基于聚集诱导发光的金属钌配合物合成及抗癌活性  

Synthesis and anticancer activity of metallic ruthenium complexes based on aggregation induced luminescence

作　　者：苏岩 唐林 苏志 于正洪 SU Yan;TANG Lin;SU Zhi;YU Zhenghong(Department of Rheumatology and Immunology,Jinling Hospital,Affiliated Hospital of Medical School,Nanjing University/General Hospital of Eastern Theater Command,PLA,Nanjing 210002,Jiangsu,China;Department of Rheumatology and Immunology,Nanjing Drum Tower Hospital,The Affiliated Hospital of Nanjing University Medical School,Nanjing 210008,Jiangsu,China;College of Chemistry and Materials Science,Nanjing Normal University,Nanjing 210023,Jiangsu,China)

机构地区：[1]南京大学医学院附属金陵医院(东部战区总医院)风湿免疫科,南京210002 [2]南京大学医学院附属鼓楼医院风湿免疫科,南京210008 [3]南京师范大学化学与材料科学学院,南京210023

出　　处：《医学研究与战创伤救治》2023年第8期796-800,共5页Journal of Medical Research & Combat Trauma Care

基　　金：国家自然科学基金(21977052,22277056)。

摘　　要：目的将具有聚集诱导发光性质的荧光基团偶联到金属前体上得到新的环金属钌配合物,研究该配合物的光谱性质及抗肿瘤活性及作用机制。方法将配体进行化学修饰后,作为配体引入到环金属钌前体中,合成得到目标配合物Ru-A。利用核磁共振氢谱及质谱对其进行了基础表征。通过紫外-可见光谱仪和荧光光谱仪检测配合物的吸收和发射光谱。利用MTT法检测配合物对肿瘤细胞的抗增殖活性。通过流式细胞术探究配合物诱导肿瘤细胞产生活性氧的水平。并在3D细胞球模型上验证了配合物的细胞毒活性。结果核磁共振氢谱及质谱结果表明成功合成了目标配合物Ru-A。光谱结果显示Ru-A在400~500 nm处显示出主要吸收峰,在725 nm处有一个较强的发射峰。与配体相比,配合物Ru-A的细胞毒性明显提高。Ru-A诱导肿瘤细胞产生活性氧,且有效抑制3D细胞球生长,导致细胞死亡。结论具有聚集诱导发光的配体引入后显著提高了环金属钌配合物对肿瘤细胞的毒性,且光物理性质得到较大提升。Objective To study the spectroscopic properties,antitumor activity and mechanism of a novel cyclometalated ruthenium complex by coupling fluorophores with the properties of aggregation-induced luminescence to metal precursors.Methods The ligand was chemically modified and introduced into the cyclometalated ruthenium precursor to synthesize the target complex Ru A.The basic characterization was performed by hydrogen NMR and mass spectrometry.The absorption and emission spectra of the complexes were detected by UV-VIS and fluorescence spectrometers.MTT assay was used to detect the antiproliferative activity of the complex on tumor cells.Flow cytometry was used to investigate the level of reactive oxygen species induced by the complex in tumor cells.The cytotoxic activity of the complex was verified on a 3D cell sphere model.Results The target complex RuA was successfully synthesized by 1H-NMR and ESI-MS.The spectral results show that Ru A has a main absorption peak at 400-500 nm and a strong emission peak at 725 nm.Compared with the ligand,the cytotoxicity of the complex RuA was significantly increased.Ru A induced tumor cells to produce reactive oxygen species,and effectively inhibited the growth of 3D cell spheres,resulting in cell death.Conclusion The introduction of ligands with aggregation-induced luminescence can significantly improve the toxicity and photophysical properties of cyclometalated ruthenium complexes to tumor cells.

关 键 词：钌类配合物 聚集诱导发光 活性氧 抗肿瘤药物 

分 类 号：R961[医药卫生—药理学]