Smithen Deborah A, Yin Huimin, Beh Michael H R, Hetu Marc, Cameron T Stanley, McFarland Sherri A, Thompson Alison
Department of Chemistry, Dalhousie University , P.O. Box 15000, Halifax, Nova Scotia B3H 4R2, Canada.
Department of Chemistry, Acadia University , 6 University Avenue, Wolfville, Nova Scotia B4P 2R6, Canada.
Inorg Chem. 2017 Apr 3;56(7):4121-4132. doi: 10.1021/acs.inorgchem.7b00072. Epub 2017 Mar 16.
The synthesis and characterization of a series of heteroleptic ruthenium(II) dyads derived from pyrrole-2-carboxylate thionoesters are reported. Ligands bearing a conjugated thiocarbonyl group were found to be more reactive toward Ru(II) complexation compared to analogous all-oxygen pyrrole-2-carboxylate esters, and salient features of the resulting complexes were determined using X-ray crystallography, electronic absorption, and NMR spectroscopy. Selected complexes were evaluated for their potential in photobiological applications, whereupon all compounds demonstrated in vitro photodynamic therapy effects in HL-60 and SK-MEL-28 cells, with low nanomolar activities observed, and exhibited some of the largest photocytotoxicity indices to date (>2000). Importantly, the Ru(II) dyads could be activated by relatively soft doses of visible (100 J cm, 29 mW cm) or red light (100 J cm, 34 mW cm), which is compatible with therapeutic applications. Some compounds even demonstrated up to five-fold selectivity for malignant cells over noncancerous cells. These complexes were also shown to photocleave, and in some cases unwind, DNA in cell-free experiments. Thus, this new class of Ru(II) dyads has the capacity to interact with and damage biological macromolecules in the cell, making them attractive agents for photodynamic therapy.
报道了一系列由吡咯 - 2 - 羧酸硫酯衍生的杂配钌（II）二元化合物的合成与表征。与类似的全氧吡咯 - 2 - 羧酸酯相比，带有共轭硫羰基的配体对Ru（II）络合更具反应性，并使用X射线晶体学、电子吸收光谱和核磁共振光谱确定了所得配合物的显著特征。对选定的配合物进行了光生物学应用潜力评估，结果所有化合物在HL - 60和SK - MEL - 28细胞中均表现出体外光动力治疗效果，观察到低纳摩尔活性，并且展现出一些迄今为止最大的光细胞毒性指数（>2000）。重要的是，Ru（II）二元化合物可以被相对低剂量的可见光（100 J/cm²，29 mW/cm²）或红光（100 J/cm²，34 mW/cm²）激活，这与治疗应用相兼容。一些化合物甚至对恶性细胞与非癌细胞表现出高达五倍的选择性。在无细胞实验中，这些配合物还显示出可光裂解DNA，在某些情况下可使DNA解旋。因此，这类新型Ru（II）二元化合物有能力与细胞中的生物大分子相互作用并对其造成损伤，使其成为光动力治疗的有吸引力的药物。
