高等学校化学学报 ›› 2018, Vol. 39 ›› Issue (4): 614-622.doi: 10.7503/cjcu20170634

• 研究论文: 无机化学 • 上一篇    下一篇

芳基锇联吡啶配合物的合成、 结构、 细胞毒性及与DNA/BSA的相互作用

郝元元, 吴琪, 李季, 葛超, 马超盈, 钱勇, 苏志(), 刘红科()   

  1. 南京师范大学化学与材料科学学院, 南京 210023
  • 收稿日期:2017-09-21 出版日期:2018-04-10 发布日期:2018-03-22
  • 作者简介:联系人简介: 苏 志, 男, 博士, 教授, 主要从事功能配合物的设计、 合成和应用研究. E-mail:zhisu@njnu.edu.cn; 刘红科, 男, 博士, 教授, 博士生导师, 主要从事新型芳基金属抗癌配合物合成、 抗癌活性及抗癌机理研究. E-mail:liuhongke@njnu.edu.cn
  • 基金资助:
    国家自然科学基金重点国际合作项目(批准号: 21420102002)、 国家自然科学基金(批准号: 21601088, 21771109, 21778033)、 江苏省333工程人才专项基金、 江苏省六大人才高峰和江苏省自然科学资金(批准号: BE2013716, BK20171472)资助

Novel Os-arene Complexes Based on Bipyridyl Derivative Ligands: Synthesis, Crystal Structure, Anticancer Activity and Interaction with DNA/BSA

HAO Yuanyuan, WU Qi, LI Ji, GE Chao, MA Chaoying, QIAN Yong, SU Zhi*(), LIU Hongke*()   

  1. School of Chemistry and Materials Science, Nanjing Normal University, Nanjing 210023, China
  • Received:2017-09-21 Online:2018-04-10 Published:2018-03-22
  • Contact: SU Zhi,LIU Hongke E-mail:zhisu@njnu.edu.cn;liuhongke@njnu.edu.cn
  • Supported by:
    † Supported by the Key International(Regional) Joint Research Program of the National Natural Science Foundation of China(No.21420102002), the National Natural Science Foundation of China(Nos.21601088, 21771109, 21778033), the “333 Talent Project” of Jiangsu Province, China, the “Summit of the Six Top Talents” Program of Jiangsu Province, China and the Natural Science Foundation of Jiangsu Province, China(Nos.BE2013716, BK20171472)

摘要:

使用N,N'螯合配体与对甲基异丙基锇或联苯锇反应, 合成了5个新型的单核联吡啶类芳基锇配合物[(η6-arene)Os(N,N')Cl][Y]. 通过X射线单晶衍射分析确定了配合物1和5的结构, 其均具有“琴凳型”构型. 利用核磁共振氢谱、 质谱和元素分析等方法, 确认了配合物1~5同构. 利用紫外光谱、 荧光光谱、 圆二色谱和琼脂糖凝胶电泳等方法研究了配合物与小牛胸腺DNA、 质粒DNA(pBR322)和牛血清白蛋白(BSA)的相互作用, 并利用噻唑蓝(MTT)比色法测定了配合物对体外肿瘤细胞生长的抑制能力. 结果表明, 配合物能与DNA及BSA发生一定程度的键合作用, 配合物1和3表现出对A549肿瘤细胞一定程度的抑制能力. 通过改变联吡啶配体上的取代基, 可以在一定程度上调控配合物的抗癌活性.

关键词: 芳基锇, 单核配合物, DNA, 牛血清白蛋白(BSA), 细胞毒活性

Abstract:

Five Os-arene complexes(1-5) with bipyridyl derivative ligands were synthesized, where complexes 1-4 were obtained directly from the corresponding precursors, complex 5, however, was received through the anion-exchange experiment from complex 3, with Cl- being replaced by P$F^{-}_{6}$. Single crystal structure analyses of complexes 1 and 5 revealed that both complexes adopted typical “piano-stool” conformations, where the “piano stool” consisted of the π-bond to the arene group, the Os-Cl and two Os-N bonds. The anticancer activities of the complexes towards variable cancer cells were determined by MTT assay. Complexes 1 and 3 exhibited moderate cytotoxicity towards human lung cancer cells(A549) than complexes 2 and 4. The interactions between the complexes with DNA/BSA were studied by utilization of UV-Vis, fluorescence and CD spectroscopy, and agarose gel electrophoresis. The results indicated that the synthesized complexes except complex 2 could effectively bind to DNA via intercalation. The fluorescence quenching was observed as complexes 1-4 were added into the BSA solution. The quenching constants(KSV) of complexes 1-4 were larger than 104 L/mol, suggesting that the quenching mechanism was static quenching. CD spectra illuminated that the complexes could induce intrinsic conformational changes in DNA. The mobility changes of the formⅠband were clearly observed in the presence of complexes 1 and 3 by gel electrophoresis assays.

Key words: Osmium-arene, Mononuclear complex, DNA, Bovine serum albumin(BSA), Cytotoxic activity

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