钌配合物断裂DNA及其机理研究

DNA是遗传信息的携带者和基因表达的物质基础,金属配合物与DNA的相互作用研究受到广泛关注,成为生物无机化学的重要研究内容之一.与其他类型金属配合物相比,钌配合物具有良好的热力学稳定性以及丰富的光化学、光物理和氧化还原特性,其作为DNA断裂试剂也引起人们的极大兴趣.以近年一些代表性的研究工作为例,本文对钌配合物在DNA断裂作用机制方面的研究进展进行了综述.     

桑色素及其配合物与DNA作用的比较

采用光度法、粘度法和电化学方法考察了桑色素及其配合物和DNA的作用.并对桑色素合铜(Ⅱ)、桑色素合锌(Ⅱ)、桑色素合钴(Ⅱ)、桑色素与DNA作用的方式进行了比较.Cu(Ⅱ), Zn(Ⅱ), Co(Ⅱ)桑色素配合物与DNA作用时的荧光光谱性质类似,不同于配体.钴(Ⅱ)配合物的电化学行为与铜(Ⅱ)配合物相似,不同于锌(Ⅱ)配合物.三种配合物的存在,都可引起DNA的粘度增加.但钴(Ⅱ)配合物对EB-DNA复合物的荧光光谱影响很小,而铜(Ⅱ)、锌(Ⅱ)配合物对EB-DNA复合物的荧光光谱影响较大.实验结果表明,与DNA之间的作用,钴(Ⅱ)配合物弱于铜(Ⅱ)、锌(Ⅱ)配合物.这可能是钴(Ⅱ)配合物的抗肿瘤活性低于与DNA嵌入结合的铜(Ⅱ)、锌(Ⅱ)配合物的原因之一.     

电化学诱导咪唑铜配合物断裂DNA的研究

二价咪唑铜配合物可以在电极表面发生氧化还原反应,该过程对应于单电子准可逆过程.荧光光谱电化学结果表明,还原产物一价咪唑铜配合物可以被空气中的O₂氧化为二价.在中性的Tris-HCl缓冲溶液中,配合物与DNA之间存在弱相互作用,其键合常数仅为2.7×10²L/mol.荧光光谱及电化学结果表明为嵌入式作用.据此建立了一种电化学诱导咪唑铜配合物对DNA断裂的新方法,并采用差示扫描量热(DSC)法检验了断裂结果.     

DNA与金属锇配合物相互作用的表面电化学研究

采用自己建立的DNA表面电化学研究微量方法, 研究了单双链DNA与两种锇配合物(联吡啶锇和二氯菲咯啉锇)的相互作用. 研究发现, 两种锇配合物都是通过静电作用与DNA结合, 其作用方式不受溶液离子强度的影响. 并计算得到了联吡啶锇和二氯菲咯啉锇与dsDNA和ssDNA相互作用的多个热力学和动力学参数, 如结合常数K_3＋或K_2＋, 结合常数比K_3＋/K_2＋, 离子强度为零时的极限比 , 结合自由能ΔG_b, 解离速度常数k, 结合位点数s.     

基于电中性锇配合物的低背景DNA电化学传感器

采用紫外光谱和电化学方法研究了一种电中性锇配合物Os(DPPZ)(PC)(H₂O)DPPZ=联吡啶并[3,2-a,2',3'-c]吩嗪, PC=2,6-吡啶二羧酸}与DNA的相互作用. 紫外光谱结果表明, DNA的加入引起配合物特征吸收峰的减色及红移效应, 说明二者之间存在嵌插作用. 循环伏安实验结果表明, 配合物溶液中加入DNA后, 氧化还原峰电流降低且式电位正移, 证实了二者之间的嵌插作用模式. 将该配合物作为杂交指示剂对CaMV35S启动子基因片段进行检测发现, 在单链探针DNA修饰电极上未观察到指示剂的电化学信号, 而在杂交后的双链DNA电极上呈现灵敏的电化学响应, 表明传感器具有较高的信噪比. 定量分析实验结果表明, 在最佳条件下, 杂交指示剂在传感器上的还原峰电流与目标序列浓度在8.0×10^-10~2.8×10^-9 mol/L范围内呈良好的线性关系. 选择性实验结果表明, 该传感器对互补序列、碱基错配序列和非互补序列具有良好的识别能力.     

稀土配合物抗癌药物的研究进展

稀土与配体在一定条件下可生成稀土配合物,而稀土配合物大多兼具稀土、配体的功能.因为稀土的抗肿瘤作用,致使稀土配合物也具有抗肿瘤活性,且发现其抗肿瘤活性明显优于稀土或配体.通过实验表明人体可以吸收微量稀土元素,产生有害毒性或副作用.因此如何研究出高效、低毒的稀土配合物抗癌药物是当今的主要研究目标.对近几年来已研究出且具备...     

荧光法研究手性金属配合物与DNA的作用机理

以溴化乙锭为荧光探针，研究手性金属配合物［Ｎｉ（ｐｈｅｎ）３］＾＋和［Ｆｅ（ｐｈｅｎ）３］＾２＋与ＤＮＡ的反应机理。结果表明，配合物与ＤＮＡ作用存在插入和静电结合两种模式，即部分菲咯啉配体插入ＤＮＡ双螺旋碱基对中，同时带正电荷的配合物与ＤＮＡ的磷酸基团发生静电结合。     

单核锇配合物的合成、晶体结构及其与DNA的作用

使用溶剂热合成法,以p-bitmb配体(1,4-二(1-咪唑基-亚甲基)-2,3,5,6-四甲基苯)与[(η6-cymene)Os(μ-Cl)Cl]2或[(η6-bip)Os(μ-Cl)Cl]2为原料,合成了2种单核芳基锇配合物,并利用核磁、质谱、元素分析和X射线单晶衍射等手段对配合物进行了表征。配合物1属于单斜晶系,P21/c空间群,为一个单核锇的结构。中心锇原子与2个配体p-bitmb上的氮原子以及氯原子进行配位,2个配体的另一个咪唑基团通过一个亚甲基碳原子进行连接形成咪唑嗡离子,形成一个类似"碗"状的结构。一个氯离子通过氢键装载在结构的空腔内。利用核磁共振氢谱研究了结构中亚甲基的来源,并研究了配合物在缓冲溶液中的稳定性。用紫外吸收光谱、圆二色谱以及粘度法研究了配合物与DNA的相互作用,结果表明,配合物中的亚甲基来自于溶剂二氯甲烷。配合物以嵌入的方式与CT-DNA相互作用,结合常数分别为3.222×10~4 L·mol-1 (1)和1.53×10~4 L·mol-1 (2),同时配合物会减弱DNA的碱基堆积作用并可以使DNA发生解旋。     

桑色素及其配合物与DNA作用的研究

桑色素 (Morin)是黄酮类化合物 ,具有一定的抗肿瘤活性 [1] .前文 [2 ] 以桑色素为配体合成了 6种过渡金属的配合物 ,并研究了这些配合物与配体对超氧阴离子自由基的清除作用和抗肿瘤活性 .研究表明 ,配合物对超氧阴离子自由基的清除作用明显高于配体 ,桑色素合铜 ( )和桑色素合锌 ( )配合物对 Hep- 2 ,BHK- 2 1和 HL - 6 0癌细胞瘤株的抑制作用强于配体 .配合物具有比单一有效成分更显著的药效 [3 ,4 ] .本文采用荧光方法和电化学方法研究了桑色素和抗肿瘤活性较强的桑色素合铜 ( )、桑色素合锌 ( )与 DNA在生理条件下的相互作用 ,试图…     

The preparation of nano‐scope chitosan‐oligomer copper complexes and their interaction with DNA

Water‐soluble low molecular weight chitosan of nanometer level and its copper complexes were prepared, and characterized by IR spectra, elemental analysis and gel permeation chromatography (GPC). The modes and mechanism of these copper complexes interaction with DNA were studied by a fluorescent probe method and electrophoresis analysis. It is suggested that there are electrostatic and intercalation modes of copper complexes interacting with DNA. At first, the cationic complex electrostaticly binds to the negatively charged phosphate backbone of DNA, and then a portion of the complex intercalates between the base pairs on the DNA duplex strand. Copyright © 2005 John Wiley & Sons, Ltd.     

Hbbimp的金属配合物的合成、表征及与DNA的作用研究

合成了四种2,6-N,N-二[二(2-苯并咪唑甲基)]氨甲基-4-甲基苯酚(Hbbimp)的金属(Zn2+、Mn2+、Eu3+、Nd3+)配合物,并用红外、此外、摩尔电导、元互分析表征了它们的结构。用凝胶电泳实验研究了它们与PBR322DNA的作用,发现在37℃时四种金属配合物与DNA的作用效果均不明显;在50℃,pH8.0时,仅两种稀土(Eu3+和Nd3+)配合物可将大部分超螺旋DNA(CCC带)转化为缺刻产物(OC带);在37℃,[H2O2]<1×10-3mol/L,[稀土配合物]:[H2O2]=1∶20时,配合物在较低浓度时即可将CCC带全部转化为OC带.     

DFT studies of temperature effect on coordination chemistry of Cu(II)-trimethoprim complexes

The computational analysis of geometrically different copper-trimethoprim complexes, experimentally formed at two different temperatures, was performed using Density Functional Theory (DFT) method. Initial geometries of copper-trimethoprim complexes 1, 2, and 3 were obtained from crystallographic data. These three geometries of complexes 1, 2, and 3 were fully optimized using B3LYP/BLYP hybrid density functional methods along with 6-31G and LANL2DZ basis sets at two temperatures, 298 and 352 K. The results obtained were compared with the experimental data and show that complex 1 is the most stable geometry while complex 3 is unstable/intermediate geometry and can be converted to stable form after the recrystallization process. Moreover, LANL2DZ basis set gives more accurate (with respect to experimental) results as compared to 6-31G.     

Polymer complexes. LXXII. Spectroscopic studies,thermodynamics, DNA binding and biological activity of polymer complexes

A novel series of copper polymer complexes ( 1 – 4 ) were synthesized and characterized using various spectroscopic techniques. Spectra of all polymer complexes a tetragonal distorted geometry for the Cu(II) ion. The electronic spectra, magnetic moments and electron spin resonance results indicate tetragonal distortion geometry for the Cu(II) polymer complexes. The effects of various solvents on absorption spectra of the ligand are discussed. A prediction of the interaction of the ligand against anti‐cancer receptors was carried out using AutoDock server. The affinity of the compounds to calf thymus DNA was determined through UV–visible DNA binding titration, and intrinsic binding constant (K_b) was found to be 4.16 × 10³, 3.10 × 10⁵, 3.18 × 10⁴ and 2.91 × 10⁵ for polymer complexes 1 – 4 , respectively. The antimicrobial activity of the polymer complexes against bacterial species (Bacillus cereus, Staphylococcus aureus, Escherichia coli, Klebsiella pneumonia, Enterococcus faecalis and Pseudomonas aeruginosa) and fungal species (Aspergillus niger, Fusarium oxysporum and Candida albicans) was investigated.     

DNA structure, binding mechanism and biology functions of polypyridyl complexes in biomedicine

There is considerable research interest and vigorous debate about the DNA binding of polypyridyl complexes including the electron transfer involving DNA. In this review, based on the fluorescence quenching experiments, it was proposed that DNA might serve as a conductor. From the time-interval CD spectra, the different binding rates of A- and A-enantiomer to calf thymus DNA were observed. The factors influencing the DNA-binding of polypyridyl complexes, and the potential bio-functions of the complexes are also discussed.     

Effects of geometric isomerism and anions on the kinetics and mechanism of the stepwise formation of long-range DNA interstrand cross-links by dinuclear platinum antitumor complexes

Reported herein is a detailed study of the kinetics and mechanism of formation of a 1,4-GG interstrand cross-link by the dinuclear platinum anticancer compound [15N][{cis-PtCl(NH3)2}2{mu-NH2(CH2)6NH2}]2+ (1,1/c,c (1)). The reaction of [15N]1 with 5'-{d(ATATGTACATAT)2} (I) has been studied by [1H,15N] HSQC NMR spectroscopy in the presence of different concentrations of phosphate. In contrast with the geometric trans isomer (1,1/t,t), there was no evidence for an electrostatic preassociation of 1,1/c,c with the polyanionic DNA surface, and the pseudo-first-order rate constant for the aquation of [(15)N]1 was actually slightly higher (rather than lower) than that in the absence of DNA. When phosphate is absent, the overall rate of formation of the cross-link is quite similar for the two geometric isomers, occurring slightly faster for 1,1/t,t. A major difference in the DNA binding pathways is the observation of phosphate-bound intermediates only in the case of 1,1/c,c. 15 mM phosphate causes a dramatic slowing in the overall rate of formation of DNA interstrand cross-links due to both the slow formation and slow closure of the phosphate-bound monofunctional adduct. A comparison of the molecular models of the bifunctional adducts of the two isomers shows that helical distortion is minimal and globally the structures of the 1,4 interstrand cross-links are quite similar. The effect of carrier ligand was investigated by similar studies of the ethylenediamine derivative [15N]1-en. A pKa value of 5.43 was determined for the [15N]1,1/c,c-en diaquated species. The rate of reaction of [15N]1-en with duplex I is similar to that of 1,1/c,c and the overall conformation of the final adduct appears to be similar. The significance of these results to the development of "second-generation" polynuclear platinum clinical candidates based on the 1,1/c,c chelate (dach) series is discussed.     

Synthesis,structural and spectral properties of Au complexes: luminescence properties and their non‐covalent DNA binding studies

Gold complexes of 1,3‐ bis‐pyridylimidazolium chloride ( L1 ), 1,3‐bis‐[2,6‐diisopropylphenyl]imidazolium chloride ( L2 ) and 1,3‐bis‐[benzyl]benzimidazolium chloride ( L3 ) were synthesized and characterized by analytical methods. For the complexes, electronic spectral results show that there is a marked difference in the band feature observed in the spectra, ascribed to the greater relativistic effect of gold. In fluorescence studies, the complexes develop emission bands in the visible region (400–600 nm) after excitation at around 350 nm. Au complex–DNA binding was studied, and it was observed that genomic DNA isolated from the U373‐GB cell line was fragmented and in some cases degraded by the Au complexes. Furthermore, the intensity of the DNA band increased when concentration of the metal complex was augmented. This study shows that the DNA cleavage is mediated by the Au complex. Copyright © 2013 John Wiley & Sons, Ltd.     

Synthesis,interaction with double-helical DNA and biological activity of new Pt(II) and Pd(II) complexes with phenylglycine

The mononuclear palladium(II) (1) and platinum(II) (2) complexes containing phenylglycine have been synthesized and characterized by elemental analysis, IR spectra, and ¹H NMR spectra. The structure of 1 was determined by X-ray diffractometry. The interaction between the complexes and fish sperm DNA (FS-DNA), adenosine-5′-triphosphate (ATP), and adenine (Ade) were investigated by UV absorption spectra, the interaction mode of the complex binding to DNA was studied by fluorescence spectra and viscometry. The results indicate that the two complexes have different binding affinities to DNA, complex 2 > complex 1. Gel electrophoresis assay demonstrates that the two complexes have the ability to cleave pBR322 plasmid DNA. Cytotoxicity experiments were carried out toward four different cancer cell lines, and 1 shows lower inhibitory efficiency than 2, consistent with the binding affinities towards DNA.     

荧光法研究丝裂霉素C与DNA的作用机制

以溴化乙锭(ethidiumbromide,EB)为荧光探针,研究了丝裂霉素C(mitomycinC,MMC)与小牛胸腺DNA(CTDNA)的作用机制。对荧光光谱、偏振荧光、Scatchard图、DNA热变性曲线等研究的结果表明,经Na2S2O4还原活化后的MMC能与DNA发生作用,并且存在沟槽和部分嵌入两种结合方式。这一结果进一步证实了前人提出的MMC与DNA之间发生交联反应的结论。