物理化学学报 >> 2013, Vol. 29 >> Issue (10): 2162-2172.doi: 10.3866/PKU.WHXB201308152

热力学,动力学和结构化学 上一篇    下一篇

联吡啶[3,2-a:2’,3-c]-7-氮杂-吩嗪铜(I)配合物的合成、表征及其与DNA的相互作用

高云燕1, 曹璐1, 欧植泽1, 陈晨1, 李嫕2, 王雪松2   

  1. 1 西北工业大学理学院, 空间应用物理与化学教育部重点实验室, 西安 710072;
    2 中国科学院理化技术研究所, 光化学转换与功能材料重点实验室, 北京 100190
  • 收稿日期:2013-06-20 修回日期:2013-08-15 发布日期:2013-09-26
  • 通讯作者: 欧植泽, 高云燕 E-mail:ouzhize@nwpu.edu.cn;gaoyunyan@nwpu.edu.cn
  • 基金资助:

    国家自然科学基金(21073143);教育部“春晖计划”基金(Z2009-1-71002, Z2009-1-71006);西北工业大学基础研究基金(JC200822, JC20100239)及西北工业大学研究生创新基金资助项目

Synthesis and Characterization of a Cu(I) Complex of Dipyrido[3,2-a:2’,3’-c]-7-aza-phenazine and Its Interaction with DNA

GAO Yun-Yan1, CAO Lu1, OU Zhi-Ze1, CHEN Chen1, LI Yi2, WANG Xue-Song2   

  1. 1 Key Laboratory of Space Applied Physics and Chemistry of the Ministry of Education, School of Science, Northwestern Polytechnical University, Xi'an 710072, P. R. China;
    2 Key Laboratory of Photochemical Conversion and Optoelectronic Materials, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing 100190, P. R. China
  • Received:2013-06-20 Revised:2013-08-15 Published:2013-09-26
  • Contact: OU Zhi-Ze, GAO Yun-Yan E-mail:ouzhize@nwpu.edu.cn;gaoyunyan@nwpu.edu.cn
  • Supported by:

    The project was supported by the National Natural Science Foundation of China (21073143),"Chunhui Project" fromthe Ministry of Education of China (Z2009-1-71002, Z2009-1-71006), NPU Foundation for Fundamental Research, China (JC200822, JC20100239), and NPU Foundation for Graduate Innovation, China.

摘要:

合成了邻菲罗啉衍生物联吡啶[3,2-a:2',3'-c]-7-氮杂-吩嗪(dpapz)及其铜(I)配合物[Cu(dpapz)2]PF6, 利用核磁共振氢谱(1H NMR), 傅里叶变换红外(FTIR)光谱, 高分辨质谱(HR ESI-MS)等对合成的化合物进行了表征.采用紫外-可见吸收光谱,荧光光谱, DNA熔解温度实验和循环伏安方法研究了dpapz和[Cu(dpapz)2]PF6与小牛胸腺DNA(CT DNA)的相互作用. 配体dpapz与小牛胸腺DNA(CT DNA)作用时未观察到吸收峰红移并且减色效应较小(<30%), 且DNA熔解温度也上升较小(ΔTm=7.8 ℃), 说明dpapz以沟槽结合的方式与CT DNA相互作用. 而[Cu(dpapz)2]PF6与CT DNA作用时, 可观测到较小的吸收峰红移(2-3 nm)和较大的减色效应(>50%), 同时DNA熔解温度上升较大(ΔTm=11.1 ℃), 表明[Cu(dpapz)2]PF6以静电相互作用和部分扦插的方式与DNA结合. 溴乙锭(EB)荧光竞争实验和循环伏安实验进一步证实了这一结论. 配体dpapz和[Cu(dpapz)2]PF6与DNA的结合常数分别为2.88×105和5.32×105 mol·L-1. 光照条件下, [Cu(dpapz)2]PF6产生单重态氧的能力与dpapz相当, 但产生超氧负离子自由基的能力要弱于dpapz. 活性氧猝灭实验表明, 超氧负离子自由基、单重态氧和羟基自由基均参与了dpapz和[Cu(dpapz)2]PF6对DNA的光损伤作用. [Cu(dpapz)2]PF6对DNA的亲和性要高于对dpapz的, 使得[Cu(dpapz)2]PF6对质粒DNA的光损伤效率明显强于dpapz.

关键词: 邻菲罗啉衍生物, Cu(I)配合物, DNA光损伤, 活性氧, DNA作用模式

Abstract:

A 1,10-phenanthroline dipyrido[3,2-a:2',3'-c]-7-aza-phenazine derivative (dpapz) and its Cu(I) complex [Cu(dpapz)2]PF6 are prepared and characterized by proton nuclear magnetic resonance spectroscopy (1H NMR), Fourier transform infrared spectroscopy (FTIR), and high resolution electrospray ionization mass spectrometry (HR ESI-MS). The interactions of dpapz and [Cu(dpapz)2]PF6 with calf thymus DNA (CT DNA) are studied by ultraviolet-visible spectroscopy (UV-Vis), fluorescence spectroscopy, DNA melting temperature, and cyclic voltammetry. When the ligand dpapz interacts with DNA, there is no red shift of the absorption peak and only a small hypochromic (<30%) effect on the absorption spectra. In addition, the interaction leads to a slight increase in the melting temperature of DNA (ΔTm=7.8 ℃). All the results indicate that groove binding is the primary interaction of dpapz with CT DNA. However, when [Cu(dpapz)2]PF6 interacts with DNA, there is a red shift of the absorption peak (2-3 nm), a large hypochromic effect on the absorption spectrum (>50%), and a significant increase in the melting temperature of DNA (ΔTm=11.1 ℃), indicating that [Cu(dpapz)2]PF6 electrostatically associates with DNA in a partial intercalation manner. The complexes of dpapz and [Cu(dpapz)2]PF6 with DNA are further confirmed by ethidium bromide (EB) fluorescence assays and cyclic voltammetry. The association constants for dpapz and [Cu(dpapz)2]PF6 with CT DNA are 2.88×105 and 5.32×105 mol·L-1, respectively. The yield of singlet oxygen produced by [Cu(dpapz)2]PF6 is similar to that of dpapz, while the yield of superoxide anion radical for [Cu(dpapz)2]PF6 is lower than that of dpapz. Active oxygen quencher experiments indicate that singlet oxygen, superoxide anion radicals, and hydrogen radicals all take part in the photocleavage of DNA by [Cu(dpapz)2]PF6 and dpapz. However, [Cu(dpapz)2]PF6 causes more photodamage of plasmid DNA than does dpapz, most likely because of its higher affinity for DNA.

Key words: Phenanthroline derivative, Cu(I) complex, Photocleavage of DNA, Active oxygen, Mode of DNAinteraction

MSC2000: 

  • O642