1,10-邻菲啰啉衍生物钌配合物的合成、 表征及与DNA和BSA的相互作用

doi:10.7503/cjcu20180370

高等学校化学学报 ›› 2019, Vol. 40 ›› Issue (1): 30.doi: 10.7503/cjcu20180370

1,10-邻菲啰啉衍生物钌配合物的合成、表征及与DNA和BSA的相互作用

赵雅晨¹, 李季¹, 张培培¹, 刘姝娴¹, 魏代娜¹, 苏志¹, 钱勇¹, 王飞利²(), PeterJohnSadler³, 刘红科¹()

1. 南京师范大学化学与材料科学学院, 南京 210023
2. 西北大学化工学院, 西安 710069
3. Department of Chemistry, University of Warwick, Coventry CV47AL, UK

收稿日期:2018-05-21 出版日期:2019-01-10 发布日期:2018-12-20
作者简介:
联系人简介:刘红科, 男, 博士, 教授, 博士生导师, 主要从事新型芳基钌、锇抗癌配合物合成、抗癌活性及抗癌机理方面的研究. E-mail: liuhongke@njnu.edu.cn;王飞利, 女, 副教授, 主要从事金属配合物的合成、结构与生物活性方面的研究. E-mail:hgwfli@nwu.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)、江苏省自然科学基金(批准号: BE2013716, BK20171472)和江苏省六大人才高峰项目资助.

Synthesis, Characterization and DNA, BSA Interactions of Mononuclear Ruthenium Complexes with Modified 1,10-Phenanthrolines Ligands^†

ZHAO Yachen¹, LI Ji¹, ZHANG Peipei¹, LIU Shuxian¹, WEI Daina¹, SU Zhi¹, QIAN Yong¹, WANG Feili^2,^*(), Peter John Sadler³, LIU Hongke^1,^*()

1. School of Chemistry and Materials Science, Nanjing Normal University, Nanjing 210023, China
2. School of Chemical Engineering, Northwestern University, Xi’an 710068, China;
3. Department of Chemistry, University of Warwick, Coventry CV4 7AL, UK

Received:2018-05-21 Online:2019-01-10 Published:2018-12-20
Contact: WANG Feili,LIU Hongke E-mail:hgwfli@nwu.edu.cn;liuhongke@njnu.edu.cn
Supported by:
† Supported by the Key International(Regional) Joint Research Program of National Natural Science Foundation of China(No. 21420102002), the National Natural Science Foundation of China(Nos. 21601088, 21771109, 21778033), the Natural

摘要/Abstract

摘要：

通过2-(4-吡啶)-咪唑[4,5-f]-1,10-邻菲啰啉(L₁)与[Ru(η⁶-cymene)(μ-Cl)Cl]₂反应合成了3种新型芳基钌配合物, 并利用新配体2-(4-咪唑基苯基)咪唑[4,5-f]-1,10-邻菲啰啉(L₂)与RuCl₃反应合成了配合物4. 利用核磁共振波谱、质谱等对配合物进行了表征. 通过紫外光谱和圆二色谱研究了配合物在缓冲溶液中的稳定性及与CT-DNA的相互作用, 利用荧光光谱研究了配合物与牛血清蛋白的作用, 用乌氏黏度计测试了配合物对DNA黏度的影响, 并通过荧光光谱、凝胶电泳研究了配合物4在不同pH条件下的荧光响应及与pBR322 DNA的作用. 结果表明, 配合物通过嵌入的方式与DNA作用, 并对DNA的二级结构产生影响; 配合物1~4均可与牛血清蛋白的一个位点发生相互作用并使其发生静态荧光猝灭. 配合物4在光照条件下有活性氧生成, 可以使pBR322 DNA断裂并在酸性溶液中荧光增强.

关键词: 芳基钌配合物, 1,10-邻菲啰啉, DNA作用, BSA作用, 光断裂

Abstract:

Three novel arene-ruthenium complexes(1—3) were synthesized from 2-(4-pyridinyl)imidazo[4,5-f]-1,10-phenanthroline(L₁) and [(η⁶-cymene)Ru(μ-Cl)Cl]₂. A polypyridine-ruthenium complex(4) was synthesized from RuCl₃ and 2-(4-(1H-imidazol-1-yl)phenyl)-1H-imidazo[4,5-f]-1,10-phenanthroline(L₂). All the complexes were characterized by ¹H NMR, elemental analysis and ESI-MS. UV-Vis, circular dichroism and fluorescence techniques were used to study the interactions between complexes 1—4 and calf thymus DNA(CT-DNA) or BSA, respectively. Viscosity measurements were carried out to clarify further the interaction mode of complexes 1—4 with DNA. In addition, the interactions of complex 4 with pBR322 DNA were studied by gel electrophoresis, and the pH-related fluorescence spectra of complex 4 were recorded in various pH solutions. The results show that these complexes could interact with DNA via intercalation and disturbing the secondary structure of DNA. The static quenching for complexes 1—4 were observed when these complexes were titrated with BSA protein. Only one binding site was observed between these complexes and BSA and the binding constants were calculated. Under the UV light(365 nm), complex 4 could generate ¹O₂ and cleave pBR322-DNA efficiently and its fluorescencewere enhanced more than 56% when the solution pH was changed from 11.37 to 1.74.

Key words: Ruthenium-arene complex, ,10-Phenanthroline, Interaction with DNA, Interaction with BSA, Photocleavage

中图分类号:

O614

TrendMD:

赵雅晨, 李季, 张培培, 刘姝娴, 魏代娜, 苏志, 钱勇, 王飞利, PeterJohnSadler, 刘红科. 1,10-邻菲啰啉衍生物钌配合物的合成、表征及与DNA和BSA的相互作用. 高等学校化学学报, 2019, 40(1): 30.

ZHAO Yachen,LI Ji,ZHANG Peipei,LIU Shuxian,WEI Daina,SU Zhi,QIAN Yong,WANG Feili,Peter John Sadler,LIU Hongke. Synthesis, Characterization and DNA, BSA Interactions of Mononuclear Ruthenium Complexes with Modified 1,10-Phenanthrolines Ligands^†. Chem. J. Chinese Universities, 2019, 40(1): 30.

图/表 11

Scheme 1 Synthesis of complexes 1—4

Fig.1 UV spectra of complexes 1(A), 2(B), 3(C) and 4(D) in DMSO/PBS[Complex]=50 μmol/L; DMSO/PBS volume ratio is 5:95; pH≈7.4.

Fig.2 UV-Vis absorption spectra of complexes 1(A), 2(B), 3(C) and 4(D)in the absence and in the presence of increasing concentration of CT-DNAThe arrows show the changes upon increasing amounts of CT-DNA; [Complex]=50 μmol/L, [DNA]=0—36 μmol/L.

Fig.3 CD spectra of CT-DNA in the absence and in the presence of complex 1(A), 2(B), 3(C) or 4(D)(A), (B), (C) [DNA]=100 μmol/L, [Complex]=0—70 μmol/L; (D) [DNA]=200 μmol/L, [Complex]=0—40 μmol/L.

Fig.4 Effect of the addition of increasing amounts of ethidium bromide(EB) or complexes 1—4 on the relative viscosity of CT-DNA(100 μmol/L) in PBS(pH=7.4) at 25 ℃

Fig.5 Agarose gel electrophoresis assay to investigate the DNA cleavage induced by complex 4Lanes 1: DNA alone; lanes 2—7: DNA + complex 4(with light); lane 8: DNA+complex 4(without light, [complex 4]=10 μmol/L). The DNA concentration is 10 μmol/L. The concentrations of complex 4 from lane 2 to lane 7 are 0.5, 1, 2.5, 5, 7.5, 10 μmol/L, respectively.

Fig.6 Fluorescence spectra of BSA with different concentrations of complexes 1—4The arrows show the changes upon increasing amounts of complex. (A—D) [BSA]=3 μmol/L, [complex]=0—20 mmol/L.

Table 1 KSV data, binding constant, and binding site of complexes 1—4 with BSA

System	K_SV/(L·mol^-1)	K_q/(L·mol^-1·s^-1)	K/(L·mol^-1)	n
1-BSA	5.04×10⁴	5.04×10¹²	5.06×10⁵	1.17
2-BSA	3.34×10⁴	3.34×10¹²	3.90×10⁵	1.22
3-BSA	3.85×10⁴	3.85×10¹²	3.02×10⁴	0.99
4-BSA	2.72×10⁵	2.72×10¹³	6.61×10⁶	1.32

Fig.7 Fluorescence spectra of complex 4 with different pH values [Complex 4]=10 μmol/L.

Fig.8 Fluorescence spectra of complex 4 with different pH values[Complex 4]=10 μmol/L.

Fig.9 Changes of DCF fluorescence intensity in complex 4-treated MCF-7 cell

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1,10-邻菲啰啉衍生物钌配合物的合成、表征及与DNA和BSA的相互作用

Synthesis, Characterization and DNA, BSA Interactions of Mononuclear Ruthenium Complexes with Modified 1,10-Phenanthrolines Ligands^†

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1,10-邻菲啰啉衍生物钌配合物的合成、 表征及与DNA和BSA的相互作用

Synthesis, Characterization and DNA, BSA Interactions of Mononuclear Ruthenium Complexes with Modified 1,10-Phenanthrolines Ligands†

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1,10-邻菲啰啉衍生物钌配合物的合成、表征及与DNA和BSA的相互作用

Synthesis, Characterization and DNA, BSA Interactions of Mononuclear Ruthenium Complexes with Modified 1,10-Phenanthrolines Ligands^†