不对称大环双核Ni(Ⅱ)配合物的DNA切割性能研究

本文利用模板导向的方式合成了一种含有不对称侧链的大环双核金属Ni(Ⅱ)配合物(大环配体由3-溴甲基-5-甲基水杨醛,乙二胺,N,N-二(氨丙基)-2呋喃甲胺分步合成得到),其结构通过红外光谱、元素分析、X-射线单晶衍射进行了表征。利用紫外光谱、分子荧光和粘度试验对配合物与DNA的相互作用进行了研究,结果表明配合物与CT-DNA的结合常数K=4.8×104mol-1.L荧光淬灭常数Ksv=7.12×103mol-1.L;同时机理研究表明配合物与CT-DNA结合方式为插入模式。     

两个多胺铜配合物的合成，晶体结构以及DNA切割活性

本文以配体N,N′-二(3-氨丙基)-4-甲氧基苄胺(amba)与4,4′-联吡啶,铜盐反应合成了两种多胺Cu(Ⅱ)配合物[Cu(amba)Cl2](1)和[Cu(4,4′-bipy)(amba)(ClO4)]ClO4(2),通过红外光谱、质谱和X-射线单晶衍射对其结构进行了表征。利用紫外吸收光谱、分子荧光,电化学以及粘度试验研究了配合物与小牛胸腺DNA(CT-DNA)的相互作用方式。通过紫外吸收光谱得到配合物1和2与DNA的结合常数Kb分别为1.3×104 mol-1.L和1.7×104 mol-1.L,荧光光谱得到配合物1和2的荧光淬灭常数分别为1.04×103mol-1.L和1.81×103 mol-1.L,表明了配合物1和2与CT-DNA结合方式均为静电模式。凝胶电泳实验的结果表明配合物对pBR322 DNA的切割均为水解切割。     

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。     

单取代大环多胺铜(Ⅱ)-铂(Ⅱ)异核配合物的合成、表征及其与DNA的作用

本文以1-[N-2′-(2″-吡啶基)乙基]甲氨酰甲基-1,4,7,10-四氮杂环十二烷为配体合成了一种铜(Ⅱ)-铂(Ⅱ)异核配合物,并用X-射线衍射单晶结构分析测定了配合物的晶体结构。该配合物晶体属三斜晶系,P1空间群,铜(Ⅱ)以五配位方式形成变形四方锥构型,铂(Ⅱ)以四配位方式形成平面四方构型。琼脂糖凝胶电泳实验证明配合物既能结合DNA,也能在还原剂存在下切割DNA。圆二色光谱表明配合物与DNA以非嵌入方式结合。     

镍(Ⅱ)、镉(Ⅱ)与去甲基斑蝥酸钠和咪唑配合物的结构、与DNA/BSA的作用及抗增殖活性(英文)

以2种配体去甲基斑蝥酸钠(Na2DCA=7-氧杂二环[2.2.1]庚烷-2,3-二甲酸钠)和咪唑(IM),分别与镍(Ⅱ)和镉(Ⅱ)的醋酸盐通过溶液法合成了2种配合物[Ni(IM)(DCA)(H2O)2]·2H2O(1),[Cd2(IM)4(DCA)2]·2H2O(2)。应用元素分析、热重分析、红外光谱及X-射线单晶衍射法对配合物的组成和结构进行了表征。配合物1与2的中心离子分别与咪唑的亚胺氮原子、去甲基斑蝥酸根的羧基氧原子和醚键氧原子配位,配位数均为6,分别为单核(1)和双核(2)配合物。通过紫外光谱法、荧光光谱法和粘度法研究了配合物与DNA的相互作用。结果表明,配合物能通过部分插入模式与DNA发生较强的结合作用(Kb:5.51×103(1)、1.01×103(2)L·mol-1)。同时,利用荧光光谱法研究了配合物与牛血清白蛋白(BSA)的相互作用。配合物能与BSA发生强烈的相互作用(KA:1.91×105(1)和6.17×105(2)L·mol-1),结合位点数均为1。测试了配合物对人肝癌细胞(SMMC7721)和人乳腺癌(MCF-7)的体外抗增殖活性。结果显示,配合物对不同癌细胞具有选择性抑制作用。镍配合物(1)对SMMC7721的抗癌活性较去甲基斑蝥酸钠有明显提高。     

吡咯甲亚胺镍/铜/锌配合物的合成、荧光性质及镍、铜配合物的晶体结构

合成并表征了3个配合物NiL(1),Cu_2L_2(2)和Zn_2L_2(3)(H_2L=1,2-双(3,5-二甲基-4-乙氧羰基-吡咯-2-基)苯)。单晶衍射结果表明在配合物1中,脱质子配体用4个氮原子与金属Ni(Ⅱ)配位,中心金属离子为扭曲的平面正方形配位构型。而双核配合物2拥有双螺旋结构,每个配体桥联2个具有平面正方形配位构型的铜中心。推测配合物3和2的结构类似。此外还研究了配体和配合物的荧光性质。     

配合物[Ni(IDB)2]2·(SO4)2·3CH3CH2OH·CH3OH·5H2O的合成、晶体结构及其荧光光谱的研究

标题配合物是由三齿配体Ⅳ,Ⅳ-二(2-苯并咪唑甲基)亚胺(IDB)与NiSO4·6H2O在甲醇-乙醇溶液中反应得到的紫色 晶体.X射线衍射测定了其单晶结构.结构分析表明,镍(Ⅱ)分别与两个IDB配体中的苯并咪唑的四个氮和胺基的两个 氮配位形成畸变的八面体构型.研究了纳米金和小牛胸腺DNA对配合物荧光的影响,探讨了配合物的荧光猝灭与恢复 的可能机理.     

2-(2-吡啶基)苯并噻唑的Cu(Ⅱ),Ni(Ⅱ),Cd(Ⅱ)金属配合物的合成以及与DNA相互作用的研究

以金属Cu(Ⅱ),Ni(Ⅱ),Cd(Ⅱ)为中心离子,分别合成2-(2-吡啶基)苯并噻唑为配体的配合物,其中得到了以Cu(Ⅱ)为中心离子的晶体,并培养出了单晶.该配合物是五配位的三斜晶系,上述金属配合物都能与DNA结合,并能有效断裂DNA链,可以通过与癌症细胞的DNA发生解旋DNA的作用从而引起癌症细胞DNA的损伤,使癌细胞的DNA在复制和转录的过程中受到阻碍,从而阻止癌细胞的生长和分裂,并导致癌细胞的死亡.为其在药物开发和分子生物学中的应用提供了有价值的信息.     

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.     

双希夫碱型Cu（Ⅱ）和Mn（Ⅱ）配合物的合成及其生物活性的研究

本文设计合成了一种具有较好平面性和疏水性的新型3,5-二碘水杨醛缩4,4’-二氨基二苯甲烷双席夫碱的Cu(Ⅱ)和Mn(Ⅱ)的配合物,用红外光谱、元素分析、TG-DSC和摩尔电导对其结构进行表征,并对双席夫碱的结构、配合物的稳定常数及配合物与ct-DNA的作用情况进行研究。结果表明,配合物的结构为M2L2(M=Cu(Ⅱ)和Mn(Ⅱ)),稳定常数分别为3.78×105和1.96×105L/mol,结合常数分别为3.78×105和1.96×105L/mol,通过键合常数可知两种配合物可以很好地以插入模式与DNA结合,它们与DNA的作用强弱顺序为:Cu2L2Mn2L2。     

钯(Ⅱ)三元配合物稳定性及其与DNA作用研究

合成了[Pd(bipy)(DL-gly)]Cl•2H₂₂O(2)两个钯三元配合物. 配合物１和２的稳定常数对数值lgβ分别为13.81和13.71, 表征常数ΔlgK、lgX高于统计值, 表明在配合物分子内存在d-p π电子协同效应. 紫外光谱、荧光光谱结果表明, 配合物１和２与鱼精DNA主要以插入方式键合, 键合常数分别为2.37×10⁶(1)和4.57×10⁶(2). CD光谱图也显示, 配合物与DNA分子之间发生了作用. 质粒pBR322 DNA的凝胶电泳图表明, 配合物浓度在3.0０×10^-3～7.5０×10^-4 mol •L^-1范围内对DNA分子有切割作用, 配合物浓度低于3.75×10^-4 mol •L^-1时则主要以插入方式与DNA键合.     

DNA binding, prominent DNA cleavage and efficient anticancer activities of tris(diimine)iron(II) complexes

The complexes rac-[Fe(diimine)(3)](ClO(4))(2)1-4, where diimine = 2,2'-bipyridine (bpy) 1, 1,10-phenanthroline (phen) 2, 5,6-dimethyl-1,10-phenanthroline (5,6-dmp) 3 and dipyrido[3,2-d:2',3'-f]quinoxaline (dpq) 4, have been isolated, characterized and their interaction with calf thymus DNA studied by using a host of physical methods. The X-ray crystal structure of rac-[Fe(5,6-dmp)(3)](ClO(4))(2)3 has been determined and the packing diagram shows the presence of two enantiomeric forms of the complex cations in the same unit cell. The structures of 1-4 in solution have also been studied using UV-Visible, Cyclic Voltammetry and ESI-MS data and all data available suggests that they retain their solid state structures even in solution. The absorption spectral titrations of the iron(ii) complexes with CT DNA reveal that the DNA binding affinities of the complexes vary in the order, 4 (K(b): 9.0 × 10(3)) > 2 (6.8 × 10(3)) > 3 (4. 8 × 10(3)) > 1 (2.9 × 10(3) M(-1)). The DNA interaction of dpq complex (4) involves partial insertion of the extended phen ring in between the DNA base pairs, which is deeper than that of phen (2). The 5,6-dmp (3) complex is involved in groove binding in the major groove of DNA. The lower DNA binding affinity of 1 is due to electrostatic interaction of the cationic complexes with exterior phosphates of DNA. The EthBr displacement assay and DNA viscosity study support these DNA binding modes and the above trend in DNA binding affinities. The complexes of 1 and 2 show induced CD (ICD) upon interaction with CT DNA while 3 and 4 bound to DNA exhibit inversion in the positive band with the helicity band showing very small changes, which implies that 3 and 4 bind enantiopreferentially to DNA. The DNA cleavage abilities of 1-4 have been observed at 10 μM concentration of complexes in the presence of 100 μM H(2)O(2) and the DNA cleavage efficiency (> 90%) follows the order 3 > 1 > 2 > 4. The anticancer activity of 1-4 against human breast cancer cell line (MCF-7) has also been studied. The IC(50) values of the complexes at different incubation time intervals of 24 and 48 h follow the order, 3 (0.8, 0.6) < 4 (20.0, 17.0) < 2 (28.0, 22.0) < 1 (32.0, 29.0 μM). Interestingly, 3 exhibits anticancer activity more potent than 1, 2 and 4 and cisplatin for both 24 and 48 h. It induces cell death both through apoptosis and necrosis mechanisms, as revealed by morphological assessment data obtained by using AO/EB and Hoechst 33258 fluorescence staining methods.     

A series of oxyimine-based macrocyclic dinuclear zinc(II) complexes enhances phosphate ester hydrolysis, DNA binding, DNA hydrolysis, and lactate dehydrogenase inhibition and induces apoptosis

A symmetrical macrocyclic dizinc(II) complex (1) has been synthesized by using the ligand (L(1)) [μ-11,24-dimethyl-4,7,16,19-tetraoxa-3,8,15,20-tetraazatricyclo-[20.3.1.1(10,13)] heptacosa-1(25),2,7,9,11,13(27),14,20,22(26),23-decaene-26,27-diol]. A series of unsymmetrical macrocyclic dizinc(II) complexes (2-6) has been synthesized by Schiff base condensation of bicompartmental mononuclear complex [ZnL] [μ-3,16-dimethyl-8,11-dioxa-7,12-diazadicyclo-[1.1(14,18)] heptacosa-1,3,5(20),6,12,14,16,18(19)-octacaene-19,20-diolato)zinc(II)] with various diamines like 1,2-diamino ethane (L(2)), 1,3-diamino propane (L(3)), 1,4-diamino butane (L(4)), 1,2-diamino benzene (L(5)), and 1,8-diamino naphthalene (L(6)). The ligand L(1) and all the zinc(II) complexes were structurally characterized. To corroborate the consequence of the aromatic moiety in comparison to the aliphatic moiety present in the macrocyclic ring on the phosphate ester hydrolysis, DNA binding and cleavage properties have been studied. The observed first order rate constant values for the hydrolysis of 4-nitrophenyl phosphate ester reaction are in the range from 2.73 × 10(-2) to 9.86 × 10(-2) s(-1).The interactions of complexes 1-6 with calf thymus DNA were studied by spectroscopic techniques, including absorption, fluorescence, and circular dichroism spectroscopy. The DNA binding constant values of the complexes were found in the range from 1.80 × 10(5) to 9.50 × 10(5) M(-1), and the binding affinities are in the following order: 6 > 5 > 1 > 2 > 3 > 4. All the dizinc(II) complexes 1-6 effectively promoted the hydrolytic cleavage of plasmid pBR322 DNA under anaerobic and aerobic conditions. Kinetic data for DNA hydrolysis promoted by 6 under physiological conditions give the observed rate constant (k(obs)) of 4.42 ± 0.2 h(-1), which shows a 10(8)-fold rate acceleration over the uncatalyzed reaction of ds-DNA. The comparison of the dizinc(II) complexes 1-6 with the monozinc(II) complex [ZnL] indicates that the DNA cleavage acceleration promoted by 1-6 are due to the efficient cooperative catalysis of the two close proximate zinc(II) cation centers. The ligand L(1), dizinc(II) complexes 1, 3, and 6 showed cytotoxicity in human hepatoma HepG2 cancer cells, giving IC(50) values of 117, 37.1, 16.5, and 8.32 μM, respectively. The results demonstrated that 6, a dizinc(II) complex with potent antiproliferative activity, is able to induce caspase-dependent apoptosis in human cancer cells. Cytotoxicity of the complexes was further confirmed by the lactate dehydrogenase enzyme level in HepG2 cell lysate and content media.     

Synthesis, characterization, interaction with DNA, and cytotoxic effect in vitro of new mono- and dinuclear Pd(II) and Pt(II) complexes with benzo[d]thiazol-2-amine as the primary ligand

A series of novel Pd(II) and Pt(II) complexes, [PdL(2)Cl(2)]·DMF (1), [Pd(2)(L-H)(2)(bpy)Cl(2)]·(H(2)O)(2)·DMF (2), [Pd(2)(L-H)(2)(phen)Cl(2)]·2H(2)O (3), [PtL(2)Cl(2)]·H(2)O (4), [Pt(2)(L-H)(2)(bpy)Cl(2)]·2H(2)O (5), and [Pt(2)(L-H)(2)(phen)Cl(2)]·H(2)O (6), where bpy = 2,2'-bipyridine, phen = 1,10-phenanthroline, and L = 1,3-benzothiazol-2-amine, have been synthesized and characterized. The competitive binding of the complexes to DNA has been investigated by fluorescence spectroscopy. The values of the apparent DNA binding constant, calculated from fluorescence spectral studies, were 3.8 × 10(6) (K(app)(4)), 2.9 × 10(6) (K(app)(1)), 2.4 × 10(6) (K(app)(6)), 2.0 × 10(6) (K(app)(5)), 1.2 × 10(6) (K(app)(3)), and 6.9 × 10(5) (K(app)(2)). The binding parameters for the fluorescence Scatchard plot were also determined. On the basis of the data obtained, it indicates that the six complexes bind to DNA with different binding affinities in the relative order 4 > 1 > 6 > 5 > 3 > 2. Viscosity studies carried out on the interaction of complexes with Fish Sperm DNA (FS-DNA) suggested that all complexes bind by intercalation. Gel electrophoresis assay demonstrates that all the complexes can cleave the pBR 322 plasmid DNA and bind to DNA in a similar mode. The cytotoxic activity of the complexes has been also tested against four different cancer cell lines. The results show that all complexes have activity against KB, AGZY-83a, Hep-G2, and HeLa cells. In general, the Pt(II) complexes were found to be more effective than the isostructural Pd(II) complexes. The mononuclear complexes exhibited excellent activity in comparison with the dinuclear complexes in these four cell lines. Moreover, on the KB cell line (the human oral epithelial carcinoma), the observed result seems quite encouraging for the six complexes with IC(50) values ranging from 1.5 to 8.6 μM. Furthermore, apoptosis assay with hematoxylin-eosin staining shows treatment with the six complexes results in morphological changes of KB cells. The results induce apoptosis in KB cells.     

DNA binding studies of new valine derived chiral complexes of tin(IV) and zirconium(IV)

Valine derived chiral complexes of SnCl4 (1) and ZrCl4 (2) were designed as potent antitumor agents. These complexes were characterized by elemental analysis, IR, 1H NMR, 119Sn NMR and ESI mass spectroscopy. In vitro binding studies of complexes 1 and 2 under physiological conditions at room temperature with CT-DNA were carried out employing UV-vis absorption titration, fluorescence studies and viscosity measurements. The extent of binding was quantified by Kb values of complexes 1 and 2 which were found to be 1.97×10(4) and 1.17×10(3) M(-1), respectively, suggesting that complex 1 has significantly greater DNA binding propensity in contrast to the complex 2. The mode of action at the molecular level was ascertained by the interaction of complex 1 with 5'GMP and 5'TMP which revealed that complex 1 binds via electrostatic mode with the oxygen of the negatively charged surface phosphate group of the DNA helix. The supercoiled pBR322 plasmid DNA cleavage activity of complex 1 was ascertained by gel electrophoresis assay.     

Synthesis, characterization, antibacterial activity, SOD mimic and interaction with DNA of drug based copper(II) complexes

Novel metal complexes of the second-generation quinolone antibacterial agent enrofloxacin with copper(II) and neutral bidentate ligands have been prepared and characterized with elemental analysis reflectance, IR and mass spectroscopy. Complexes have been screened for their in-vitro antibacterial activity against two Gram(+ve) Staphylococcus aureus, Bacillus subtilis, and three Gram((-ve)) Serratia marcescens, Escherichia coli and Pseudomonas aeruginosa organisms using the double dilution technique. The binding of this complex with CT-DNA has been investigated by absorption titration, salt effect and viscosity measurements. Binding constant is ranging from 1.3×10(4)-3.7×10(4). The cleavage ability of complexes has been assessed by gel electrophoresis using pUC19 DNA. The catalytic activity of the copper(II) complexes towards the superoxide anion (O2.-) dismutation was assayed by their ability to inhibit the reduction of nitroblue tetrazolium (NBT).     

1，4，7-三氮环壬烷衍生物铜、锌配合物切割DNA及催化对硝基苯磷酸单酯水解

系统研究了1,4,7-三(2-羟基丙基)-1,4,7-三氮环壬烷(L1)和1,2-双[N,N′-二(2-羟基丙基)-1,4,7-三氮杂环壬基]乙烷(L2)铜配合物([CuL1](ClO4)(NO3)和[Cu2L2](ClO4)4])以及锌配合物([ZnL1](ClO4)2)与CT-DNA的相互作用以及核酸酶活性和催化磷酸酯水解功能。两个铜配合物对DNA切割具有浓度、时间和pH依赖性。荧光和CD光谱实验表明[Cu2L2](ClO4)4能插入DNA双螺旋中。配位饱和的[ZnL1](ClO4)2和[Cu2L2](ClO4)4能催化对硝基苯磷酸单酯水解生成对硝基苯,[ZnL1](ClO4)2和[Cu2L2](ClO4)4催化磷酸单酯水解的表观一级反应速率常数分别为2.8×10-5min-1和5.9×10-6min-1。     

四氮大环-金属配合物与DNA作用的电化学及谱学研究

Mononuclear copper（Ⅱ）, nickel（Ⅱ） and cobalt（Ⅲ） tetracoordinate macrocyclic complexes were synthesized and spectroscopically characterized. The crystal structure of the three compounds were determined by X-ray crystallography. The electrochemical experimental results indicate that the three complexes could interact with DNA mainly by electrostatic interaction. The interaction of tetracoordinate macrocyclic cobalt（Ⅲ） complex with DNA was studied by cyclic voltammetry and UV-vis spectroscopy. The experimental results reveal that tetracoordinate macrocyc- lic cobalt（Ⅲ） complex could interact with DNA by electrostatic interaction to form a 1 ： 1 DNA association complex with a binding constant of 7.50 ×10^3 L·mol^-1.     

三齿多吡啶钴(Ⅱ)配合物的合成、表征及其与DNA的相互作用研究

合成了两种三齿多吡啶钴(Ⅱ)配合物[Co(DMPhTPY)2]2+(ClO-4)2(A)和[Co(H2Bzimpy)2]Cl2(B),用元素分析、IR对配合物的组成和结构进行了表征,测定了配合物A的晶体结构.用电子吸收光谱、荧光光谱、循环伏安法及凝胶电泳实验等方法研究了配合物与DNA的相互作用.结果表明配合物A和B与小牛胸腺(CTDNA)的作用属部分插入和静电结合,凝胶电泳实验表明配合物A在310nm光辐射15min,可使超螺旋pBR322DNA断裂为开环缺口型和线型DNA.