含苯并咪唑铜、镍的配合物的合成、晶体结构及与ct-DNA相互作用的研究
|
摘要
脱氧核糖核酸(DNA)是生物体内重要的一种大分子，对生命体的遗传和变异有着重要的意义。以小分子与DNA相互作用的研究，不仅能解释药物分子的作用机理，还能为药物分子的设计提供理论指导，是生命科学、生物化学和医药学研究的重要内容。
苯并咪唑是具有π–π共轭的一种杂环化合物，对DNA序列有很高的亲和作用，同时也具有杀菌、抗病毒等生物活性，被广泛应用于医药学、生物化学及分析化学等领域。含苯并咪唑的过渡金属配合物存在于各种重要的生物分子中，都是由组氨酸咪唑氮和金属离子配位形成的，例如脲酶、酪氨酸酶、抗坏血酸氧化酶、超氧化物歧化酶等，这些酶对生命体的新陈代谢起着非常重要的作用。因此研究含苯并咪唑的过渡金属配合物与DNA分子之间的相互作用，对于合成和开发高效低毒副作用的药物有着重要的理论意义。
本论文的研究工作主要包括以下几个方面：
1.合成了配合物[Cu(IDB)Cl_2] CH_3OH (1)，利用单晶X射线测定其晶体结构。晶体结构分析表明：配合物(1)为正交晶系，空间群为Pbca，a=1.36957(16) nm，b=1.42730(16) nm，c=1.8331(2) nm，α=β=γ=90°，Z=8，最终偏离因子R1=0.0412，wR2=0.0903。中心Cu(Ⅱ)与配体IDB中的3个N原子和2个Cl—离子配位，形成一个五配位畸变的四方锥结构。
2.合成了配合物[Ni (EDTB)]_2(ClO_4)2CH3CH2CH2CH2OH (2)，利用单晶X射线测定其晶体结构。晶体结构分析表明：配合物(2)为三斜晶系，空间群为Pī，a=1.02297(12)nm，b=1.28181(15)nm，c=1.8530(2)nm，α=72.470°，β=77.400°，γ=81.603°，Z=2，Ni(Ⅱ)离子与配体EDTB分子中的两个胺基氮原子[N(1)，N(2)]和四个苯并咪唑氮原子[N(3)，N(5)，N(7)，N(9)]配位，形成一个六配位的变形八面体构型。
3.在模拟生理条件下，利用荧光光谱法与紫外—可见光谱法，研究了配合物[Ni(IDB)_2][C_6H_4(OH)COO] ClO_4CH_3CH_2OH H_2O (3)和[Ni(EDTB)] Cl_23CH_3CH_2OH2H_2O (4)与ct–DNA的相互作用。利用荧光光谱法计算了配合物(3)与ct–DNA在不同温度下的结合常数Kb和结合位点数n。并利用溴化乙锭(EB)竞争实验探讨了配合物(3)和(4)与ct–DNA的结合模式。配合物(3)和(4)的紫外吸收强度都随ct–DNA的浓度的增加而减弱，结果表明配合物可能以嵌插方式与DNA结合。
Deoxyribonucleic acid (DNA) is an important macromolecule in organism, it hasgreat significance in the Heredity and Variation for all life. The interaction of smallmolecules and DNA is an important research topic in life science, biochemistry andmedicine; it can not only clarify drugs mechanism of action, but also can providetheoretical direction for the design of drugs.
Benzimidazole is one of heterocyclic compounds with π–π conjugate, which hasbeen widely used in medicine, biological chemistry and analytical chemistry becauseof the high affinity effect to the DNA sequence and has the biological activity ofantiseptic and anti-viral. The transition metal complexes of Benzimidazole exist in avariety of important biological molecules which form coordinations withhistidine imidazole nitrogen and metal ion, such as Urease, Tyrosinase, AscorbateOxidase and Superoxide Dismutase, these enzymes play an important rolein the metabolism of life. So the research of the interaction between transition metalcomplexes of Benzimidazole and DNA has important theoretical significancefor the synthesis and development of efficiency and low toxicity of drugs.
In this paper the research work mainly includes the following aspects:
1. The complex of [Cu (IDB) Cl_2] CH_3OH (1) has been synthesized and thecrystal structure has been determined by single crystal X–ray diffraction. The Crystalstructure analysis shows that the complex (1) belongs to Orthorhombic system withspace group Pbca, a=1.36957(16) nm, b=1.42730(16) nm, c=1.8331(2) nm, α=β=γ=90°, Z=8, the final R1=0.0412，wR2=0.0903. The five–coordinate copper (II) isa distorted square pyramid with three nitrogen atoms of the ligand (IDB) and twochlorine ions.
2. The complex of [Ni (EDTB)]2(ClO_4)2CH_3CH_2CH_2CH_2OH (2) has beensynthesized and the crystal structure has been determined by single crystal X–raydiffraction. The Crystal structure analysis shows that the complex (2) belongs toTriclinic system with space group Pī, a=1.02297(12) nm, b=1.28181(15) nm,c=1.8530(2) nm, α=72.470°, β=77.400°, γ=81.603°, Z=2. The nickel (II) ion formed six-coordinated and distorted octahedral coordination geometry, which is coordinatedwith two amine nitrogen atoms [N (1), N (2)] and four nitrogen atoms [N(3), N(5),N(7), N(9)] of benzimidazole groups from the ligand EDTB.
3. The interaction of complexes [Ni (IDB)2][C6H4(OH) COO] ClO4CH3CH2OH H2O (3) and [Ni (EDTB)] Cl_23CH_3CH_2OH2H_2O (4) with ct–DNAhad been investigated by UV–visible spectra and fluorescence spectra at thephysiological conditions. The binding constant (Kb) and the binding stoichiometry (n)of the [Ni (IDB)_2][C_6H_4(OH) COO] ClO4CH_3CH_2OH H_2O (3) to ct–DNA werecalculated from fluorescence spectra at different temperatures. The binding mode ofthe interaction between complexes (3) and (4) and ct–DNA were obtained fromEthidium Bromide (EB) competitive experiment. The absorbance of complexes (3)and (4) descend with increasing concentration of ct–DNA. These results indicatedthat the complexes could bind to ct–DNA by intercalation.
苯并咪唑是具有π–π共轭的一种杂环化合物，对DNA序列有很高的亲和作用，同时也具有杀菌、抗病毒等生物活性，被广泛应用于医药学、生物化学及分析化学等领域。含苯并咪唑的过渡金属配合物存在于各种重要的生物分子中，都是由组氨酸咪唑氮和金属离子配位形成的，例如脲酶、酪氨酸酶、抗坏血酸氧化酶、超氧化物歧化酶等，这些酶对生命体的新陈代谢起着非常重要的作用。因此研究含苯并咪唑的过渡金属配合物与DNA分子之间的相互作用，对于合成和开发高效低毒副作用的药物有着重要的理论意义。
本论文的研究工作主要包括以下几个方面：
1.合成了配合物[Cu(IDB)Cl_2] CH_3OH (1)，利用单晶X射线测定其晶体结构。晶体结构分析表明：配合物(1)为正交晶系，空间群为Pbca，a=1.36957(16) nm，b=1.42730(16) nm，c=1.8331(2) nm，α=β=γ=90°，Z=8，最终偏离因子R1=0.0412，wR2=0.0903。中心Cu(Ⅱ)与配体IDB中的3个N原子和2个Cl—离子配位，形成一个五配位畸变的四方锥结构。
2.合成了配合物[Ni (EDTB)]_2(ClO_4)2CH3CH2CH2CH2OH (2)，利用单晶X射线测定其晶体结构。晶体结构分析表明：配合物(2)为三斜晶系，空间群为Pī，a=1.02297(12)nm，b=1.28181(15)nm，c=1.8530(2)nm，α=72.470°，β=77.400°，γ=81.603°，Z=2，Ni(Ⅱ)离子与配体EDTB分子中的两个胺基氮原子[N(1)，N(2)]和四个苯并咪唑氮原子[N(3)，N(5)，N(7)，N(9)]配位，形成一个六配位的变形八面体构型。
3.在模拟生理条件下，利用荧光光谱法与紫外—可见光谱法，研究了配合物[Ni(IDB)_2][C_6H_4(OH)COO] ClO_4CH_3CH_2OH H_2O (3)和[Ni(EDTB)] Cl_23CH_3CH_2OH2H_2O (4)与ct–DNA的相互作用。利用荧光光谱法计算了配合物(3)与ct–DNA在不同温度下的结合常数Kb和结合位点数n。并利用溴化乙锭(EB)竞争实验探讨了配合物(3)和(4)与ct–DNA的结合模式。配合物(3)和(4)的紫外吸收强度都随ct–DNA的浓度的增加而减弱，结果表明配合物可能以嵌插方式与DNA结合。
Deoxyribonucleic acid (DNA) is an important macromolecule in organism, it hasgreat significance in the Heredity and Variation for all life. The interaction of smallmolecules and DNA is an important research topic in life science, biochemistry andmedicine; it can not only clarify drugs mechanism of action, but also can providetheoretical direction for the design of drugs.
Benzimidazole is one of heterocyclic compounds with π–π conjugate, which hasbeen widely used in medicine, biological chemistry and analytical chemistry becauseof the high affinity effect to the DNA sequence and has the biological activity ofantiseptic and anti-viral. The transition metal complexes of Benzimidazole exist in avariety of important biological molecules which form coordinations withhistidine imidazole nitrogen and metal ion, such as Urease, Tyrosinase, AscorbateOxidase and Superoxide Dismutase, these enzymes play an important rolein the metabolism of life. So the research of the interaction between transition metalcomplexes of Benzimidazole and DNA has important theoretical significancefor the synthesis and development of efficiency and low toxicity of drugs.
In this paper the research work mainly includes the following aspects:
1. The complex of [Cu (IDB) Cl_2] CH_3OH (1) has been synthesized and thecrystal structure has been determined by single crystal X–ray diffraction. The Crystalstructure analysis shows that the complex (1) belongs to Orthorhombic system withspace group Pbca, a=1.36957(16) nm, b=1.42730(16) nm, c=1.8331(2) nm, α=β=γ=90°, Z=8, the final R1=0.0412，wR2=0.0903. The five–coordinate copper (II) isa distorted square pyramid with three nitrogen atoms of the ligand (IDB) and twochlorine ions.
2. The complex of [Ni (EDTB)]2(ClO_4)2CH_3CH_2CH_2CH_2OH (2) has beensynthesized and the crystal structure has been determined by single crystal X–raydiffraction. The Crystal structure analysis shows that the complex (2) belongs toTriclinic system with space group Pī, a=1.02297(12) nm, b=1.28181(15) nm,c=1.8530(2) nm, α=72.470°, β=77.400°, γ=81.603°, Z=2. The nickel (II) ion formed six-coordinated and distorted octahedral coordination geometry, which is coordinatedwith two amine nitrogen atoms [N (1), N (2)] and four nitrogen atoms [N(3), N(5),N(7), N(9)] of benzimidazole groups from the ligand EDTB.
3. The interaction of complexes [Ni (IDB)2][C6H4(OH) COO] ClO4CH3CH2OH H2O (3) and [Ni (EDTB)] Cl_23CH_3CH_2OH2H_2O (4) with ct–DNAhad been investigated by UV–visible spectra and fluorescence spectra at thephysiological conditions. The binding constant (Kb) and the binding stoichiometry (n)of the [Ni (IDB)_2][C_6H_4(OH) COO] ClO4CH_3CH_2OH H_2O (3) to ct–DNA werecalculated from fluorescence spectra at different temperatures. The binding mode ofthe interaction between complexes (3) and (4) and ct–DNA were obtained fromEthidium Bromide (EB) competitive experiment. The absorbance of complexes (3)and (4) descend with increasing concentration of ct–DNA. These results indicatedthat the complexes could bind to ct–DNA by intercalation.
引文
[1] Hui–Fang Wang, Rui Shen, Ning Tang. Synthesis and characterization of the Zn (II) and Cu (II)piperidinyl isoeuxanthone complexes, DNA–binding and cytotoxic activity [J]. Eur. J. Med.Chem.2009,44:4509–4515.
[2] Zeng–Chen Liu, Bao–Dui Wang, Zheng–Yin Yang, et al. Synthesis, crystal structure, DNAinteraction and antioxidant activities of two novel water–soluble Cu2+complexes derivatedfrom2–oxo–quinoline–3–carbaldehyde Schiff–bases [J]. Eur. J. Med. Chem.2009,44:4477–4484.
[3] Yu–Lan Song, Yan–Tuan Li, Zhi–Yong Wu. Synthesis, crystal structures and DNA–bindingproperties of two new mononuclear copper (II) complexes [J]. Transition. Met. Chem.2008,33:781–789.
[4]曹凯鸣,李碧羽,彭泽国.核酸化学导论[M].上海：复旦大学出版社.1991, p23–25.
[5] Philip J. Cox, George Psomas, Christos A. Bolos. Characterization and DNA–interactionstudies of1,1–dicyano–2,2–ethylenedithiolate Ni (II) mixed–ligand complexes with2–amino–5–methyl thiazole,2–amino–2–thiazoline and imidazole, Crystal structure of [Ni(i–MNT)(2a–5mt)2][J]. Bioorg. Med. Chem.2009,17:6054–6062.
[6]高恩君,丁丽娜,刘祁涛等.钯(Ⅱ)三元配合物稳定性及其与DNA作用研究[J].物理化学学报.2005,21(10):1091–1095.
[7] Fang–Ying Wu, Fei–Yan Xie, Yu–Mei Wu, et al. Interaction of a New Fluorescent Probe withDNA and its Use in Determination of DNA [J]. J. Fluoresc.2008,18:175–181.
[8] Jun Tan, Bo–Chu Wang, Lian–Cai Zhu. DNA binding and oxidative DNA damage induced bya quercetin copper (II) complex: potential mechanism of its antitumor properties[J]. J. Biol.Inorg. Chem.2009,14(5):727–739.
[9]宋玉民,康敬万,高锦章等.钴(Ⅲ)配合物与DNA作用的研究[J].无机化学学报.2000,16(1):53–57.
[10] Lei Jia, Xi–Ming Xu, Jun Xu, et al. Synthesis, Characterization, Cytotoxic Activities, andDNA–Binding Studies of Ternary Copper (II) Complexes with New Coumarin Derivatives[J]. Chem. Pharm. Bull.2010,58(8):1003–1008.
[11]张蓉颖,庞代文,蔡汝秀. DNA与其靶向分子相互作用的研究进展[J].高等化学学报.1999,20(8):1210–1217.
[12]胡亚敏,王兴明,张欢.金属配合物与DNA相互作用的研究进展[J].化学与生物工程.2007,24(8):1–4.
[13]周庆华,杨频.二(2–苯并咪唑亚甲基)胺合铜(II)配合物与DNA作用方式的光谱研究[J].化学学报.2005,63(1):71–74.
[14]卢继新,张贵珠,黄志娜等.巯嘌呤金属配合物与小牛胸腺DNA的作用[J].化学学报.2002,60(6):967–972．
[15]席小莉,杨曼曼,杨频.8–氮杂腺嘌呤及其金属配合物与DNA的作用机理[J].光谱学与光谱分析.2006,26(12):2272–2275.
[16] Pin–xian Xi, Zhi–hong Xu, Feng–juan Chen, et al. Synthesis, Characterization, AntioxidantActivity and DNA–Binding Studies of Three Rare Earth (III) Complexes with1–(4–Aminoantipyrine)–3–tosylurea Ligand [J]. J. Fluoresc.2009,19:63–72.
[17] Zhi–Hong Xu, Feng–Juan Chen, Pin–Xian Xi, et al. Synthesis, characterization, andDNA–binding properties of the cobalt(II) and nickel(II) complexes with salicylaldehyde2–phenylquinoline–4–carboylhydrazone [J]. J. Photochem. Photobiol. A: Chem.2008,196:77–83.
[18]姚威,吴宝燕,高丽华等.一种含芴基的钌(II)配合物的合成及DNA键合性质[J].物理化学学报.2007,23(2):237–241.
[19]邹敏,刘叔文,周春琼.一种新的吡咯多胺镍配合物的合成及其与DNA的作用研[J].化学学报.2010,68(6):481–486.
[20]杨培菊.金属配合物与DNA相互作用.西北师范大学硕士学位论文.2005.
[21]周春琼,邹敏,游文玮等.吡咯多胺钴配合物的合成及与DNA的作用研究[J].无机化学学报.2010,26(2):257–262.
[22] Michael Rettig, Ahmed Kamal, R. Ramu, et al. Spectroscopic and calorimetric studies on theDNA recognition of pyrrolo[2,1–c][1,4]benzodiazepine hybrids [J]. Bioorg. Med. Chem.2009,17:919–928.
[23]王海滔,刘剑洪,张黔玲等.钌(II)多吡啶配合物与DNA相互作用的光切割与荧光性质研究[J].化学学报.2010,68(15):1507–1512.
[24]关淑霞,王丽,于海南等.苯甲醛缩2–氨基嘧啶席夫碱铜配合物的合成及其与DNA相互作用[J].化学试剂.2010,32(11):979–982.
[25] J K Barton, A T Danishefsky, J M Goldberg. J. Am. Chem. Soc.,1984,106:2172–2176.
[26] Jie Liu, Tong–Bu Lu, Liang–Nian Ji, et al. Synthesis, DNA–binding and cleavage studies ofmacrocyclic copper (II) complexes [J]. Trans Met. Chem.2003,28:116–121.
[27] Xiang–Li Wang, Hui Chao, Liang–Nian Ji, et al. Synthesis, DNA binding and oxidativecleavage studies of an asymmetric tridentate copper(II) complex [J]. Trans. Met. Chem.2007,32:125–130.
[28]杨培菊,孙坤,苏雪等.全反式维甲酸合铜(II)配合物对DNA的切割和键合作用[J].化学学报.2005,63(23):2153–2157.
[29]陈凤英,何水样,刘峰等.配合物[RE2(H2L)2(HL)2(2,6–H2PDA)(H2O)2]2H2O的合成、晶体结构及其与DNA作用方式初探[J].化学学报.2009,67(6):555–563.
[30]王镜岩,朱圣庚,徐长法.生物化学(第3版)[M].北京，高等教育出版社.2002:p507–508.
[31] En–Jun Gao, Tie–Dong Sun, Shi–Hua Liu, et al. Synthesis, characterization, interaction withDNA and cytotoxicity in vitro of novel pyridine complexes with Zn(II)[J]. Eur. J. Med.Chem.2010,45:4531–4538.
[32] Pin–Xian Xi, Zhi–Hong Xu, Feng–Juan Chen, et al. Study on synthesis, structure, andDNA–binding of Ni, Zn complexes with2–phenylquinoline–4–carboylhydrazide [J]. J. Inorg.Biochem.2009,103:210–218.
[33]周建良,春晓改,周琳姣等.新型三元铜配合物的合成、晶体结构及与DNA的相互作用[J].无机化学学报.2010,26(4):645–650.
[34]凌连生,杨洗,何治柯等. Ru(bipy)2(dppz)2+与DNA相互作用的光谱研究[J].分析科学学报.2001,17(1):11–15.
[35] Liang–Nian Ji, Qian–Ling Zhang, Jing–Gang Liu. DNA structure, binding mechanism andbiology function of polypyridyl complexs in biomedicine [J]. Science in China (series B).2001,44(3):246–259.
[36] Na Zhao, Xing–Ming Wang, Hai–Zhuan Pan, et al. Spectroscopic studies on the interactionbetween tryptophan–erbium (III) complex and herring sperm DNA [J]. Spectrochimica ActaPart A.2010,75:1435–1442.
[37]康敬万,吴海霞,卢小泉等.水溶性锌卟啉配合物的合成、表征及其与CT–DNA的作用[J].高等学校化学学报.2005,26(6):997–1001.
[38]吴建中,王雷,杨光等.钌多吡啶配合物的合成及结合DNA的研究[J].高等学校化学学报.1996,17(7):1010–1015.
[39] Ihtshamul Haq. Thermodynamics of drug–DNA interactions [J]. Arch. Biochem. Biophys.2002,403:1–15.
[40]徐宏,张鹏,杜芬等.钌(Ⅱ)多吡啶配合物与DNA相互作用的等温滴定量热研究[J].无机化学学报.2005,4(21):468–471.
[41] Zhi–Hong Xu, Pin–Xian Xi, Feng–Juan Chen, et al. Synthesis, characterization, andDNA–binding properties of copper(II), cobalt(II), and nickel(II) complexes withsalicylaldehyde2–phenylquinoline–4–carboylhydrazone [J]. Transition. Met. Chem.2008,33:267–273.
[42]康敬万,吴海霞,卓琳等. Eu3+–芦丁配合物与DNA相互作用的电化学和紫外可见吸收光谱研究[J].中国稀土学报.2005,23(4):496–500.
[43]李红,乐学义,吴建中等.铜(Ⅱ)邻菲咯啉蛋氨酸配合物与DNA相互作用的研究[J].化学学报.2003,61(2):245–250.
[44] Satyanarayana, S.; Dabrowiak, J. C.; Chaires, J. B. Neither Δ–nor Λ–tris (phenanthroline)ruthenium (II) binds to DNA by classical intercalation [J]. Biochem.1992,31(39):9319–9324.
[45] Ju Wang, Zheng–Yin Yang, Bao–Dui Wang, et al. Synthesis, Characterization andDNA–binding Properties of Ln (III) Complexes with6–Ethoxy Chromone–3–CarbaldehydeBenzoyl Hydrazone[J]. J. Fluoresc.2009,19:847–856.
[46]席小莉,杨曼曼,杨频.表柔比星–铁体系与DNA作用的光谱和电化学法研究[J].化学学报.2010,68(18):1864–1870.
[47]贺小凤,徐宏.新型钌(Ⅱ)多吡啶配合物与DNA作用的黏度法研究[J].化学研究.2005,16(1):5–8.
[48]吕冬梅，阂吉梅，张礼和.药物–DNA相互作用的序列特异性的研究进展[J].国外医学药学分册.1998,25(2):65–71.
[49] Fiel R J, Munson B R. Binding of meo–tetra (4–N–methylpyridyl) porphine to DNA [J].Nucleic Acids Res.1980,8(12):2835–2842.
[50]朱莉,彭斌,凌友等.配合物[Co2(EGTB)Cl2](BF4)25H2O与DNA相互作用的研究[J].化学学报.2008,66(24):2705–2711.
[51] D. Lawrence Arockiasamy, S. Radhika, R. Parthasarathi, et al. Synthesis and DNA–bindingstudies of two ruthenium (II) complexes of an intercalating ligand [J]. Eur. J. Med. Chem.2009,44:2044–2051.
[52] Parkinson, J. A.; Barber J.; Douglas K. T. Minor–groove recognition of theself–complementary duplex d (CGCGAATTCGCG)2by Hoechst33258: a high–field NMRstudy [J]. Biochem.1990,29(44):10181–10190.
[53]陈彦国,廖展如,李武客等.配合物[Ni(IDB)2]·[C6H4(OH) COO]·ClO4·CH3CH2OH·H2O的合成、晶体结构及催化尿素水解活性的研究[J].化学学报.2000,58(10):1191–1195.
[54]朱莉,廖展如,王哲明等.钴配合物的合成晶体结构及活性研究[J].无机化学学报.2002,18(7):731–734.
[55]覃事栋,冯思思,张红梅等.配合物[Ni(EDTB)]2Cl CH3OH C2H5OH的合成、晶体结构及SOD模拟活性的研究[J].化学学报.2005,63(13):1155–1160.
[56]石巨恩，廖展如.生物无机化学[M].华中师范大学出版社.1999, p146–160.
[57]张书良,易大年,吴天明.红外光谱分析与新技术[M].中国医药科学出版社.1993,p133.
[58]罗志刚,胡小芳,易绣光等.镍配合物[Ni(C10H8N2)(C7H4O5N3)(H2O)]·ClO4的合成及晶体结构[J].化学研究与应用.2009,21(8):1124–1128.
[59]朱莉,于贤勇,龙云飞等.2-苯并咪唑吡啶镍配合物的合成﹑晶体结构及与DNA相互作用的共振散射光谱研究[J].化学学报.2009,67(2):139–144.
[60]周庆华,杨频.二(2–苯并咪唑亚甲基)胺合锰(Ⅱ)配合物水解切割DNA[J].无机化学学报.2005,21(7):960–964.
[61] Hong Li, Xue–Yi Le, Dai–Wen Pang, et al. DNA–binding and cleavage studies of novelcopper(II) complex with L–phenylalaninate and1,4,8,9–tetra–aza–triphenylene ligands [J].J. Inorg. Biochem.2005,99:2240–2247.
[62] Jun Tan, Bo–Chu Wang, Lian–Cai Zhu. DNA binding, cytotoxicity, apoptotic inducingactivity, and molecular modeling study of quercetin zinc (II) complex [J]. Bioorg. Med.Chem.2009,17:614–620.
[63]费丹,王兴明,黎泓波等.亚甲基蓝与鲱鱼精DNA相互作用的光谱法研究[J].化学学报.2008,66(4):443–448.
[64] Qian Wang, Zheng–Yin Yang, Gao–Fei Qi, et al. Synthesis, crystal structure, antioxidantactivities and DNA–binding studies of the Ln(III) complexes with7–methoxychromone–3–carbaldehyde–(4’–hydroxy) benzoyl hydrazone [J]. Eur. J. Med.Chem.2009,44:2425–2433.
[65] Rui Shen, Peng Wang, Ning Tang. Synthesis, Crystal Structure, DNA–binding Properties andCytotoxic Activity of the Copper (II) Complex Involving Xanthone [J]. J. Fluoresc.2009,19:1073–1082.
[66]徐春,何品刚,方禹之.溴化乙锭标记DNA电化学探针的研究[J].高等学校化学学报.2000,21(8):1187–1190.
[67]宋玉民,杨培菊,王流芳等.全反式维甲酸合钐(Ⅲ)配合物与DNA作用的研究[J].化学学报.2003,61(8):1266–1270.
[68] Kalliopi C. Skyrianou, Catherine P. Raptopoulou, Vassilis Psycharis, et al. Structure, cyclicvoltammetry and DNA–binding properties of the bis (pyridine) bis (sparfloxacinato) nickel(II) complex [J]. Polyhedron.2009,28:3265–3271.
[69] Yan Lu, Yun–Lai Wang, Sheng–Hua Gao, et al. Interaction of quercetin with ovalbumin:Spectroscopic and molecular modeling studies [J]. J. Lumin.2009,129:1048–1054.
[70] Yan Lu, Mei–hua Xu, Gong–ke Wang, et al. Interaction of diethyl aniline methylphosphonatewith DNA: spectroscopic and isothermal titration calorimetry [J]. J. Lumin.2011,131(5):926–930.
[71]袁益娴,陈禹,王贻灿等.手性双核钌(II)配合物与DNA的相互作用研究[J].无机化学学报.2008,24(8):1265–1271.
[72] Guo–Wen Zhang, Xing Hu, Nan Zhao, et al. Studies on the interaction of aminocarb withcalf thymus DNA by spectroscopic methods [J]. Pestic. Biochem. Physiol.2010,98:206–212.
[73] Joseph R Lakowicz. Principles of Fluorescence Spectroscopy[M]. Third Edition, Springer.2006, p278–282.
[74]卢秀敏,陈得军,王公轲等.诺氟沙星与卵清蛋白相互作用的研究[J].光谱学与光谱分析[J].2009,29(1):236–239.
[75] Rabindranath Bera, Bijaya K. Sahoo, Kalyan S. Ghosh, et al. Studies on the interaction ofisoxazolcurcumin with calf thymus DNA [J]. Int. J. Biol. Macromol.2008,42:14–21.
[76]谢孟峡,徐晓云,王英典等.4,5,7–三羟基二氢黄酮与人血清白蛋白相互作用的光谱学研究[J].化学学报.2005,63(22):2055–2062.
[77]高恩君,程卯生,李浩洋等.三(羟甲基)甲基甘氨酸合镍(Ⅱ)配合物的结构及其与生物分子的作用研究[J].化学学报.2007,65(1):17–20.
[78]仇晓阳,徐茂田,朱海亮等.三核镍配合物Ni3(C14H8N3O5)2(C5H5N)4的合成、晶体结构和抗癌活性[J].无机化学学报.2010,26(2):355–359.
[79]陈彦国,王朝晖,李武客等.脲酶模型化合物合成、表征及对尿素水解的影响[J].华中师范大学学报(自然科学版).2000,34(3):291–294.
[80]蔡志彬,周茂.一种含噻吩基Ni(Ⅱ)配合物的合成及其与DNA的相互作用[J].化学通报.2010,(1):75–78.
[81]蒲小华,陈绘丽,韩高义等.带有位阻基团的钌多吡啶配合物与DNA键合及其光断裂DNA性质的研究[J].化学学报.2007,65(15):1464–1468.
[82] Lakowicz J R, Weber G. Quenching of fluorescence by oxygen: Probe for structuralfluctuations in macromolecules [J]. Biochemistry.1973,12:4161–4170.
[83] Rabindranath Bera, Bijaya K. Sahoo, Kalyan S. Ghosh, et al. Studies on the interaction ofisoxazolcurcumin with calf thymus DNA [J]. Int. J. Biol. Macromol.2008,42:14–21.
[2] Zeng–Chen Liu, Bao–Dui Wang, Zheng–Yin Yang, et al. Synthesis, crystal structure, DNAinteraction and antioxidant activities of two novel water–soluble Cu2+complexes derivatedfrom2–oxo–quinoline–3–carbaldehyde Schiff–bases [J]. Eur. J. Med. Chem.2009,44:4477–4484.
[3] Yu–Lan Song, Yan–Tuan Li, Zhi–Yong Wu. Synthesis, crystal structures and DNA–bindingproperties of two new mononuclear copper (II) complexes [J]. Transition. Met. Chem.2008,33:781–789.
[4]曹凯鸣,李碧羽,彭泽国.核酸化学导论[M].上海：复旦大学出版社.1991, p23–25.
[5] Philip J. Cox, George Psomas, Christos A. Bolos. Characterization and DNA–interactionstudies of1,1–dicyano–2,2–ethylenedithiolate Ni (II) mixed–ligand complexes with2–amino–5–methyl thiazole,2–amino–2–thiazoline and imidazole, Crystal structure of [Ni(i–MNT)(2a–5mt)2][J]. Bioorg. Med. Chem.2009,17:6054–6062.
[6]高恩君,丁丽娜,刘祁涛等.钯(Ⅱ)三元配合物稳定性及其与DNA作用研究[J].物理化学学报.2005,21(10):1091–1095.
[7] Fang–Ying Wu, Fei–Yan Xie, Yu–Mei Wu, et al. Interaction of a New Fluorescent Probe withDNA and its Use in Determination of DNA [J]. J. Fluoresc.2008,18:175–181.
[8] Jun Tan, Bo–Chu Wang, Lian–Cai Zhu. DNA binding and oxidative DNA damage induced bya quercetin copper (II) complex: potential mechanism of its antitumor properties[J]. J. Biol.Inorg. Chem.2009,14(5):727–739.
[9]宋玉民,康敬万,高锦章等.钴(Ⅲ)配合物与DNA作用的研究[J].无机化学学报.2000,16(1):53–57.
[10] Lei Jia, Xi–Ming Xu, Jun Xu, et al. Synthesis, Characterization, Cytotoxic Activities, andDNA–Binding Studies of Ternary Copper (II) Complexes with New Coumarin Derivatives[J]. Chem. Pharm. Bull.2010,58(8):1003–1008.
[11]张蓉颖,庞代文,蔡汝秀. DNA与其靶向分子相互作用的研究进展[J].高等化学学报.1999,20(8):1210–1217.
[12]胡亚敏,王兴明,张欢.金属配合物与DNA相互作用的研究进展[J].化学与生物工程.2007,24(8):1–4.
[13]周庆华,杨频.二(2–苯并咪唑亚甲基)胺合铜(II)配合物与DNA作用方式的光谱研究[J].化学学报.2005,63(1):71–74.
[14]卢继新,张贵珠,黄志娜等.巯嘌呤金属配合物与小牛胸腺DNA的作用[J].化学学报.2002,60(6):967–972．
[15]席小莉,杨曼曼,杨频.8–氮杂腺嘌呤及其金属配合物与DNA的作用机理[J].光谱学与光谱分析.2006,26(12):2272–2275.
[16] Pin–xian Xi, Zhi–hong Xu, Feng–juan Chen, et al. Synthesis, Characterization, AntioxidantActivity and DNA–Binding Studies of Three Rare Earth (III) Complexes with1–(4–Aminoantipyrine)–3–tosylurea Ligand [J]. J. Fluoresc.2009,19:63–72.
[17] Zhi–Hong Xu, Feng–Juan Chen, Pin–Xian Xi, et al. Synthesis, characterization, andDNA–binding properties of the cobalt(II) and nickel(II) complexes with salicylaldehyde2–phenylquinoline–4–carboylhydrazone [J]. J. Photochem. Photobiol. A: Chem.2008,196:77–83.
[18]姚威,吴宝燕,高丽华等.一种含芴基的钌(II)配合物的合成及DNA键合性质[J].物理化学学报.2007,23(2):237–241.
[19]邹敏,刘叔文,周春琼.一种新的吡咯多胺镍配合物的合成及其与DNA的作用研[J].化学学报.2010,68(6):481–486.
[20]杨培菊.金属配合物与DNA相互作用.西北师范大学硕士学位论文.2005.
[21]周春琼,邹敏,游文玮等.吡咯多胺钴配合物的合成及与DNA的作用研究[J].无机化学学报.2010,26(2):257–262.
[22] Michael Rettig, Ahmed Kamal, R. Ramu, et al. Spectroscopic and calorimetric studies on theDNA recognition of pyrrolo[2,1–c][1,4]benzodiazepine hybrids [J]. Bioorg. Med. Chem.2009,17:919–928.
[23]王海滔,刘剑洪,张黔玲等.钌(II)多吡啶配合物与DNA相互作用的光切割与荧光性质研究[J].化学学报.2010,68(15):1507–1512.
[24]关淑霞,王丽,于海南等.苯甲醛缩2–氨基嘧啶席夫碱铜配合物的合成及其与DNA相互作用[J].化学试剂.2010,32(11):979–982.
[25] J K Barton, A T Danishefsky, J M Goldberg. J. Am. Chem. Soc.,1984,106:2172–2176.
[26] Jie Liu, Tong–Bu Lu, Liang–Nian Ji, et al. Synthesis, DNA–binding and cleavage studies ofmacrocyclic copper (II) complexes [J]. Trans Met. Chem.2003,28:116–121.
[27] Xiang–Li Wang, Hui Chao, Liang–Nian Ji, et al. Synthesis, DNA binding and oxidativecleavage studies of an asymmetric tridentate copper(II) complex [J]. Trans. Met. Chem.2007,32:125–130.
[28]杨培菊,孙坤,苏雪等.全反式维甲酸合铜(II)配合物对DNA的切割和键合作用[J].化学学报.2005,63(23):2153–2157.
[29]陈凤英,何水样,刘峰等.配合物[RE2(H2L)2(HL)2(2,6–H2PDA)(H2O)2]2H2O的合成、晶体结构及其与DNA作用方式初探[J].化学学报.2009,67(6):555–563.
[30]王镜岩,朱圣庚,徐长法.生物化学(第3版)[M].北京，高等教育出版社.2002:p507–508.
[31] En–Jun Gao, Tie–Dong Sun, Shi–Hua Liu, et al. Synthesis, characterization, interaction withDNA and cytotoxicity in vitro of novel pyridine complexes with Zn(II)[J]. Eur. J. Med.Chem.2010,45:4531–4538.
[32] Pin–Xian Xi, Zhi–Hong Xu, Feng–Juan Chen, et al. Study on synthesis, structure, andDNA–binding of Ni, Zn complexes with2–phenylquinoline–4–carboylhydrazide [J]. J. Inorg.Biochem.2009,103:210–218.
[33]周建良,春晓改,周琳姣等.新型三元铜配合物的合成、晶体结构及与DNA的相互作用[J].无机化学学报.2010,26(4):645–650.
[34]凌连生,杨洗,何治柯等. Ru(bipy)2(dppz)2+与DNA相互作用的光谱研究[J].分析科学学报.2001,17(1):11–15.
[35] Liang–Nian Ji, Qian–Ling Zhang, Jing–Gang Liu. DNA structure, binding mechanism andbiology function of polypyridyl complexs in biomedicine [J]. Science in China (series B).2001,44(3):246–259.
[36] Na Zhao, Xing–Ming Wang, Hai–Zhuan Pan, et al. Spectroscopic studies on the interactionbetween tryptophan–erbium (III) complex and herring sperm DNA [J]. Spectrochimica ActaPart A.2010,75:1435–1442.
[37]康敬万,吴海霞,卢小泉等.水溶性锌卟啉配合物的合成、表征及其与CT–DNA的作用[J].高等学校化学学报.2005,26(6):997–1001.
[38]吴建中,王雷,杨光等.钌多吡啶配合物的合成及结合DNA的研究[J].高等学校化学学报.1996,17(7):1010–1015.
[39] Ihtshamul Haq. Thermodynamics of drug–DNA interactions [J]. Arch. Biochem. Biophys.2002,403:1–15.
[40]徐宏,张鹏,杜芬等.钌(Ⅱ)多吡啶配合物与DNA相互作用的等温滴定量热研究[J].无机化学学报.2005,4(21):468–471.
[41] Zhi–Hong Xu, Pin–Xian Xi, Feng–Juan Chen, et al. Synthesis, characterization, andDNA–binding properties of copper(II), cobalt(II), and nickel(II) complexes withsalicylaldehyde2–phenylquinoline–4–carboylhydrazone [J]. Transition. Met. Chem.2008,33:267–273.
[42]康敬万,吴海霞,卓琳等. Eu3+–芦丁配合物与DNA相互作用的电化学和紫外可见吸收光谱研究[J].中国稀土学报.2005,23(4):496–500.
[43]李红,乐学义,吴建中等.铜(Ⅱ)邻菲咯啉蛋氨酸配合物与DNA相互作用的研究[J].化学学报.2003,61(2):245–250.
[44] Satyanarayana, S.; Dabrowiak, J. C.; Chaires, J. B. Neither Δ–nor Λ–tris (phenanthroline)ruthenium (II) binds to DNA by classical intercalation [J]. Biochem.1992,31(39):9319–9324.
[45] Ju Wang, Zheng–Yin Yang, Bao–Dui Wang, et al. Synthesis, Characterization andDNA–binding Properties of Ln (III) Complexes with6–Ethoxy Chromone–3–CarbaldehydeBenzoyl Hydrazone[J]. J. Fluoresc.2009,19:847–856.
[46]席小莉,杨曼曼,杨频.表柔比星–铁体系与DNA作用的光谱和电化学法研究[J].化学学报.2010,68(18):1864–1870.
[47]贺小凤,徐宏.新型钌(Ⅱ)多吡啶配合物与DNA作用的黏度法研究[J].化学研究.2005,16(1):5–8.
[48]吕冬梅，阂吉梅，张礼和.药物–DNA相互作用的序列特异性的研究进展[J].国外医学药学分册.1998,25(2):65–71.
[49] Fiel R J, Munson B R. Binding of meo–tetra (4–N–methylpyridyl) porphine to DNA [J].Nucleic Acids Res.1980,8(12):2835–2842.
[50]朱莉,彭斌,凌友等.配合物[Co2(EGTB)Cl2](BF4)25H2O与DNA相互作用的研究[J].化学学报.2008,66(24):2705–2711.
[51] D. Lawrence Arockiasamy, S. Radhika, R. Parthasarathi, et al. Synthesis and DNA–bindingstudies of two ruthenium (II) complexes of an intercalating ligand [J]. Eur. J. Med. Chem.2009,44:2044–2051.
[52] Parkinson, J. A.; Barber J.; Douglas K. T. Minor–groove recognition of theself–complementary duplex d (CGCGAATTCGCG)2by Hoechst33258: a high–field NMRstudy [J]. Biochem.1990,29(44):10181–10190.
[53]陈彦国,廖展如,李武客等.配合物[Ni(IDB)2]·[C6H4(OH) COO]·ClO4·CH3CH2OH·H2O的合成、晶体结构及催化尿素水解活性的研究[J].化学学报.2000,58(10):1191–1195.
[54]朱莉,廖展如,王哲明等.钴配合物的合成晶体结构及活性研究[J].无机化学学报.2002,18(7):731–734.
[55]覃事栋,冯思思,张红梅等.配合物[Ni(EDTB)]2Cl CH3OH C2H5OH的合成、晶体结构及SOD模拟活性的研究[J].化学学报.2005,63(13):1155–1160.
[56]石巨恩，廖展如.生物无机化学[M].华中师范大学出版社.1999, p146–160.
[57]张书良,易大年,吴天明.红外光谱分析与新技术[M].中国医药科学出版社.1993,p133.
[58]罗志刚,胡小芳,易绣光等.镍配合物[Ni(C10H8N2)(C7H4O5N3)(H2O)]·ClO4的合成及晶体结构[J].化学研究与应用.2009,21(8):1124–1128.
[59]朱莉,于贤勇,龙云飞等.2-苯并咪唑吡啶镍配合物的合成﹑晶体结构及与DNA相互作用的共振散射光谱研究[J].化学学报.2009,67(2):139–144.
[60]周庆华,杨频.二(2–苯并咪唑亚甲基)胺合锰(Ⅱ)配合物水解切割DNA[J].无机化学学报.2005,21(7):960–964.
[61] Hong Li, Xue–Yi Le, Dai–Wen Pang, et al. DNA–binding and cleavage studies of novelcopper(II) complex with L–phenylalaninate and1,4,8,9–tetra–aza–triphenylene ligands [J].J. Inorg. Biochem.2005,99:2240–2247.
[62] Jun Tan, Bo–Chu Wang, Lian–Cai Zhu. DNA binding, cytotoxicity, apoptotic inducingactivity, and molecular modeling study of quercetin zinc (II) complex [J]. Bioorg. Med.Chem.2009,17:614–620.
[63]费丹,王兴明,黎泓波等.亚甲基蓝与鲱鱼精DNA相互作用的光谱法研究[J].化学学报.2008,66(4):443–448.
[64] Qian Wang, Zheng–Yin Yang, Gao–Fei Qi, et al. Synthesis, crystal structure, antioxidantactivities and DNA–binding studies of the Ln(III) complexes with7–methoxychromone–3–carbaldehyde–(4’–hydroxy) benzoyl hydrazone [J]. Eur. J. Med.Chem.2009,44:2425–2433.
[65] Rui Shen, Peng Wang, Ning Tang. Synthesis, Crystal Structure, DNA–binding Properties andCytotoxic Activity of the Copper (II) Complex Involving Xanthone [J]. J. Fluoresc.2009,19:1073–1082.
[66]徐春,何品刚,方禹之.溴化乙锭标记DNA电化学探针的研究[J].高等学校化学学报.2000,21(8):1187–1190.
[67]宋玉民,杨培菊,王流芳等.全反式维甲酸合钐(Ⅲ)配合物与DNA作用的研究[J].化学学报.2003,61(8):1266–1270.
[68] Kalliopi C. Skyrianou, Catherine P. Raptopoulou, Vassilis Psycharis, et al. Structure, cyclicvoltammetry and DNA–binding properties of the bis (pyridine) bis (sparfloxacinato) nickel(II) complex [J]. Polyhedron.2009,28:3265–3271.
[69] Yan Lu, Yun–Lai Wang, Sheng–Hua Gao, et al. Interaction of quercetin with ovalbumin:Spectroscopic and molecular modeling studies [J]. J. Lumin.2009,129:1048–1054.
[70] Yan Lu, Mei–hua Xu, Gong–ke Wang, et al. Interaction of diethyl aniline methylphosphonatewith DNA: spectroscopic and isothermal titration calorimetry [J]. J. Lumin.2011,131(5):926–930.
[71]袁益娴,陈禹,王贻灿等.手性双核钌(II)配合物与DNA的相互作用研究[J].无机化学学报.2008,24(8):1265–1271.
[72] Guo–Wen Zhang, Xing Hu, Nan Zhao, et al. Studies on the interaction of aminocarb withcalf thymus DNA by spectroscopic methods [J]. Pestic. Biochem. Physiol.2010,98:206–212.
[73] Joseph R Lakowicz. Principles of Fluorescence Spectroscopy[M]. Third Edition, Springer.2006, p278–282.
[74]卢秀敏,陈得军,王公轲等.诺氟沙星与卵清蛋白相互作用的研究[J].光谱学与光谱分析[J].2009,29(1):236–239.
[75] Rabindranath Bera, Bijaya K. Sahoo, Kalyan S. Ghosh, et al. Studies on the interaction ofisoxazolcurcumin with calf thymus DNA [J]. Int. J. Biol. Macromol.2008,42:14–21.
[76]谢孟峡,徐晓云,王英典等.4,5,7–三羟基二氢黄酮与人血清白蛋白相互作用的光谱学研究[J].化学学报.2005,63(22):2055–2062.
[77]高恩君,程卯生,李浩洋等.三(羟甲基)甲基甘氨酸合镍(Ⅱ)配合物的结构及其与生物分子的作用研究[J].化学学报.2007,65(1):17–20.
[78]仇晓阳,徐茂田,朱海亮等.三核镍配合物Ni3(C14H8N3O5)2(C5H5N)4的合成、晶体结构和抗癌活性[J].无机化学学报.2010,26(2):355–359.
[79]陈彦国,王朝晖,李武客等.脲酶模型化合物合成、表征及对尿素水解的影响[J].华中师范大学学报(自然科学版).2000,34(3):291–294.
[80]蔡志彬,周茂.一种含噻吩基Ni(Ⅱ)配合物的合成及其与DNA的相互作用[J].化学通报.2010,(1):75–78.
[81]蒲小华,陈绘丽,韩高义等.带有位阻基团的钌多吡啶配合物与DNA键合及其光断裂DNA性质的研究[J].化学学报.2007,65(15):1464–1468.
[82] Lakowicz J R, Weber G. Quenching of fluorescence by oxygen: Probe for structuralfluctuations in macromolecules [J]. Biochemistry.1973,12:4161–4170.
[83] Rabindranath Bera, Bijaya K. Sahoo, Kalyan S. Ghosh, et al. Studies on the interaction ofisoxazolcurcumin with calf thymus DNA [J]. Int. J. Biol. Macromol.2008,42:14–21.