ABSTRACT
A new water soluble zinc complex has been prepared and structurally characterized. The Zn(II) complex was synthesized by the reaction of 2,6-diacetylpyridine dihydrazone (dph) with {4-[(2E)-2-(hydroxyimino)acetyl]phenoxy} acetic acid (H2L) in the presence of zinc(II) acetate. Single crystal X-ray diffraction study revealed that the zinc ion is situated in distorted trigonal-bipyramidal environment where the equatorial position is occupied by the nitrogen atom of pyridine ring and the oxygen atoms of acetate groups of two oxime ligands (H2L) whereas the axial positions of the zinc complex are occupied by the imine nitrogen atoms of dph ligand. Characterization of the complex with FTIR, (1)H and (13)C NMR, UV-vis and elemental analysis also confirmed the proposed structure. Interaction of the Zn(II) complex with calf-thymus DNA (CT-DNA) was investigated through UV-vis spectroscopy and viscosity measurements. The results suggest that the complex preferably bind to DNA through the groove binding mode. The zinc complex cleaves plasmid pBR 322 DNA in the presence and absence of an oxidative agent (H2O2), possibly through a hydrolytic pathway which is also supported by DNA cleave experiments in the presence of different radical scavengers. The nuclease activity of the zinc complex significantly depends on concentration of the complex and incubation time both in the presence and absence of H2O2. DNA cleave activity is inhibited in the presence of methyl green indicating that the zinc complex seems to bind the major groove of DNA.
Subject(s)
Acetic Acid/chemistry , DNA/metabolism , Hydrocarbons, Chlorinated/chemical synthesis , Hydrocarbons, Chlorinated/metabolism , Pyridines/chemistry , Zinc/chemistry , Animals , Cattle , Chemistry Techniques, Synthetic , DNA/chemistry , DNA Cleavage/drug effects , Deoxyribonucleases/metabolism , Hydrocarbons, Chlorinated/chemistry , Hydrocarbons, Chlorinated/pharmacology , Models, Molecular , Molecular Conformation , ViscosityABSTRACT
Two new Cu(II) complexes of Schiff base-hydrazone ligands, hydroxy-N'-[(1Z)-1-(4-hydroxyphenyl)ethylidene]benzohydrazide [H3L(1)] and ethyl 2-(4-(1-(2-(4-(2-ethoxy-2-oxoethoxy)benzoyl)hydrazono)ethyl)phenoxy)acetate (HL(2)) have been synthesized and then characterized by microcopy and spectral studies. X-ray powder diffraction illustrates that [Cu(L(2))2] complex is crystalline in nature whereas [Cu(H2L(1))2]·2H2O has an amorphous structure. Binding of the copper complexes with Calf thymus DNA (CT-DNA) has been investigated by UV-visible spectra, exhibiting non-covalent binding to CT-DNA. DNA cleavage experiments have been also investigated by agarose gel electrophoresis in the presence and absence of an oxidative agent (H2O2). The effect of complex concentration on the DNA cleavage reaction has been also studied. Both copper complexes show nuclease activity, which significantly depends on concentrations of the complexes, in the presence of H2O2 through oxidative mechanism whereas they slightly cleavage DNA in the absence an oxidative agent.
Subject(s)
Acetophenones/chemistry , Coordination Complexes/chemistry , Copper/chemistry , DNA Cleavage/drug effects , Hydrazones/chemistry , Acetophenones/pharmacology , Animals , Cattle , Coordination Complexes/pharmacology , Copper/pharmacology , DNA/chemistry , DNA/metabolism , Hydrazones/pharmacology , Models, MolecularABSTRACT
Two new copper(II) complexes with the condensation products of methyl 2-naphthyl ketone with 4-hydroxybenzohydrazide, 4-hydroxy-N'-[(1Z)-1-(naphthalen-2-yl)ethylidene]benzohydrazide [HL(1)] and (Z)-ethyl 2-(4-(2-(1-(naphthalen-2-yl)ethylidene)hydrazinecarbonyl)phenoxy)acetate (HL(2)) were synthesized and characterized by elemental analysis, infrared spectra, UV-Vis electronic absorption spectra, magnetic susceptibility measurements, TGA, powder XRD and SEM-EDS. The binding properties of the copper(II) complexes with calf thymus DNA were studied by using the absorption titration method. DNA cleavage activities of the synthesized copper complexes were examined by using agarose gel electrophoresis. The effect of complex concentration on the DNA cleavage reactions in the absence and presence of H2O2 was also investigated. The experimental results suggest that the copper complexes bind significantly to calf thymus DNA by both groove binding and intercalation modes and cleavage effectively pBR322 DNA. The mechanistic studies demonstrate that a hydrogen peroxide-derived species and singlet oxygen ((1)O2) are the active oxidative species for DNA cleavage.
