Oxidative cleavage of DNA by a new ferromagnetic linear trinuclear copper(II) complex in the presence of H2O2/sodium ascorbate

A new trinuclear copper(II) complex has been synthesized and structurally characterized: [Cu(3)(L)(2)(HCOO)(2)(OH)(2)](infinity) (HL = (N-pyrid-2-ylmethyl)benzenesulfonylamide). In the complex, the central copper ion is six-coordinated. The coordination spheres of the terminal copper atoms are square pyramidal, the apical positions being occupied by a sulfonamido oxygen of the contiguous trimer. As a consequence, the complex can be considered a chain of trinuclear species. The three copper atoms are in a strict linear arrangement, and adjacent coppers are connected by a hydroxo bridge and a bidentate syn-syn carboxylato group. The mixed bridging by a hydroxide oxygen atom and a bidentate formato group leads to a noncoplanarity of the adjacent basal coordination planes with a dihedral angle of 61.4(2) degrees. Susceptibility measurements (2-300 K) reveal a strong ferromagnetic coupling, J = 79 cm(-1), leading to a quartet ground state that is confirmed by the EPR spectrum. The ferromagnetic coupling arises from the countercomplementarity of the hydroxo and formato bridges. The trinuclear complex cleaves DNA efficiently, in the presence of hydrogen peroxide/sodium ascorbate. tert-Butyl alcohol and sodium azide inhibit the oxidative cleavage, suggesting that the hydroxyl radical and singlet oxygen are involved in the DNA degradation.     

Efficient plasmid DNA cleavage by a mononuclear copper(II) complex

The Cu(II) complex of the ligand all-cis-2,4,6-triamino-1,3,5-trihydroxycyclohexane (TACI) is a very efficient catalyst of the cleavage of plasmid DNA in the absence of any added cofactor. The maximum rate of degradation of the supercoiled plasmid DNA form, obtained at pH 8.1 and 37 degrees C, in the presence of 48 microM TACI.Cu(II), is 2.3 x 10(-3) s(-1), corresponding to a half-life time of only 5 min for the cleavage of form I (supercoiled) to form II (relaxed circular). The dependence of the rate of plasmid DNA cleavage from the TACI.Cu(II) complex concentration follows an unusual and very narrow bell-like profile, which suggests an high DNA affinity of the complexes but also a great tendency to form unreactive dimers. The reactivity of the TACI.Cu(II) complexes is not affected by the presence of several scavengers for reactive oxygen species or when measured under anaerobic conditions. Moreover, no degradation of the radical reporter Rhodamine B is observed in the presence of such complexes. These results are consistent with the operation of a prevailing hydrolytic pathway under the normal conditions used, although the failure to obtain enzymatic religation of the linearized DNA does not allow one to rule out the occurrence of a nonhydrolytic oxygen-independent cleavage. A concurrent oxidative mechanism becomes competitive upon addition of reductants or in the presence of high levels of molecular oxygen: under such conditions, in fact, a remarkable increase in the rate of DNA cleavage is observed.     

Oxidative C-H and C-C bond cleavage by a (2,2'-bipyridine)copper(I) chloride complex

Acetonitrile is easily oxygenated at ambient reaction conditions to copper(II) oxalate [Cu(bpy)(ox)] n mediated by copper(I) chloride in the presence of 3,5-di-tert-butylcatechol and 2,2'-bipyridine. In the case of other nitriles (e.g., propionitrile), instead, the unusual and selective 1,4-extradiol cleavage of 3,5-di-tert-butylcatechol occurs to give copper(II) tert-butylmaleate [Cu(bma)(bpy)(H2O)]n in good yield.     

Synthesis,characterization, DNA binding and cleavage properties of a ternary copper(II) Schiff base complex

A ternary coordination complex 2Cu(C₁₄H₈NO₃Cl)(C₁₂H₈N₂)·3CH₃OH of a Schiff base (C₁₄H₈NO₃Cl: 4-chloroanthranilic acid–salicylaldehyde) was synthesized from 4-chloroanthranilic acid, salicylaldehyde, copper acetate and 1,10-phenanthroline and characterized by physicochemical and spectroscopic methods. X-ray crystallography shows that the copper atom is five coordinated by the imine nitrogen, two nitrogen atoms from 1,10-phenanthroline, the hydroxyl oxygen and the carboxylate oxygen atom. The interaction of the complex with calf-thymus DNA was investigated by UV absorption spectroscopy, fluorescence emission spectroscopy and viscosity. In addition, the cleavage reaction with pBR322 supercoiled plasmid DNA was investigated. The complex binds to DNA and also exhibits significant DNA cleavage activity.     

Potential-modulated DNA cleavage by (N-salicylideneglycinato)copper(II) complex.

The interaction of aqua (N-salicylideneglycinato)copper(II) (Cu(salgly)2+) complex with calf thymus DNA has been investigated by cyclic voltammetry. Potential-modulated DNA cleavage in the presence of Cu(salgly)2+ complex was performed at a gold electrode in a thin layer cell. DNA can be efficiently cleaved by electrochemically reducing Cu(salgly)2+ complex to Cu(salgly)+ complex at -0.7 V (vs. Ag/AgCl). When the solution was aerated with a small flow of O2 during electrolysis, the extent of DNA cleavage was dramatically enhanced, and hydroxyl radical scavengers inhibited DNA cleavage. These results suggested that O2 and hydroxyl radical were involved in potential-modulated DNA cleavage reaction. The percentage of DNA cleavage was enhanced as the working potential was shifted to more negative values and the electrolysis time was increased. It was also dependent on the ratio of Cu(salgly)2+ complex to DNA concentration. The cleaved DNA fragments were separated by high performance liquid chromatography (HPLC). The experimental results indicated that the method for potential-modulated DNA cleavage by Cu(salgly)2+ complex was simple and efficient.     

Oxidative DNA strand scission induced by a trinuclear copper(II) complex

A novel trinuclear copper(II) complex, Cu3-L (L = N,N,N',N',N' ',N' '-hexakis(2-pyridyl)-1,3,5-tris(aminomethyl)benzene), exhibited efficient oxidative strand scission of plasmid DNA. The solution behavior of the complex has been studied by potentiometric titration, UV spectroscopy, and cyclic voltammetry. The data showed that there are three redox-active copper ions in the complex with three types of bound water. The complex demonstrated a moderate binding ability for DNA. Cu3-L readily cleaves plasmid DNA in the presence of ascorbate to give nicked (form II) and then linear (form III) products, while the cleavage efficiency using H2O2 is less than by ascorbate, suggesting that the cleavage mode of the trinuclear complex is somewhat different from the traditional Fenton-like catalysis. Meanwhile, Cu3-L is far more efficient than its mononuclear analogue Cu-DPA (DPA = 2,2'-dipyridylamine) at the same [Cu2+] concentration, which suggests a possible synergy between the three or at least two Cu(II) centers in Cu3-L that contributes to its relatively high nucleolytic efficiency. Furthermore, the presence of standard radical scavengers does not have clear effect on the cleavage efficiency, suggesting the reactive intermediates leading to DNA cleavage are not freely diffusible radicals.     

Synthesis, characterization, plasmid cleavage and cytotoxicity of cancer cells by a copper(II) complex of anthracenyl-terpyridine

Metallo-organic compounds are interesting to study for their antitumor activity and related applications. This paper deals with the syntheses, characterization, structure determination of a copper complex of anthracenyl terpyridine (1) and its plasmid cleavage and cytotoxicity towards different cancer cell lines. The complex binds CT-DNA through partial intercalation mode. The plasmid cleavage studies carried out using pBR322 and pUC18 resulted in the formation of all the three forms of the plasmid DNA. Plasmid cleavage studies carried out with a non-redoxable Zn(2+) complex (2) supported the role of the redox activity of copper in 1. The complex 1 showed remarkable antiproliferative activity against cancer cell lines, viz., cervical (HeLa, SiHa, CaSki), breast (MCF-7), liver (HepG2) and lung (H1299). A considerable lowering was observed in the IC(50) values of HPV-infected (viz., HeLa, SiHa, CaSki) vs. non-HPV-infected cell lines (MCF-7, HepG2, H1299). Antiproliferative activity of 1 was found to be much higher than the carboplatin when treated with the same cell lines. Incubation of the cells with 1 results in granular structures only with the HPV-infected cells and not with others as studied by phase contrast and fluorescence microscopy. The lower IC(50) value observed in case of 1 with HPV-infected cell lines may be correlated with the involvement of HPV oncoprotein. The role of HPV has been further augmented by transfecting the MCF-7 cells (originally not possessing HPV copy) with e6 oncoprotein cDNA. To our knowledge this is the first copper complex that causes cell death by interacting with HPV oncoprotein followed by exhibition of remarkable antiproliferative activity.     

Electrochemical detection of scDNA cleavage in the presence of macrocyclic hexaaza-copper(II) complex

The hexaaza macrocyclic copper(II) complex Cu(II)L(L=1,8-Dihydroxyethyl-1,3,6,8,10,13-hexaazacyclotetradecane), which has octahedral structure similar to some natural complexes, is synthesized and purified. In this study, oxidative breakage DNA by the reaction of Cu(II)L with H2O2 and ascorbate has been investigated by gel electrophoresis experiments. In electrochemical experiments, the on scDNA-modified glassy carbon electrode(GCE) is cleaved by the Cu(II)L and redox changing of the metal catalyst without adding any other reagents. Above all, the need for concentration of scDNA is much lower than that of gel electrophoresis experiments and the process of the performance is easy. Furthermore, Cyclic Voltammetry (CV) and A.C. Impedance, which are performed to monitor scDNA cleavage at the scDNA-modified glassy carbon electrode (GCE), are fast, simple and highly efficient. The mechanism of the damage can be suggested: Fenton.     

DNA-binding and cleavage studies of a dinuclear copper(II) complex with a 26-membered hexaazamacrocycle

The complex, [Cu₂LCl₂]Cl₂ · 3H₂O, where L = the macrocyclic ligand bis-p-xylylBISDIEN Schiff base, has been prepared and characterized by elemental analysis, i.r. and mass spectra. The binding of the complex with calf thymus DNA has been investigated using absorption spectroscopy, cyclic voltammetry, fluorescence spectroscopy and viscosity measurements. The results suggest that the complex can bind to CT DNA by intercalation via the aromatic ring on the macrocycle into the base pairs of DNA. The complex exhibits efficient nuclease activity.     

Helical-chain copper(II) complexes and a cyclic tetranuclear copper(II) complex with single syn-anti carboxylate bridges and ferromagnetic exchange interactions

Tridentate Schiff-base carboxylate-containing ligands, derived from the condensation of 2-imidazolecarboxaldehyde with the amino acids beta-alanine (H2L1) and 2-aminobenzoic acid (H2L5) and the condensation of 2-pyridinecarboxaldehyde with beta-alanine (HL2), D,L-3-aminobutyric acid (HL3), and 4-aminobutyric acid (HL4), react with copper(II) perchlorate to give rise to the helical-chain complexes [[Cu(mu-HL1)(H2O)](ClO4)]n (1), [[Cu(mu-L2)(H2O)](ClO4).2H2O]n (2), and [[Cu(mu-L3)(H2O)](ClO4).2H2O]n (3), the tetranuclear complex [[Cu(mu-L4)(H2O)](ClO4)]4 (4), and the mononuclear complex [Cu(HL5)(H2O)](ClO4).1/2H2O (5). The reaction of copper(II) chloride with H2L1 leads not to a syn-anti carboxylate-bridged compound but to the chloride-bridged dinuclear complex [Cu(HL1)(mu-Cl)]2 (6). The structures of these complexes have been solved by X-ray crystallography. In complexes 1-4, roughly square-pyramidal copper(II) ions are sequentially bridged by syn-anti carboxylate groups. Copper(II) ions exhibit CuN2O3 coordination environments with the three donor atoms of the ligand and one oxygen atom belonging to the carboxylate group of an adjacent molecule occupying the basal positions and an oxygen atom (from a water molecule in the case of compounds 1-3 and from a perchlorate anion in 4) coordinated in the apical position. Therefore, carboxylate groups are mutually cis oriented and each syn-anti carboxylate group bridges two copper(II) ions in basal-basal positions with Cu...Cu distances ranging from 4.541 A for 4 to 5.186 A for 2. In complex 5, the water molecule occupies an equatorial position in the distorted octahedral environment of the copper(II) ion and the Cu-O carboxylate distances in axial positions are very large (>2.78 A). Therefore, this complex can be considered as mononuclear. Complex 6 exhibits a dinuclear parallel planar structure with Ci symmetry. Copper(II) ions display a square-pyramidal coordination geometry (tau = 0.06) for the N2OCl2 donor set, where the basal coordination sites are occupied by one of the bridging chlorine atoms and the three donor atoms of the tridentate ligand and the apical site is occupied by the remaining bridging chlorine atom. Magnetic susceptibility measurements indicate that complexes 1-4 exhibit weak ferromagnetic interactions whereas a weak antiferromagnetic coupling has been established for 6. The magnetic behavior can be satisfactorily explained on the basis of the structural data for these and related complexes.     

Syntheses,characterization and DNA cleavage studies of acyclic copper(II) complexes

Two novel acyclic copper(II) complexes, Cu(L₁) (1) {L₁ = N,N-1,2-ethanediylbis[N-(phenylmethyl)glycinato]} and Cu(L₂) (2), {L₂ = N,N-1,2-ethanediylbis[N-[(3-nitrophenyl)methyl]glycinato]} have been synthesized and characterized by elemental analysis and ES-MS. Thermal denaturation, fluorescence spectroscopy and cyclic voltammetry have been conducted to assess the interaction of the two complexes with calf thymus DNA. Interestingly, the two copper(II) complexes have been found to cleave circular plasmid pBR322 DNA to the nicked form (Form II) and the linear form (Form III) under aerobic conditions.     

Electrochemical synthesis and structural characterization of a novel mixed-valence copper(I)-copper(II) complex: {[bis(ethylenediamine)copper(II)] bis[diiodocuprate(I)]}

A novel, mixed-valent copper(I)-copper(II) complex, {[bis(ethylene-diamine)copper(II)] bis[diiodocuprate(I)]} (1), has been prepared by electrochemical dissolution of a sacrificial copper anode in a solution of ethylenediamine (en), I2 and tetraethylammoniumperchlorate (TEAP) as supporting electrolyte in acetonitrile (AcN)and characterized by single-crystal X-ray structure determination. The crystal structure of the complex 1 shows that it consists of a CuI2 polymer formed from I- ligands bridging Cu(I) ions, with a nearly square planar geometry of bivalent Cu(II) atoms chelated by two ethylenediamine ligands. The results also show that direct electrosynthesis of the complex had high current efficiency, purity and electrolysis yield.     

八羟基喹啉铜(Ⅱ)配合物的DNA结合和切割活性及与牛血清白蛋白相互作用（英文）

利用紫外吸收光谱、荧光光谱、圆二色光谱(CD)和琼脂糖凝胶电泳等手段研究了八羟基喹啉铜(Ⅱ)配合物Cu[8-OHQ]2与DNA和蛋白质的相互作用.实验结果表明,在生理条件下,Cu[8-OHQ]2能通过插入方式较强的与CT-DNA结合,诱导DNA构象的改变.其本征结合常数Kb为1.15(±0.01)×105 L/mol,表观结合常数Kapp为4.21×106 L/mol.再者,琼脂糖凝胶电泳实验表明,在生理条件和抗坏血酸(Vc)存在情况下,Cu[8-OHQ]2能有效地将超螺旋pBR322质粒DNA切割成缺刻和线性,甚至降解为小的片断.机理研究表明扩散的·OH,H2O2和1 O2都不是在切割过程中起作用的活性氧物种(ROS);copper-oxo中间体可能是此切割过程中主要的活性氧物种.另外,Cu[8-OHQ]2也能以适中的结合力与牛血清白蛋白(BSA)结合而猝灭BSA内源荧光,猝灭机理为静态猝灭.所有这些结果表明Cu[8-OHQ]2具有作为潜在化疗试剂的生物活性.     

Ferrocene-conjugated copper(II) dipyridophenazine complex as a multifunctional model nuclease showing DNA cleavage in red light

The copper(II) complex [Cu(L)(dppz)](ClO₄)₂ (1) having a tripodal ligand ferrocenylmethylbis(2-pyridylmethylamine) (L) with a pendant ferrocenyl unit and a planar NN-donor dipyrido-[3,2-a:2′,3′-c]-phenazine (dppz) base is prepared and its DNA binding and cleavage properties studied. The complex is redox active showing cyclic voltammetric responses at 0.52 and –0.01 V vs. SCE due to Fe(III)/Fe(II) and Cu(II)/Cu(I) couples, respectively. The complex that binds to the major groove of DNA shows dual chemical nuclease activity involving both the metal centres. The complex displays efficient photo-induced DNA cleavage activity in visible laser light of 458 and 568 nm wavelengths forming cleavage active hydroxyl radicals. Significant DNA cleavage is also observed in red light of 647 nm within the photodynamic therapy (PDT) window.     

Extraction of copper(II) and nickel(II) by cyclic trioximes and cyclic furazan oximes

The extraction properties of 1,2,3-cyclopentanetrione trioxime (H₃CPT) and its furazan, and of 4-t-butyl-1,2,6-cyclohexanetrione trioxime (H₃BHT) and its furazan are described. H₃CPT was found to be too soluble in water and was therefore of no use in extraction but H₃BHT was satisfactory. The extracted copper and nickel chelates of H₃BHT precipitate by agglomeration caused by intermolecular hydrogen bonding and/or coordination of the third oxime group. This precipitation blocked back extraction. The furazan oximes derived from these trioximes did not form copper or nickel chelates under extraction conditions.     

Preparation,structural and thermal characterization of cobalt(II) and copper(II) complexes with 3-hydroxypicolinamide

Cobalt(II) and copper(II) complexes of 3-hydroxypicolinamide (3-OHpia), namely [Co(3-OHpia)₂(H₂O)₂](NO₃)₂ (1), [Co(3-Opia)₂(H₂O)₂] (2) and [Cu(3-OHpia)₂(NO₃)₂] (3), were prepared and characterized by IR spectroscopy and TG/DTA methods. The molecular and crystal structures of 1 and 3 were determined by X-ray crystal structure analysis. Complexes 1 and 3 were obtained by reaction of 3-hydroxypicolinamide with cobalt(II) nitrate or copper(II) nitrate, respectively, in a mixture of ethanol and water. Complex 2 was prepared by reaction of cobalt(II) acetate and 3-OHpia in aqueous solution. X-ray structural analysis revealed octahedral coordination polyhedra in both 1 and 3 and the same N,O-chelated coordination mode of 3-OHpia. The coordination sphere of the cobalt(II) center in 1 is completed by two coordinated water ligands and that of the copper(II) center in 3 by two coordinated nitrate anions. There are also two uncoordinated nitrate ions in 1 which compensate the positive charge of cobalt(II). The crystal structures of 1 and 3 are dominated by intermolecular O–H···O and N–H···O hydrogen bonds. The thermogravimetric study indicated the loss of two coordinated water molecules in 1 and 2 and of one 3-OHpia ligand together with N₂ molecule in 3 at lower temperatures (up to 300 °C).     

Thermal and structural characterization of copper(II) complexes with phenyl-2-pyridylketoxime (HPPK)

Journal of Thermal Analysis and Calorimetry - Copper(II) complexes of different nuclearity with phenyl-2-pyridylketoxime (HPPK), such as mononuclear [Cu(HPPK)(PPK)X], whereby...