Synthesis,characterization and in vitro biological assays of copper(II) and nickel(II) complexes with furan‐­2­‐carboxylic acid hydrazide

Two transition metal complexes, [Cu(FH)₃]⋅2Cl⋅2H₂O and [Ni(FH)₃]⋅2Cl⋅2H₂O, were synthesized from the reactions of furan‐2‐carboxylic acid hydrazide with CuCl₂⋅2H₂O and NiCl₂⋅6H₂O. The synthesized complexes were characterized using analytical and various spectral techniques. The structures of the complexes were determined using single‐crystal X‐ray diffraction. The interactions of the complexes with calf thymus DNA (CT‐DNA) were studied using absorption, fluorescence, cyclic voltammetric and viscosity measurements. The experimental results showed that the complexes could interact with CT‐DNA through intercalation. A gel electrophoresis assay demonstrated the ability of the complexes to cleave pBR322 DNA. The binding interaction of the complexes with bovine serum albumin was investigated using a fluorescence spectroscopic method. The radical scavenging ability, assessed using a series of antioxidant assays involving 2,2‐diphenyl‐2‐picrylhydrazyl radical, hydroxyl radical and nitric oxide radical, showed that the complexes possess significant radical scavenging properties. Further, the in vitro cytotoxic effect of the complexes examined on cancerous cell lines, such as human cervical cancer cells (HeLa) and human breast cancer cell line (MCF‐7), showed that the complexes exhibit significant anticancer activity.     

Synthesis,crystal structures,DNA binding and cleavage properties and protein binding activities of three mononuclear cobalt(II) complexes

Three new mononuclear cobalt(II) complexes containing ligands with extended planar quinoxaline moieties, {dipyrido[3,2‐a:2′,3′‐c]phenazine (dppz) or dipyrido[3,2‐d:2′,3′‐f]quinoxaline (dpq)}, viz. [Co(dppz)(acac)₂] · CH₃OH ( 1 ), [Co(dpq)(tfnb)₂] ( 2 ) and [Co(dpq)(dbm)₂] ( 3 ), where acac = acetylacetonate, tfnb = benzoyltrifluoroacetone and dbm = dibenzoylmethane, have been synthesized and structurally characterized as octahedral complexes. The binding ability of the complexes with calf thymus (CT)‐DNA has been investigated by spectroscopic and viscosity measurements. Results indicate that all complexes bind to CT‐DNA via intercalative mode, and the DNA binding affinity of dppz complex 1 is apparently stronger than that of dpq complexes 2 and 3 . Furthermore, DNA photocleavage experiments indicate that these complexes are efficient DNA cleaving agents in UV‐A (365 nm) and hydroxyl radical (HO^·), singlet oxygen (¹O₂) and superoxide anion (¹O₂^?) serve as the major cleavage active species. In addition, interaction of the complexes with bovine serum albumin (BSA) was investigated using UV ? visible and fluorescence methods, which indicated that all complexes could quench the intrinsic fluorescence of BSA in a static quenching process. Copyright © 2014 John Wiley & Sons, Ltd.     

Hexanuclear Zn(II) and Mononuclear Cu(II) Complexes containing imino phenol ligands: Exploitation of their Catalytic and Biological Perspectives

A unique hexanuclear zinc(II) ( 1 ) and two mononuclear copper(II) ( 2 and 3 ) complexes anchored with imino phenol ligand HL ¹ and HL ² were synthesized with good yield and purity (where HL ¹  = 4‐tert‐butyl‐2,6‐bis((mesitylimino)methylphenol and HL ²   =  5‐tert‐butyl‐2‐hydroxy‐3‐((mesitylimino)methyl)benzaldehyde). These complexes were characterized by utilizing various spectroscopic protocols like NMR, FTIR, UV as well as ESI‐Mass spectrometry, elemental analysis and single crystal X‐ray diffraction studies. Their potential to bind calf thymus DNA (CT‐DNA) was tested utilizing different techniques such as UV–visible and fluorescence spectroscopy. The experiment implies that they interact with CT‐DNA via non‐intercalative mode with moderate capabilities (K_b ~ 10⁴ M^?1). On the other hand, these complexes have high capabilities to quench the fluorescence of bovine serum albumin (BSA) following the static pathway. In addition, they are active catalysts for the oxidation reaction of 3,5‐di‐tert‐butylcatechol (3,5‐DTBC) to 3,5‐di‐tert‐butylquinone (3,5‐DTBQ) under aerobic condition. From the recorded EPR signals of all complexes, it has been concluded that the oxidation reaction proceeds via ligand oriented radical pathway instead of metal based redox participation. Kinetic studies using 1 – 3 indicate that it follows Michaelis–Menten type of equation with moderate to high turnover number (k_cat). Apart from these aspects, complexes 1 – 3 were screened for their cytotoxic behavior towards HeLa cells (human cervical carcinoma) and found quite active with comparable IC₅₀ values to cisplatin.     

Synthesis,DNA binding,nuclease activity and cytotoxic studies of a wheel‐shaped octanuclear copper(II) complex based on 1,2,4‐triazole

The antitumor activity shown by many platinum complexes has produced a strong interest in research of new organometallic compounds. Among the metal compounds synthesized and tested, copper compounds have received considerable attention because of their cytotoxic activity against solid tumors. A novel wheel‐shaped octanuclear copper(II) complex with a 1,2,4‐triazole derivative ligand formulated as [Cu₈L₄](ClO₄)₈?11H₂O ( 1 ) (L = 3,5‐bis((bis(2‐hydroxylethyl)amino)methyl)‐4 H‐1,2,4,‐triazole‐4‐amine) has been synthesized and structurally characterized. In 1 , eight Cu atoms are linked through 1,2,4‐triazole units and alkoxide bridges to form a centrosymmetric octanuclear Cu(II) metallomacrocycle. The interaction of complex 1 with calf thymus DNA has been studied using UV absorption, fluorescence and circular dichroism spectroscopies, viscosity measurements and cyclic voltammetry. The apparent binding constant (k_app) value for 1 is 1.59 × 10⁵ M^?1. Furthermore, complex 1 displays efficient oxidative cleavage of supercoiled DNA in the presence of external agents, the rate constant for the conversion of supercoiled to nicked DNA being 2.67 × 10^?5 s^?1. Interestingly, cytotoxicity studies on the MCF‐7 human breast cancer cell line show that the IC₅₀ value of 1 is less than that of cisplatin for the same cell line, revealing that it has the potential to act as an effective metal‐based anticancer drug. Copyright © 2016 John Wiley & Sons, Ltd.     

DNA Binding Studies and Cytotoxicity of Ethylenediamine 8‐Hydroxyquinolinato Palladium(II) Chloride

Interaction between ethylenediamine 8‐hydroxyquinolinato palladium(II) chloride and calf thymus DNA (CT‐DNA) in aqueous solution were studied by UV‐Visible absorption, fluorescence spectroscopic techniques and gel chromatography at temperatures of 300 K and 310 K. The complex bound strongly and intercalatively to the CT‐DNA. The results of the cytotoxicity assay of the Pd(II) complex on the leukemia cell line, K562 indicated lower cytotoxicity than cisplatin. The Pd(II) complex is considered an agent with potential antitumor activity. The calculation of several binding and thermodynamic parameters of the inclusion Pd(II) complex with CT‐DNA may provide deeper insights into the mechanism of action of these types of complexes with nucleic acids.     

Methyl substituent effect on one‐dimensional copper(II) coordination polymers containing biologically active ligands: Synthesis,characterization, DNA interactions and cytotoxicities

Three novel water‐soluble copper(II) complexes – {[Cu(phen)(trp)]ClO₄·3H₂O}_n ( 1 ), {[Cu(4‐mphen)(trp)]ClO₄·3H₂O}_n ( 2 ) and [[Cu(dmphen)(trp)(MeOH)][Cu(dmphen)(trp)(NO₃)]]NO₃ ( 3 ) (phen: 1,10‐phenanthroline; 4‐mphen: 4‐methyl‐1,10‐phenanthroline; dmphen: 4,7‐dimethyl‐1,10‐phenanthroline; trp: l ‐tryptophan) – have been synthesized and characterized using various techniques. Complexes 1 and 2 are isostructural, and exist as one‐dimensional coordination polymers. Complex 3 consists of two discrete copper(II) complexes containing [Cu(trp)(dmphen)(MeOH)]⁺, [Cu(trp)(dmphen)(NO₃)] and one nitrate anion. The binding interaction of the complexes with calf thymus DNA (CT‐DNA) was investigated using thermal denaturation, electronic absorption and emission spectroscopic methods, revealing that the complexes could interact with CT‐DNA via a moderate intercalation mode. The binding activity of the complexes to CT‐DNA follows the order: 3  >  2 > 1 . The pUC19 DNA cleavage activity of the complexes was investigated in the absence and presence of external agents using the agarose gel electrophoresis method. Especially, in the presence of H₂O₂ as an activator, the pUC19 DNA cleavage abilities of the complexes are clearly enhanced at low concentration. Addition of hydroxyl radical scavenger dimethylsulfoxide shows a marked inhibition of the pUC19 DNA cleavage activity of the complexes. In vitro cytotoxic effect of the complexes was examined on human tumor cell lines (Caco‐2, A549 and MCF‐7) and healthy cells (BEAS‐2B). The potent cytotoxic effect of complex 3 , with IC₅₀ values of 1.04, 1.16 and 1.72 μM, respectively, is greater relative to clinically used cisplatin (IC₅₀ = 22.70, 31.1 and 22.2 μM) against the Caco‐2, A549 and MCF‐7 cell lines.     

Synthesis,Characterization, and DNA Binding Studies of a Nickel(II) Complex Containing the 1,3‐Bis(1‐propylbenzimidazol‐2‐yl)‐2‐oxapropane

A complex of formula [Ni(pobb)₂](pic)₂, (pobb = 1,3‐bis(1‐propylbenzimidazol‐2‐yl)‐2‐oxapropane, pic = 2,4,6‐trinitrophenol), has been synthesized and structurally characterized by physico‐chemical and spectroscopic methods. The crystals crystallize in the monoclinic system, space group C2/c, a = 25.766(11) Å, b = 14.943(7) Å, c = 19.543(14) Å, α = 90°, β = 129.722(4)°, γ = 90°, Z = 4. The coordination environment around nickel(II) atom can be described as a distorted octahedral geometry. The interactions of the ligand pobb and the nickel (II) complex with calf thymus DNA (CT‐DNA) are investigated by using electronic absorption titration, ethidium bromide‐DNA displacement experiments and viscosity measurements. The experimental evidence indicated the compounds interact with calf thymus DNA through intercalation.     

Zinc(II)‐N2O2 ligation complex‐based DNA/protein binder and cleaver having enhanced cytotoxic and phosphatase activity

The alkyne arms containing zinc(II) N₂O₂ ligation complexes ( 1 ) and ( 2 ) were prepared from 2,2′‐{cyclohexane‐1,2‐diylbis[nitrilo(E)methylylidene]}bis[5‐(prop‐2‐yn‐1‐yloxy)phenol] (L¹) and 2,2′‐{1,2‐phenylenebis[nitrilo(E)methylylidene]}bis[5‐(prop‐2‐yn‐1‐yloxy)phenol] (L²) and characterized by analytical and various spectral techniques. The molecular geometry of 1 and 2 was optimized by Density Functional Theory (DFT) at B3LYP/6‐311G(d,p) level and compared with literature. The complexes are stable in solution, and their solution structure was assessed using NMR and ESI‐MS spectroscopy. Topological analysis of the electron density and nature of the bonding in the complexes has been determined by using Bader's AIM method. The interaction and binding modes of calf thymus DNA (CT‐DNA) with complexes ( 1 and 2 ) were investigated by using absorption and emission spectral and viscometric studies. The nuclease activity investigated through gel electrophoresis reveals that 1 and 2 exhibits a significant DNA cleavage activity via a hydrolytic pathway and is further confirmed by an experiment performed in the presence of T4 ligase. The protein binding ability of 1 and 2 with bovine serum albumin (BSA) protein evaluated show good protein binding propensity. In‐vitro cytotoxicity of the complexes has shown significant activity against human brain tumor (U87 MG) and breast carcinoma (BT20) cancer cell lines. The comet assay has been used to determine the extent of DNA fragmentation in cancer cells. The phosphatase activity investigated through kinetic measurements establishes that the zinc complexes possess significant hydrolytic efficiency and follow the order 2  >  1 . The DFT calculations have also been carried out to support the proposed mechanistic pathway of catalytic activity.     

Characterization, Crystal Structure and Initial DNA Binding Interaction of Two Cu（Ⅱ） Complexes with 4,5-Diazafluoren-9-one

Two new complexes [Cu（dafo）2（en）]（ClO4）2·2H2O （en=NH2CH2CH2NH2） 1 and [Cu（dafo）2（dap）]（ClO4）2·2H2O [dap=NH2CH2CH（CH3）NH2] 2 （dafo=4,5-diazafluoren-9-one） have been synthesized and characterized by elemental analysis, IR and UV spectra. Meanwhile, the complex 1 has been characterized by single crystal X-ray diffraction analysis. The initial DNA binding interactions of the complexes 1 and 2 have been investigated by UV spectra, emission spectra and cyclic voltammogram. Concluding the results of three methods used to measure the interaction of complexes 1 and 2 with DNA, the action mode of the two complexes with DNA is intercalation, and character of ligands and steric effect may affect the interaction of the complexes with DNA.     

Biological evaluation of organometallic palladium(II) complexes containing 4‐hydroxybenzoic acid (3‐ethoxy‐2‐hydroxybenzylidene)hydrazide: Synthesis,structure, DNA/protein binding,antioxidant activity and cytotoxicity

New palladium(II) complexes, [Pd(PPh₃)L] ( 2 ) and [Pd(AsPh₃)L] ( 3 ), were synthesized using 4‐hydroxybenzoic acid (3‐ethoxy‐2‐hydroxybenzylidene)hydrazide ( 1 ) ligand (H₂L), and characterized using various physicochemical techniques. The molecular structures of 2 and 3 were determined using single‐crystal X‐ray diffraction, which reveals a square planar geometry around the palladium(II) metal ion. In vitro DNA binding studies were conducted using UV–visible absorption spectroscopy, emission spectroscopy, cyclic voltammetry and viscosity measurements, which suggest that the metal complexes act as efficient DNA binders. The interaction of ligand H₂L and complexes 2 and 3 with bovine serum albumin (BSA) was investigated using UV–visible and fluorescence spectroscopies. Absorption and emission spectral studies indicate that complexes 2 and 3 interact with BSA protein more strongly than the parent ligand. The free radical scavenging potential of all the synthesised compounds ( 1 – 3 ) was also investigated under in vitro conditions. In addition, the in vitro cytotoxicity of the complexes to tumour cells lines (HeLa and MCF‐7) was examined using the MTT assay method.     

Preparation,characterizations and biological evaluations of new copper(II) complexes containing ONO pincer type ligands

A new heterocyclic Schiff bases, 6‐methyl/8methyl‐2‐oxo‐1,2‐dihydroquinoline‐3‐carboxaldehyde semicarbazones (H₂‐6MOQsc‐H) ( H ₂ L ¹ ) and (H₂‐8MOQsc‐H) ( H ₂ L ² ) and their corresponding copper(II) complexes [CuCl₂(H₂‐6MOQsc‐H)].3H₂O ( 1 ), [CuCl₂(H₂‐8MOQsc‐H)].3H₂O ( 2 ), [CuNO₃(H₂‐6MOQsc‐H)(H₂O)].NO₃ ( 3 ) and [CuNO₃(H₂‐8MOQsc‐H)(H₂O)].NO₃ ( 4 ) have been synthesized and characterized by various physicochemical techniques. The single crystal X‐ray diffraction and spectral data revealed that all of the complexes ( 1‐4 ), the ligands coordinated to the Cu(II) ion in a neutral manner via ONO donor atoms and all the complexes exhibited distorted squarepyramidal geometry. The consequence of electronegativity and ring size of nitrogen heterocyclic moiety of ONO donor type of copper(II) chelates on nucleic acid interaction and albumin binding was investigated by in vitro experiments. The interaction of compounds with calf‐thymus DNA (CT‐DNA) has been explored by absorption and emission titration, which exposed those ligands/complexes, could bind with CT‐DNA through electrostatic interaction. The results of gel electrophoresis proved the ability of complexes ( 1‐4 ) to cleave the pBR322 plasmid DNA. The interaction of serum albumin (BSA) was investigated by UV‐Vis, fluorescence, synchronous and three dimensional fluorescence spectra. In addition, radical scavenging activity, antifungal activity and cytotoxicity of the newly synthesized compounds were also evaluated. From the results of in vitro studies, it is seen that complex 3 has more potential as compared with other complexes and ligands.     

Isomeric Effect on the anticancer Behavior of two Zinc (II) complexes based on 3,5‐bis(1‐imidazoly) pyridine: Experimental and Theoretical Approach

Two isomeric Zinc (II) complexes constructed by 3,5‐bis(1‐imidazoly) pyridine has been synthesized and characterized by single crystal X‐ray diffraction, elemental analyses and infrared spectroscopy. The binding mode and ability of complex 1–2 with CT‐DNA were studied by UV and fluorescence spectra. The intrinsic binding constant K_b (K_b1 = 2.305 × 10⁴ M^?1, K_b2 = 3.095 × 10⁴ M^?1) and the observed association constant K_obs (K_obs1 = 1.523*10⁶ M^?1, K_obs2 = 2.057*10⁶ M^?1) indicated that the insertion ability of complex 2 with CT‐DNA is stronger than complex 1. Gel electrophoresis showed that complexes have a good ability to hydrolyze cleavage pBR322 plasmid DNA. The cytotoxicity and apoptosis studies showed that complexes exhibited excellent cytotoxic activity against HeLa cells, especially complex 2 had better growth inhibition than Cisplatin. Molecular docking study simulated the binding model of complexes with DNA (PDB:4av1), showing an imidazole plane of complex 2 can be inserted into a DNA base pair in relative parallel. Both complexes can be used as potential anticancer agents.     

Synthesis,crystal structures and DNA/human serum albumin binding of ternary Cu(II) complexes containing amino acids and 6‐(pyrazin‐2‐yl)‐1,3,5‐triazine‐2,4‐diamino

Two water‐soluble 6‐(pyrazin‐2‐yl)‐1,3,5‐triazine‐2,4‐diamino (pzta)‐based Cu(II) complexes, namely [Cu(l ‐Val)(pzta)(H₂O)]ClO₄ ( 1 ) and [Cu(l ‐Thr)(pzta)(H₂O)]ClO₄ ( 2 ) (l ‐Val: l ‐valinate; l ‐Thr: l ‐threoninate), were synthesized and characterized using elemental analyses, molar conductance measurements, spectroscopic methods and single‐crystal X‐ray diffraction. The results indicated that the molecular structures of the complexes are five‐coordinated and show a distorted square‐pyramidal geometry, in which the central copper ions are coordinated to N,N atoms of pzta and N,O atoms of amino acids. The interactions of the complexes with DNA were investigated using electronic absorption, competitive fluorescence titration, circular dichroism and viscosity measurements. These studies confirmed that the complexes bind to DNA through a groove binding mode with certain affinities (K_b = 4.71 × 10³ and 1.98 × 10³ M^?1 for 1 and 2 , respectively). The human serum albumin (HSA) binding properties of the complexes were also evaluated using fluorescence and synchronous fluorescence spectroscopies, indicating that the complexes could quench the intrinsic fluorescence of HSA in a static quenching process. The relevant thermodynamic parameters revealed the involvement of van der Waals forces and hydrogen bonds in the formation of complex–HSA systems. Finally, molecular docking technology was also used to further verify the interactions of the complexes with DNA/HSA.     

Synthesis and structural and DNA binding studies of mono‐ and dinuclear copper(II) complexes constructed with ─O and ─N donor ligands: Potential anti‐skin cancer drugs

Mononuclear and dinuclear copper(II) complexes with thiophenecarboxylic acid, [Cu(3‐TCA)₂(2,2′‐bpy)] ( 1 ), [Cu(3‐Me‐2‐TCA)₂(H₂O)(2,2′‐bpy)] ( 2 ), [Cu(5‐Me‐2‐TCA)₂(H₂O)(2,2′‐bpy)] ( 3 ) and [Cu₂(2,5‐TDCA)(DMF)₂(H₂O)₂(2,2′‐bpy)₂](ClO₄)₂ ( 4 ) (where 3‐TCA = 3‐thiophenecarboxylic acid; 3‐Me‐2‐TCA = 3‐methyl‐2‐thiophenecarboxylic acid; 5‐Me‐2‐TCA = 5‐methyl‐2‐thiophenecarboxylic acid; 2,5‐TDCA = thiophene‐2,5‐dicarboxylic acid; 2,2′‐bpy = 2,2′‐bipyridyl; DMF = N,N‐dimethylformamide), were synthesized. Compounds 1 – 4 were extensively characterized using both analytical and spectroscopic methods. Additionally, the solid‐state structures of 1 and 4 were unambiguously established from single‐crystal X‐ray diffraction studies. The hexacoordinated Cu(II) centre in 1 (CuO₄N₂) is a distorted octahedral geometry whereas the pentacoodinated 4 (CuO₃N₂) has distorted square pyramidal geometry. Compounds 1 and 4 exhibit intermolecular hydrogen bonding which leads to the formation of two‐ and three‐dimensional supramolecular architectures, respectively. Spectrophotometric and computational investigations suggest that these compounds bind with DNA in minor groove binding such that K_b = 4.9 × 10⁵ M^?1 and K_sv = 3.4 × 10⁵ M^?1, and binding score of ?5.26 kcal mol^?1. The binding affinity of these complexes to calf thymus DNA is in the order 2 > 3 > 4 > 1 . Methyl‐substituted thiophene ring increases the DNA binding affinity whereas unsubstituted thiophene ring DNA binding rate is reduced. The methyl group on the thiophene ring would sterically hinder π–π stacking of the ring with DNA base pairs, and subsequently they are involved in hydrophobic interaction with the DNA surface rather than partial intercalative interaction. Compounds 1 – 4 show pronounced activity against B16 mouse melanoma skin cancer cell lines as measured by MTT assay yielding IC₅₀ values in the micromolar concentration range. The compounds could prove to be efficient anti‐cancer agents, since at a concentration as low as 2.1 μg ml^?1 they exerted a significant cytotoxic effect in cancer cells whereas cell viability was not affected in normal cells.     

A pseudo trinuclear nickel–sodium complex containing tris(8-methyl-2-oxo-quinolidineamino ethylamine): Synthesis,spectral characterization,X-ray crystallography and in vitro biological evaluations

A new mixed nickel–sodium complex has been synthesized from Ni(ClO₄)₂ and tris(8-methyl 2-oxo-quinolidine amino ethylamine) with a 1:1 molar ratio in methanol and has been characterized by various analytical, spectroscopy and X-ray diffraction studies which confirmed an octahedral geometry around the nickel ion. Further, structural optimization of the complex was performed using DFT calculations. The ligand and complex were evaluated for their binding affinity with CT-DNA and an intercalative type of binding interaction was proposed from the absorption and fluorescence titration experiments. Albumin binding interaction of the ligand and complex was determined by absorption, fluorescence and synchronous spectral techniques at room temperature, suggesting the static quenching mechanism of BSA with the compounds. Antioxidant studies revealed the radical scavenging potential of Ni(II) complex. The anticancer activity of the ligand and complex was probed via in vitro cytotoxicity against human breast (MCF7) and lung (A549) cancer cell lines by MTT assay. Further, cytological changes observed in acridine orange/ethidium bromide and DAPI staining methods validated the cytotoxic potential of the complex.     

Synthesis,crystal structures,DNA/bovine serum albumin binding,DNA cleavage and cytotoxicity of five mononuclear zinc(II) complexes

Five new mononuclear zinc(II) complexes containing ligands with extended planar phenanthroline moieties (dipyrido‐[3,2‐a:2′,3′‐c]phenazine (dppz) or dipyrido[3,2‐d:2′,3′‐f] quinoxaline (dpq)), namely [Zn(dppz)(acac)₂]⋅CH₃OH ( 1 ), [Zn(dppz)(dbm)(OAc)] ( 2 ), [Zn(dpq)(dbm) (OAc)] 1.5H₂O ( 3 ), [Zn(dpq)(tfnb)(OAc)] ( 4 ) and [Zn(dpq)(tfnb)₂] ( 5 ), where acac = acetylacetonate, tfnb = benzoyltrifluoroacetone and dbm = dibenzoylmethane, were synthesized and structurally characterized. The binding ability of complexes 1 – 5 with calf thymus DNA was investigated by spectroscopic titration methods and viscosity measurements. Results indicate that all complexes bind to calf thymus DNA via intercalative mode, and the DNA binding affinities of dppz complexes 1 and 2 are apparently stronger than those of dpq complexes 3 – 5 . DNA photocleavage experiments reveal that these complexes are efficient DNA cleaving agents and they are more active in UV‐A (365 nm) than in visible light. In particular, the in vitro cytotoxicity of the complexes for human cancer cell line A549 demonstrates that the five compounds have anticancer activity with low IC₅₀ values. Meanwhile, interaction of the complexes with bovine serum albumin investigated using UV–visible and fluorescence methods indicates that all complexes can quench the intrinsic fluorescence of bovine serum albumin in a static quenching process.     

DNA/BSA‐binding property and in vitro anticancer activity of a new dicopper(II) complex with N‐(2‐hydroxy‐5‐nitrophenyl)‐N′‐[3‐(diethylamino)propyl]oxamide as bridging ligand: Synthesis and crystal structure

A new oxamido‐bridged dicopper(II) complex formulated as [Cu₂(ndpox)(bpy)(CH₃OH)₂]‐ (ClO₄), where H₃ndpox is N‐(2‐hydroxy‐5‐nitrophenyl)‐N′‐[3‐(diethylamino)propyl]oxamide; and bpy represents 2,2′‐bipyridine, was synthesized and structurally characterized using X‐ray single‐crystal diffraction and other methods. In the molecule, the endo‐ and the exo‐copper(II) ions bridged by the cis ‐ndpox³⁻ ligand are in {N₃O₂} and {N₂O₃} square‐ pyramidal environments, respectively. There is a three‐dimensional hydrogen bonding network dominated by O‐H···O and C‐H···O interactions in the crystal. The reactivity toward DNA/protein bovine serum albumin (BSA) revealed that the complex could interact with herring sperm DNA (HS‐DNA) through the intercalation mode, and effectively quench the intrinsic fluorescence of BSA via a static process. Cytotoxicity studies suggest that the complex displays selective cancer cell antiproliferative activity. The present investigation confirmed that the combined effects of both electron‐withdrawing and hydrophobic groups on the bridging ligand in the dicopper(II) complex systems can increase DNA/BSA‐binding ability and in vitro anticancer activity.     

Synthesis,crystal structure,DNA/bovine serum albumin binding and antitumor activity of two transition metal complexes with 4‐acylpyrazolone derivative

Two new complexes, namely [Cu₆L₆] ( 1 ) and [Zn(HL)₂] ( 2 ) (H₂L = N‐(1‐phenyl‐3‐methyl‐4‐propenylidene‐5‐pyrazolone)‐2‐furancarboxylic acid hydrazide), have been synthesized and characterized. Single crystal X‐ray analysis indicates that complex 1 has a hexanuclear structure and complex 2 exhibits a mononuclear structure. The DNA/bovine serum albumin (BSA) binding properties of complexes 1 and 2 were investigated by absorption spectroscopy and fluorescence quenching. Both complexes could effectively intercalate to DNA with calculated quenching constants of 2.6 × 10⁵ and 1.25 × 10⁵ M^?1, respectively. The quenching mechanism of the intrinsic fluorescence of BSA by the complexes was found to be a static one. The cytotoxicities of 1 and 2 were investigated in two human tumor cell lines, human esophageal cancer cells (Eca‐109) and cervical cancer cells (HeLa). Complex 1 exhibits higher antitumor activity than 2 . Furthermore, 1 can inhibit HeLa cells by inducing apoptosis and G0/G1 phase cell cycle arrest. All results demonstrate that 1 and 2 both have DNA/BSA binding capacity and antitumor activity.     

Synthesis and structure of a new ternary monocopper(II) complex containing mixed ligands of 2,2′‐diamino‐4,4′‐bithiazole and picrate: in vitro anticancer activity,molecular docking and reactivity towards DNA

A new ternary monocopper(II) complex with co‐ligands of 2,2′‐diamino‐4,4′‐bithiazole (dabt) and picrate (pic), namely [Cu(dabt)(pic)₂], has been synthesized and characterized using elemental analyses, molar conductance measurements, infrared and electronic spectral studies and single‐crystal X‐ray diffraction. The crystal structure analyses revealed that the copper(II) ion has a {CuN₂O₄} distorted octahedral coordination environment. The hydrogen bonding interactions contribute to a three‐dimensional supramolecular structure in the crystal. The reactivity towards herring sperm DNA showed that the copper(II) complex can interact with DNA in the mode of intercalation. The molecular docking of the complex with DNA sequence d(ACCGACGTCGGT)₂ demonstrated that the copper(II) complex is stabilized by hydrogen bonding interaction. The in vitro anticancer activities suggested that the copper(II) complex is active against selected tumor cell lines. The effects of the two co‐ligands in the copper(II) complex on DNA‐binding events and in vitro anticancer activity are preliminarily discussed. Copyright © 2016 John Wiley & Sons, Ltd.     

Two MnII,CuII complexes derived from 3,5‐bis(1‐imidazoly) pyridine: Synthesis,DNA binding,Molecular docking and cytotoxicity studies

Two complexes [MnL₂ (H₂O)₂]·2ClO₄ (complex 1) and [CuL(H₂O)₃]·2NO₃ (complex 2) (where L = 3,5‐bis(1‐imidazoly) pyridine) were designed and synthesized. The structures of the complexes were characterized by X‐ray crystallography, elemental analyses, and infrared spectrum. The interaction capacity of the complexes with calf thymus DNA has been investigated by UV and fluorescence spectroscopy. Gel electrophoresis assay demonstrated the ability of the complexes to cleave the pBR322 plasmid DNA. Efficient binding properties of DNA were established by UV–vis, fluorescence, and gel electrophoresis. The intrinsic binding constants (K_b) were calculated to be 0.1524, 0.1041 for complexes 1–2, respectively. The cytotoxic activity of the two complexes exhibited a higher cytotoxicity against HeLa cell lines and lower cytotoxicity toward the normal cell lines. Flow cytometry demonstrated the cancer cell inhibitory rate of two complexes. Furthermore, computer‐aided molecular docking studies were performed to visualize the binding mode of the drug candidate at the molecular level. Interestingly, complex 1 exhibited a significant cancer cell inhibitory rate than cisplatin and other complexes.