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：

---

双[吡咯基Ru(II)]三联体：一类用于金属有机光动力治疗的新型光敏剂


制备了基于双[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中心被各种有机连接体分开，以评估有机发色团对化合物的光谱和体外光动力治疗（PDT）特性的影响。双[吡咯基Ru(II)]三元组在整个可见光区域有强烈吸收，其中几个成员在600-620 nm及更长波长处具有摩尔消光系数(e) ≥10 ⁴ 。磷光量子产率 (F _p ) 通常小于 0.1%，并且在某些情况下无法检测到。单线态氧量子产率 (F _D ) 范围为 5% 至 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，无论使用的光波长如何。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，宽带可见光（28 J cm ^-2 、7.8 mW cm ^-2 ）和 625- nm红光（100 J cm ^-2 、42 mW cm ^-2 ）光。带有芘基连接基的双[吡咯基 Ru(II)] 三联体 ( 5h ) 特别有效，EC ₅₀值为 1 nM，PI >27,000，具有可见光和 625 nm 光（100 J cm）的亚纳摩尔活性^-2 , 28 毫瓦·厘米^-2 )。 先导化合物5h也在使用 HL60 细胞系的肿瘤球体测定中进行了测试，并且在这种更耐受的模型中表现出更大的光细胞毒性（EC ₅₀ = 60 nM 和 PI>1,200，625 nm 光），尽管暗细胞毒性较低。 5小时的体外PDT效应延伸至细菌，其中用可见光获得针对变形链球菌和金黄色葡萄球菌的亚微摩尔EC ₅₀值和PI >300。这种活性在 625 nm 红光下减弱，但 PI 仍接近 50。5h芘基连接体贡献的配体定位³ ππ* 状态可能在其对癌细胞和细菌的光毒性作用中发挥关键作用。