表柔比星-铜体系与DNA作用的光谱和电化学法研究

表柔比星是临床上广泛用于治疗增殖很快的肿瘤. 应用紫外、荧光、黏度、循环伏安等方法研究了表柔比星及表柔比星-Cu^2＋体系与DNA的作用. 结果发现: 在pH＝7.4时, 表柔比星可与Cu^2＋形成稳定体系. 加入DNA后表柔比星-Cu^2＋体系的紫外吸收明显降低; Scatchard图表明表柔比星-Cu^2＋体系对溴化乙锭(EB)与DNA的结合为竞争性抑制; 同时此体系可使DNA-EB体系荧光偏振度增大; 使DNA的热变性温度(t_m)上升; 黏度增大; 循环伏安法表明DNA的加入使得表柔比星及表柔比星-Cu^2＋体系的式量电位正移; 凝胶电泳表明表柔比星-Cu^2＋体系对pBR322 DNA有非常好的水解切割活性. 综合以上结果得出: 表柔比星及表柔比星-Cu^2＋体系与DNA之间均为嵌插作用; 表柔比星-Cu^2＋体系具有更好的水解切割活性. 这些结果可为合理改善药效、降低抗癌药物毒性和设计新药提供依据.     

表柔比星-铁体系与DNA作用的光谱和电化学法研究

表柔比星是临床上广泛用于治疗增殖很快肿瘤的药物.应用紫外、荧光、园二色、黏度、循环伏安等方法研究了表柔比星及表柔比星-Fe2+体系与DNA的作用.结果发现,在pH=7.4时表柔比星可与Fe2+形成稳定体系,加入DNA后表柔比星-Fe2+体系的紫外吸收明显降低.Scatchard图表明,表柔比星-Fe2+体系对溴化乙锭(EB)与DNA的结合为竞争性抑制,同时此体系可使DNA-EB体系荧光偏振度增大,使DNA的热变性温度(tm)上升,黏度增大.循环伏安法表明,DNA的加入使得表柔比星及表柔比星-Fe2+体系的式量电位正移.园二色谱法表明,随着表柔比星-Fe2+体系的加入,DNA碱基间作用能迅速减弱.综合以上结果得出:表柔比星及表柔比星-Fe2+体系与DNA之间均为嵌插作用,而且表柔比星-Fe2+体系具有比单纯表柔比星更好的嵌插效果.这些结果可为合理改善药效、降低抗癌药物毒性和设计新药提供依据.     

(E)-2-乙氧基乙基-2-氰基-3-((4-(2,4-二氟苯氧基)苄基)氨基)-3-甲氧基丙烯酸酯对超螺旋质粒DNA的特异性切割(英文）

研究了一种新型丙烯酸酯 (E)-2-乙氧基乙基-2-氰基-3-((4-(2,4-二氟苯氧基)苄基)氨基)-3-甲氧基丙烯酸酯(MAZ)对超螺旋pUC19 DNA的定点切割作用。利用紫外吸收、荧光光谱、凝胶电泳和DNA测序技术研究其核酸切割特异性。紫外吸收光谱的红移和减色效应,以及静态荧光淬灭表明MAZ与DNA的作用属于典型的插入模式。不仅如此,凝胶电泳条带的变化以及DNA测序结果表明DNA的定点切割是通过DNA双链的分步水解完成。     

全反式维甲酸合钇(Ⅲ)配合物对DNA的切割和键合作用(英)

以紫外光谱、荧光光谱、粘度法和凝胶电泳方法研究了全反式维甲酸合钇(Ⅲ)配合物与DNA的作用。结果表明，该配合物能在生理条件下比配体和金属离子更有效地切割质粒DNA，体系离子强度和pH值的变化对配合物的切割活性有较大影响，自由基捕捉剂的加入不影响配合物的切割活性。该配合物对DNA的切割可能通过水解机理进行。该配合物可使DNA的粘度增加，使EB-DNA体系的荧光强度和DNA溶液的紫外吸收强度降低。据此推断，该配合物主要以嵌入方式与DNA作用。     

曙红B及变色酸与核酸作用的光谱学性质研究

利用荧光光谱法、紫外-可见吸收光谱法、圆二色谱法、凝胶电泳法对曙红B及变色酸与核酸的作用机理进行了探讨. 当ct-DNA浓度增加时,曙红B和变色酸的荧光光谱呈荧光增强趋势;紫外-可见光谱呈下降趋势;并使ct-DNA圆二色谱正负峰吸收强度呈现一定的降低;琼脂糖凝胶电泳实验中,二者在泳道中与DNA作用发出的荧光在紫外灯下皆清晰可见. 并将所得结果与溴化乙锭-DNA体系性质进行对比,为寻找高效低毒的DNA分子荧光探针提供了实验基础.     

两个带呋喃悬臂不对称大环双核铜配合物的合成、结构及性质(英文)

合成并表征了2个不对称大环双核铜配合物[Cu2(L1)Cl2]·CH3CN(1)和[Cu2(L2)Br2]·CH3CN·H2O(2)。配合物与CT-DNA的作用通过紫外-可见光谱,粘度实验,圆二色谱和凝胶电泳实验进行了研究。紫外-可见光谱的结果表明配合物与DNA的结合常数分别为6.2×105和7.2×105,圆二色谱的实验表明配合物能与DNA较好的结合,粘度实验表明配合物与DNA的结合为非典型的插入模式,凝胶电泳实验显示配合物通过氧化机理对DNA有较强的切割活性。     

(E)-2-氰基-3-[4-(2,4-二氟苯氧基)-苄氨基]-3-甲氧基-丙烯酸2-乙氧基乙酯对超螺旋质粒DNA的特异性切割（英文）

研究了一种新型丙烯酸酯(E)-2-氰基-3-[4-(2,4-二氟苯氧基)-苄氨基]-3-甲氧基-丙烯酸2-乙氧基乙酯(MAE)对超螺旋pUC19 DNA的定点切割作用。利用紫外吸收、荧光光谱、凝胶电泳和DNA测序技术研究其核酸切割特异性。紫外吸收光谱的红移和减色效应,以及静态荧光猝灭表明MAE与DNA的作用属于典型的插入模式。不仅如此,凝胶电泳条带的变化以及DNA测序结果表明DNA的定点切割是通过DNA双链的分步水解完成。     

光谱联合电泳法研究双酚A与肿瘤相关DNA的相互作用

研究双酚A与人类肿瘤相关DNA(抑癌基因p53 DNA和癌基因C-myc DNA)的相互作用。分别采用紫外、荧光和圆二色等光谱方法和聚丙烯酰胺凝胶电泳法研究了双酚A与人类肿瘤相关DNA(抑癌基因p53 DNA和癌基因C-myc DNA)的相互作用模式。其中紫外、荧光和圆二色滴定实验均表明了嵌插作用的存在,离子强度实验、KI猝灭对比实验和凝胶电泳实验证实了静电和嵌插作用的共同作用,可进一步影响DNA的双螺旋构象。     

硫杂蒽酮镍（II）配合物与DNA的作用研究

合成了O-（硫杂蒽酮-[2]-基）-氧乙酸镍（II）配合物。通过元素分析,IR, DTA-TG谱对其结构进行了表征。研究表明：配体羧羰基脱质子后与镍离子配位,配合物中含有一定量的配位水。同时以紫外可见光谱、荧光光谱、园二色谱,电化学方法和凝胶电泳方法研究了该配合物与DNA的作用。结果表明,该配合物能在生理条件下比配体和金属离子更有效地切割质粒DNA,自由基捕捉剂的加入不影响配合物的切割活性。该配合物使DNA溶液的紫外吸收强度和园二色吸收强度降低,DNA的存在可使该配合物的氧化还原活性降低。与溴化乙锭和DNA的竞争反应说明,该配合物主要以嵌入方式与DNA结合。     

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

应用紫外、荧光、黏度等方法, 对二(2-苯并咪唑亚甲基)胺合铜(II)配合物与小牛胸腺DNA作用方式进行了研究. 配合物与DNA作用时, 使紫外吸收明显减色, 荧光降低, 黏度降低; Scatchard图表明配合物对溴化乙锭(EB)与DNA的结合为非竞争性抑制. 实验结果表明, 配合物与DNA作用方式可能为静电结合.     

蚕沙叶绿素锌配合物对DNA的光断裂作用

利用从蚕沙中提取的叶绿素(CHL)制得了锌叶绿素(Zn-CHL)配合物.采用紫外-可见光谱、CD光谱和黏度法研究了Zn-CHL与小牛胸腺DNA(ct-DNA)的相互作用,并采用琼脂糖凝胶电泳研究了光照条件下Zn-CHL对pBR322 DNA的切割能力.结果表明,Zn-CHL与ct-DNA的作用方式属于外部结合模式,其结合常数为2.32×105L/mol,Zn-CHL在可见光照射下具有切割DNA的能力.     

配合物[Co2(EGTB)Cl2]•(BF4)2•5H2O与DNA相互作用的研究

用紫外光谱法、荧光光谱法、黏度法、凝胶电泳法研究了双核钴(II)配合物[Co2(EGTB)Cl2]•(BF4)2•5H2O和DNA的相互作用, 在pH＝7.2的缓冲体系中, 求得配合物与DNA的结合常数. 结果表明, 配合物在接近生理条件下能有效地断裂pBR322DNA, 同时可使DNA的粘度增加, 使EB-DNA体系的荧光强度降低. 配合物与DNA的荧光光谱和紫外光谱表明, 配合物与DNA的作用既存在部分插入结合又存在静电结合模式.     

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.     

DNA-binding spectra and cleavage studies on Ce(III) complex of 2-[(Trifluoroaceto)aceto]thinophene-piperidine ligands

A kind of complex of CeTTA₄ · HP (TTA = 2-[(Trifluoroaceto)aceto]thinophene, HP = piperidine) has been synthesized and characterized, and its DNA-binding properties of CeTTA₄ · HP using UV spectra, fluorescent spectra, thermal denaturation, viscometry, molecular modeling and CV (cyclic voltammetry). The results show that the binding-mode between CeTTA₄ · HP and DNA is intercalation. The interaction between the complex and DNA has also been investigated by gel electrophoresis. Interestingly, we found that the CeTTA₄ · HP complex can cleave circular plasmid pBR322 DNA at pH 7.2 and 37°C. In addition, BDNPP was chosen (bis(2,4-dinitrophenyl)-phosphate) as a model compound to further study its cleavage mechanism for pBR322 DNA. From the first-order kinetics equation, we prove indirectly the mechanism may be hydrolytic cleavage.     

Studies on the Interaction of Dinitratobis（phen） Cadmium Complex with DNA

DNA-binding properties of the dinitratobis（phen） cadmium complex [Cd（phen）2（NO3）2] （where phen = 1,10-phenanthroline） have been investigated with absorption titration, fluorescence spectroscopy, viscosity measurement, molecular modeling and density functional theory （DFT） calculations. The results indictate DNA-binding mode of the complex to be weak groove binding rather than partial intercalative interaction expected of the extended planar aromatic phen ring. In addition, the DNA cleavage study was carried out by gel electrophoresis experiment. The results showed that the complex both hardly cleaves pBR322 DNA in the absence and present ascorbate. So it is suggested that the formation of cadmium complex can decrease cadmium toxicity to some extents.     

基于镱和铒的α-噻吩甲酰丙酮-哌啶配合物与DNA之间相互作用的DNA探针和切割研究

两种[Ln(TTA)4].HP (Ln =Yb, Er)配合物被合成并表征。通过紫外可见光谱、荧光光谱、粘度和分子模拟研究了他们与DNA的键合特征。研究结果表明：它们能插入双链的DNA。更重要的是它们的荧光强度能被DNA增强,因此,一种灵敏的荧光检测DNA的方法被发展。两种配合物与质粒DNA的切割反应在凝胶电泳上展开。有意义的是,我们发现在pH=7.2 和 37℃下,两种化合物都能切割超螺旋质粒DNA。另外,我们选择BDNPP作为模型化合物进一步研究了它们对质粒DNA的切割机理,从一级动力学方程,我们间接证明可能是水解切割机理。     

Synthesis, Characterization, DNA-binding Properties and DNA Cleavage of a New Ternary Copper(Ⅱ) Complex with Mixed-ligands of Tridentate Schiff Base and 1,10-Phenanthroline

A new copper(II) complex, [Cu(naph‐leu)phen]CH₃OH·0.5H₂O, in which naph‐leu is the tridentate Schiff base ligand derived from the condensation of 2‐hydroxy‐1‐naphthaldehyde and L‐leucine, phen is phenanthroline, has been synthesized and characterized by elemental analyses, IR spectra and single crystal X‐ray diffraction. The DNA‐binding properties of this complex have been investigated by absorption spectra, fluorescence spectra and circular dichroism (CD) spectra, as well as viscosity measurement. Results show that this copper(II) complex binds to calf thymus DNA (CT‐DNA) in an intercalative mode and its intrinsic binding constant K_b is 4.87×10³ L·mol^?1. Furthermore, the DNA cleavage activity of this copper(II) complex has also been investigated by submarine gel electrophoresis. Interestingly, it was found that this complex can cleave the supercoiled plasmid pBR322 DNA to both nicked and linear forms.     

具有分子内折叠结构锌配合物的合成，与DNA键合及其对DNA切割作用研究

本文报道了一个锌配合物[Zn(bipy)(pmal)(H2O)]·2H2O（其中bipy = 2,2’-联吡啶, pmal = 苯基丙二酸）的合成,晶体结构及其光谱学研究。并通过单晶X射线衍射,元素分析,红外光谱等手段对它进行了表征。同时,利用紫外光谱和荧光光谱方法考察了该配合物与小牛胸腺DNA的键和作用。琼脂糖凝胶电泳实验的结果说明该配合物的平面结构对pBR 322DNA切割作用显著。     

Synthesis,DNA-binding,cytotoxicity, and cleavage studies of unsymmetrical oxovanadium complexes

An unsymmetrical oxovanadium complex [VO(SAA)(phen)] (1) (SAA?=?salicylidene anthranilic acid, phen?=?phenanthroline) and its derivative [VO(MOSAA)(phen)] (2) (MOSAA?=?2-hydroxy-4-methoxysalicylidene anthranilic) have been synthesized and characterized by elemental analysis, UV-Vis, ES-MS, IR, and ¹H NMR. The interaction of these two complexes with calf thymus DNA (CT-DNA) was investigated by absorption titration, fluorescence spectra, viscosity measurements, and thermal denaturation. Their photocleavage reactions with pBR322 supercoiled plasmid DNA were investigated by gel electrophoresis. The cytotoxicity of these two complexes against myeloma cell (Ag8.653) and gliomas cell (U251) have been assessed by MTT assay. The results show that both 1 and 2 bind to CT-DNA in classical intercalation, and the DNA-binding affinity of 1 is larger than that of 2. These complexes enhance the oxidative cleavage of supercoiled pBR322 DNA and both complexes have cytotoxic activities against Ag8.653 and U251 cell lines. Complex 1 has more potent inhibitory effect against the two cell lines than 2.