Department of Inorganic Chemistry, Faculty of Chemistry, Jagiellonian University, Ingardena 3, 30-060 Krakow, Poland.
Department of Inorganic Chemistry, Faculty of Chemistry, Jagiellonian University, Ingardena 3, 30-060 Krakow, Poland; Institut of Organic and Analytical Chemistry, University of Orléans, UMR-CNRS 7311, rue de Chartres, BP 6759, 45067 Orléans Cedex 2, France.
J Inorg Biochem. 2014 May;134:83-91. doi: 10.1016/j.jinorgbio.2014.02.001. Epub 2014 Feb 14.
A novel long-lifetime highly luminescent ruthenium polypyridyl complex containing 2-nitroimidazole moiety [Ru(dip)2(bpy-2-nitroIm)]Cl2 (dip=4,7-diphenyl-1,10-phenanthroline, bpy-2-nitroIm=4-[3-(2-nitro-1H-imidazol-1-yl)propyl]-2,2'-bipyridine) has been designed cancer treatment and imaging. The luminescence properties of the synthesized compound strongly depend on the oxygen concentration. Under oxygen-free conditions quantum yield of luminescence and the average lifetime of emission were found to be 0.034 and 1.9 μs, respectively, which is ca. three times higher in comparison to values obtained in air-equilibrated solution. The binding properties of the investigated ruthenium complex to human serum albumin have been studied and the apparent binding constant for the formation of the protein-ruthenium adduct was determined to be 1.1×10(5)M(-1). The quantum yield and the average lifetime of emission are greatly enhanced upon binding of ruthenium compound to the protein. The DNA binding studies revealed two distinguished binding modes which lead to a decrease in luminescence intensity of ruthenium complex up to 60% for [DNA]/[Ru]<2, and enhancement of emission for [DNA]/[Ru]>80. Preliminary biological studies confirmed fast and efficient accumulation of the ruthenium complex inside cells. Furthermore, the ruthenium complex was found to be relatively cytotoxic with LD50 of 12 and 13 μM for A549 and CT26 cell lines, respectively, under normoxic conditions. The retention and cellular uptake of ruthenium complex is enhanced under hypoxic conditions and its LD50 decreases to 8 μM for A549 cell line.
一种新型长寿命高发光钌多吡啶配合物，含有 2-硝基咪唑部分[Ru(dip)2(bpy-2-nitroIm)]Cl2（dip=4,7-二苯基-1,10-菲咯啉，bpy-2-nitroIm=4-[3-(2-硝基-1H-咪唑-1-基)丙基]-2,2'-联吡啶），已被设计用于癌症治疗和成像。合成化合物的发光性质强烈依赖于氧浓度。在无氧条件下，发光量子产率和发射平均寿命分别为 0.034 和 1.9μs，分别比在空气平衡溶液中获得的值高约 3 倍。研究了所合成的钌配合物与人血清白蛋白的结合特性，并确定了形成蛋白质-钌加合物的表观结合常数为 1.1×10(5)M(-1)。当钌化合物与蛋白质结合时，量子产率和发射平均寿命大大提高。DNA 结合研究揭示了两种不同的结合模式，导致钌配合物的发光强度降低高达 60%，对于[DNA]/[Ru]<2，以及发射增强对于[DNA]/[Ru]>80。初步生物学研究证实，该钌配合物能够快速有效地在细胞内积累。此外，在常氧条件下，该钌配合物对 A549 和 CT26 细胞系的 LD50 分别为 12 和 13μM，具有相对细胞毒性。在缺氧条件下，钌配合物的保留和细胞摄取增强，其 LD50 降低至 A549 细胞系的 8μM。
