Synthesis and DNA cleavage activity of artificial receptor 1,4,7-triazacyclononane containing guanidinoethyl and hydroxyethyl side arms

A novel phosphodiester receptor 1-(2-guanidinoethyl)-4-(2-hydroxyethyl)-1,4,7-triazacyclononane hydrochloride 1 was synthesized. DNA cleavage efficiency of 1 exhibits remarkable increases compared with its ZnII complex and corresponding nonguanidinium compound N-(2-hydroxyethyl)-1,4,7-triazacyclononane and parent 1,4,7-triazacyclononane. Kinetic data of DNA cleavage promoted by 1 fit to a Michaelis-Menten-type equation with kmax of 0.160 h-1 giving 107-fold rate acceleration over uncatalyzed DNA. The acceleration is driven by the spatial proximity of the nucleophilic hydroxyl group and the electrophilic activation for the phosphodiester by the guanidinium group.     

Synthesis,magnetic properties,DNA binding and cleavage activity of a new oxalato bridged copper(II) complex

A novel oxalato‐bridged copper(II) complex has been prepared and structurally characterized: [Cu(bpa)(μ‐C₂O₄)].H₂O (bpa = bis(2‐pyridylmethyl) amine). In the complex, the copper ion is linked in an unusual μ_1,2,3‐C₂O₄^2? bridging mode, generating one‐dimensional zigzag chain disposition. Variable‐temperature magnetic susceptibility studies (2–300 K) reveal a weak ferromagnetic coupling, J = 0.63 cm^?1, between the copper ions. The interaction of the complex with CT‐DNA has been studied using UV–visible absorption and emission spectral methods, and the binding constant of the complex with CT‐DNA is K_app = 9 × 10⁴ m ^?1, which indicates that the interaction of the complex with DNA is a moderate intercalative mode. Furthermore, the complex cleaves supercoiled plasmid DNA efficiently in the presence of hydrogen peroxide. The mechanistic investigations suggest that the hydroxyl radical and singlet oxygen are involved in the DNA degradation. Copyright © 2012 John Wiley & Sons, Ltd.     

A new nickel(II) complex with the thiosemicarbazone of quinoline-2-carboxaldehyde: structure,DNA-binding,cleavage, and cytotoxic activities

[Ni(QTS)₂]?·?Cl?·?CH₃OH, where QST?=?quinoline-2-carboxaldehyde thiosemicarbazone, has been synthesized and characterized. The complex crystallized in a monoclinic system with space group P2(1)/n. Nickel(II) is situated in a distorted octahedral geometry with two tridentate ligands and one ligand is mono-deprotonated to coordinate to nickel(II). Interaction of the nickel(II) complex with calf thymus DNA was investigated by electronic absorption, CD, and fluorescence spectra. The results suggest that nickel(II) complex binds to DNA through a groove binding mode. The nickel(II) complex exhibited efficient DNA cleavage at micromolar concentration in the presence of ascorbate with hydroxyl radicals as the active species. In vitro cytotoxicity assay showed that the nickel(II) complex was more potent against MCF-7 cell line but less active against A-549 cell line than cisplatin at the concentrations tested.     

Synthesis,characterization, DNA interaction and cleavage activity of new mixed ligand copper(II) complexes with heterocyclic bases

Mixed ligand complexes having the formulae Cu(RPO)₂Py₂, Cu(RPO)₂Im₂ and Cu(DBO)₂Py₂ [RPO = resacetophenone oxime, DBO = 2,4-dihydroxybenzophenone oxime, Py = pyridine and Im = imidazole] have been synthesized and characterized by UV–Vis, IR, ESR, cyclic voltammetry and magnetic susceptibility methods. Absorption studies revealed that each of these octahedral complexes is an avid binder of calf thymus DNA. The apparent binding constants for mixed ligand complexes are in order of 10⁴–10⁵ M⁻¹. Based on the data obtained in the DNA binding studies a partial intercalative mode of binding is suggested for these complexes. The nucleolytic cleavage activity of the adducts was carried out on double stranded pBR322 circular plasmid DNA by using a gel electrophoresis experiment in the presence and absence of oxidant (H₂O₂). All the metal complexes cleaved supercoiled DNA by hydrolytic and oxidative paths. The oxidative path dominates the hydrolytic cleavage. The hydrolytic cleavage of DNA is evidenced from the control experiments showing discernable cleavage inhibition in the presence of the hydroxyl radical inhibitor DMSO or the singlet oxygen quencher azide ion.     

Synthesis,structure, DNA binding and cleavage ability of a new copper ciprofloxacin complex

The structure of 1 consists of [Cu(HCp)(phen)(H₂O)]²⁺ (HCp is ciprofloxacin and phen is 1,10-phenanthroline), two acetates, and four free water molecules. In each cation, copper displays a distorted square pyramid, coordinated to ring 3-carboxylate and 4-oxo oxygen from HCp, two nitrogens from phen, and one water molecule. There are five water molecules in each discrete complex with one coordinated to Cu center, and the other four linked to each other by intermolecular hydrogen bonds. Two uncoordinated acetates make the compound neutral. The complex exhibits higher DNA binding compared to HCp at the same conditions by fluorescence and viscosity measurements. Combining its structure with the DNA-binding result, the binding mechanism may be explained by intercalation. Moreover, 1 shows significant cleavage of DNA in the presence of a reducing agent, such as ascorbate by gel electrophoresis using supercoiled pBR322 DNA in Tris-HCl buffer (pH 7.4). The complex also has a higher activity against Gram-positive bacteria Staphylococcus aureus and Gram-negative bacteria Klebsiella pneumoniae than HCp.     

Nuclease activity of copper(II) complex containing 1,10-phenanthroline-5,6-dione and L-phenylalanine ligands

The interaction between CT-DNA and a ternary copper (II) complex, [Cu(phendio)(L-Phe)(H₂O)](ClO₄)·H₂O (CuPP, phendio = 1,10-phenanthroline-5,6-dione, L-Phe = L-phenylalanine), has been conducted by electronic spectra, fluorescence spectroscopy and cyclic voltammetry. It has been found that the max. absorption peak from the electronic spectra is red shifted and the intensity is weakened and that the values of peak current from cyclic voltammetry are decreased significantly in the presence of DNA compared with that in the absence of DNA. At the same time, the complex can quench the emission intensity of EB-DNA system. The existence of the intercalation mode between the complex and DNA was proven. By submarine gel electrophoresis, we found that the copper(II) complex can cleave circular plasmid pBR322 DNA into nicked and linear forms in the presence of ascorbic acid and H₂O₂. __________ Translated from Acta Scientiarum Naturalium Universitatis Nankaiensis, 2007, 40(1): 32–36 [译自: 南开大学学报(自然科学版)]     

Studies on the DNA binding and cleavage activity of a synthesized polyamide containing dipeptide Ser-His

The DNA binding and cleavage activity of a synthetic polyamide containing dipeptide Ser-His has been investigated by spectroscopic techniques, such as electronic absorbance and circular dichroism (CD) spectropolarimetry, as well as gel electrophoresis. The results show that the molecule has a strong interaction with DNA and can improve DNA-cleavage ability about 100 fold as compared with single dipeptide Ser-His.     

Synthesis,crystal structure,DNA binding,and DNA cleavage of a zinc complex containing N,N-bis(2-pyridylmethyl)amine

A water-soluble zinc complex, [Zn(bpea)Cl₂] (1) (bpea?=?N,N-bis(2-pyridylmethyl)ethylamine), was prepared to serve as a nuclease mimic. The complex was characterized by X-ray, infrared, and UV spectroscopy. Interactions of the complex with calf thymus-DNA (ct-DNA) have been investigated by UV absorption and fluorescence spectroscopies; the mode of ct-DNA binding for 1 has been proposed. DNA cleavage activities by 1 were performed in the absence of external agents. The influences of different complex concentrations or reaction times on DNA cleavage were studied.     

DNA cleavage,cytotoxic and antioxidant properties of Cistus laurifolius L. extracts

In this study, extracts of the root, branch and leaf parts of Cistus laurifolius L. were prepared using hexane, methylene chloride and ethanol solvents. DNA cleavage, cytotoxic and antioxidant properties of the prepared extracts were then investigated. The cytotoxic properties of the extracts were investigated in A549, DU-145, PNT-1A, MDA-MB231, CRL-4010 and HCT-116 cell lines. Among all prepared extracts, T4 (seed–methylene chloride) extract showed cytotoxic effects on more cancer cell lines compared to other extracts. Antioxidant tests were performed by DPPH (2,2-diphenyl-1-picrylhydrazil) radical scavenging and Folin-Ciocalteu methods. In both tests, it was determined that T7 (seed–ethanol) extract has a very strong antioxidant effect (IC₅₀ = 0,000015 μg/ml for the DPPH method). In DNA cleavage studies, the results obtained confirm the protection of DNA from hydroxyl radical damage in the presence of methanolic plant extracts. Consequently, we determined that some of the Cistus laurifolius L. extracts have significant biological properties on the studied cell lines.     

Synthesis,crystal structure,DNA binding,and oxidative cleavage activity of copper(II)-bipyridyl complexes containing tetraalkylammonium groups

Two copper(II) complexes of disubstituted 2,2′-bipyridine (bpy = 2, 2′-bipyridine) with tetraalkylammonium groups, [Cu(L¹)₂Br](ClO₄)₅·2H₂O (1) and [Cu(L²)₂Br](ClO₄)₅·H₂O (2) (L¹ = [4, 4′-(Et₃NCH₂)₂-bpy]²⁺, L² = [4, 4′-((n-Bu)₃NCH₂)₂-bpy]²⁺), have been synthesized and characterized. X-ray crystallographic study of 1 indicates that Cu(II) is a distorted trigonal bipyramidal or square pyramid. DNA binding of both complexes was studied by UV spectroscopic titration. In the presence of reducing reagents, the cleavage of plasmid pBR322 DNA mediated by both complexes was investigated and efficient oxidative cleavage of DNA was observed. Mechanistic study with reactive oxygen scavengers indicates that hydrogen peroxide and singlet oxygen participate in DNA cleavage.     

Novel pyrazole fused heterocyclic ligands: Synthesis,characterization, DNA binding/cleavage activity and anti-BVDV activity

A series of novel pyrazole fused heterocyclic derivatives were synthesized via a two-step procedure or a one-pot two step method,and their catalytic DNA cleavage abilities and anti-BVDV activities were also evaluated.The results obtained indicated that compounds 3b-3c could catalyze the cleavage of supercoiled DNA(pUC 19 plasmid DNA) to nicked DNA under physiological conditions with high yields via a hydroiytic mechanism.The studies on anti-viral activities against bovine viral diarrhea virus(BVDV) demonstrated that some of the pyrazole derivatives showed pronounced anti-BVDV activity with interesting EC_(50) values and no significant cytotoxicity.Among them,compound 31 showed the highest antiviral activity(EC_(50) = 0.12 μmoI/L) and was 10 fold more than that of the positive control ribavirin(EC_(50)= 1.3 μmol/L),which provided a potential candidate for the development of anti-BVDV agents.     

Synthesis, spectral characterization of Schiff base transition metal complexes: DNA cleavage and antimicrobial activity studies

A new series of transition metal complexes of Cu(II), Ni(II), Co(II), Mn(II), Zn(II), VO(IV), Hg(II) and Cd(II) have been synthesized from the Schiff base (L) derived from 4-aminoantipyrine, 3-hydroxy-4-nitrobenzaldehyde and o-phenylenediamine. Structural features were obtained from their elemental analyses, magnetic susceptibility, molar conductance, mass, IR, UV-Vis, ¹H NMR and ESR spectral studies. The data show that these complexes have composition of ML type. The UV-Vis, magnetic susceptibility and ESR spectral data of the complexes suggest a square-planar geometry around the central metal ion except VO(IV) complex which has square-pyramidal geometry. The redox behaviour of copper and vanadyl complexes was studied by cyclic voltammetry. Antimicrobial screening tests gave good results in the presence of metal ion in the ligand system. The nuclease activity of the above metal complexes shows that Cu, Ni and Co complexes cleave DNA through redox chemistry whereas other complexes are not effective.     

Synthesis and DNA cleavage properties of ternary Cu(II) complexes containing histamine and amino acids

The ternary complexes of [Cu^II(Hist)(Tyr)]⁺1 and [Cu^II(Hist)(Trp)]⁺2 have been synthesized, structurally characterized and their DNA binding and cleavage abilities probed. The intrinsic binding constants (K_b) for complexes/CT-DNA were also determined (K_b = 2.7 × 10² for complex 1 and K_b = 2.2 × 10² for complex 2). These complexes exhibit their nuclease activity on plasmid DNA, which seems to depend on the nature of the aromatic moiety. The DNA hydrolytic cleavage rate constants were also determined for complexes 1 and 2, which are 0.91 and 0.79 h⁻¹, respectively.     

Synthesis and optical characterization of novel azacrown ethers containing an acridinone or an N-methylacridinone unit as potential fluorescent chemosensors

Four new achiral and four new chiral monoazacrown ethers containing an acridinone or an N-methylacridinone fluorescent signalling unit were prepared by reacting chloromethyl-substituted acridinone derivatives with achiral monoazacrown ethers with different cavity sizes and enantiopure monoaza-18-crown-6 ethers having two methyl and two isobutyl groups on their chiral centres, respectively. The operation of these chemosensors is based on the photoinduced electron transfer (PET) process, thus they show fluorescence enhancement in the presence of cationic guests. Their fluorescent behaviour as well as their complexation properties towards selected metal ions and the enantiomers of α-(1-naphthyl)ethylammonium perchlorate and potassium mandelate were examined.     

Synthesis,crystal structure,spectroscopy, and nuclease activity of copper(II) complexes containing N,N-bis(2-pyridylmethyl)amine ligand

[Cu(bpea)Cl]ClO₄ (1) and a new copper(II) complex [Cu(bpma)(Ph-COO)(H₂O)]ClO₄ (2) [bpea?=?N,N-bis(2-pyridylmethyl)ethylamine; bpma?=?N,N-bis(2-pyridylmethyl)methylamine] have been synthesized. Complex 2 was crystallized in monoclinic space group P2₁/c with unit cell parameters a ?=?16.460(6)?Å, b ?=?11.222(4)?Å, c?=?12.522(5)?Å, and β?=?97.985(6)°. Interactions of the complexes with calf thymus DNA (CT-DNA) have been investigated by UV absorption, fluorescence, and cyclic voltammetry; thus, modes of CT-DNA binding for the complexes have been proposed. Furthermore, DNA cleavage activities by the complexes were performed in the absence of any external agents. The influence of complex concentration or reaction time on the DNA cleavage was studied.     

Synthesis,crystal structure,magnetic property and DNA cleavage activity of a new terephthalate-bridged tetranuclear copper(II) complex

A new terephthalate-bridged tetranuclear copper(II) complex has been synthesized and structurally characterized by X-ray crystallography: [Cu₄(L)₂(tp)(dmf)₂] (1) (H₃L = 1,3-bis(salicylideneamino)propan-2-ol, tp = terephthalate and dmf = N,N′-dimethylformamide). The dinucleating pentadentate character of the ligand (H₃L) and the desired pair-of-dimers arrangement, through the incorporation of the bridging terephthalate moiety, is clearly evident from the structure of 1. The copper atoms are coordinated in a slightly distorted square pyramidal arrangement within each dinucleating half of the complex and are bridged mono-atomically by the secondary alkoxo oxygen of the ligand and di-atomically by the terephthalate moiety. The apical position is occupied by the oxygen atom of the dmf. The structure of 1 reveals a short intramolecular Cu–Cu separation (ca. 3.1 Å), in combination with long intramolecular copper separations (ca. 11 Å). The variable temperature-dependent susceptibility measurement (2–300 K) of 1 reveals a dominant ferromagnetic coupling, 2J = 18.70 cm⁻¹. Complex 1 binds to double-stranded CT (calf-thymus) DNA giving a K_app value of 1.25 × 10⁷ M⁻¹ and displays efficient cleavage of supercoiled pUC19 DNA in the presence of H₂O₂ following a hydroxyl radical pathway.     

Synthesis and characterization of heteroleptic Schiff base transition metal complexes: a study of anticancer,antimicrobial, DNA cleavage and anti-TB activity

In search of effective bioactive compounds, we have synthesized the new Co(II), Ni(II), and Cu(II) complexes of the Schiff base derived from 8-formyl-7-hydroxy-4-methylcoumarin and 2-hydrazino benzothiazole and characterized by analytical, spectroscopic (IR, NMR, UV–vis, Mass), magnetic, powder X-ray diffraction data (PXRD) and TGA studies. Elemental analysis suggests the stoichiometry of the synthesized complexes and the solution electronic spectral study revealed the octahedral geometry of the compounds. Thermal analysis shows the presence of water molecule outside the coordination sphere and powder-XRD patterns have been studied to test the degree of crystallinity of the complexes and unit cell calculations were made. All the synthesized compounds were tested against human ovarian cancer cell line (PA-1). The synthesized metal complexes exhibited enhanced activity against the tested bacterial (Staphylococcus aureus and Escherichia Coli) and fungal strains (Candida albicans and Aspergillus fumigatus) as compared to free ligand (LH). The results of the DNA-cleavage activity suggest that the ligand and its metal complexes can cleave CT-DNA at different degrees. Further, anti-tuberculosis activity was done using microplate almar blue assay. Among all these synthesized compounds, the Cu(II) complex exhibits good cleaving ability compared to other newly synthesized metal complexes.     

DNA-binding,oxidative DNA cleavage,and coordination mode of later 3d transition metal complexes of a Schiff base derived from isatin as antimicrobial agents

A Schiff base, obtained by the condensation of isatin monohydrazone with 2,3,5-trichlorobenzaldehyde, and its Co(II), Ni(II), Cu(II), and Zn(II) complexes have been synthesized and characterized. The interaction of these complexes with DNA is investigated using viscosity, absorption titration, and electrochemical techniques. The results indicate that the complexes bind to Calf thymus DNA through intercalation. Oxidative cleavage activities of the complexes are studied using supercoiled pBR322 DNA by gel electrophoresis. Antimicrobial study reveals that copper and zinc complexes are better antimicrobial agents than the Schiff base and its other complexes.     

Synthesis,characterization, DNA binding,photo-induced DNA cleavage,and antimicrobial activity of metal complexes of a Schiff base derived from bis(3-aminophenyl)malonamide

The peptide linkage Schiff base (H₂L) and its complexes have been synthesized and fully characterized by elemental analysis, UV–Vis, FTIR, ¹H-NMR, ¹³C-NMR, EPR, and FAB-mass spectra. The stoichiometry of the complexes is [ML] (where M = Cu(II), Co(II), Ni(II), Zn(II), and VO(IV)). All the complexes exhibit square-planar geometry except the vanadyl complex which has square-pyramidal geometry. Interactions of the complexes and free ligand with double-stranded calf thymus DNA (CT-DNA) are studied by UV-spectrophotometric, electrochemical, and viscosity measurements. The data suggest that all the complexes form adducts with DNA and distort the double helix by changing the base stacking. Vanadyl complex forms a weaker adduct to CT-DNA than other complexes, probably due to the square-pyramidal geometry. CT-DNA induces extensive distortion in the planarity of vanadyl complex as EPR spectral calculations reveal. The intrinsic binding constants (K _b) of [ZnL], [CuL], [CoL], and [NiL] are 1.1 × 10⁵, 1.4 × 10⁵, 0.8 × 10⁵, and 0.6 × 10⁵ M^?1, respectively. Photo-induced DNA cleavage indicates that all complexes cleave DNA effectively. Control DNA cleavage experiments using pUC19 supercoiled (SC) DNA and minor groove binder distamycin suggest major groove binding for the synthesized complexes. The antimicrobial results indicate that the complexes inhibit the growth of bacteria and fungi more than the free ligand.