having molar extinction coefficients (e) ≥10⁴ at 600–620 nm and longer. Phosphorescence quantum yields (F_p) were generally less than 0.1% and in some cases undetectable. The singlet oxygen quantum yields (F_D) ranged from 5% to 77% and generally correlated with their photocytotoxicities toward human leukemia (HL-60) cells regardless of the wavelength of light used. Dark cytotoxicities varied ten-fold, with EC₅₀ values in the range of 10–100 µM and phototherapeutic indices (PIs) as large as 5,400 and 260 with broadband visible (28 J cm^-2, 7.8 mW cm^-2) and 625-nm red (100 J cm^-2, 42 mW cm^-2) light, respectively. The bis[pyrrolyl Ru(II)] triad with a pyrenyl linker (5h) was especially potent, with an EC₅₀ value of 1 nM and PI >27,000 with visible light and subnanomolar activity with 625-nm light (100 J cm^-2, 28 mW cm^-2). The lead compound 5h was also tested in a tumor spheroid assay using the HL60 cell line and exhibited greater photocytotoxcicity in this more resistant model (EC₅₀=60 nM and PI>1,200 with 625-nm light) despite a lower dark cytotoxicity. The in vitro PDT effects of 5h extended to bacteria, where submicromolar EC₅₀ values and PIs >300 against S. mutans and S. aureus were obtained with visible light. This activity was attenuated with 625-nm red light, but PIs were still near 50. The ligand-localized ³ππ* state contributed by the pyrenyl linker of 5h likely plays a key role in its phototoxic effects toward cancer cells and bacteria.

中文翻译：

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Bis[Pyrrolyl Ru(II)] Triads：一类用于金属有机光动力疗法的新型光敏剂

制备了一个基于双[吡咯基 Ru(II)] 三联体支架的十个双核 Ru(II) 配合物的新家族，其中两个 Ru(bpy) ₂中心被各种有机接头隔开，以评估有机发色团对化合物的光谱和体外光动力疗法 (PDT) 特性的影响。双[吡咯基钌(II)]三元组在整个可见光区域强烈吸收，有几个成员 在 600-620 nm 和更长时具有摩尔消光系数 (e) ≥10 ^{4 。}磷光量子产率 (F _p ) 通常低于 0.1%，在某些情况下无法检测到。单线态氧量子产率 (F _D) 范围从 5% 到 77%，并且通常与它们对人类白血病 (HL-60) 细胞的光细胞毒性相关，而不管使用的光波长如何。暗细胞毒性变化十倍，EC ₅₀ 值在 10–100 µM 范围内，光疗指数 (PI) 高达 5,400 和 260，宽带可见（28 J cm ^-2、7.8 mW cm ^-2）和 625- nm 红色 (100 J cm ^-2 , 42 mW cm ^-2 ) 光，分别。具有芘基接头 ( 5h ) 的双[吡咯基 Ru(II)] 三元组特别有效，EC ₅₀ 值为 1 nM，PI >27,000，可见光和亚纳摩尔活性，在 625-nm 光 (100 J cm ^-2 , 28 毫瓦厘米^-2）。 还使用 HL60 细胞系在肿瘤球体测定中测试了先导化合物 5h ，尽管暗细胞毒性较低，但在这种更具抗性的模型（EC ₅₀ =60 nM 和 PI>1,200，625 nm 光）中表现出更大的光细胞毒性。5h的体外 PDT 效应  扩展到细菌，其中亚微摩尔 EC ₅₀值和对S. mutans 和 S. aureus的 PI > 300 在  可见光下获得。这种活性在 625 nm 红光下减弱，但 PI 仍接近 50。 由5h的芘基接头贡献的配体定位的³ ππ* 状态  可能在其对癌细胞和细菌的光毒性作用中起关键作用。