In vitro anti‐proliferative and in silico docking studies of heteroleptic copper(II) complexes of pyridazine‐based ligands and ciprofloxacin

Three heteroleptic copper(II) complexes of the type [Cu(L^1–3)(cf)(ClO₄)] ( 1 – 3 ), where cf = ciprofloxacin, have been synthesized using pyridazine‐based ligands 3‐chloro‐6‐(salicylidenehydrazinyl)pyridazine (HL¹), 3‐chloro‐6‐(4‐diethylaminosalicylidenehydrazinyl)pyridazine (HL²) and 3‐chloro‐6‐(5‐bromosalicylidenehydrazinyl)pyridazine (HL³). Electronic spectral data and magnetic moment values suggest octahedral geometry for the synthesized copper(II) complexes. Electrochemical data of the copper(II) complexes present an irreversible one‐electron reduction wave in the cathodic potential region (E_pc) between ?0.631 and ?0.670 V. Frontier molecular orbital calculations were carried out, and the obtained low‐energy gap supports the bio‐efficacy of the complexes. All the complexes were screened for their in vitro cytotoxicity activity against three human cancerous (breast adenocarcinoma (MCF‐7), hepatoma (HepG‐2) and cervical (HeLa)) and one non‐cancerous (non‐tumorigenic human dermal fibroblast (NHDF)) cell lines using MTT assay, in which complex 2 exhibited higher activity. The apoptosis induction by the complexes was analysed using the Hoechst dye staining method with MCF‐7 cell line, which indicates higher apoptotic activity of complex 2 . A molecular docking study was carried out to ascertain the binding affinity of the synthesized heteroleptic copper(II) complexes with phosphoinositide 3‐kinase gamma (PI3Kγ) receptor.     

Biocatalysis,DNA–protein interactions,cytotoxicity and molecular docking of Cu(II), Ni(II), Zn(II) and V(IV) Schiff base complexes

Four mononuclear metal complexes (Cu(II) ( 1 ), Ni(II) ( 2 ), Zn(II) ( 3 ) and V(IV) ( 4 )) were synthesized using the Schiff base ligand 2,2′‐{cyclohexane‐1,2‐diylbis[nitrilo(1E )eth‐1‐yl‐1‐ylidine]}bis[5‐(prop‐2‐yn‐1‐yloxy)phenol] and structurally characterized by various spectral techniques. The catecholase‐mimicking activities of 1 – 4 were investigated and the results reveal that all the complexes have ability to oxidize 3,5‐di‐tert ‐butylcatechol (3,5‐DTBC) to 3,5‐di‐tert ‐butylquinone in aerobic conditions. Electrospray ionization mass spectrometry studies were performed for 1 – 4 in the presence of 3,5‐DTBC to determine the possible complex–substrate intermediates. X‐band electron paramagnetic resonance spectroscopy results indicate that the metal centres are involved in the catecholase activity. Ligand‐centred radical generation was further confirmed by density functional theory calculation. The phosphatase‐like activity of 1 – 4 was investigated using 4‐nitrophenylphosphate as a model substrate. All the complexes exhibit excellent phosphatase activity in acetonitrile medium. The interactions of 1 – 4 with calf thymus DNA (CT‐DNA) and bovine serum albumin (BSA) protein were investigated using absorption and fluorescence titration methods. All the complexes strongly interact with CT‐DNA and BSA protein. The complexes exhibit significant hydrolytic cleavage of supercoiled pUC19 DNA. Complexes 1 – 4 exhibit significant in vitro cytotoxicity against MCF7 (human breast cancer) and MIA‐PA‐CA‐2 (human pancreatic cancer) cell lines. Moreover, the molecular docking technique was employed to determine the binding affinity with DNA and protein molecules.     

Synthesis,characterization, DNA binding,apoptosis and molecular docking of three Mn(II), Zn(II) and Cu(II) complexes with terpyridine‐based carboxylic acid

A series of novel cytotoxic compounds, [Mn(cpt)₂], [Zn(tpt)(H₂O)₂]?DMA?2(H₂O) and [Cu(tpt)]?DMA (cpt = 4′‐(4‐carboxyphenyl)‐2,2′:6′,2″‐terpyridine, tpt = 4‐(2,4,6‐tricarboxylphenyl)‐2,2′:6′,2″‐terpyridine, DMA = (CH₃)₂NH), were isolated and characterized. The structures of these complexes were characterized using single‐crystal X‐ray diffraction. The mode and extent of binding between fish sperm DNA and the complexes were investigated using fluorescence spectroscopy and molecular docking. These results indicate the ability of the complexes to bind to DNA with different binding affinities. The binding of the Zn(II) complex with DNA is stronger than that of the corresponding Cu(II) analogue, which is expected due to the z* effect and geometry. The ability of these complexes to cleave pBR322 plasmid DNA was demonstrated using gel electrophoresis assay, showing that the complexes have effective DNA cleavage activity. In addition, the cytotoxic effects of these complexes were examined on HeLa cells (human cervix epithelia carcinoma cells) in vitro. The three complexes exhibit different cytotoxic effects and decent cancer cell inhibitory rate. This means that the structures and type of metal have a great influence on the activity of these novel complexes.     

Biological and catalytic evaluation of Ru(II)‐p‐cymene complexes of Schiff base ligands: Impact of ligand appended moiety on photo‐induced DNA and protein cleavage,cytotoxicity and C‐H activation

Two organometallic Ru(II)‐p‐cymene complexes of the type [Ru(η⁶‐p‐cymene)(L)Cl]PF₆ 1 and 2 , where L is N,N‐bis(4‐isopropylbenzylidene)ethane‐1,2‐diamine (bien, L1 ) or N,N‐bis (pyren‐2‐ylmethylene)ethane‐1,2‐diamine (bpen, L2 ) have been prepared and characterized well. Because of appended pyrenyl groups in coordinated bpen ligand, the complex 2 exhibits higher DNA and protein binding than complex 1 in which isopropylbenzyl groups are incorporated. Interestingly, the luminescent characteristic complex 2 is unique in displaying DNA cleavage after light activation by UVA light at 365 nm through oxygen dependent mechanism. AFM analysis attests the photo‐induced DNA fragmentation ability of complex 2 . Also, the complex 2 cleaves the protein after light exposure in a non‐specific manner suggesting that it can act as a protein photo cleaving agent. In contrast to the trend of DNA and protein interaction of complexes, the complex 1 exhibits cytotoxic activity against human breast carcinoma ( MCF‐7 ) and liver carcinoma ( HepG2 ) with potency higher than that of complex 2 due to enhanced hydrophobicity of isopropyl groups present in p‐cymene and bien ligands. Indeed, complex 2 is inactive against MCF‐7 and HepG2 cancer cell lines even up to 200 μM concentration. The AO/EB staining assay reveals that the complex 1 is able to induce late apoptotic mode of cell death in breast cancer cells, which is further confirmed by inter‐nucleosomal DNA cleavage. Furthermore, the complexes 1 and 2 are evaluated for their catalytic activities and found to be working well for the β‐carboline directed C–H arylation to afford the desired products in good yield (40–47%).     

Heteroleptic Schiff base complexes containing terpyridine as chemical nucleases and their biological potential: A study of DNA binding and cleaving,antimicrobial and cytotoxic tendencies

Amidst the very many metallodrugs for the treatment of cancer regularly reported, the development of the next generation of compounds with an aim of overcoming the shortcomings by enhancing biological activity and cytotoxicity but exhibiting low toxicity is essential. Herein we report such octahedral metal(II) complexes ( 1 – 12 ) containing triazole‐derived Schiff base as the scaffold. The complexes were synthesized and characterized by means of elemental analysis and various spectroscopic techniques. The complexes were subjected to various investigations that involved their interaction with calf thymus DNA and supercoiled pBR322 DNA. In vitro antimicrobial studies were also conducted in addition to the use of spectrophotometric, spectrofluorometric, cyclic voltammetric and hydrodynamic techniques. Although all complexes showed activity, complex 9 revealed excellent DNA proclivity, DNA cleaving tendencies and antimicrobial efficacy. All copper(II) complexes were evaluated for their antiproliferative activity against a panel of human cancer cell lines (HeLa, Hep‐2, MCF‐7 and NHDF). Complexes 1 – 12 showed activity against all the cell lines with low toxicity towards normal cell line, and the activity of complex 9 towards Hep‐2 was prominent. The effect of the ligand system on the complexes is also discussed along with the importance of tuning the ligand system.     

Preparation,characterization and biological evaluation of two chiral binuclear copper(II) complexes

Two chiral Cu(II) complexes of [Cu₂(R‐L)₂](PF₆)₂·2C₂H₅OH ( 1 ) and [Cu₂(S‐L)₂](PF₆)₂·2C₂H₅OH ( 2 ) (HL = 2‐(Bis(quinolin‐2‐ylmethyl)amino)‐1‐propanol) were designed and synthesized to serve as chemical nucleases and anticancer drugs. X‐ray crystallography revealed that two complexes contain chiral binuclear cations and PF₆^? anions. The interaction of two complexes with CT‐DNA was researched via various spectroscopic techniques and viscosity measurement, indicating that the complexes were bound to CT‐DNA by a classical intercalation binding mode. In addition, the two complexes exhibited remarkable DNA cleavage activity with an optimal dosage of 10 μM in the absence of any exogenous oxidant agent. Both of the complexes showed excellent in vitro cytotoxicity on A549 cell lines with IC₅₀ values in the low micromolar range. Moreover, complex 2 could damage DNA of A549 cells into fragmentation and then induced cell apoptosis in a dose‐dependent manner, which was demonstrated by comet assay and Hoechst 33342 staining experiment. Further research showed that complex 2 could also induce G₂ and S phase cell cycle arrest.     

Ligational behavior of new mononucleating NOO ethyl pyruvate Schiff base towards 3d metal(II) ions: an emphasis on antiproliferative and photocleavage property

A series of Co(II), Ni(II), Cu(II), and Zn(II) complexes of a tridentate hydrazone were prepared and characterized by various spectro‐analytical techniques and magnetic moment studies. The complexes were found to be monomeric and non‐electrolytes. The copper complex is electrochemically active in the applied potential range. The compounds synthesized in the present study have shown promising antiproliferative activity when screened using the in vitro method against two human cancer cell lines: HeLa and HepG2. The Escherichia coli DNA‐binding properties of all the compounds were investigated with UV–visible absorption spectrophotometric titrations, viscosity measurements, DNA melting experiments and gel electrophoreses measurements. The compounds were demonstrated to act as DNA intercalators with appreciable DNA‐binding constant values. Copyright © 2012 John Wiley & Sons, Ltd.     

Novel water soluble bis(μ‐chloro) bridged Cu(II) binuclear and mononuclear complexes: Synthesis,characterization and biological evaluation

A water soluble chloro bridged binuclear copper(II) complex (3) and mononuclear complex (4) have been synthesized from chloro substituted 2‐oxo‐1,2‐dihydroquinolin‐3‐yl‐methylene‐2 hydroxybenzohydrazide 1 and 2 and CuCl₂·2H₂O. The structures of the complexes have been determined by single crystal X‐ray diffraction. The binding interactions of the ligands and complexes with CT‐DNA and protein have been evaluated by absorption and emission spectroscopic method. CT‐DNA and ethidium bromide (EB) competitive studies revealed that the compounds could interact with CT‐DNA through intercalation binding mode. Interactions of the compounds with BSA were also studied by UV−visible, fluorescence and synchronous fluorescence spectroscopic methods which showed that the compounds had a strong binding affinity with BSA through static quenching process. The cytotoxic effect of the compounds examined on cancer cell lines, such as A549 (lung cancer) and MCF7 (breast cancer) cell lines showed that all four compounds exhibited substantial cytotoxic activity.     

Novel 3‐Hydroxy‐2‐naphthoic hydrazone and Ni(II), Co(II) and Cu(II) Complexes: Synthesis,Spectroscopic Characterization,Antimicrobial, DNA Cleavage and Computational Studies

A novel hydrazone ligand derived from condensation reaction of 3‐hydroxy‐2‐naphthoic hydrazide with dehydroacetic acid, and its Ni(II), Cu(II) and Co(II) complexes were synthesized, characterized by spectroscopic, elemental analyses, magnetic susceptibility and conductivity methods, and screened for antimicrobial, DNA binding and cleavage properties. Spectroscopic analysis and elemental analyses indicated the formula, [MLCl₂], for the complexes; square planar geometry for the nickel, and tetrahedral geometry for copper and cobalt complexes. The non‐electrolytic natures of the complexes in Dimethyl Sulphoxide (DMSO) were confirmed by their molar conductance values in the range of 6.11–14.01 Ω^?1cm²mol^?1. The copper complex had the best antibacterial activity against Staphylococcus aureus (ATCC 29213). DNA cleavage activities of the compounds, evaluated on pBR322 DNA, by agarose gel electrophoresis, in the presence and absence of oxidant (H₂O₂) and free radical scavenger (DMSO), indicated no activity for the ligand, and moderate activity for the complexes, with the copper complex cleaving pBR322 DNA more efficiently in the presence of H₂O₂. When the complexes were evaluated for antibacterial and A‐DNA activity using Molecular docking technique, the copper complex was found to be most effective against Gram‐positive (S. aureus) bacteria. [CuLCl₂] showed good hydrogen bonding interaction with the major‐groove (C₂^.G₁₃ base pair) of A‐DNA. Density functional theory (DFT) calculations of the structural and electronic properties of the complexes revealed that [CuLCl₂] had a smaller HOMO‐LUMO gap, suggesting a higher tendency to donate electrons to electron‐accepting species of biological targets.     

Cu (II) and Co (II/III) complexes of N,O‐chelated Schiff base ligands: DNA interaction,protein binding,cytotoxicity, cell death mechanism and reactive oxygen species generation studies

A series of copper (II) ( 1 and 3 ) and cobalt (II/III) ( 2 , 4 and 5 ) complexes comprising different imino‐phenolate ligands DCH , DTH and DBH ₂ (where DCH = 2,4‐dichloro‐6‐((mesitylimino)methyl)phenol, DTH = 2,4‐di‐tert‐butyl‐6‐((mesitylimino)methyl) phenol and DBH ₂ = 2,4‐dibromo‐6‐((mesitylimino)methyl)phenol) have been prepared with excellent yield and high purity. By utilizing different spectroscopic tools such as UV–visible, electrospray ionization (ESI)‐mass, Fourier‐transform infrared (FTIR) spectrometry and elemental analysis, the prepared complexes ( 1 – 5 ) were thoroughly characterized. The molecular structure of the synthesized complexes was ascertained by using single‐crystal X‐ray diffraction studies (SCXRDs). The experiment reveals that Complexes 1 – 5 bind to calf thymus DNA (CT‐DNA) through non‐intercalative way with good interacting abilities. However, 1 – 5 are excellent quenchers of the fluorescence intensity of bovine serum albumin (BSA) following the static pathway. Additionally, they had shown remarkable cytotoxic potential against MCF‐7 (mammary gland adenocarcinoma) and A549 (lung adenocarcinoma) cell lines. The IC₅₀ values associated with these complexes were much lower than the conventional drug cisplatin. Apoptosis‐induced cell death was confirmed from the DNA fragmentation studies and Hoechst 33342 staining. The 2′,7′‐dichlorofluorescein diacetate (DCFDA) assay indicates that the complex mediated reactive oxygen species (ROS) generation is accountable for governing the apoptosis mechanism via oxidative cell distress. Apart from these studies, by carrying out density functional theory (DFT) method, highest occupied molecular orbital–lowest unoccupied molecular orbital (HOMO–LUMO) energy gap calculations and optimized structures of the synthesized complexes were accomplished.     

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.     

Probing of effective pyrazolone based metallonucleases: Molecular docking and in vitro biological critiques

Four novel tryptophan based metal (II) complexes of the type [ML (Try)₂] were prepared by using pyrazolone derived Schiff base ligand. The proposed structure was confirmed by physicochemical methods which reveal octahedral coordination environment around the metal center. Intercalative binding mode of the complexes with CT DNA was confirmed by electronic absorption titration, viscosity measurements and fluorescence spectroscopy. Efficiency of DNA cleavage ability of the metal complexes was explored by the gel electrophoresis technique. The antimicrobial activities of the metal complexes showed potent biocidal activity. The percentage of free radical scavenging activity shows that the complexes are very reactive towards DPPH. Moreover, their cytotoxicity was tested against the two cancer cell lines (MCF‐7 and HepG2) and one normal cell line (NHDF) respectively. The MTT assay shows that the complexes have the anticancer efficacy. Moreover, the complexes exhibit a limited cytotoxicity effect on normal cell line NHDF. The morphological changes of apoptosis cell death were investigated by using Hoechst 33258 staining method. In addition, the Molecular docking studies was executed to consider the nature of binding and binding affinity of the synthesized compounds with DNA (PDB: 1BNA) and protein (PDB: 3hb5).     

Synthesis,characterization, DNA binding,cytotoxicity and molecular docking properties of Cu (II) and Mn (II) complexes with 1,4‐bis (pyrazol‐1‐yl) terephthalic acid

Two novel complexes, [Cu (L)(H₂O)]?H₂O ( 1 ) and [Mn (H₂O)₆] ?L ?H₂O ( 2 ) (L = 1,4‐bis (pyrazol‐1‐yl) terephthalic acid), were synthesized under hydrothermal conditions. They were characterized using elemental analysis, infrared spectroscopy and single‐crystal X‐ray diffraction. Intramolecular weak interactions, such as hydrogen bonds, and intermolecular interactions play important roles in the construction of the complexes. The interaction of these complexes with fish sperm DNA (FS‐DNA) was monitored and binding constants were determined using UV–visible spectroscopy, which revealed their ability to bind to FS‐DNA, with binding constants for the two complexes of 1.88 × 10⁴ M^?1 ( 1 ) and 1.06 × 10⁴ M^?1 ( 2 ). Viscosity experiments further demonstrated the binding of the complexes to DNA. The complexes were further studied using gel electrophoresis assay with supercoiled plasmid pBR322 DNA. In addition, anticancer activities of the metal complexes investigated through MTT assays in vitro indicated good cytotoxic activity against cancer cell lines. Flow cytometry and apoptosis experiments showed that these complexes induced apoptosis of two different cancer cell lines (HeLa and KB cells), demonstrating a significant cancer cell inhibitory rate. Finally, a further molecular docking technique was employed to confirm the binding of the complexes towards the molecular target DNA.     

Synthesis,crystal structure and biological properties of a cis‐dichloridobis(diimine)copper(II) complex

The mechanisms of interaction of inorganic complexes with DNA are important in the design and development of new metal‐based drug molecules. The limitations of cis‐platin have encouraged the design and development of new metal‐based target‐specific anticancer drugs having reduced side effects. The complex cis‐dichloridobis(1,2,5‐thiadiazolo[3,4‐f][1,10]phenanthroline‐κ²N¹,N¹⁰)copper(II), [CuCl₂(C₁₂H₆N₄S)₂], has been synthesized and characterized. The complex crystallizes in the monoclinic space group C2/c. The covalent binding of the complex with DNA was studied by absorption spectroscopy. The anticancer activity of the complex on the Human Lung Carcinoma (A549) cell line was investigated by MTT assay. The complex exhibits higher toxicity than cis‐platin and induces an apoptotic mode of cell death.     

Structure and cytotoxicity of zinc (II) and cobalt (II) complexes based on 1,3,5‐tris(1‐imidazolyl) benzene

Three novel complexes, [Zn (tib)₂·(H₂O)₂]·(NO₃)₂ ( 1 ), [Co (tib)₂]·2NO₃ ( 2 ) and [Co₂(tib)₂(btc)]·H₂O ( 3 ) [H₄btc = 1,2,4,5‐benzenetetracarboxylic acid; H₂tib = 1,3,5‐tris(1‐imidazolyl)benzene], were synthesized and characterized by single‐crystal X‐ray, IR and elemental analysis. The interaction of these complexes with FS‐DNA (fish sperm DNA) was monitored, and binding constants were determined using UV/Vis, which revealed that they have the ability to bind to FS‐DNA. DNA‐binding constants (K) for the three complexes were 2.2 × 10⁴ m ^?1, 0.7 × 10⁴ m ^?1 and 0.09 × 10⁴ m ^?1, respectively. The interaction capacity of the complexes with FS‐DNA has been investigated by fluorescence spectroscopy. Stern–Volmer quenching plot values for complexes 1 , 2 and 3 were 0.3784, 0.1028 and 0.076, respectively. The viscosity measurement suggested that complexes 1 , 2 and 3 interact with DNA in an intercalation mode. In addition, anti‐cancer activities of these complexes investigated through MTT assays in vitro indicated that the complexes showed good cytotoxic activity against cancer cell lines. Cytotoxic activity of test complexes against two different cancer cell lines (HeLa and KB cells) showed significant cancer cell inhibition rates. Flow cytometry experiments and morphological apoptosis studies showed that the complexes induced apoptosis of HeLa tumor cell lines. Finally, a further molecular docking technique was employed to confirm the binding of the complexes toward the molecular target DNA.     

Fabrication,spectroscopic characterization,calf thymus DNA binding investigation,antioxidant and anticancer activities of some antibiotic azomethine Cu(II), Pd(II), Zn(II) and Cr(III) complexes

This study was conducted to prepare novel azomethine chelates of Cu(II), Pd(II), Zn(II) and Cr(III) with tridentate dianionic azomethine OVAP ligand 2‐[(2‐hydroxyphenylimino)methyl]‐6‐methoxyphenol. The prepared compounds were characterized using elemental analyses and spectral, conductivity, magnetic and thermal measurements. The spectroscopic data suggest that the parent azomethine ligand binds to the investigated metal ions through both deprotonated phenol oxygen and azomethine nitrogen atoms, and adopts distorted octahedral geometry in the case of Cr(III) and Cu(II) ions while tetrahedral and square planar geometries for Zn(II) and Pd(II) ions, respectively. In order to confirm the molecular geometry of the investigated azomethine chelator and its complexes, theoretical density functional theory calculations were employed. Correlation between experimental observations and theoretical calculations of geometry optimization results are in a good agreement. Absorption titration was used to explore the interaction of the investigated azomethine metal chelates with calf thymus DNA, and the binding constant as well as Gibbs free energy were evaluated. Viscosity measurements and gel electrophoresis studies suggest intercalative and replacement binding modes of the azomethine metal chelates with calf thymus DNA. Additionally, the antimicrobial activity of the complexes was screened against some pathogenic bacteria and fungi. This biological study shows that the complexes exhibit a marked inhibitory effect compared to the corresponding ligand and standard drug s. Furthermore, the effect of the novel compounds as antioxidants was determined by reduction of 1,1‐diphenyl‐2‐picrylhydrazyl and compared with that of vitamin C. Finally, in vitro cell proliferation via MTT assay was investigated against colon carcinoma cells (HCT‐116), hepatic cellular carcinoma cells (HepG‐2(and breast carcinoma cells (MCF‐7) to calculate the cytotoxicity of the prepared compounds. Cell proliferation is inhibited for all compounds and in a dose‐dependent manner in the sequence of OVAPPd > OVAPCu > OVAPZn > OVAPCr > OVAP azomethine ligand.     

Dicoumarol complexes of Cu(II), Fe(II) and Fe(III): preparation,characterization, in‐vitro antibacterial and DNA binding activity

3‐3′‐Benzylidenebis[4‐hydroxycoumarin] or 4‐nitro,3‐3′‐benzylidenebis[4‐hydroxycoumarin] or 4‐methoxy,3‐3′‐benzylidenebis[4‐hydroxycoumarin] and their complexes with Cu(II), Fe(II) and Fe(III) were synthesized and characterized using ¹H‐NMR, ¹³C‐NMR, IR spectra, electronic spectra, magnetic measurements and elemental analyses. The ligands, metal salts, complexes, control and standard drug were tested for their in‐vitro antibacterial activity against Bacillus cereus, Staphylococcus aureus, Escherichia coli, Bacillus subtilis, Salmonella typhi, and Serratia marcescens. The metal complexes exhibit good activity against bacterial strains compared with parental compounds and moderate compared with the standard drug (ciprofloxacin). In‐vitro DNA‐binding activity was carried out using agarose gel electrophoresis. The synthesized compounds show effective DNA‐binding activity. Copyright © 2007 John Wiley & Sons, Ltd.     

Three novel Ni(II), VO(II) and Cr(III) mononuclear complexes encompassing potentially tridentate imine ligand: Synthesis,structural characterization,DNA interaction,antimicrobial evaluation and anticancer activity

Three novel Cr(III),VO(II) and Ni(II) imine complexes derived from the condensation of 2‐aminophenol (AP) with 2‐hydroxynaphthaldehyde (HN) were synthesized. The prepared HNAP imine ligand and its complexes were investigated via various physicochemical tools. The results suggest that the parent ligand behaves as a dibasic tridentate ONO ligand, when coordinated to Cr(III) in octahedral and to Ni(II) in tetrahedral geometry. In the case of VO(II), it coordinates in distorted square pyramidal geometry. Also, the prepared compounds were screened for their antimicrobial activities against pathogenic bacteria, Escherichia coli (−ve), Bacillus subtilis (+ve) and Staphylococcus aureus (+ve), and some types of fungi, Aspergillus niger , Candida glabrata and Trichophyton rubrum . The results indicate that the complexes show a stronger antimicrobial efficiency compared to the pro‐ligand. The interaction of the prepared complexes with calf thymus DNA was investigated using spectral, viscosity and gel electrophoresis measurements. The obtained results clearly demonstrate that the binding affinity with calf thymus DNA follows the order HNAPCr > HNAPV > HNAPNi. The cytotoxic activity of the prepared compounds on human colon carcinoma cells (HCT‐116 cell line), hepatic cellular carcinoma cells (HepG‐2cell line) and breast carcinoma cells (MCF‐7cell line) was examined. From these results it is found that the investigated complexes have potent cytotoxicity against growth of carcinoma cells compared to the corresponding imine pro‐ligand.     

Novel 13,14‐dimethyl‐5,8‐dioxa‐2,11,13,14‐tetraaza‐1,12‐diphosphabicyclo [10.1.1] tetradecane 1,12‐dioxide ligand and its Ni(II), Co(II), and Cu(II) complexes: Synthesis,characterization, antimicrobial,DNA cleavage,and computational studies

A novel diazadiphosphetidine ligand derived from the reaction of 2,4‐dichloro‐1,3‐dimethyl‐1,3,2,4‐diazadiphosphetidine‐2,4‐dioxide and 2,2′‐(ethane‐1,2‐diylbis[oxy])bis(ethan‐1‐amine) and its Ni(II), Cu(II), and Co(II) complexes have been synthesized, characterized by spectroscopic, elemental analyses, magnetic susceptibility, and conductivity methods, and screened for antimicrobial, DNA binding, and cleavage properties. Spectroscopic analysis and elemental analyses indicate the formula [M(H₂L)Cl₂] for the Cu(II), Co(II), Ni(II), and Zn(II) complexes and octahedral geometry for all the complexes. The non‐electrolytic nature of the complexes in dimethyl sulfoxide (DMSO) was confirmed by their molar conductance values, which are in the range 12.32–6.73 Ω^?1 cm² mol^?1. Computational studies have been carried out at the density functional theory (DFT)‐B3LYP/6‐31G(d) level of theory on the structural and spectroscopic properties of diazadiphosphetidine H₂L and its binuclear Cu(II), Co(II), Ni(II), and Zn(II) complexes. Six tautomers and geometrical isomers of the diazadiphosphetidine ligand were confirmed using semiempirical AM1 and DFT method from DMOL³ calculations. The copper complex had the best antibacterial activity against Staphylococcus aureus (ATCC 29213). DNA cleavage activities of the compounds, evaluated on pBR322 DNA by agarose gel electrophoresis in the presence and absence of an oxidant (H₂O₂) and a free‐radical scavenger (DMSO), indicated no activity for the ligand and moderate activity for the complexes, with the copper complex cleaving pBR322 DNA more efficiently in the presence of H₂O₂.     

Dinuclear Ruthenium(II) Complexes That Induce and Stabilise G‐Quadruplex DNA

A series of dinuclear ruthenium(II) complexes were synthesised, and the complexes were determined to be new highly selective compounds for binding to telomeric G‐quadruplex DNA. The interactions of these complexes with telomeric G‐quadruplex DNA were studied by using circular dichroism (CD) spectroscopy, fluorescence resonance energy transfer (FRET) melting assays, isothermal titration calorimetry (ITC) and molecular modelling. The results showed that the complexes 1 , 2 and 4 induced and stabilised the formation of antiparallel G‐quadruplexes of telomeric DNA in the absence of salt or in the presence of 100 mM K⁺‐containing buffer. Furthermore, complexes 1 and 2 strongly bind to and effectively stabilise the telomeric G‐quadruplex structure and have significant selectivity for G‐quadruplex over duplex DNA. In comparison, complex 3 had a much lesser effect on the G‐quadruplex, suggesting that possession of a suitably sized plane for good π–π stacking with the G‐quadruplets is essential for the interaction of the dinuclear ruthenium(II) complexes with the G‐quadruplex. Moreover, telomerase inhibition by the four complexes and their cellular effects were studied, and complex 1 was determined to be the most promising inhibitor of both telomerase and HeLa cell proliferation.