DNA Cleavage Properties Research Articles

Cu(II)–dipeptide complexes of 2-(4′-thiazolyl)benzimidazole: Synthesis, DNA oxidative damage, antioxidant and in vitro antitumor activity

Two new Cu(II)–dipeptide complexes of 2-(4′-thiazolyl)benzimidazole, [Cu(Gly-Gly)(TBZ)(Cl)]·4H2O (1) and [Cu(Gly-l-Leu)(TBZ)(Cl)]·H2O (2) (Gly-Gly=glycyl-glycine anion, Gly-l-Leu=glycyl-l-leucine anion and TBZ=2-(4′-thiazolyl)benzimidazole) have been synthesized and characterized by elemental analyses, molar conductance measurements and spectroscopy methods (IR, UV–visible, electrospray ionization mass spectra (ESI-MS) and EPR). The DNA binding and cleavage properties of the complexes monitored by multi-spectroscopic techniques (UV absorption, fluorescence and circular dichroism), viscosity determination and agarose gel electrophoresis indicated that the complexes bound to calf thymus (CT)-DNA via a partial intercalative mode with considerable intrinsic binding constants (Kb=1.64×105M−1 for 1 and 2.59×105M−1 for 2), and cleaved pBR322 DNA efficiently in the mediation of ascorbic acid (AA), probably via an oxidative damage mechanism induced by OH. The antioxidant activities of the complexes have been evaluated by means of modified nitroblue tetrazolium (NBT) photoreduction and cellular antioxidant activity (CAA) assays using HepG2 cells as a model, and it was found that IC50 values of 1 and 2 for dismutation of O2− were 0.172 and 0.247μM, respectively, and the CAA50 values were 10.57 and 10.74μM. In addition, the complexes were subjected to in vitro cytotoxicity against three human carcinoma cell lines (HeLa, A549 and HepG2), which revealed that the complexes exhibited effective cytotoxicity (IC50 values varying from 33.17 to 100μM) and selective inhibition toward HeLa cell lines. These findings indicate that the complexes have the potential to act as effective metallopeptide chemotherapeutic agents.

DNA binding, photo-induced DNA cleavage and cytotoxicity studies of lomefloxacin and its transition metal complexes

This work was focused on a study of the DNA binding and cleavage properties of lomefloxacin (LMF) and its ternary transition metal complexes with glycine. The nature of the binding interactions between compounds and calf thymus DNA (CT-DNA) was studied by electronic absorption spectra, fluorescence spectra and thermal denaturation experiments. The obtained results revealed that LMF and its complexes could interact with CT-DNA via partial/moderate intercalative mode. Furthermore, the DNA cleavage activities of the compounds were investigated by gel electrophoresis. Mechanistic studies of DNA cleavage suggest that singlet oxygen (1O2) is likely to be the cleaving agent via an oxidative pathway, except for Cu(II) complex which proceeds via both oxidative and hydrolytic pathways. Antimicrobial and antitumor activities of the compounds were also studied against some kinds of bacteria, fungi and human cell lines.

Synthesis, characterization, DNA interaction, and in vitro cytotoxicity activities of two ruthenium(II) complexes with disubstituted 2,2′-dipyridyl ligands bearing ammonium groups

The DNA binding, cleavage, and cytotoxic properties of two new Ru(II) complexes [Ru(bpy)2L](PF6)4 (L: L1 = (5,5′-((n-Me)3NCH2)2-bpy)2+; L2 = (5,5′-((n-Et)3NCH2)2-bpy)2+) have been investigated. The results show that both Ru(II) complexes bind to DNA through an electrostatic binding mode. The binding affinity constant can reach 104 M−1 and 1 has a higher binding affinity than 2. Equilibrium dialysis experiments revealed that the complexes are candidates for enantioselective binding to CT-DNA. Moreover, further analysis of the ruthenium complexes revealed that 1 has a higher and more efficient DNA cleavage activity than 2. In vitro cytotoxicity studies of both complexes showed that they exhibited moderate antitumor activity against HeLa, A549, and CNE-2 cancer cells. In addition, 2 displayed higher in vitro cytotoxicity than 1.

Mononuclear dioxomolybdenum(VI) thiosemicarbazonato complexes: Synthesis, characterization, structural illustration, in vitro DNA binding, cleavage, and antitumor properties

Four dioxomolybdenum(VI) complexes were synthesized by reacting [MoO2(acac)2] with N-ethyl-2-(5-bromo-2-hydroxybenzylidene) hydrazinecarbothioamide (1), N-ethyl-2-(5-allyl-3-methoxy-2-hydroxybenzylidene) hydrazinecarbothioamide (2), N-methyl-2-(3-tert-butyl-2-hydroxybenzylidene) hydrazinecarbothioamide (3), and N-ethyl-2-(3-methyl-2-hydroxybenzylidene) hydrazinecarbothioamide (4). The molecular structures of 1, 2, and all the synthesized complexes were determined using single crystal X-ray crystallography. The binding properties of the ligand and complexes with calf thymus DNA (CT-DNA) were investigated via UV, fluorescence titrations, and viscosity measurement. Gel electrophoresis revealed that all the complexes cleave pBR 322 plasmid DNA. The cytotoxicity of the complexes were studied against the HCT 116 human colorectal cell line. All the complexes exhibited more pronounced activity than the standard reference drug 5-fluorouracil (IC50 7.3μM). These studies show that dioxomolybdenum(VI) complexes could be potentially useful in chemotherapy.

Synthesis, singlet-oxygen photogeneration, two-photon absorption, photo-induced DNA cleavage and cytotoxic properties of an amphiphilic β-Schiff-base linked Ru(II) polypyridyl–porphyrin conjugate

A novel porphyrin–polypyridyl ruthenium(II) conjugate (TPP–Ru), in which the ruthenium(II) polypyridyl moiety is linked to the β-position of the tetraphenylporphyrin via a Schiff base linkage, has been synthesized and characterized by 1H NMR, HRMS and UV–visible spectroscopy. The relative singlet oxygen quantum yield and two-photon absorption cross-section of this conjugate, together with its photo-induced DNA cleavage and cytotoxic activities were measured. The results show that the amphiphilic ruthenium(II) polypyridyl–porphyrin conjugate is an effective DNA photocleavage agent, with potential application in one- and two-photon absorption anti-cancer photodynamic therapy.

Cytotoxic, DNA binding, DNA cleavage and antibacterial studies of ruthenium–fluoroquinolone complexes

Six new Ru(II) and Ru(III) complexes have been synthesized and characterized by elemental analysis, LC-MS, electronic spectra, IR spectra and magnetic moment measurements. DNA-binding properties of Ru complexes have been studied by means of absorption spectrophotometry and viscosity measurements as well as their HS DNA cleavage properties by means of agarose gel electrophoresis. The experimental results show that all the complexes can bind to DNA via partial intercalative mode. The K b values of complexes were found in the range 2.14 × 10 4 to 2.70 × 10 5 M−1. All the complexes show excellent efficiency of cleaving DNA than respective fluoroquinolones. Brine shrimp lethality bioassay has been performed to check the cytotoxic activity. The IC 50 values of the complexes are in the range of 6.27 to 16.05 μg mL−1.

Synthesis, crystal structures and characterization of late first row transition metal complexes derived from benzothiazole core: Anti-tuberculosis activity and special emphasis on DNA binding and cleavage property

Air and moisture stable coordination compounds of late first row transition metals, viz. Co(II), Ni(II), Cu(II) and Zn(II), with a newly designed ligand, 2-(2-benzo[d]thiazol-2-yl)hydrazono)propan-1-ol (LH), were prepared and successfully characterized using various spectro-analytical techniques. The molecular structures of the ligand and nickel complex were unambiguously determined by single-crystal X-ray diffraction method. The [Ni(LH)2]Cl2.3H2O complex is stabilized by intermolecular CH⋯π stacking interactions between the methyl hydrogen and the C18 atom of the phenyl ring (C11–H11B⋯C18) forming 1D zig-zag chain structure. Both, the ligand and its copper complex, were electrochemically active in the working potential range, showing quasi-reversible redox system. The interactions of all the compounds with calf thymus DNA have been comprehensively investigated using electronic absorption spectroscopy, viscosity, electrochemistry and thermal denaturation studies. The cleavage reaction on pBR322 DNA has been monitored by agarose gel electrophoresis. The results showed that the ligand can bind to CT-DNA through partial intercalation, whereas the complexes bind electrostatically. Further, [Ni(LH)2]Cl2.3H2O and [CuLCl(H2O)2] complexes in the series have high binding and cleavage affinity towards pBR322 DNA. Additionally, all the compounds were screened for anti-tuberculosis activity. All the complexes revealed an MIC value of 0.8 μg/mL, which is almost 8 times active than standard used (Streptomycin, 6.25 μg/mL).

Synthesis, characterization, fluorescence and biological studies of Mn(II), Fe(III) and Zn(II) complexes of Schiff bases derived from Isatin and 3-substituted-4-amino-5-mercapto-1,2,4-triazoles

A series of Mn(II), Fe(III) and Zn(II) complexes have been synthesized with Schiff bases derived from isatin and 3-substituted-4-amino-5-mercapto-1,2,4-triazole. The elemental, spectroscopic (Infrared, nuclear magnetic resonance, ultraviolet-visible, fast atom bombardment-mass, fluorescence and electrochemistry) and magnetic studies suggested that the metal complexes possess octahedral geometry. The Schiff bases and their metal complexes exhibit fluorescent properties. The antimicrobial studies of Schiff bases and their metal complexes against various bacterial (Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa and Bacillus subtilis) and fungal (Aspergillus niger, and Penicillium chrysogenum) species by the minimum inhibitory concentration method revealed that the metal complexes possess more healing antibacterial activities than the Schiff bases. DNA cleavage property of Mn(II), Fe(III) and Zn(II) complexes revealed the important role of metal ion in the biological system.

Synthesis, crystal structure, DNA cleavage properties, and protein binding activities of an unsymmetrical dinuclear copper(II) complex

[Cu2L(phen)(H2O)3(ClO4)](ClO4)3 {phen = 1,10-phenanthroline, L = 4-((bis(pyridine2-ylmethyl)amino)methyl)-N,N-bis(pyridin-2-ylmethyl)aniline} was prepared and characterized by physical chemical techniques. The X-ray single-crystal structure analysis shows an unsymmetrical dinuclear species. The interaction of the complex with calfthymus DNA (CT-DNA) was studied by various spectroscopic and viscosity measurements, which indicate that the complex can interact with CT-DNA through intercalation. In the presence of H2O2, the complex can cleave pBR322 DNA more efficiently and hydroxyl radicals (HO.) may serve as the major cleavage active species. Interactions of the compound with bovine serum albumin (BSA) were also investigated using UV−Vis and fluorescence spectroscopic methods. The results show that the complex quenches the intrinsic fluorescence of BSA by a static quenching mechanism.

Synthesis, spectral, dna binding and cleavage properties of ruthenium(II) Schiff base complexes containing PPh3/AsPh3 as co-ligands

A dihydroxybenzaldehyde Schiff base ligands (L1-L3) and its ruthenium(II) complexes, have been synthesized and characterized on the basis of elemental analysis, 1H, 13C, 31P NMR, mass spectra, UV-vis and IR spectra. The binding of ruthenium(II) complexes have been investigated by UV-vis absorption spectroscopy. The experiment reveals that all the compounds can bind to DNA through an electrostatic mode and intrinsic binding constant (Kb) has been estimated under similar set of experimental conditions. Absorption spectral study indicate that the ruthenium(II) complexes has intrinsic binding constant in the range of 1.6-8.6 X 104 M-1. The complex [Ru(CO)(PPh3)2(L3)] bind more strongly than that of the other complexes. In addition, DNA cleavage property were tested for all ruthenium(II) complexes.

Mixed ligand μ-phenoxo-bridged dinuclear copper(ii) complexes with diimine co-ligands: efficient chemical nuclease and protease activities and cytotoxicity

The water soluble mixed ligand copper(II) complexes of the type [Cu(sal)(diimine)(ClO4)]21-5, where sal is salicylaldehyde and diimine is 2,2'-bipyridine (bpy, 1), 1,10-phenanthroline (phen, 2), 5,6-dimethyl-1,10-phenanthroline (5,6-dmp, 3), 3,4,7,8-tetramethyl-1,10-phenanthroline (3,4,7,8-tmp, 4) or dipyrido[3,2-d:2',3'-f]quinoxaline (dpq, 5), and [Cu(sal)(phen)(NO3)]2 (2a) have been successfully isolated and characterized by elemental analysis and other spectral techniques. The DNA binding and cleavage properties of 1-5 have been explored by using various physical and biochemical methods. The coordination geometry around copper(II) in the X-ray structures of 1, 2, 2a and 4 is described as an elongated octahedron. The UV-Vis and EPR spectral and ESI-MS studies reveal that in solution the dinuclear complexes dissociate into essentially mononuclear [Cu(sal)(diimine)]+ species with square-based geometry. The absorption spectral titrations and competitive DNA binding studies reveal that the intrinsic DNA binding affinity of the complexes depends upon the diimine co-ligand and is of the order of dpq (5) > 3,4,7,8-tmp (4) > 5,6-dmp (3) > phen (2) > bpy (1). The complexes 2 and 5 are involved in a partial intercalative interaction with DNA base pairs, while 3 and 4 are involved in a hydrophobic interaction with DNA and 1 is involved in an electrostatic interaction with DNA, which is supported by viscosity studies. Interestingly, only 3 and 4 are selective in exhibiting a positive induced CD band (ICD) upon binding to DNA suggesting that they induce a B to A conformational change in DNA. All the complexes exhibit an oxidative DNA cleavage ability, which varies as 5 > 4 > 3 > 2 > 1. While 4 and 5 are unique in displaying prominent double-strand DNA cleavage even in the absence of an activator, 2 and 3 display only single-strand DNA cleavage. Interestingly, all the complexes exhibit oxidative double-strand DNA cleavage in the presence of ascorbic acid, with 4 and 5 showing a DNA cleavage activity more prominent than 1 and 2. The ability of the complexes to bind and cleave the protein BSA varies in the order, 4 > 3 > 5 > 2 > 1. Interestingly, 3 and 4 cleave the protein in the presence of H2O2 as an activator in a non-specific manner suggesting that they can act as chemical proteases. It is remarkable that all the complexes exhibit cytotoxicity against human breast cancer cell lines (MCF-7) with a potency more than the widely used drug cisplatin indicating that they have the potential to act as effective anticancer drugs in a time dependent manner. The morphological assessment data obtained by using Hoechst 33258 staining reveal that 3 and 4 induce apoptosis much more effectively than the other complexes. Also, the alkaline single-cell gel electrophoresis study (comet assay) suggests that the same complexes induce DNA fragmentation more efficiently than others.

DNA/BSA binding, DNA cleavage and electrochemical properties of new multidentate copper(ii) complexes

A new series of multidentate copper(ii) complexes [Cu(L1−5)](ClO4) (1–5) were synthesized and characterized for their DNA/BSA binding, DNA cleavage, cytotoxic properties and antimicrobial activities.

Two Novel Ternary Dicopper(II) μ-Guanazole Complexes with Aromatic Amines Strongly Activated by Quantum Dots for DNA Cleavage

Two novel (μ-guanazole)-bridged binuclear copper(II) complexes with 1,10-phenanthroline (phen) or 2,2'-bipyridine (bipy), [Cu2(μ-N2,N4-Hdatrz)(phen)2(H2O)(NO3)4] (1) and [Cu2(μ-N1,N2-datrz)2(μ-OH2)(bipy)2](ClO4)2 (2) (Hdatrz = 3,5-diamino-1,2,4-triazole = guanazole), have been prepared and characterized by X-ray diffraction, spectroscopy, and susceptibility measurements. Compounds 1 and 2 differ in the aromatic amine, which acts as a coligand, and in the Cu···Cu'-bridging system. Compound 1, which contains two mono-bridged copper ions, represents the first example of a discrete Cu-(NCN-trz)-Cu' complex. Compound 2, with two triply bridged copper ions, is one of the few compounds featuring a Cu-[(NN-trz)2 + (O-aquo)]-Cu' unit. Both compounds display antiferromagnetic coupling but of different magnitude: J (μ2,4-triazole) = -52 cm(-1) for 1 and J (μ1,2-triazolate) = -115 cm(-1) for 2. The DNA binding and cleavage properties of the two compounds have been investigated. Fluorescence, viscosimetry, and thermal denaturation studies reveal that both complexes have high affinity for DNA (1 > 2) and that only 1 acts as an intercalator. In the presence of a reducing agent like 3-mercaptopropionic acid, 1 produces significant oxidative DNA cleavage, whereas 2 is inactive. However, in the presence of very small quantities of micelles filled with core-shell CdSe-ZnS quantum dots (15 nM), 1 and 2 are considerably more active and become highly efficient nucleases as a result of the different possible mechanisms for promoting cooperative catalysis (metal-metal, metal-hydrogen bonding, metal-intercalation, and metal-nanoparticle). Electrophoresis DNA-cleavage inhibition experiments, X-ray photoelectron spectroscopy studies, and fluorescence ethidium bromide displacement assays reveal that in these novel nucleases the QDs act as redox-active protein-like nanoparticle structures that bind to the DNA and deliver electrons to the copper(II) centers for the generation of Cu(I) and reactive oxygen species.

Effect of 1,10-phenanthroline on DNA binding, DNA cleavage, cytotoxic and lactate dehydrogenase inhibition properties of Robson type macrocyclic dicopper(II) complex

DNA targeting macrocyclic dicopper(II) complex, [Cu2L(H2O)2](phen)2(ClO4)2 (L = μ-11,23-dimethyl-3,7,15,19-tetraazatricyclo-[19.3.1.19,13,21] he p t a c o s a-1(24), 2, 7, 9, 11, 13(26), 14, 19, 21(25), 22-decaene-25,26-diol) (2), has been synthesized and characterized. This has been synthesized by reacting a Robson type macrocyclic precursor dicopper(II) complex [Cu2L(H2O)2](ClO4)2 (1) and 1,10-phenanthroline in ethanol. Solution ESR, electronic, and ESI-MS spectral studies suggest that 1,10-phenanthroline replaces coordinated water in 1, giving 2. The influence of the phenanthroline on DNA binding, cleavage, and anticancer properties of 2 have been investigated. Complex 2 displays better DNA binding and cleavage than 1. The dicopper(II) complexes 1 and 2 show cytotoxicity in human cervical HeLa cancer cells, giving IC50 values of 79.41 and 15.82 μM, respectively. Antiproliferative properties of 1 and 2 were confirmed by Trypan Blue exclusive assay and lactate dehydrogenase enzyme level in HeLa cancer cell lysate and content media.

Synthesis and DNA Cleavage Properties of Triazacrown Derivatives

AbstractNew metal‐free DNA cleaving reagent 1, 1,4,7‐triazacrown (TACN) both with aminoethyl, hydroxyethyl side arms and a planar anthraquinone linked by an alkyl (1,6‐hexamethylene) spacer has been synthesized and characterized by NMR and MS spectrometry. For comparison, the corresponding aminoethyl, hydroxyethyl triazacrown derivative 2 without the anthraquinone has also been synthesized. DNA‐binding properties via fluorescence and CD spectroscopy indicate that the binding affinity of 1 with DNA is much stronger than that of 2. Agarose gel electrophoresis was used to assess plasmid pUC19 DNA cleavage. Kinetic data of DNA cleavage promoted by 1, 2 and parent triazacrown (TACN) 3 under physiological condition give the 15‐fold and 234‐fold rate acceleration of compound 1 over 2 and parent triazacrown 3. Radical scavenger inhibition study suggests that DNA cleavage promoted by 1 may be a non‐oxidative pathway through the transphosphorylation and then hydrolysis. The dramatic rate acceleration is due not only to the anthraquinone moiety of compound 1 intercalating into DNA base pairs via stacking interaction, but also the cooperative catalysis of the nucleophilic hydroxyl and the electrophilic ammonium group for the cleavage of phosphodiester of DNA.

Antimicrobial, DNA cleavage, and antioxidant properties of new series of metal(II) complexes derived from naphthofuran-2-carbohydrazide Schiff base: synthesis and physico-chemical studies

Metal complexes of the type [NiL2Cl2]·H2O and ML2Cl2 [M = Co(II), Cu(II), Cd(II), Zn(II), and Hg(II)] where L = Schiff base, derived from condensation of naphthofuran-2-carbohydrazide and 2-chloro-3-formylquinoline have been synthesized. The chelation of the complexes have been inferred through elemental analyses, IR, electronic mass, 1H NMR, ESR spectral data, magnetic and thermal studies. The measured low molar conductance values in DMF indicate the complexes to be non-electrolytic in nature. The cyclic voltammetric investigation suggested that, the Cu(II) complex is of single electron transfer quasi-reversible nature. The free ligand and its complexes have been evaluated for their in vitro antibacterial and antifungal activities by minimum inhibitory concentration method. The influence of DNA cleavage on all the complexes was analyzed by agarose gel electrophoresis method. The free ligand with its complexes has been studied for their antioxidant activity by DPPH method. The results of bioassay revealed that, the metal complexes are active than the free ligand and their biological activity increases on complexation.

Characterization of DNA topoisomerase I from Mycobacterium tuberculosis: DNA cleavage and religation properties and inhibition of its activity

Type I DNA topoisomerases from bacteria catalyse relaxation of negatively supercoiled DNA in a Mg2+ dependent manner. Although topoisomerases of distinct classes have been subjected for anti-cancer and anti-infective drug development, bacterial type I enzymes are way behind in this regard. Our studies with Mycobacterium smegmatis topoisomerase I (MstopoI) revealed several of its distinct properties compared to the well studied Escherichia coli topoisomerase I (EctopoI) suggesting the possibility of targeting the mycobacterial enzyme for inhibitor development. Here, we describe Mycobacterium tuberculosis topoisomerase I (MttopoI) and compare its properties with MstopoI and EctopoI. The enzyme cleaves DNA at preferred sites in a pattern similar to its ortholog from M. smegmatis. Oligonucleotides containing the specific recognition sequence inhibited the activity of the enzyme in a manner similar to that of MstopoI. Substitution of the acidic residues, D111 and E115 which are involved in Mg2+ co-ordination, to alanines affected the DNA relaxation activity. Unlike the wild type enzyme, D111A was dependent on Mg2+ for DNA cleavage and both the mutants were compromised in religation. The monoclonal antibody (mAb), 2F3G4, developed against MstopoI inhibited the relaxation activity of MttopoI. These studies affirm the characteristics of MttopoI to be similar to MstopoI and set a stage to target it for the development of specific small molecule inhibitors.

Effect of coordinated ligands on antiproliferative activity and DNA cleavage property of three mononuclear Cu(II)-terpyridine complexes

Three mononuclear copper(II) complexes, [Cu(tpy)Cl2] 1, [Cu(tpy)(NO3)2(H2O)] 2 and [Cu(Ptpy)Cl2]·H2O·HCl 3 have been synthesised and characterized by various spectroscopic techniques and single crystal X-ray diffraction. Complexes 1 and 3 have five coordinate geometry in solid state, whereas complex 2 has six coordinate geometry. Mass spectral and EPR evidence suggest that in solution all the three complexes exist predominantly as a four coordinate species. Molecular modelling and DNA cleavage studies indicate that complexes 1 and 2 are DNA minor groove binders, whereas 3 is an intercalator. All the three complexes show nuclease activity in the presence of hydrogen peroxide. The three complexes have been found to be cytotoxic towards A549 lung adenocarcinoma cells.

Synthesis and characterization of novel square planar copper(II)–dipeptide–1,10-phenanthroline complexes: Investigation of their DNA binding and cleavage properties

In view of the importance of aromatic moieties in DNA binding and cleavage, two new Cu(II)–dipeptide–phen (phen=1,10-phenanthroline) complexes, viz. [Cu(II)(boc(tos)-his-trp-ome)(phen)](ClO4)2 (1) and [Cu(II)(boc(tos)-his-tyr-ome)(phen)](ClO4)2 (2) were synthesized, comprehensively characterized and their structures reported. The physico-chemical data and molecular modeling approaches support that the complexes are arranged in a distorted square planar geometry. To provide an insight on the mode and affinity of the interaction of these complexes with calf thymus (CT) DNA the following experiments were carried out: thermal denaturation (Tm), UV–Vis absorption, competitive binding, viscosity and fluorescence spectroscopy studies. These experimental results indicate that the complexes interact through stacking between the base pairs of double helix DNA. The overall binding constants (Kb) were determined as 3.33×104 and 2.82×104M−1 for 1 and 2 respectively. The complexes converted supercoiled plasmid pUC19 DNA (SC DNA) into its nicked (NC) form both in the absence (hydrolytic cleavage) and presence (oxidative cleavage) of H2O2. The control experiments demonstrate that no diffusible radical species were involved in the hydrolytic cleavage, but in the presence of H2O2, hydroxyl radical (OH) species were generated and initiated the cleavage reaction by an oxidative pathway. The rate constants for the hydrolysis of the phosphodiester bond were determined as 1.70h−1 and 1.82h−1 for 1 and 2 respectively. This amounts to a (4.7–5.0)×107-fold rate enhancement compared to non-catalyzed DNA cleavage, which is significant. These complexes exhibit better DNA binding and cleavage abilities compared to similar reported complexes.

Synthesis, structure and biological activities of mixed ligand copper(II) and nickel(II) complexes of N′-(1E)-[(5-bromo-2-hydroxyphenyl)methylidene]benzoylhydrazone

We have made an effort to synthesize ternary complexes [Cu2(L)2(Him)2]·CH3OH 1, [Cu(L)(bipy)] 2 and [Ni(HL)(PMDT)]BF43 (H2L=N′-(1E)-[(5-bromo-2-hydroxyphenyl)methylidene]benzoylhydrazone; Him=imidazole; bipy=2,2′-bipyridine and PMDT=N,N,N′,N″,N″-pentamethyldiethylenetriamine). Their crystal structures were determined by X-ray diffraction method. Single crystal X-ray of 1 revealed the geometry of phenoxo bridged copper center and the distance between the two Cu(II) ion is 3.245Å. The two copper ions are penta coordinated with distorted square pyramidal geometries. Magnetic measurements of dicopper complex 1 exhibited the presence of antiferromagnetic exchange interaction. The observed trend in the spin Hamiltonian parameters in complexes 1 and 2g||>g⊥>2.0023 and |A⊥|≪|A|||≈163–173×10−4cm−1) indicates dx2-y2 band ground state with tetragonal site symmetry for copper(II). Complex 3 was crystallized in orthorhombic crystal system having six coordination numbers. Superoxide dismutase activities of all these complexes have been revealed to catalyze the dismutation of superoxide (O2-) and IC50 values were evaluated. DNA cleavage properties and antibacterial activity have been measured and discussed.