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• New copper(II) thiosemicarbazone complexes have been synthesized and characterized. • The DNA/protein interactions of complexes were studied by a variety UV–Vis and fluorescent spectroscopic techniques. • The antimicrobial activity against four different bacteria and five fungi have also been examined. • The antiproliferative activity was evaluated against MCF-7, A459, HeLa and HEK 293 cell lines. • Assay on HEK 293 cell lines showed that the compounds were less toxic to normal cells. The newly synthesized ligands (HL1 - HL3) of 5-methoxyisatin thiosemicarbazone with different N-terminal substituents and their copper(II) complexes 1 – 3 respectively were exposed to spectral and structural characterization. The spectral studies reveal that the ligands show a tridentate mode of binding (ONS donor) with Cu(II) to form square planar complexes. The crystal structure of the ligand HL1 and complex 1 were confirmed by single crystal XRD. The compounds were subjected to DNA/BSA interaction studies using electronic and fluorescence spectroscopic techniques. The binding studies showed that, the complexes (1 – 3) were able to bind with DNA/BSA macromolecules with good binding constant. In which 1 (K b = 0.83 × 105 M−1) shows good interaction with the DNA while 3 shows better interaction with BSA (K b = 2.4 × 105 M−1). The complexes (1 – 3) were also tested for antimicrobial activity, radical scavenging activity and in vitro anti-proliferative activity. Complex 3 have shown potent efficacy with broad spectrum antimicrobial activity against the microorganisms, whereas the complex 1 has shown decent scavenging properties compared to the reference drug (ascorbic acid) with an IC 50 value of 19.23 ± 1.05 µM. Further the, anti-proliferative activity study revealed that, the complex 1 has exhibited broad spectrum activity against MCF-7, A549 and HeLa with IC 50 values 14.83 ± 0.45 μM, 17.88 ± 0.16 μM and 6.89 ± 0.42 μM, respectively compared to standard drug Doxorubicin. [ABSTRACT FROM AUTHOR]

A number of alternatives were made to overcome numerous life-threatening infectious diseases by metal-based anticancer compounds. At present, thiosemicarbazones and their metal complexes have received significant consideration as a result of their metal DNA-interaction, structural diversity and availability of bonding modes. In this study, the coordination characteristics of nine diimine copper(II) complexes with sulfur containing ligands, [Cu(L)2] (1–3), [Cu(L)(bpy)]Cl (4–6) and [Cu(L)(phen)]Cl (7–9) (L = H(L1)–H(L3), phen = 1,10-phenanthroline, bpy = 2,2′-bipyridyl, H(L1) = (Z)-2-((4-methoxynaphthalen-1-yl)methylene)-N-methylhydrazinecarbothioamide, H(L2) = (Z)-N-ethyl-2-((4-methoxynaphthalen-1-yl)methylene)hydrazinecarbothioamide and H(L3) = (Z)-2-((4-methoxynaphthalen-1-yl)methylene)-N-phenylhydrazinecarbothioamide] have been synthesized from 4-methoxy-1-naphthaldehyde along with N(4)-substituted thiosemicarbazide derivatives. The synthesized ligands and their Cu(II) complexes were characterized through different spectroscopic techniques and square-planar coordination was proposed. Biological evaluation such as DNA-cleavage, antibacterial and in vitro cytotoxicity of thiosemicarbazone ligands and their resultant Cu(II) complexes were analyzed. Interestingly, Cu(II) complex containing heteroaromatic moiety 9 had potential cytotoxic activity with strong DNA-interaction. In the future, these may be helpful to design more effective novel chemotherapeutic drugs. [ABSTRACT FROM AUTHOR]

A series of mono imine (C=N) group that contained Wittig-based Schiff-Base ligands was optimized using the DFT-based computational method and Gaussian 09 program package. These optimized molecules were docked with Quadruplex DNA (PDB ID: 1KF1) and duplex DNA (PDB ID: 1BNA) using AutoDock Vina program along with the reference molecules. Schiff-Base ligands derived from fused aromatic rings contained amines and precursor aldehyde (PA-5 both Z and E isomers) showed lower binding energy for G-quadruplex DNA among all and N-5 category both Z and E isomer Schiff-Base ligands have shown high selectivity for G-quadruplex DNA over duplex DNA which is a very important phenomenon to develop the G-quadruplex DNA stabilizers. For a few Schiff-Base molecules like Ligand-6 (1-{[2-Hydroxy-5-(2-pyren-1-yl-vinyl)-benzylidene]-amino}-naphthalen-2-ol) of N-5 category both Z and E isomers with groove binding and end stacking modes, molecular dynamic calculations were carried out. The study revealed that Ligand-6 of N-5 category E isomer with groove binding mode has higher stabilizing effect on G-quadruplex DNA in spite of having the higher binding energy value. Among Schiff-Base copper(II) complexes, Complex-3 (E-(1-{[2-Hydroxy-5-(2-pyren-1-yl-vinyl)-benzylidene]-amino}-naphthalen-2-ol)Cu) is having high binding affinity for G-quadruplex DNA as compared to others. [ABSTRACT FROM AUTHOR]

The title Cu2+–chloride coordination polymer with the 4,4′-bi-1,2,4-triazole ligand (btr), [Cu4Cl8(C4H6N6)3]n, crystallizes in the non-centrosymmetric ortho­rhom­bic space group Fdd2. The two independent Cu2+ cations adopt distorted square-pyramidal geometries with {Cl2N2+Cl} coordination polyhedra. The metal atoms are bridged by μ-Cl anions forming left- and right-handed helical chains of sequence [–(μ-Cl)CuCl–]n along the c-axis direction. In the perpendicular directions, the btr ligands act in μ- and μ3– coordination modes in a 2:3 ratio. The μ-btr bridges connect neighboring helices of the same handedness, whereas the μ3-btr ligands link the helices of opposite handedness, leading to a racemic three-dimensional framework. The structure is consolidated by weak C—H· · ·Cl and C—H· · ·N inter­actions. [ABSTRACT FROM AUTHOR]

Abstract The kernel idea for this paper came from our more recent development of a mass spectrometric model equation, based on stochastic dynamics. It treats quantitatively the experimental intensity of analytes and their fragment ions under soft ionization conditions. The effort has resulted to exact universally applicable and empirically testable relationship, between mass spectrometric stochastic dynamic diffusion and the intensity. A linear correlation at high level of statistical significance occurs between D SD and the corresponding quantum chemical diffusions, obtained within the Arrhenius' approximation. It provides bridge between experimental MS parameters and 3D structure of analyte ions. Furthermore, we have claimed that the total intensity of the ions is proportional to their D SD parameter according to our model equation; or I tot ~ D SD. As evident from the small–scale of our contributions, so far, the simplistic theoretical concept and corresponding model equation need to be translated into a broad practical employment, because of; there is extended the capability of mass spectrometry beyond its routine application as irreplaceable method for quantitative analysis to the analytical practice. The superior features of the mass spectrometric instrumentation can offer us a new perspective of looking at the implementation of the method to exact 3D structural analysis in condense phase. As far as any such statement should be strongly quantified from the point of view of the chemometrics, this work deals with application of our stochastic dynamic concept of mass spectrometric diffusion to structural analysis of complex ions of CuII–ion with glycylhomopentapeptide and its dimeric associates. The large difference in the coordination fashion of oligopeptides, and competitive fragment paths together with the variety of the coordination modes of CuII–ion; and accounting, in parallel, for the different oxidation states of copper allows for us to demonstrate the great capability of our theoretical concept, studying so challenging research area. The experimental design is based on high resolution electrospray ionization mass spectrometric data in positive operation mode. High accuracy ab initio and methods based on theory on functional of density are used. Both static and molecular dynamic methods are employed. Graphical abstract Unlabelled Image Highlights • Electrospray ionization mass spectrometric quantification of diffusion parameters • Stochastic dynamic approach for quantification of the mass spectrometric intensity • Complexes of CuII–ion with glycylhomopentapeptide and its oligomeric associates • 3D structural analysis [ABSTRACT FROM AUTHOR]

The present study involved preparing of the barbiturate derivatives and corresponding copper(II) complexes. Catalytic activities of the copper(II)-barbiturate complexes were examined for the peroxidative oxidation of cyclohexane. Barbiturate derivatives were prepared by the reaction of 5-formylbarbiturates and primary aryl amines. The corresponding copper(II) complexes were synthesized by treatment of copper(II) acetate monohydrate with the prepared barbiturate derivatives. All the novel compounds were characterized by elemental analysis and spectroscopic methods. The structures of 3b and 3j were determined with X-ray crystallography. The X-ray crystallographic studies revealed that complexes 3b and 3j are 2-D coordination polymers. Also, the catalytic activities of the copper(II) complexes were examined for the peroxidative oxidation of cyclohexane under mild conditions. The results showed that the yields of the oxidation products were in the range 11.3–22.1%, depending upon the complex used and the promoter. [ABSTRACT FROM AUTHOR]

Two one‐dimensional (1D) coordination polymers (CPs), namely catena‐poly[[[aqua(2,2′‐bipyridine‐κ2N,N′)(nitrato‐κO)copper(II)]‐μ‐1,3‐bis(pyridin‐4‐yl)propane‐κ2N:N′] nitrate], {[Cu(NO3)(C10H8N2)(C13H14N2)(H2O)]·NO3}n (1), and catena‐poly[[[aqua(nitrato‐κO)(1,10‐phenanthroline‐κ2N,N′)copper(II)]‐μ‐1,3‐bis(pyridin‐4‐yl)propane‐κ2N:N′] nitrate], {[Cu(NO3)(C12H8N2)(C13H14N2)(H2O)]·NO3}n (2), have been synthesized using [Cu(NO3)(NN)(H2O)2]NO3, where NN = 2,2′‐bipyridine (bpy) or 1,10‐phenanthroline (phen), as a linker in a 1:1 molar ratio. The CPs were characterized by elemental analysis, IR spectroscopy, thermogravimetric analysis and single‐crystal X‐ray structure determination. The 1,3‐bis(pyridin‐4‐yl)propane (dpp) ligand acts as a bridging ligand, leading to the formation of a 1D polymer. The octahedral coordination sphere around copper consists of two N atoms from bpy for 1 or phen for 2, two N atoms from dpp, one O atom from water and one O atom from a coordinated nitrate anion. Each structure contains two crystallographically independent chains in the asymmetric unit and the chains are linked via hydrogen bonds into a three‐dimensional network. [ABSTRACT FROM AUTHOR]

The structures of three copper‐containing complexes, namely (benzoato‐κ2O,O′)[(E)‐2‐({[2‐(diethylamino)ethyl]imino}methyl)phenolato‐κ3N,N′,O]copper(II) dihydrate, [Cu(C7H5O2)(C13H19N2O)]·2H2O, 1, [(E)‐2‐({[2‐(diethylamino)ethyl]imino}methyl)phenolato‐κ3N,N′,O](2‐phenylacetato‐κ2O,O′)copper(II), [Cu(C8H7O2)(C13H19N2O)], 2, and bis[μ‐(E)‐2‐({[3‐(diethylamino)propyl]imino}methyl)phenolato]‐κ4N,N′,O:O;κ4O:N,N′,O‐(μ‐2‐methylbenzoato‐κ2O:O′)copper(II) perchlorate, [Cu2(C8H7O2)(C12H17N2O)2]ClO4, 3, have been reported and all have been tested for their activity in the oxidation of d‐galactose. The results suggest that, unlike the enzyme galactose oxidase, due to the precipitation of Cu2O, this reaction is not catalytic as would have been expected. The structures of 1 and 2 are monomeric, while 3 consists of a dimeric cation and a perchlorate anion [which is disordered over two orientations, with occupancies of 0.64 (4) and 0.36 (4)]. In all three structures, the central Cu atom is five‐coordinated in a distorted square‐pyramidal arrangment (τ parameter of 0.0932 for 1, 0.0888 for 2, and 0.142 and 0.248 for the two Cu centers in 3). In each species, the environment about the Cu atom is such that the vacant sixth position is open, with very little steric crowding. [ABSTRACT FROM AUTHOR]

Self‐assembled functional supramolecular metallopolymers have demonstrated application potential in cancer therapy. Herein, a copper polypyridyl complex was found able to self‐assemble into a supramolecular metallopolymer driven by the intermolecular interactions, which could enhance the uptake in cancer cells through endocytosis, and thus effectively inhibiting tumor growth in vivo without damaging to the major organs. This study provides a facile way to achieve enhanced anticancer efficacy by using self‐assembled metallopolymers. [ABSTRACT FROM AUTHOR]

Graphical abstract New copper(II) complexes containing the non-steroidal anti-inflammatory drug niflumic acid as ligand have been synthesized and characterized. Cytotoxic effects of the complexes on tumoral human cell lines have also been evaluated. Highlights • Five new copper(II)-niflumate complexes have been synthesized and characterized. • Their structures have been determined by X-ray diffraction and DFT calculations. • Cytotoxic effects of the complexes on tumoral human cell lines have been evaluated. • The niflumate coordination mode affects cytotoxicity against the cell line HT-144. Abstract Five new copper(II) niflumate complexes, [Cu(en) 2 (nif) 2 ], 1 , [Cu(unsym- dmen)(nif) 2 ], 2 , [Cu(pn) 2 (nif) 2 ][Cu(pn) 2 (H 2 O) 2 ](nif) 2 3 , [Cu(β- pic) 2 (nif) 2 ], 4 , [Cu(γ- pic) 2 (nif) 2 ] 5 (where en = ethylenediamine, pn = propan-1,3-diamine, unsym-dmen = 1,1-dimethyl-ethylenediamine, β -pic = 3-methylpyridine, γ -pic = 4-methylpyridine, nif = niflumate) have been synthesized by using appropriate starting materials and methanol-water (4:1 v/v) as solvent. All the above synthesized complexes 1 – 5 have been characterized by spectroscopic methods (UV–Vis, FT-IR, and EPR). The structures of complexes 1 , 3 and 5 have been unambiguously determined by single crystal X-ray structure determination which clearly revealed that these complexes are mononuclear complexes. The structure of complex 4 has been optimized by DFT calculations. In all complexes 1 – 5 , niflumate ligand shows direct coordination to central copper(II) ion leading to covalent character of these complexes, although the complex 3 also contains cationic moiety [Cu(p n) 2 (nif) 2 ]2+ and two nifumate ions. The ability of all the complexes to show cytotoxicity against human cancer cell lines has also been evaluated. [ABSTRACT FROM AUTHOR]

Graphical abstract Copper(II) complexes with N′-methylsarcosinamide (SarMeam), [CuCl 2 (SarMeam) 2 ] · H 2 O (1) and [Cu(NO 3) 2 (SarMeam) 2 ] (2), were tested on human bladder cancer cell lines as well on Gram-negative and Gram-positive bacteria. The complexes showed excellent potency towards one human bladder cancer cell line. No toxicity was noticed, as observed by comet assay and differential staining. Highlights • [CuCl 2 (SarMeam) 2 ] · H 2 O (1) and [Cu(NO 3) 2 (SarMeam) 2 ] (2) were synthesized. • Both complexes are active against human bladder cancer cells. • IC 50 value of [CuCl 2 (SarMeam) 2 ] · H 2 O (1) is 19 μM (T24 cancer cells). • No cytotoxicity and genotoxicity was observed. Abstract Two copper(II) complexes, [CuCl 2 (SarMeam) 2 ] · H 2 O (1) and [Cu(NO 3) 2 (SarMeam) 2 ] (2) were obtained by reactions of N ′-methylsarcosinamide (SarMeam) with copper(II) chloride and copper(II) nitrate in aqueous solutions. The complexes were characterized by X-ray crystallography, IR and UV-Vis spectroscopy, thermal analysis (TG-DTA) and DFT calculations. The octahedral coordination environments around the copper(II) ions in complexes 1 and 2 consisted of two N,O -bidentate N ′-methylsarcosinamide ligands and two chloride or nitrate ions, respectively, forming trans isomers. The [CuCl(H 2 O)(SarMeam) 2 ]+ and [Cu(H 2 O) 2 (SarMeam) 2 ]2+ species formed upon dissolution of 1 by successive substitution of coordinated chloride ions with water molecules, while dissolution of 2 led exclusively to the formation of [Cu(H 2 O) 2 (SarMeam) 2 ]2+. [Cu(OH)(H 2 O)(SarMeam) 2 ]+ species formed in basic solutions by deprotonation of coordinated ligands and then transformed to a planar [Cu(SarMeam −H) 2 ]. Complexes 1 and 2 decomposed in highly acidic or basic solutions, giving [Cu(H 2 O) 6 ]2+ or Cu(OH) 2 , respectively. The water-soluble complexes 1 and 2 were biologically evaluated and tested on human bladder cancer T24 and UM-UC-3 cell lines and a panel of Gram-negative and Gram-positive bacteria. They showed excellent potency towards human bladder cancer T24 cell line and no activity against bacterial strains. At the same time no toxicity was noticed on normal human cells, as observed by the cell viability and comet assay on peripheral blood leukocytes. [ABSTRACT FROM AUTHOR]

Abstract: The reaction of bis(pyrazol-1-yl)acetic acid (L) with copper(II) bromide provides two new complexes: [Cu(L-H)Br(µ-Br)]2 (1) and [Cu(L)2]⋅4H2O (2). Complex 1 is prepared by the stoichiometric reaction of L-H with copper(II) bromide in tetrahydrofuran. Dissolution of 1 in methanol causes its conversion into the bis-ligated complex (2), a highly hygroscopic material. Complex 2 can also be synthesized directly by the stoichiometric reaction of L-H with CuBr2 in methanol. Complex 1 is dimeric, interlinked by two bridging bromide ligands, and possesses terminal bromide ligands on each copper atom. The two pyrazolyl ligands in 1 coordinate with the nitrogen atoms to complete the coordination sphere of copper, resulting in a highly distorted geometry that lies between a trigonal bipyramidal or square pyramidal geometry with wide bond angles between the trans-oriented pyrazolyl nitrogen atoms and bromide ligands. Complex 2 assumes a pseudo-trigonal prismatic geometry with the deprotonated carboxylic acid that interacts weakly with copper.Graphical Abstract: Reaction of bis(pyrazol-1-yl)acetic acid (L-H) with copper(II) bromide provides two new complexes: [Cu(L-H)Br(µ-Br)]2 (1) and [Cu(L)2]⋅4H2O (2), these compounds represent the first, well-defined, independent copper(II) compounds supported by the base bis(pyrazolyl)acetic acid ligand. [ABSTRACT FROM AUTHOR]

An approach for the synthesis of new organic ligands combining in their structure pyridine, benzothiazole, and polyethylene glycol fragments was developed, proceeding from 6-hydroxy-2-(pyridin-2-yl)benzothiazole and mono- or ditosyl-substituted polyethylene glycols. The ligand 2-(2-{[2-(pyridin-2-yl)benzothiazol-6-yl]oxy}ethoxy)ethanol (L) in the reaction with Cu(ClO4)2•6 H2O and CuCl2•2 H2O formed coordination compounds of the composition L2Cu(ClO4)2•7 H2O and LCuCl2•0.5 H2O, respectively. [ABSTRACT FROM AUTHOR]

Abstract Two new acyl thiourea derivatives (1 and 2) and their Ni(II) and Cu(II) complexes (1a , 1b , 2a and 2b) have been synthesized. These compounds have been characterized by FT-IR, UV–Vis spectra, 1H and C13 NMR spectroscopic techniques, and have displayed satisfactory elemental analysis. X-ray crystallographic studies reveal that compound 2a is a cis -complex and crystallizes in monoclinic crystal system, with space group P 2 1 / c. The ligands act as bidentate chelators in complexes and coordinated to the central atom through O and S atoms. Moreover, cytotoxic, antibacterial and antifungal activities of compounds have been assayed against Brine shrimp eggs, three Gram negative strains including Enterobacter aerogenes, Bordetella bronchiseptica and Salmonella typhimurium and three fungal strains such as Aspergillus fumigatus, Fusariumsolani and Mucor specie, respectively. Compound 2 has displayed good activity. Graphical abstract Image 1 Highlights • Two new acyl thiourea derivatives and their metal complexes have been synthesized. • The compounds have been characterized spectroscopically. • Single crystal X-ray diffraction studies suggest four coordinated geometry for complex 2a. • Compound 1a displays strong antifungal activity. [ABSTRACT FROM AUTHOR]

The [Cu8(S-mal)4(bptc)(H2O)12] · 0.5H4bptc · 7.5H2O coordination polymer is obtained by heating the copper(II) nitrate, S-malic acid (H3mal), and biphenyl-3,3′,5,5′-tetracarboxylic (H4bptc) acid solution in the water-N,N-diethylformamide mixture. The crystal structure is determined from XRD data. The compound has a three-dimensional homochiral framework with channels filled by crystallization molecules of tetracarboxylic acid and water. The composition and structure of the coordination polymer obtained are confirmed by X-ray powder diffraction, IR spectroscopy, thermogravimetric analysis, and elemental analysis. [ABSTRACT FROM AUTHOR]

Ideal drugs to cure cancer leave normal cells unharmed while selectively turning tumor cells unviable. Several copper complexes have been able to selectively slow down tumor proliferation. We hypothesized that Cu(smz)2(bipy)·H2O (1)—a copper-complex that has two ligands capable of interacting with DNA—would outperform Cu(smz)2(OH2)·2H2O (2), and also that supporting 1 on mesoporous silica spheres would decrease even further tumor cell viability in vitro. After exposing osteosarcoma cells (MG-63) and normal phenotype cells of bone origin (MC3T3-E1) to either complex, we studied their toxic effect and mechanisms of action. We determined cell viability (MTT assay) and quantified formation of reactive oxygen species (oxidation of DHR-123 to rhodamine). Moreover, we assessed genotoxicity from (i) formation of micronucleus (MN assay) and (ii) damage of DNA (Comet assay). After the exposure of 1 supported on silica spheres, we tested cell viability. Our results confirm our hypotheses: inhibition of tumor cells follows: supported 1 > dissolved 1 > 2. Future work that enhances the load of the complex exclusively in mesopores may improve the ability of 1 to further inhibit tumor cell viability. [ABSTRACT FROM AUTHOR]

Two novel copper(II) complexes, Cu2L2(bipy) and Cu2L2(H2O)4·3H2O of Schiff base ligands derived from the condensation of L-tert-leucine and L-isoleucine with 2,4-dihydroxybenzaldehyde, are synthesized and characterized by single crystal X-ray diffraction. Compounds crystallize in the orthorhombic crystal system. The Cu2L2(bipy) complex has a distorted square planar geometry with an N2O2 coordination environment. Water is contained in supramolecular network pores. On the other hand, in the Cu2L2(H2O)4·3H2O complex, both copper atoms adopt a five-coordinated distorted square-pyramidal geometry with an NO4 coordination environment and guest water molecules form a 1D water chain. Both complexes build a 2D supramolecular network. [ABSTRACT FROM AUTHOR]

The new cyclodiphosph(V)azane derivatives (1,3-dimethyl-2,4-dioxo-2',4'-bis(2,4-bis(dimethylaminopropylimino)cyclodiphosph(V)azane (H2L1) (1,3-dimethyl-2,4-dioxo-2',4'-bis(2,4-bis(dimethylaminoethylimino)cyclodiphosph(V)azane (H2L2) and (1,3-dimethyl-2,4-dioxo-2'-(dimethylaminoethylimino)-4'-(dimethylaminopropyl-imino)cyclodiphosph(V)azane (H2L3) containing four active coordination centers (NNNN) and their Cu(II) complexes have been synthesized and characterized by elemental analyses, spectroscopic methods, molar conductance as well as thermal and magnetic measurements. The UV–Vis and mass spectra of the ligands and their Cu(II) complexes were also recorded. The copper(II) complexes were found to have magnetic moments of 1.58–1.69 B. M. corresponding to one unpaired electron. The possible geometries of the complexes were assigned on the basis of EPR, electronic, and infrared spectral studies. The absence of water molecules in all complexes was supported by thermal studies. All the thermal decomposition processes ended with the formation of CuO. The kinetic and thermodynamic parameters have been calculated. The ligand (H2L3) and its Cu(II) complexes were screened for their anticancer studies against human breast cancer cell lines MCF-7 and minimum inhibitory concentration was calculated. The screening was extended to the antibacterial activity using Kirby–Bauer single disk susceptibility test for all compounds. [ABSTRACT FROM AUTHOR]

Abstract Six new copper (II) complexes with dimethylglyoxime and the amino acids tryptophan, glutamate, proline, arginine and valine were prepared and characterized using elemental analysis, molar conductance, melting points, UV–Vis and IR spectroscopy. The compounds prepared are solids, insoluble in water, ethanol and methanol, but soluble in dimethylsulfoxide (DMSO) and dimethylformamide (DMF). The IR study shows that dimethylglyoxime as primary ligand is coordinated to the metal ion in a bidentate manner with NN donor sites of the oxime function. The secondary ligand is coordinated by the carboxylate oxygen and the N atom of the amino acid, with the exception of glutamate, which is coordinated through the N atom of the amine function. Spectroscopic studies show that all the synthesized copper (II) complexes have an octahedral geometry. The electrochemical behavior of these compounds was determined by cyclic voltammetry, which indicated an irreversible oxidation corresponding to Cu(I) → Cu(II). The antimicrobial activity of ligands and their complexes were studied by the agar diffusion technique using DMSO as solvent on different species of pathogenic bacteria (Escherichia coli and Bacillus cereus) and fungi (Candida albicans and Aspergillus niger). It has been found that some of the complexes are antimicrobially active and show higher activity than the free ligand. Metal chelation affects significantly the antimicrobial behavior of the ligands. In addition, these compounds were screened for their in vitro antioxidant properties using 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging. The results obtained show that the antioxidant activity is moderate for complexes with tryptophan and glutamate, but the complex with arginine shows a good antioxidant activity in comparison with ascorbic acid as positive control. Highlights • Synthesis of mixed ligand copper (II) complexes with dimethylglyoxime and amino acids. • Spectroscopic techniques are used for characterization. • Electrochemical studies: cyclic voltammetry. • Biological activities: Antibacterial and Antioxidant activities. [ABSTRACT FROM AUTHOR]

Copper(II) complexes of five peptide ligands containing at least three histidine residues have been tested as catalysts in catechol oxidation and superoxide dismutation. All systems exhibit considerable catechol oxidase-like activity, and the Michaelis-Menten enzyme kinetic model is applicable in all cases. Beside the Michaelis-Menten parameters, the effects of pH, catalyst and dioxygen concentration on the reaction rates are also reported. Considering the rather different sequences, the observed oxidase activity seems to be a general behavior of copper(II) complexes with multihistidine peptides. Interestingly, in all cases {Nim/2Nim,2N−} coordinated complexes are the pre-active species, the bound amide nitrogens were proposed to be an acid/base site for facilitating substrate binding. The studied copper(II)-peptide complexes are also able to effectively dismutate superoxide radical in the neutral pH range. [ABSTRACT FROM AUTHOR]

Graphical abstract 4,5-Diazafluorene N -glycopyranosyl hydrazones retaining the structural integrity of the parent carbohydrates: scaffolds for potential bioactive metallo-organic compounds. Highlights • Novel N1 -(4,5-diazafluoren-9-yliden)- N2 -glycopyranosylhydrazines were synthesized. • The stereoselective process preserves the cyclic structure of the carbohydrate. • Several copper(II) complexes having a 2:1 ligand to metal mole ratio were prepared. • The cytotoxicity of Cu(II) complexes in cancer cell lines is similar to cisplatin. • Cu(II) complexes can bind and stabilize DNA sequences, including G-quadruplex DNA. Abstract A series of novel N1 -(4,5-diazafluoren-9-yliden)- N2 -glycopyranosyl hydrazines was prepared in synthetically useful yields by treatment of 9 H -4,5-diazafluoren-9-hydrazone with different unprotected monosaccharides. The reactions with the monosaccharides tested afforded stereoselectively, and exclusively, cyclic derivatives, whose structures correspond to N -β-glycopyranosyl hydrazones except for the d -arabinose derivative that agrees with the α-anomer. Several copper(II) complexes having a 2:1 ligand to metal mole ratio were also prepared. The metal complexes can bind DNA sequences and preferentially stabilize G-quadruplex DNA structures over dsDNA. The fucose, rhamnose and deoxyglucose copper(II) complexes exhibited a cytotoxic activity against cultured HeLa and PC3 tumor cells comparable to other metal complexes normally used for chemotherapeutic purposes, such as cisplatin. [ABSTRACT FROM AUTHOR]

Molecular structure of [Cu(clon) 2 (α-pic) 2 ]. [Display omitted] Three novel mononuclear copper(II) complexes 1 – 3 with clonixinate anion (clon) derived from clonixin (Hclon) and α-, β-, or γ-methylpyridine (α-, β-, or γ-pic) were synthesised. The compounds were characterised by IR, UV–Vis and EPR spectroscopy and elemental analysis. The redox properties of the prepared complexes were studied by square wave voltammetry. The structure of the complexes [Cu(clon) 2 (α-pic) 2 ] (1), [Cu(clon) 2 (β-pic) 2 ] (2), [Cu(clon) 2 (γ-pic) 2 ] (3) was determined by single-crystal X-ray analysis and the intermolecular interactions were studied by Hirshfeld surface analysis. The interaction of the studied complexes with calf thymus DNA was investigated by UV–Vis absorption titration and further investigation of the possible intercalative mechanism of action was carried out by fluorescence quenching studies with ethidium bromide-DNA adduct monitored via fluorescence emission spectroscopy. Interactions with bovine serum albumin were also evaluated by fluorescence emission spectroscopy. The cytotoxicity and selectivity of 1 – 3 were studied in vitro on a human breast cancer cell line (MCF-7), a lung cancer cell line (A549), a human glioblastoma cell line (U-118MG) and healthy human fetal lung fibroblast cells (MRC-5). All three complexes showed low to moderate ability to interact with calf thymus DNA, probably through partial intercalation, high and reversible binding to serum albumin and promising cytotoxic effects on the MCF-7 cancer cell line with reasonable selectivity for complexes 1 and 2. Finally, the mitochondrial respiratory capacity of MCF-7 tumour cells was also studied and showed a reduced activity after the addition of the studied complexes. [ABSTRACT FROM AUTHOR]

A series of amine (1 – 6) and imine (5′ , 6′) based copper(II) complexes with tridentate (NNO) ligand donors were synthesized and characterized using modern analytical techniques. All the complexes were subjected to 2-aminophenol (OAP) oxidation to form 2-aminophenoxazin-3-one, as a functional analogue of an enzyme, phenoxazinone synthase. In addition, a critical comparison of the reactivity using the amine-based complexes with their respective imine counterparts was achieved in both experimental as well as theoretical studies. For instance, the kinetic measurement revealed that the imine-based copper(II) complexes (k cat , 2.4 × 105–6.2 × 106 h−1) are better than amine-based (k cat , 6.3 × 104–3.9 × 105 h−1) complexes. The complex-substrate adducts [Cu(L3)(OAP)] (7) and [Cu(L3 ′)(OAP)] (7′) were characterized for both systems by mass spectrometry. Further, the DFT study was performed with amine- (3) and imine- (3′) based copper(II) complexes, to compare their efficacy in the oxidation of OAP. The mechanistic investigations reveal that the key elementary step to determine the reactivity of 3 and 3′ is the proton-coupled electron transfer (PCET) step occurring from the intermediates 7 / 7′. Further, the computed HOMO-LUMO energy gap of 7′ was smaller than 7 by 0.8 eV, which indicates the facile PCET compared to that of 7. Moreover, the coupling of the OAP moiety using imine-complexes (ΔG R.E = −5.8 kcal/mol) was found to be thermodynamically more favorable than amine complexes (ΔG R.E = +3.3 kcal/mol). Overall, the theoretical findings are in good agreement with the experimental results. The role of electronic and auxiliary ligands in copper(II) complexes were studied for PHS mimicking activity. [Display omitted] • Synthesis and characterization of amine and imine based Cu(II) complexes. • Effective PHS activity with remarkable rate in the oxidation of o -aminophenol. • Reactivity and mechanism of amine vs imine based Cu(II) complexes was studied. [ABSTRACT FROM AUTHOR]

The aim of this study was to construct a nanostructured lipid system as a strategy to improve the in vitro antibacterial activity of copper(II) complexes. New compounds with the general formulae [CuX2(INH)2]·nH2O (X = Cl− and n = 1 (1); X = NCS− and n = 5 (2); X = NCO− and n = 4 (3); INH = isoniazid, a drug widely used to treat tuberculosis) derived from the reaction between the copper(II) chloride and isoniazid in the presence or absence of pseudohalide ions (NCS− or NCO−) were synthesized and characterized by infrared spectrometry, electronic absorption spectroscopy, electron paramagnetic resonance (EPR) spectroscopy, elemental analysis, melting points and complexometry with 2,2′,2′′,2′′′-(Ethane-1,2-diyldinitrilo)tetraacetic acid (EDTA). The characterization techniques allowed us to confirm the formation of the copper(II) complexes. The Cu(II) complexes were loaded into microemulsion (MEs) composed of 10% phase oil (cholesterol), 10% surfactant [soy oleate and Brij® 58 (1:2)] and 80% aqueous phase (phosphate buffer pH = 7.4) prepared by sonication. The Cu(II) complex-loaded MEs displayed sizes ranging from 158.0 ± 1.060 to 212.6 ± 1.539 nm, whereas the polydispersity index (PDI) ranged from 0.218 ± 0.007 to 0.284 ± 0.034. The antibacterial activity of the free compounds and those that were loaded into the MEs against Staphylococcus aureus ATCC® 25923 and Escherichia coli ATCC® 25922, as evaluated by a microdilution technique, and the cytotoxicity index (IC50) against the Vero cell line (ATCC® CCL-81TM) were used to calculate the selectivity index (SI). Among the free compounds, only compound 2 (MIC 500 μg/mL) showed activity for S. aureus. After loading the compounds into the MEs, the antibacterial activity of compounds 1, 2 and 3 was significantly increased against E. coli (MIC’s 125, 125 and 500 μg/mL, respectively) and S. aureus (MICs 250, 500 and 125 μg/mL, respectively). The loaded compounds were less toxic against the Vero cell line, especially compound 1 (IC50 from 109.5 to 319.3 μg/mL). The compound 2- and 3-loaded MEs displayed the best SI for E. coli and S. aureus, respectively. These results indicated that the Cu(II) complex-loaded MEs were considerably more selective than the free compounds, in some cases, up to 40 times higher.

A series of four water-soluble salicylaldehyde thiosemicarbazones with a positively charged trimethylammonium moiety ([H2LR]Cl, R = H, Me, Et, Ph) and four copper(II) complexes [Cu(HLR)Cl]Cl (1–4) were synthesised with the aim to study (i) their antiproliferative activity in cancer cells and, (ii) for the first time for thiosemicarbazones, the interaction with membrane transport proteins, specifically organic cation transporters OCT1–3. The compounds were comprehensively characterised by analytical, spectroscopic and X-ray diffraction methods. The highest cytotoxic effect was observed in the neuroblastoma cell line SH-5YSY after 24 h exposure and follows the rank order: 3 > 2 > 4 > cisplatin > 1 >> [H2LR]Cl. The copper(II) complexes showed marked interaction with OCT1–3, comparable to that of well-known OCT inhibitors (decynium 22, prazosin and corticosterone) in the cell-based radiotracer uptake assays. The work paves the way for the development of more potent and selective anticancer drugs and/or OCT inhibitors.

Copper(II) acetate has reacted in methanol with quinaldinic acid (quinoline-2-carboxylic acid) to form [Cu(quin)2(CH3OH)]∙CH3OH (1) (quin− = an anionic form of the acid) with quinaldinates bound in a bidentate chelating manner. In the air, complex 1 gives off methanol and binds water. The conversion was monitored by IR spectroscopy. The aqua complex has shown a facile substitution chemistry with alicyclic secondary amines, pyrrolidine (pyro), and morpholine (morph). trans-[Cu(quin)2(pyro)2] (2) and trans-[Cu(quin)2(morph)2] (4) were obtained in good yields. The morpholine system has produced a by-product, trans-[Cu(en)2(H2O)2](morphCOO)2 (5) (morphCOO− = morphylcarbamate), a result of the copper(II) quinaldinate reaction with ethylenediamine (en), an inherent impurity in morpholine, and the amine reaction with carbon dioxide. (pyroH)[Cu(quin)2Cl] (3) forms on the recrystallization of [Cu(quin)2(pyro)2] from dichloromethane, confirming a reaction between amine and the solvent. Similarly, a homologous amine, piperidine (pipe), and dichloromethane produced (pipeH)[Cu(quin)2Cl] (11). The piperidine system has afforded both mono- and bis-amine complexes, [Cu(quin)2(pipe)] (6) and trans-[Cu(quin)2(pipe)2] (7). The latter also exists in solvated forms, [Cu(quin)2(pipe)2]∙CH3CN (8) and [Cu(quin)2(pipe)2]∙CH3CH2CN (9). Interestingly, only the piperidine system has experienced a reduction of copper(II). The involvement of amine in the reduction was undoubtedly confirmed by identification of a polycyclic piperidine compound 10, 6,13-di(piperidin-1-yl)dodecahydro-2H,6H-7,14-methanodipyrido[1,2-a:1′,2′-e][1,5]diazocine.

The copper(II) complex ethylene-N-(salicylideniminato)-N'-(3-methoxy-salicylideniminato)copper(II) [Cu(Sal-CH3OSal)en] with the asymmetric N2O2 Schiff base was synthesized. The complex was identified by the NMR, IR, and UV-Vis spectroscopy and voltammetry methods. The crystal structure of the complex was determined by the X-ray structural analysis. [ABSTRACT FROM AUTHOR]

The test method of determination of the pyridoxine (vitamin B 6) containing hydroxyaryl group comprises its azo coupling with chromogenic indicator diazo test strip, a reagent with functional diazoaryl group attached to the cellulose carrier through 1,3-diphenoxypropane bridge. This test strip reaction affords cellulose-tethered tetradentate chelating agent capable of forming chromogenic blue-violet complex with CuII ion. [ABSTRACT FROM AUTHOR]

Two new ligands were synthesized with the goal of copper stabilization, N,N'-(2-methylpyridine)-2,11-diaza[3,3](2,6)pyridinophane ( Pic N4) and N-(methyl),N'-(2-methylpyridine)-2,11-diaza[3,3](2,6)pyridinophane ( PicMe N4), by selective functionalization of H N4 and TsH N4. These two ligands, when reacted with various copper salts, generated both Cu(II) and Cu(I) complexes. These ligands and Cu complexes were characterized by various methods, such as NMR, UV-Vis, MS, and EA. Each compound was also examined electrochemically, and each revealed reversible Cu(II)/Cu(I) redox couples. Additionally, stability constants were determined via spectrophotometric titrations, and radiolabeling and cytotoxicity experiments were performed to assess the chelators relevance to their potential use in vivo as 64 Cu PET imaging agents., Competing Interests: Conflicts of Interest: The authors declare no competing financial interest.

A mononuclear square-planar Cu II complex of (5-methyl-1 H -pyrazol-3-yl)carbamate, [Cu(C 5 H 6 N 3 O 2 ) 2 ]·4H 2 O, was synthesized using a one-pot reaction from 5-methyl-3-pyrazolamine and copper(II) acetate in water under ambient conditions. The adsorption of carbon dioxide from air was facilitated by the addition of di-ethano-lamine to the reaction mixture. While di-ethano-lamine is not a component of the final product, it plays a pivotal role in the reaction by creating an alkaline environment, thereby enabling the adsorption of atmos-pheric carbon dioxide. The central copper(II) atom is in an (N 2 O 2 ) square-planar coordination environment formed by two N atoms and two O atoms of two equivalent (5-methyl-1 H -pyrazol-3-yl)carbamate ligands. Additionally, there are co-crystallized water mol-ecules within the crystal structure of this compound. These co-crystallized water mol-ecules are linked to the Cu II mononuclear complex by O-H⋯O hydrogen bonds. According to Hirshfeld surface analysis, the most frequently observed weak inter-molecular inter-actions are H⋯O/O⋯H (33.6%), H⋯C/C⋯H (11.3%) and H⋯N/N⋯H (9.0%) contacts., (© Sirenko et al. 2023.)

Graphical abstract New five cationic and neutral discrete copper(II) α-hydroxycarboxylate complexes with 2,2′-dipyridylamine were isolated. Four of these compounds have been studied by single-crystal X-ray diffraction and also we analyzed their intermolecular interactions by Hirshfeld surfaces. Abstract The reaction of CuCO 3 ·Cu(OH)₂ with three different α-hydroxyacids (H 2 L′) and the nitrogen donor coligand 2,2′-dipyridylamine (dipyam) has produced five new discrete copper(II) complexes. Two kind of compounds have been isolated: neutral complexes of formula [Cu(H 2 L′) 2 (dipyam)] and cationic [Cu(H 2 L′)(dipyam) 2 ](H 2 L′) complexes. Four of these compounds have been studied by single-crystal X-ray diffraction and the analysis of their molecular crystal structures were also performed by the analysis of their Hirshfeld surfaces. The thermal behaviour has also been investigated. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • The characterization of two new polymeric copper(II) complexes bearing 2-chlorobenzhydrazide is reported for first time. • A copper(II) complex has been more active than benznidazole, a drug used in the treatment of Chagas disease. • A complex exhibited a good selectivity index. Abstract We report here the characterization of two new polymeric copper(II) complexes containing 2-chlorobenzhydrazide (2-CH) and two N,N -donor ligands, namely, 1,10-phenanthroline (phen) and 4-4′-dimethoxy-2-2′-bipyridine (dmb). The structure of a new polymeric copper(II) complex in which a perchlorate anion acts as a bridge ligand is discussed in detail. In both complexes, spectral data reveals a bidentate coordination mode for hydrazide, perchlorate and N,N -donor ligand. These metal complexes and their free ligands were evaluated for their trypanocidal and cytotoxic activities and the complex with 1,10-phenanthroline has been much more active than benznidazole, a drug used in the treatment of Chagas disease. [ABSTRACT FROM AUTHOR]

A facile electrochemical method was developed by in‐situ electrochemical complexation of Cu(II) ions with uric acid (UA), xanthine (XA) and hypoxanthine (HXA) on the disposable graphite pencil electrode (DGPE) surface for sensitive and selective simultaneous determination of UA, XA and HXA in phosphate buffer solution (PBS, pH 7.00±0.20). Raman Spectroscopy revealed the fluorescence nature of the corresponding Cu(II) – complexes of phosphate ions, UA, XA and HXA on DGPE while Density Function Theory (DFT) calculation was used to estimate their binding energies which are responsible for the enhanced peaks of UA, XA, and HXA as a result of their stronger interaction with copper atoms than phosphate ions. Square wave voltammetry was used in the analytical part. The calculated limits of detections were 14.42 nM, 5.04 nM and 4.93 nM for UA, XA and HXA, respectively. Potential interferences showed almost no significant effect on the peaks of UA, XA, and HXA, and the developed method was successfully utilized for simultaneous determination of the three analytes on human serum and urine with impressive percentage recovery. [ABSTRACT FROM AUTHOR]

Abstract: Four copper(II) coordination compounds from 2-benzimidazole propionic acid (Hbzpr) and 4-(benzimidazol-2-yl)-3-thiobutanoic acid (Hbztb) were synthesized and fully characterized by elemental analyses, electronic spectroscopy, FT-IR and mass spectrometry. The molecular structure for the four complexes was confirmed by single-crystal X-ray crystallography. The DNA-interacting properties of the two trinuclear and two mononuclear compounds were investigated using different spectroscopic techniques including absorption titration experiments, fluorescence spectroscopy and circular dichroism spectroscopy. Trinuclear [Cu3(bzpr)4(H2O)2](NO3)2·3H2O·CH3OH (2) and [Cu3(bzpr)4Cl2]·3H2O (3) bind to DNA through non-intercalative interactions, while for mononuclear [Cu(bzpr)2(H2O)]·2H2O (1) and [Cu(bztb)2]·2H2O (4), at minor concentrations in relation to the DNA, a groove binding interaction is favored, while at higher concentrations an intercalative mode is preferred. The nuclease properties of all complexes were studied by gel electrophoresis, which showed that they were able to cleave supercoiled plasmid DNA (form I) to the nicked form (form II). Compound 4 is even capable of generating linear form III (resulting from double-strand cleavage). The proposed mechanism of action involves an oxidative pathway (Fenton-type reaction), which produces harmful reactive species, like hydroxyl radicals.Graphical abstract: [ABSTRACT FROM AUTHOR]

The reaction of the copper(II) diclofenac complex [Cu( dicl ) 2 (H 2 O) 2 ] ( 1 ) ( dicl  = deprotonated diclofenac (H dicl )) with the chelating N-donor ligands ethylenediamine ( en ), propan-1,3-diamine ( pn ), unsymmetrical dimethylethylene-diamine ( unsym-dmen ) and N , N , N ′, N ′-tetramethylethylene-diamine ( temed ) in methanol-water (4:1 v/v) yielded the novel copper(II) complexes [Cu( en ) 2 (H 2 O) 2 ]( dicl ) 2 ·2H 2 O ( 2 ), [Cu( pn ) 2 (H 2 O) 2 ]( dicl ) 2 ·2H 2 O ( 3 ), [Cu( unsym-dmen ) 2 (H 2 O)]( dicl ) 2 ·H 2 O ( 4 ) and [Cu( temed )( dicl ) 2 ] ( 5 ), respectively. All the synthesized complexes were characterized by spectroscopic (UV–vis, FT-IR) methods. The structures of complexes 2 , 3 and 5 were unambiguously determined by single-crystal X-ray crystallography. X-ray structures of complexes clearly revealed the ionic structure of complexes 2 , 3 and the covalent structure of complex 5 . The geometry of complex 4 was optimized by Density Functional Theory (DFT) calculations. The ability of the complexes 1–5 to bind to calf-thymus DNA was monitored in vitro by diverse techniques (UV–vis spectroscopy, cyclic voltammetry, viscosity measurements) and via competitive studies with ethidium bromide. The interaction of complexes 1–5 with bovine serum albumin was studied in vitro by fluorescence emission spectroscopy and the corresponding binding constants were calculated. The biological behavior of complexes 1–5 was compared with previously reported Cu(II), Mn(II) and Ni(II) complexes of diclofenac. [ABSTRACT FROM AUTHOR]

Graphical abstract Formation of (Glu)H x (PA) and Cu(Glu)H x (PA) complexes in the Cu(II)/glutamic acid/polyamine systems was established. The structure of the complexes is discussed in the light of the results of alteration in complex geometry when dynamic equilibrium at room temperature is changed during freezing. The effect of metal ions on adduct concentration is presented. Highlights • Noncovalent interactions between glutamic acid (Glu) and tetramines were investigated. • Cu/Glu/polyamine systems were studied by potentiometric and spectroscopic methods. • Mode of interaction and stability of the complexes were determined. • Inversion effect in the systems was observed. • Influence of metal ions on the formed adducts was evaluated. Abstract Metal-free systems of glutamic acid (Glu) with 3,3,3- tet or spermine (Spm) and ternary systems of Cu(II) ions with Glu and 3,3,3- tet or Spm were studied using the potentiometric and spectral methods: Vis, NMR and EPR. The composition, stability and mode of interaction in the formed (Glu)H x (PA) and Cu(Glu)H x (PA) species were established. Biogenic spermine interacts with Glu in a different way to its homologue 3,3,3- tet. In ternary systems Cu(II)/Glu/Spm, metallation involves all available nitrogen atoms from Spm, while in the form Cu(Glu)(3,3,3-tet) the uncoordinated –NH 2 group species 3,3,3- tet can create a centre for potential interaction with other bioligands. In glassy state at 77 K EPR shows that only stable CuL 2 type complexes exist with an axial symmetry. The geometrical structure of the complexes is discussed in the light of the results of alteration in complex structure when dynamic equilibrium at room temperature is changed during freezing. In this paper we have also quantitatively calculated how the change in the concentration of Cu(II) affects the level of molecular complexes. It was found that the introduction of Cu(II) into the studied binary ligand/ligand systems results in changes in the concentration of the molecular complexes in aqueous solution. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Synthesis of new napthyl-pyrazole ligand with biological potentiality. • Preparation of symmetric dinuclear chloro and azido bridged Cu(II) complexes. • Complexes are structurally characterized and additionally DFT, CV and EPR studies were done. • Cytotoxicity effect, DNA cleavage activities of the new compounds. • Rational discussion on structure-activity relationship will be accounted by the scientific community. Abstract Symmetric dinuclear chloro copper(II) complex [Cu(L)(Cl)(µ -Cl)] 2 (1) and azo dinuclear azido copper(II) complex [Cu 2 (L) 2 (N 3) 3 (µ 2 -N 3)] n (2) [where L represents (5-methyl-pyrazol-1-ylmethyl)-napthalen-1-ylmethyl-amine] have been synthesized to examine the effect of napthyl group in the structure of pyrazole based dinuclear copper(II) complexes in DNA nuclease activity. The structure of 1 and 2 are characterized by X-ray crystallography, electrochemistry and various spectroscopic techniques. Coordinating ligand L is generated in situ from bis(3,5-dimethyl-pyrazol-1-ylmethyl)-napthalen-1-ylmethyl-amine (A) during complexation. Cytotoxic potential of free ligand (A), synthesized complexes 1 , 2 and one cobalt(II) complex derived from ligand A, CoII(A)Cl 2 (3) are analyzed using MTT cytotoxicity assay in U937 human monocytic cell line. Complexes 1 and 2 show very potent cytotoxicity (IC 50 = 13–17 μM); the best IC 50 value is found for 1. LDH assay revealed that A and 3 has greater necrotic activity than the copper complexes. However, the results of DNA cleavage study clearly demonstrated that symmetric bridged dinuclear complexes with napthyl group lead to high level of nuclease activity 72–75% in the presence of glutathione. The bridged dinuclear copper(II) complexes undergo facile transformation to Cu(I) centre through inner sphere electron transfer mechanism (ISET) in presence of glutathione which facilitate the formation of free radicals/ions for DNA cleavage. Lacking of any reducible metal center in mononuclear cobalt(II) complex make it inactive towards free radicals generation in DNA cleavage activity. [ABSTRACT FROM AUTHOR]

Four new complexes of copper(II) consisting of two different chromone derivatives with carbonyl and amine donor atoms: 7-aminoflavone ( L 1 ) and 7-amino-2-methylchromone ( L 2 ), were synthesized and characterized by X-ray diffraction, UV–Vis, FT-IR, EPR spectroscopy, MS and elemental analysis. The complexes were synthesized using 2:1 ligand-to-metal ratio, but while three products [Cu( L 2 ) 2 Cl 2 ] 2 ( 1b ), Cu( L 1 ) 2 (ClO 4 ) 2 (H 2 O) 2 ( 2a ), Cu( L 2 ) 2 (ClO 4 ) 2 (H 2 O) 2 ( 2b ) maintained the applied stoichiometry, the fourth compound showed an unexpected 1:1 ratio and was identified as [Cu( L 1 )Cl 2 ] n ( 1a ). In all four compounds, the chromone derivatives were found to act as monodentate O - or N -ligands. Interestingly, in a doubly chloro-bridged dinuclear complex 1b each Cu(II) cation interacts with one L 2 ligand through the carbonyl O- donor, and with another L 2 molecule through the amine N -donor, so the complex adopts a square pyramid geometry. According to a single-crystal X-ray diffraction analysis the complex 2b is a distorted mononuclear octahedron with the central Cu(II) cation interacting only with oxygen donors (two perchlorate anions, two L 2 ligands, and two water molecules). The structural characteristics of 1a and 2a complexes were elucidated from EPR measurements, where their g-tensor components were compared to those observed for 1b and 2b , the structures of which were determined by X-ray diffraction method. DFT calculations were performed to estimate the most favored mode of coordination, whereas comparative Hirshfeld surface studies were used to characterize intermolecular interactions in the studied complexes. Magnetic interactions of 1a and 2a were also analyzed. [ABSTRACT FROM AUTHOR]

Abstract Copper (II) complexes are promising in the development of new synthetic models for cancer treatment. In this context, we synthesized a new copper complex containing the pharmacophore group 1,4-dioxo-2-butenyl, the Bis((( Z )-4-((4-chlorophenyl) amino)-4-oxobut-2-enoyl)oxy) copper compound and we evaluated its antitumor activity in 4 T1 murine mammary adenocarcinoma cells and their toxicogenic effect in Swiss mice. The compound demonstrated cytotoxicity and genotoxicity to 4 T1 cells, and after cell cycle arrest in G1, which occurred by the increase in ATM and p21 expression, it induced the cells to apoptosis by increasing BAX and caspase-7. In vivo the compound was genotoxic in mice but did not show permanent damage, observed by the absence of increased micronucleus frequency, and did not induce changes in the biometric parameters of the animals. These results indicate that the new copper complex, described firstly in this work, presents therapeutic potential for breast cancer. Graphical abstract Unlabelled Image Highlights • The RC1 compound is cytotoxic to 4T1 murine mammary adenocarcinoma cells. • RC1 induces arrest in the G1 phase increasing the expression of ATM and p21. • RC1 induces apoptosis increasing BAX and Caspase-7 genes, and inhibition of BCL-2. • RC1 in vivo unchanged biometric parameters and is less genotoxic than cisplatin. • The RC1 compound has therapeutic potential for breast cancer. [ABSTRACT FROM AUTHOR]

Reactions of the Schiff base ligand OH-C 6 H 4 -CH NC(CH 2 OH) 3 (H 4 L) with copper(II) salts in various reaction media afforded complexes [Cu 4 (H 2 L) 4 ]·MeOH ( 1 ·MeOH), [Cu 2 (O 2 CMe) 2 (H 3 L) 2 ] ( 2 ), [Cu 4 (H 2 L) 4 (H 2 O) 2 ]·1.5dmf ( 3 ·1.5dmf), [Cu 4 (H 2 L) 4 (H 2 O)]·MeOH ( 4 ·MeOH) and [Cu 4 (H 2 L) 4 ] 2 ·2H 2 O·7MeOH ( 5 ·2H 2 O·7MeOH). Compounds 1 , 3 and 4 consist of neutral tetranuclear entities in which the Cu II ions are coordinated by the tridentate Schiff base ligands, forming a tetranuclear Cu 4 O 4 cubane-like configuration. Compound 5 contains similar cubane-like tetranuclear entities which are further linked through the hydroxyl groups of the ligands thus forming dimers of cubanes. Compound 2 contains a neutral dinuclear entity in which the Cu II ions are bridged through the Schiff base and the acetate ligands, comprising distorted Cu 2 O 2 core. The Schiff base ligand adopts five different coordination modes and two deprotonation states in the structures of 1 – 5 acting simultaneously as chelating and bridging agent between the metal ions. The lattice structures of 1 – 5 exhibit interesting 3D networks based on hydrogen bonded metal clusters and they are studied with Hirshfeld Surface analysis methods. [ABSTRACT FROM AUTHOR]

Cu(II) phenanthroline complexes are able to cleave DNA and show cytotoxic activity against cancer cells. Also, the biological activity of hydrazone-based compounds has been reported in the literature. This motivated us to combine these two systems. Hydrazone-functionalized phenanthroline ligands with acetyl and benzoyl substituents were synthesized and characterized. The DNA cleavage activity of the corresponding Cu(II) complexes 3 and 4 was compared to the one of the well-known [Cu(phen) 2 ] 2+ complex ( 1 ) and [Cu(phenD) 2 ] 2+ complex ( 2 , phenD = 1,10-phenanthroline-5,6-dione, the precursor of hydrazone-functionalized phenanthrolines). In the presence of ascorbate, but also in its absence, oxidative cleavage of DNA was proven by quenching therein involved reactive oxygen species (ROS), specifically hydrogen peroxide and superoxide anion radicals. Only complexes 2 – 4 were active in the absence of ascorbate, but not [Cu(phen) 2 ] 2+ ( 1 ). The surprising occurrence of ROS in the absence of any activating agent indicates that 2 – 4 represent self-activating artificial metallonucleases. Thereby, self-activation was most prominent for the novel hydrazone-based complexes 3 and 4 . Cyclic voltammetry and circular dichroism spectroscopy were applied to get an insight in redox behavior and DNA binding characteristics of the Cu(II) complexes and thus to explain their different nuclease activity. [ABSTRACT FROM AUTHOR]

Two new salicylatocopper(II) complexes of formula [Cu(3-Mesal) 2 (inia) 2 ] 2 1 and [Cu(4-MeOsal) 2 (H 2 O)]·H 2 O 2 , (where 3-Mesal = 3-methylsalicylate, inia = isonicotinamide, 4-MeOsal = 4-methoxylsalicylate) have been studied in solid state or in solutions. The coordination environment of compound 1 differs from complex 2 , but both compounds build up 2-D supramolecular framework. The spectral and magnetic properties are in good agreement to their structure. Moreover, the cyclic voltammetric study, as well as the superoxide dismutase activity of prepared complexes has been studied in solution by NBT assay, and compared with the activity of the parent ligand, copper acetate and native SOD enzyme. SOD mimetic activity of the prepared compounds exhibited rather different IC 50 values for compound 1 and 2 . The SOD activity together with the redox stability is related to the composition and structure of the complexes. [ABSTRACT FROM AUTHOR]

Two triply-bridged dinuclear copper(II) complexes of formula [LCu(μ-OH)(μ-OAc)(μ-X)CuL]X⋅0.5H2O where L is a bidentate ligand of N-(pyridine-2-ylmethyl)propane-2-amine and X=Cl, 1 and Br, 2 were synthesized and characterized by elemental analyses, spectroscopic techniques (IR, UV-Vis, EPR), thermal analysis, conductance measurements, and single-crystal X-ray structure determination. The structures of both complexes are similar. The complexes show a distorted square-pyramidal arrangement around each copper(II) ion with a CuN2O2X chromophore in which both copper(II) ions are connected by a hydroxo bridge and a triatomic syn-syn carboxylato bridge in equatorial positions and a halide ion bridge at the axial site. The chromotropism behavior of the complexes, including solvato-, thermo-, and halochromism, were investigated in detail. Their halochromism was investigated in the pH range of 2.0-11.0 by visible absorption spectroscopy. The reversible color variations from blue to colorless are attributable to deprotonation and protonation of the ligands. The complexes show reversible thermochromism in solution due to dissociation and recombination of ligands to copper ions. [ABSTRACT FROM AUTHOR]

In the present work a family of novel secnidazole-derived Schiff base compounds and their copper(II) complexes were synthesized. The antimicrobial activities of the compounds were evaluated against clinically important anaerobic bacterial strains. The compounds exhibited in vitro antibacterial activity against Bacteroides fragilis, Bacteroides thetaiotaomicron, Bacteroides vulgatus, Bacteroides ovatus, Parabacteroides distasonis and Fusubacterium nucleatum pathogenic anaerobic bacteria. Upon coordination to copper(II) the antibacterial activity significantly increased in several cases. Some derivatives were even more active than the antimicrobial drugs secnidazole and metronidazole. Therefore, the compounds under study are suitable for in vivo evaluation and the microorganisms should be classified as susceptible to them. Electrochemical studies on the reduction of the nitro group revealed that the compounds show comparable reduction potentials, which are in the same range of the bio-reducible drugs secnidazole and benznidazole. The nitro group reduction potential is more favorable for the copper(II) complexes than for the starting ligands. Hence, the antimicrobial activities of the compounds under study might in part be related to intracellular bio-reduction activation. Considering the increasing resistance rates of anaerobic bacteria against a wide range of antimicrobial drugs, the present work constitutes an important contribution to the development of new antibacterial drug candidates. [ABSTRACT FROM AUTHOR]

The current study reports the synthesis of copper complexes of a tridentate Schiff base ligand. The compounds of the type [Cu(L)X]∙n(H2O) (where L = tridentate ONN Schiff base ligand, X = Cl−, Br−, SCN−, NO3−, CH3COO−), were characterized on the basis of elemental analyses, FT-IR, UV-vis, molar conductance, 1H-NMR, XRD and thermal analyses. The spectra revealed that the Schiff base ligand acts as a tridentate ligand through two azomethine nitrogen atoms and a phenolic oxygen atom. The molar conductance measurements of the complexes in DMF correspond to non-electrolytic nature. TGA and DTA studies results gave insight into the dehydration, thermal stability, and thermal decomposition. Square-planar geometry has been assigned to the prepared complexes as indicated by the electronic spectral measurements. Cu(II) compounds showed antiradical potential against DPPH and ABTS radicals. The antimicrobial potential of the Schiff base ligand and its Cu(II) complexes were evaluated by the rapid p-iodonitrotetrazolium chloride (INT) colorimetric assay against some selected bacteria strains: Staphylococcus aureus and Enterococcus faecalis (Gram +ve); Klebsiella pneumoniae and Pseudomonas aeruginosa (Gram −ve), and fungi (Candida albicans and Cryptococcus neoformans). The compounds showed a broad spectrum of antibacterial and antifungal activities, with MIC values ranging from 48.83 to 3125 μg/mL. [ABSTRACT FROM AUTHOR]

In the recent decades, flavonoid metal complexes have been widely investigated for their multifaceted role in enabling osteoblast differentiation and bone formation. Silibinin complexed with copper(II) ion has been synthesized along with two mixed ligand complexes, namely copper(II) silibinin-phenanthroline and neocuproine as co-ligands, and their positive role in promoting neovacularization and osteoblast differentiation was investigated. Silibinin mono complex [Cu(sil)(H2O)2] and [Cu(sil)(phen)] showed similar UV-visible absorption in the region of 315 and 222 nm, whereas Cu(silibinin)(neocuproine) [Cu(sil)(neo)] showed a blueshift in the 320 nm transition. The involvement of carbonyl group present in the C-ring in metal ion chelation was identified by FT-IR analysis. Thermal gravimetric analysis (TGA) depicted that [Cu(sil)(neo)] has higher thermal stability when compared with the control silibinin and Cu-silibinin mono, and phen complexes. Cu-silibinin complexes were found to be non-toxic to human MG-63 cells and mouse mesenchymal stem cells (MSCs). Our investigations identified the positive role of these complexes in promoting osteoblast differentiation by enhancing calcium deposition and alkaline phosphatase (ALP) activity at the cellular level and stimulation of osteoblastic marker genes such as Runx2, ALP, type 1 collagen, and OCN mRNAs expression at the molecular level. These complexes also supported angiogenesis by upregulation of VEGF and Ang 1 expression in mouse MSCs. Hence, our results suggest that the potential of these metal complexes along with mixed ligand complexes promoted osteoblast differentiation, thus warranting its candidature for bone tissue regeneration application. [ABSTRACT FROM AUTHOR]