两亲性大环多胺La(III)配合物的合成、表征及催化质粒DNA水解的研究

近年来,人工核酸切割试剂的研究一直是化学生物学、生物化学和分子生物学中最为活跃的前沿领域之一。最近的研究结果表明大环多胺金属配合物在磷酸二酯水解方面表现出独特的催化性能,能作为化学核酸酶有效的催化DNA和RNA的磷酸二酯键的水解[1-2]。尤其是电荷较高的金属阳离子形     

Some divalent metal(II) complexes of novel potentially tetradentate Schiff base N,N′‐bis(2‐carboxyphenylimine)‐2,5‐thiophenedicarboxaldhyde: Synthesis,spectroscopic characterization and bioactivities

A novel tetradentate dianionic Schiff base ligand, N ,N ′‐bis(2‐carboxyphenylimine)‐2,5‐thiophenedicarboxaldhyde (H₂L) and some first row d‐transition metal chelates (Co(II), Cu(II), Ni(II) and Zn(II)) were synthesized and characterized using various physicochemical and spectroscopic methods. The spectroscopic data suggested that the parent Schiff base ligand coordinates through both deprotonated carboxylic oxygen and imine nitrogen atoms. The free Schiff base and its metal chelates were screened for their antimicrobial activities for various pathogenic bacteria and fungi using the agar well diffusion method. The antibacterial and antifungal activities of all the newly synthesized compounds are significant compared to the standard drugs ciprofloxacin and nystatin. The antioxidant activities of the compounds were determined by reduction of 1,1‐diphenyl‐2‐picrylhydrazyl and compared with that of vitamin C as a standard. DNA binding ability of the novel Schiff base and its complexes was investigated using absorption spectroscopy, fluorescence spectroscopy, viscosity measurements and thermal denaturation. The obtained results clearly demonstrate that the binding affinity with calf thymus DNA follows the order: Cu(II) complex > Ni(II) complex > Zn(II) complex > Co(II) complex >H₂L. Furthermore, the DNA cleavage activity of the newly synthesized ligand and its metal complexes was investigated using supercoiled plasmid DNA (pUC18) gel electrophoresis.     

多羟乙基双核大环多胺La(III)配合物对双对硝基苯酚磷酸二酯和DNA 催化水解作用研究

合成了一类新型多羟乙基双核大环多胺La(III)配合物, 其结构经1H NMR, MS, 元素分析等表征. 通过紫外分光光谱法和琼脂糖凝胶电泳技术, 研究了双核大环多胺La(III)配合物催化双对硝基苯酚磷酸二酯的水解反应和对质粒DNA(pUC18)的催化水解作用. 结果表明: 双核大环多胺La(III)配合物可以有效催化双对硝基苯酚磷酸二酯水解和促进质粒DNA在生理条件下的水解裂解. 双对硝基苯酚磷酸二酯的水解速率提高了2.36×104倍. 讨论了配合物结构对水解反应的影响.     

Role of Knoevenagel condensate pyrazolone derivative Schiff base ligated transition metal complexes in biological assay and cytotoxic efficacy

A new bioessential Knoevenagel condensate Schiff base ligand (L) was synthesized by the reaction of 3‐(4‐hydroxy‐3‐methoxybenzyl)pentane‐2,4‐dione and 4‐aminoantipyrine. The ligand forms monomeric divalent transition metal complexes ( 1 – 4 ) which were characterized using spectral and analytical data. All these complexes have the general formula [ML]Cl₂, where M = Co(II), Ni(II), Cu(II) and Zn(II). They are electrolytic in nature and adopt square planar geometry. The binding propensity of these complexes with calf thymus DNA was investigated using absorption spectrophotometric titration, cyclic voltammetry and viscosity measurements. The binding constant values imply that the complexes bind with DNA via intercalation mode. The in vitro antibacterial and antifungal activities reveal that the complexes have good antimicrobial efficacy against a set of pathogens. The nucleolytic cleavage activity of these complexes on pUC18 DNA was investigated using agarose gel electrophoresis. Also, the in vitro cytotoxicity of the synthesized complexes against a panel of human tumour cell lines (MCF‐7 and HeLa) and normal cell lines (NHDF and HEK) was assayed using the MTT method. Interestingly, complex 1 exhibits more potent anticancer activity than cisplatin and other complexes.     

缬氨酸Schiff碱金属铜配合物对质粒DNA的切割作用

缬氨酸Schiff碱金属铜配合物(PBP-L-Val-Cu)是新合成的一类非酶类切割工具, 合成了4种类型样品分别为L-CH3 Cu, D-CH3 Cu, L-Ph Cu和D-Ph Cu. 以质粒DNA(pUC18)为材料,分别对这4种类型化合物进行核酸切割效率的研究, 得出适合的反应体系后, 通过琼脂糖凝胶电泳对反应不同时间后核酸切割产物进行检测, 最终分别得到每种化合物将超螺旋型DNA切割成为开环型DNA和直线型DNA的切割效率, 经比较得出L-CH3 Cu型的切割效率是最快的. 将直线型DNA切割产物用琼脂糖凝胶回收试剂盒进行回收, 得到的直线型切割产物可以在T4连接酶的作用下重新连接起来. 利用酶切法对切口进行检测, 结果表明, 切割作用是具有特异性的. 另外, 该化合物对质粒pNQ216也具有切割活性.     

Catalytic hydrolysis of phosphate diester （BNPP） and plasmid DNA by mononuclear macrocyclic polyamine metal complexes

The activities of the catalytic hydrolysis of phosphate diester(BNPP)[bis(p-nitrophenyl)phosphate diester]and plasmid DNA (pUC18)by mononuclear macrocyclic polyamine metal complexes have been investigated in this paper.The results showed that the highest activity in hydrolysis of BNPP was obtained with 1e-Zn(Ⅱ)complex(composed of lipophilic group)as catalyst.The hydrolysis rate enhancement is up to 3.64×10~4 fold.These metal complexes could effectively promote the cleavage of plasmid DNA(pUC18)at physiol...     

Synthesis,characterization, DNA binding and nuclease activity of binuclear copper(II) complexes of cuminaldehyde thiosemicarbazones

Binuclear copper(II) complexes of thiosemicarbazones derived from cuminaldehyde (p-isopropyl benzaldehyde) and substituted thiosemicarbazides NH₂NHC(S)NHR, where R = H, Me, Et or Ph have been synthesized and characterized. The ESR indicates that the dissociation of dimeric complex into mononuclear [Cu(L)Cl(DMSO)₃] units in polar solvents like DMSO, where L = monoanionic thiosemicarbazone. The molecular ion peak in the LC-MS coincides with the formula weight of the complexes. The absorption titration studies revealed that each of these complexes is an avid binder to calf thymus-DNA. The apparent binding constants are in the order of 10⁷–10⁸ M⁻¹. The nucleolytic cleavage activities of the ligands and their complexes were assayed on pUC18 plasmid DNA using gel electrophoresis in the presence and absence of H₂O₂. The ligands showed increased nuclease activity when administered as copper complexes. All these copper(II) complexes behave as an efficient chemical nucleases with hydrogen peroxide activation. These studies revealed that the complexes exhibit both oxidative and hydrolytic chemistry in DNA cleavage.     

Complex Formation Equilibria of Amine-Bridged Dinuclearpalladium(II) Complexes with DNA Constituents

The complex formation equilibria involving trans-diamminepalladium(II) chloride (Pd^II), 1,6-hexanediamine (HDA), and DNA constituents were investigated. The formation constant of all possible mononuclear and binuclear complexes were determined at 25 °C and 0.1 mol⋅L⁻¹ NaNO₃. The speciation diagrams of the binuclear complex of Pd^II–HDA–DNA reveal that these complexes predominate in the physiological pH range and the reaction of the binuclear complex Pd^II–HDA–Pd^II with DNA constituents is quite feasible.     

DNA interaction,free radical scavenging and in‐vitro antibacterial activity of drug‐based copper(II) complexes

The Cu(II) complexes of type [Cu(cpf)(Aⁿ)Cl] (Aⁿ = terpyridines, cpf = ciprofloxacin) were synthesized and characterized using IR, mass and reflectance spectra. The free ligands and their complexes were evaluated for their in‐vitro antimicrobial activity against a panel of Gram‐positive and Gram‐negative bacteria. The complexes exhibit better or equal inhibition in comparison to free fluoroquinolones. Binding interactions of the complexes with calf thymus (CT DNA) were investigated by absorption titration, viscosity studies and DNA melting temperature experiment. The cleavage reaction on pUC19 DNA was monitored by agarose gel electrophoresis. The lower concentration of the complexes was catalysed the dismutation of superoxide radical at biological pH, which indicates that the complexes can act as a possible model for superoxide dismutase. Copyright © 2011 John Wiley & Sons, Ltd.     

Synthesis,characterization, DNA binding,oxidative damage of DNA strand scission,and antimicrobial activities of β-diketone condensed Schiff-base transition metal complexes

Co(II), Ni(II), Cu(II), Zn(II), and VO(IV) complexes containing a versatile β-diketone Schiff-base ligand (obtained by the condensation of 3-furan-2-ylmethylene-2,4-dione and 2-aminophenol) have been synthesized and characterized. Microanalytical, magnetic, and spectroscopic data reveal that the central metal is coordinated to two oxygens of phenolate and two nitrogens of imine of the ligand. Binding of synthesized complexes with calf thymus DNA has been investigated by spectroscopic and electrochemical methods and viscosity measurements. The complexes are able to form adducts with DNA and to distort the double helix by changing the base stacking. Electrostatic binding of vanadyl complex is observed from the weak hypochromism in electronic absorption spectra and no change in the viscosity with DNA. Oxidative DNA cleavage activities of the complexes are studied with supercoiled pUC19 DNA using gel electrophoresis. The hydroxyl radical (OH^?) is likely to be the species responsible for the cleavage of pUC19 DNA by the synthesized complexes. Under our experimental conditions, the vanadyl complex has no significant cleavage of DNA. The compounds have been screened for activity against several bacterial and fungal strains and the results are compared with the activity of standard drugs.     

Synthesis,structure, DNA interaction,and hydrolytic function toward bis(<Emphasis Type="Italic">p</Emphasis>-nitrophenyl) phosphate of a heterobinuclear macrocyclic complex

An asymmetrical bis-pyridine pendant-armed macrocyclic heterobinuclear complex, [ZnNiL](ClO₄)₂·CH₃CN (H₂L was derived from the condensation between 3,3′-((ethane-1,2-diylbis((pyridin-2-ylmethyl)azanediyl))bis(methylene))bis(2-hydroxy-5-methylbenzaldehyde) and 1.3-diaminopropane), has been synthesized and characterized by physico-chemical and spectroscopic methods. The asymmetric unit contains two complete macrocyclic complexes that are nevertheless quite similar to one another. The Zn–Ni separations, bridged by the two phenoxides, are 3.107 and 3.141 Ǻ, respectively. The phosphate hydrolysis catalyzed by the complex was investigated using bis(4-nitrophenyl)phosphate (BNPP) as the substrate. The catalytic rate constant (k _cat) is 1.64 × 10⁻³ s⁻¹ at pH 7.4 and 25 °C, which is 10⁸-fold higher than that of the corresponding uncatalyzed reaction. The interaction between the complex and calf thymus (CT) DNA was investigated by UV–vis absorption, viscosity experiments, and cyclic voltammetry. The complex shows good binding propensity to calf thymus DNA via intercalation with a binding constant of 5 × 10⁴ M⁻¹. The agarose gel electrophoresis studies show that the complex has a concentration-dependent DNA cleavage activity.     

硫杂蒽酮类稀土配合物的合成、表征及与DNA的作用(I)

合成了新的O-(硫杂蒽酮-[2]-基)-氧乙酸及其稀土配合物. 通过元素分析, IR, ¹H NMR, UV, DTA-TG和¹³C NMR谱对其结构进行了表征. 研究表明: 配体羧羰基脱质子后与金属离子配位, 2位氧原子也与金属离子配位, 配合物中含有一定量的配位水, 配合物为非电解质类型. 同时, 研究了O-(硫杂蒽酮-[2]-基)-氧乙酸稀土配合物对质粒DNA的切割作用. 结果表明: 铕的配合物对DNA的切割较明显, 且当配合物浓度增加时, 质粒DNA的超螺旋构型逐渐减少, 而缺刻、开环型构型逐渐增多. 在相同条件下, Eu(III)离子对质粒pBR322DNA几乎没有切割作用; 配体O-(硫杂蒽酮-[2]-基)-氧乙酸对质粒pBR322DNA也有切割作用, 但配合物EuL₃对质粒pBR322DNA的切割作用明显强于配体, 表明稀土离子Eu(III)与配体生成配合物后有较好的协同切割作用.     

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。     

A novel bioactive tyramine derived Schiff base and its transition metal complexes as selective DNA binding agents

A novel tyramine derived Schiff base, 3-4-dimethoxybenzylidene-4-aminoantipyrinyl-4-aminoethylphenol(L) and a series of its transition metal complexes of the type, ML2Cl2 where, M=Cu(II), Ni(II), Co(II) and Zn(II) have been designed and synthesized. Their structural features and other properties were deduced from the elemental analysis, magnetic susceptibility and molar conductivity as well as from mass, IR, UV-vis, 1H NMR and EPR spectral studies. The binding properties of these complexes with calf thymus DNA (CT-DNA) were investigated using electronic absorption spectroscopy, viscosity measurement, cyclic voltammetry and molecular docking analysis. The results reveal that the metal(II) complexes interact with DNA through minor groove binding. The interaction has also been investigated by gel electrophoresis. Interestingly, it was found that all the complexes could cleave the circular plasmid pUC19 super coiled (SC) DNA efficiently in the presence of AH2 (ascorbic acid). The complexes showed enhanced antifungal and antibacterial activities compared to the free ligand.     

Designing,structural elucidation,comparison of DNA cleavage,and antibacterial activity of metal(II) complexes containing tetradentate Schiff base

Macrocyclic complexes of Cu(II), Ni(II), Co(II), and Zn(II)of a tetradentate Schiff base ligand derived from 3-benzalideneacetoacetanilide and N-(2-aminoethyl)-1,3-ropanediamine were synthesized. The nature of the complexes and the geometry have been inferred from their microanalytical data, magnetic susceptibility measurements, IR, UV-Vis, ¹H NMR, ESR, and mass spectral techniques. The low electrical conductance of the complexes supports the neutral nature. Monomeric nature of the complexes is assessed from their magnetic susceptibility values.The in vitro biological screening effects of the investigated compounds were tested against the bacteria E. coli, S. aureus, S. typhi, and K. pneumoniae by the well diffusion method using agar nutrient as the medium. A comparative study of minimum inhibitory concentration (MIC) values of the Schiff base and its complexes indicate that the metal complexes exhibit higher antibacterial activity than the free ligand and the control (streptomycin). The cyclic voltammetry method was used to probe the interaction of a Cu(II) complex with pUC18 DNA. Information of the binding ratio and intercalation mode can be obtained from its electrochemical data. Cyclic voltammetric measurements showed that the Cu(II) complex undergoes a reversible reduction at biologically accessible potentials. From the study, it is understood that the copper complex prefers to bind with DNA in Cu(II) rather than Cu(I) oxidation state. The DNA cleavage ability of the complexes was monitored by gel electrophoresis using supercoiled pUC18 DNA in tris-HCl buffer. The text was submitted by the authors in English     

4-氯-2-(1H-咪唑并[4,5-f][1,10]菲咯啉)苯酚铜(Ⅱ)配合物的晶体结构及其与DNA的相互作用

利用菲咯啉酮衍生物4-氯-2-(1H-咪唑并[4,5-f][1,10]菲咯啉)苯酚(HL)设计合成了一种新的单核铜配合物[Cu(L)(5-Cl-sal)(DMF)]ClO_4·DMF(5-Cl-Hsal=5-氯-水杨醛),用元素分析和X射线单晶衍射等手段对配合物进行了表征。该配合物晶体属三斜晶系,P1空间群。用紫外吸收光谱、荧光光谱和凝胶电泳等方法研究了配合物与DNA的相互作用。结果表明,配合物以插入方式与CT-DNA结合,结合常数为1.02×10~3 L·mol~(-1)。同时配合物也能较大程度淬灭EB-DNA复合物的荧光,表观键合常数为4.37×10~5L·mol_(-1),略小于经典键合常数107 L·mol~(-1)。淬灭机理为动态淬灭。凝胶电泳实验研究表明配合物在H_2O_2存在下可将pBR322质粒DNA切割为开环缺口型DNA和线型DNA,配合物浓度越大,切割效果越好。机理研究显示,配合物切割DNA的反应是由羟基自由基(·OH)和单线态氧(~1O_2)作为活性物种的氧化切割过程。     

Topoisomerase Inhibition,Nucleolytic and Electrolytic Contribution on DNA Binding Activity Exerted by Biological Active Analogue of Coordination Compounds

The neutral mononuclear copper complexes with the quinolone antibacterial drug ciprofloxacin and bipyridine derivatives have been synthesized and characterized. Complexes were screened for their antibacterial activity against three Gram⁽⁻⁾ and two Gram⁽⁺⁾ bacteria, and study suggests inhibition of gyrase activity by metal complexes as the possible mechanism. The nucleolytic activity of adducts was carried out on double stranded pUC19 DNA using gel electrophoresis in the presence of radical scavenging agents that suggest hydrolytic cleavage mechanism for plasmid DNA.     

Interaction between Bifunctional Dioxo Macrocyclic Polyamine Co(II) Complex and DNA in Metallomicellar System

Artificial enzymes are non-protein molecules that are more simple than natural enzymes, but they also possess high efficiency and specificity. In recent years, the study of enzyme models is one of the most active fields1-2, especially chemical nuclease. Micelles, dynamic colloidal aggregates formed by amphipathic surfactant molecules, can mimic the hydrophobic structure of active site of enzymes because they offer a hydrophobic microenviornment which is similar to the important part located …     

Arm effects of mononuclear armed cyclen copper complexes on DNA cleavage

Novel cyclen copper(II) complexes appending different side arms were synthesized as DNA cleavage agents. Both the intermediates and mononuclear complexes were characterized by ¹H NMR, ESI-HRMS, Elemental analyses and IR, and their catalytic activities for DNA cleavage and DNA binding abilities were investigated. The results indicate that the copper(II) complexes could catalyze the cleavage of supercoiled DNA (pUC 19 plasmid DNA) under physiological conditions to produce nicked DNA with high yields (nearly 100%) via an oxidative mechanism in the absence of exogenous agents; The copper complex bearing an 9-anthryl group gave superior DNA interactions to those bearing phenyl or methyl groups.     

Mass spectrometric identification and characterization of antimony complexes with ribose-containing biomolecules and an RNA oligomer

Mass spectrometric techniques have been used to study the interaction of inorganic Sb(V) with biomolecules containing a ribose or deoxyribose moiety. Electrospray (ES) mass spectra of reaction mixtures containing inorganic Sb(V) and one of several biomolecules (adenosine, cytidine, guanosine, uridine, adenosine-5′-monophosphate, adenosine-3′,5′-cyclic monophosphate, ribose, or 2′-deoxyadenosine) afforded high-mass antimony-containing ions corresponding to Sb(V)–biomolecule complexes of stoichiometry 1:1, 1:2, or 1:3. The complexes were characterized by collision-induced dissociation (CID) tandem mass spectrometry (MS) using ion-trap multistage MS. The CID results revealed that Sb(V) binds to the ribose or deoxyribose moiety. Structures are proposed for the Sb–biomolecule complexes. Analysis of the reaction mixtures by reversed-phase chromatography coupled on-line to either inductively coupled plasma (ICP) MS or ES–MS showed that in solution Sb(V) forms complexes with all the analyzed biomolecules with vicinal cis hydroxyl groups. Evidence (from size-exclusion chromatography ICP–MS and direct infusion ES–MS) of complexation of Sb(V) with an RNA oligomer, but not with a DNA oligomer, supports the suggestion that the presence of vicinal cis hydroxyl groups is critical for complexation to occur. This is the first direct evidence of complexation of Sb(V) with RNA. Results obtained by studying the effect of changing reaction conditions, i.e. pH, reaction time, and Sb/biomolecule molar ratio, on the extent of Sb–biomolecule formation suggest the reaction may be of physiological importance. Selected reaction monitoring (SRM) and precursor-ion-scanning tandem MS were investigated to determine their potential to detect trace levels of the Sb–biomolecule complexes in biological samples. Application of SRM MS–MS in combination with high-performance liquid chromatography enabled successful detection of an Sb–adenosine complex that had been spiked into a complex biological matrix (liver homogenate).Electronic Supplementary Material Supplementary material is available for this article at and is accessible for authorized users.