Stability constants of thiocyanato complexes of cobalt(II), nickel(II) and copper(II) in methanol.

A spectrophotometric study of cobalt(II), nickel(II) and copper(II) thiocyanato complexes was carried out in methanol at 25 degrees C and at a constant ionic strength of 1 M. Under the experimental conditions, two mononuclear complexes are identified with each of the three metal ions. Their stability constants are determined with a recent PC program SIRKO and the calculated values are: for cobalt, log beta 1 = 1.6, log beta 2 = 2.7; for nickel, log beta 1 = 1.8, log beta 2 = 3.0; and for copper, log beta 1 = 3.0, log beta 2 = 3.6.     

Synthesis and characterisation of copper(II), zinc(II) and cobalt(II) complexes of salicylglycine, a metabolite of aspirin

Copper(II), nickel(II) and cobalt(II) complexes of the aspirin metabolite salicylglycine (H₂L), of stoichiometry M(HL)₂·solvate, have been prepared and characterised. In these complexes salicylglycinate is coordinated to the metal via its carboxylato group and possibly also its amide oxygen in the copper(II) complex. Under basic conditions copper(II) forms the complex Cu(LH₋₁)·2H₂O·MeOH, in which the ligand is coordinated to the metal via its carboxylate and phenolate oxygen atoms and the deprotonated peptide nitrogen atom.     

Synthesis and DNA cleavage activities of mononuclear macrocyclic polyamine zinc(II), copper(II), cobalt(II) complexes which linked with uracil

Mononuclear macrocyclic polyamine zinc(II), copper(II), cobalt(II) complexes, which could attach to peptide nucleic acid (PNA), were synthesized as DNA cleavage agents. The structures of these new mononuclear complexes were identified by MS and (1)H NMR spectroscopy. The catalytic activities on DNA cleavage of these mononuclear complexes with different central metals were subsequently studied, which showed that copper complex was better catalyst in the DNA cleavage process than zinc and cobalt complexes. The effects of reaction time, concentration of complexes were also investigated. The results indicated that the copper(II) complexes could catalyze the cleavage of supercoiled DNA (pUC 19 plasmid DNA) (Form I) under physiological conditions to produce selectively nicked DNA (Form II, no Form III produced) with high yields. The mechanism of the cleavage process was also studied.     

Antibacterial Co(II), Ni(II), Cu(II) and Zn(II) complexes of Schiff bases derived from fluorobenzaldehyde and triazoles

Antibacterial Schiff bases derived from 1,2,4-triazoles as well as their metal complexes incorporating cobalt(II), nickel(II), copper(II) and zinc(II) have been synthesized and characterized. Physico-chemical studies suggest that an octahedral geometry for the cobalt(II), nickel(II) and zinc(II)and square-planer geometry for the copper(II) complexes. These complexes have been screened for antibacterial activity against three Gram-positive (Staphylococcus aureus, Staphylococcus epidermidis and Bacillus subtilis) and two Gram-negative (Salmonella typhi and Pseudomonas aeruginosa) bacterial strains, and results compared with the activity of the free ligands. The metal complexes were found to be more potent against one or more bacterial strains than the free ligands.     

Copper(II), cobalt(II) and nickel(II) complexes of alkyl-substituted tris(2-benzimidazolylmethyl)amines and their ternary copper(II) systems containing several thiolates

Copper(II), cobalt and nickel(II) complexes of tris(benzimidazolylmethyl)amine(1) and of its methyl(2), isobutyl(3) or isopropyl(4)-substituted derivatives of one of the backbone methylene groups were prepared and characterized. The ligands (1)–(3) afforded trigonal bipyramidal copper(II) complexes, whereas ligand (4) gave a tetrahedrally distorted tetragonal one because of the steric hindrance arising from the isopropyl group. All the cobalt(II) complexes prepared were supposed to be tetrahedral or pseudotrigonal bipyramidal, and all the nickel(II) complexes to be slightly tetrahedrally distorted octahedral. Ternary copper(II) systems containing several thiolates as the third component exhibited intense blue, brown or green color under a reduced temperature by virtue of the charge transfer bands, S^? → Cu.     

Antibacterial Co(II), Ni(II), Cu(II) and Zn(II) Complexes of Schiff bases Derived from Fluorobenzaldehyde and Triazoles

Antibacterial Schiff bases derived from 1,2,4-triazoles as well as their metal complexes incorporating cobalt(II), nickel(II), copper(II) and zinc(II) have been synthesized and characterized. Physico-chemical studies suggest that an octahedral geometry for the cobalt(II), nickel(II) and zinc(II)and square-planer geometry for the copper(II) complexes. These complexes have been screened for antibacterial activity against three Gram-positive (Staphylococcus aureus, Staphylococcus epidermidis and Bacillus subtilis) and two Gram-negative (Salmonella typhi and Pseudomonas aeruginosa) bacterial strains, and results compared with the activity of the free ligands. The metal complexes were found to be more potent against one or more bacterial strains than the free ligands.     

Regulation of peroxo-bridge formation between cobalt(II)-carnosine complexes by histidine: Possible involvement in polycythemia

The mechanisms by which histidine stabilizes the cobalt(II)-carnosine complex from oxidation to cobalt(III) in aqueous solution are investigated with ¹H-nmr, laser Raman, and Fourier transform-infrared spectroscopy. Histidine has at least three effects on the cobalt(II)-carnosine complex. First, over the concentration range of at least 5 to 250 mM, histidine stabilizes the cobalt(II)-carnosine complex from oxidation by excluding solvent molecules from the equatorial coordination positions. Second, at the upper end of this concentration range, histidine reduces the strained nonplanarity of the equatorial coordination positions around the cobalt(II) ion that results from tridentate chelation by carnosine. Bidentate ligation by histidine causes the carnosine to bind as a bidentate ligand also. Third, bidentate ligation of two carnosine molecules to the equatorial coordination positions of Co(II) ion places the β-alanyl residues inthe vicinity of the two axial coordination positions and thereby inhibits the binding of molecular oxygen. Substitution of a molecule of histidine for one of these two carnosine molecules makes an axial coordination position available for binding oxygen. The first two effects are expected to stabilize the cobalt(II) ion from rapid oxidation, whereas the third effect is expected to give long-term stability of the peroxo-bridged complex. Since bidentate ligation of histidine is favored over monodentate ligation only when the concentration of Co(II) ion is not limiting and is inhibited by high concentrations of carnosine in the same solution, the results presented provide a possible explanation for the observation that the stability of the Co(II) complexes toward oxidation and their ability to bind molecular oxygen depend on both the relative and absolute concentrations of Co(II) ion, carnosine, and histidine in solution. Furthermore, these results provide additional support to the suggestion that the high activity of carnosinase in kidney is involved in part in regulation of the oxygen sensor in this organ.     

Biosorption of copper(II) and cobalt(II) from aqueous solutions by crab shell particles

Biosorption of each of the heavy metals, copper(II) and cobalt(II) by crab shell was investigated in this study. The biosorption capacities of crab shell for copper and cobalt were studied at different particle sizes (0.456-1.117 mm), biosorbent dosages (1-10 g/l), initial metal concentrations (500-2000 mg/l) and solution pH values (3.5-6) in batch mode. At optimum particle size (0.767 mm), biosorbent dosage (5 g/l) and initial solution pH (pH 6); crab shell recorded maximum copper and cobalt uptakes of 243.9 and 322.6 mg/g, respectively, according to Langmuir model. The kinetic data obtained at different initial metal concentrations indicated that biosorption rate was fast and most of the process was completed within 2h, followed by slow attainment of equilibrium. Pseudo-second order model fitted the data well with very high correlation coefficients (>0.998). The presence of light and heavy metal ions influenced the copper and cobalt uptake potential of crab shell. Among several eluting agents, EDTA (pH 3.5, in HCl) performed well and also caused low biosorbent damage. The biosorbent was successfully regenerated and reused for five cycles.     

Preferences of kanamycin A towards copper(II). Effect of the resulting complexes on immunological mediators production by human leukocytes

The widespread presence of pathogenic bacteria is a cause of permanent demand for investigating the properties of antimicrobial agents. The chemical basis of several toxic effects induced by antibiotics still remains unclear. Aminoglycosides, highly ototoxic and nephrotoxic drugs, are capable of copper(II) ions chelating. In this study we established the affinity of kanamycin A towards copper(II), in contrast with other metal ions: iron(III), nickel(II), cobalt(II) and zinc(II) by means of potentiometry. Circular dichroism spectroscopy was applied to monitor the competition of copper(II) partition between kanamycin A and human serum albumin. We show, that the drug is able to digest Cu(II) ions from HSA to some extent and comparing the stability constants for metal and antibiotic with those, obtained for the N-terminal Asp-Ala-His-Lys (DAHK) sequence, which constitutes a copper(II) binding domain within albumin, we demonstrate that the Cu(II)-kanamycin A complex formation is possible also in blood plasma. Bioassays and immunoassay were used to find out the possibility of Cu(II)-kanamycin A complexes to induce cytokines: tumor necrosis factor (TNF), interferon (IFN) and interleukin-10 (IL-10) in human peripheral blood leukocytes. The effect on the cytokines release was dose and time dependent and the interdependence between IL-10 and TNF stimulation was found. We report that Cu(II)-aminoglycoside systems can act as moderate inducers of TNF-alpha, IFN-alpha/beta and IL-10 released from human leukocytes. We have also found that these complexes are non-toxic for human A549 cells.     

Equilibrium and kinetics of the dinuclear complex formation between N,N′-ethylenebis(salicylideneiminato)copper(II) and metal(II,I) ions in acetonitrile

The equilibrium constants and rate constants of the reactions between N,N′-ethylenebis(salicylideneiminato)copper(II) ([Cu(salen)]) and metal(II,I) ions in acetonitrile have been spectrophotometrically determined. [Cu(salen)] acts as a didentate ligand to form a dinuclear complex. The rate constants for the very labile Mn(II), Fe(II), and Zn(II) ions were directly evaluated using a variable flow-rate instrument that was newly constructed for this study. The rate constants of the dinuclear complex formation for a series of metal(II) ions vary in parallel with those of the acetonitrile solvent exchange on the corresponding metal(II) ions. This finding indicates that the dinuclear complex formation reaction of the metal(II) ions proceeds via almost the same reaction mechanism as for the acetonitrile solvent exchange reaction.     

Complexes of dibenzoyldisulphide with metal halides. Part III. Complexes of dibenzoyldisulphide with cobalt(II), nickel(II), manganese(II), copper(II), iron(III) and chromium(III) halides

Adducts (1:1) of halides of cobalt(II), nickel(II), manganese(II), copper(II), iron(III) and chromium(III) with dibenzoyldisulphide have been isolated and characterized on the basis of elemental analysis, molar conductance, magnetic susceptibility, infrared spectra, molecular weight and thermogravimetric analysis data.     

Copper(II) complexes derived from (2-carboxymethoxy-phenylamino)acetic acid and analogue

The synthesis and characterization of mononuclear copper complex of (3-oxo-2,3-dihydro-benzo[1,4]oxazin-4-yl)-acetic acid (1) and a tetranuclear copper complex of (2-carboxymethoxy-phenylamino)acetic acid (2) is reported. The sodium salt 1 on reaction with copper(II) chloride hexahydrate followed by treatment with pyridine gave a mononuclear copper complex; whereas, a tetra-nuclear complex in the case of reaction of 2 with copper(II) chloride hexahydrate and 2,2′-bipyridine was obtained. In tetra-nuclear copper(II) complex the NH group co-ordinates to copper and cluster has five co-ordination around copper(II).     

Antifungal cobalt(II), copper(II), nickel(II) and zinc(II) complexes of furanyl-,thiophenyl-, pyrrolyl-, salicylyl- and pyridyl-derived cephalexins

Some novel cephalexin-derived furanyl, thiophenyl, pyrrolyl, salicylyl and pyridyl Schiff's bases and their cobalt (II), copper (II), nickel (II) and zinc (II) complexes have been synthesized and studied for their antifungal properties against Trichophyton longifusus, Candida albicans, Aspergillus flavus, Microsporum canis, Fusarium solani and Candida glaberata. The presence of metal ions in the investigated Schiff's base complexes reported here lead to significant antifungal activity, whereas the parent ligands were generally less active.     

Copper(II), cobalt(II) and nickel(II) complexes of lapachol: synthesis,DNA interaction,and cytotoxicity

Three novel copper(II), cobalt(II), and nickel(II) complexes of lapachol (Lap) containing 110-phenanthroline (phen) ligand, [M(Lap)₂(phen)] (M=Cu(II), 1, Co(II), 2, and Ni(II), 3), have been synthesized and characterized using, elemental analysis and spectroscopic studies. Their interactions with calf thymus DNA (CT DNA) were investigated using viscosity, thermal denaturation, circular dichorism, fluorescence quenching, and electronic absorption spectroscopy. The DNA cleavage abilities of 1–3 have been studied, where cleavage activity of copper complex 1 is more than the complexes 2 and 3. The in vitro cytotoxic potential of the complexes 1–3 against human cervical carcinoma (HeLa), human liver hepatocellular carcinoma (HepG-2), and human colorectal adenocarcinoma (HT-29) cells indicated their promising antitumor activity with quite low IC₅₀ values in the range of .15–2.41 μM, which are lower than those of cisplatin.     

Cytotoxic activity, X-ray crystal structures and spectroscopic characterization of cobalt(II), copper(II) and zinc(II) coordination compounds with 2-substituted benzimidazoles

Herein we present the synthesis, structural and spectroscopic characterization of coordination compounds of cobalt(II), copper(II) and zinc(II) with 2-methylbenzimidazole (2mbz), 2-phenylbenzimidazole (2phbz), 2-chlorobenzimidazole (2cbz), 2-benzimidazolecarbamate (2cmbz) and 2-guanidinobenzimidazole (2gbz). Their cytotoxic activity was evaluated using human cancer cell lines, PC3 (prostate), MCF-7 (breast), HCT-15 (colon), HeLa (cervic-uterine), SKLU-1 (lung) and U373 (glioblastoma), showing that the zinc(II) and copper(II) compounds [Zn(2mbz)₂Cl₂]·0.5H₂O, [Zn(2cmbz)₂Cl₂]·EtOH, [Cu(2cmbz)Br₂]·0.7H₂O and [Cu(2gbz)Br₂] had significant cytotoxic activity. The isostructural cobalt(II) complexes showed not significant activity. The cytotoxic activity is related to the presence of halides in the coordination sphere of the metal ion. Recuperation experiments with HeLa cells, showed that the cells recuperated after removing the copper(II) compounds and, on the contrary, the cells treated with the zinc(II) compounds did not. These results indicate that the mode of action of the coordination compounds is different.     

Magnetic circular dichroic spectra of cobalt(II) substituted metalloenzymes.

The magnetic circular dichroic (MCD) spectra of cobalt(II) sugstituted metalloenzymes have been studied and compared to a series of four-, five-, and six-coordinate cobalt(II) model complexes previously examined (T. A. Kaden et al. (1974), Inorg. Chem. 13, 2582). The MCD spectra of cobalt substituted carboxypeptidase A, procarboxypeptidase ta, and thermolysin are consistent with earlier deductions of tetrahedral coordination from absorption spectra and also with X-ray structure analysis. Inhibitors fail to alter their MCD spectra significantly. The MCD spectra of cobalt alkaline phosphatase and carbonic anhydrase are more complex and their pH dependence and alteration by inhibitors are discussed in terms of known cobalt(II) models.     

The syntheses and properties of cobalt(II), nickel(II) and copper(II) complexes with some heterocyclic dithiocarbamates

New cobalt(II), Nickel(II) and copper(II) dithiocarbamato complexes of the type M(Rdtc)₂ (Rdtc = 4-phenylpiperidinedithiocarbamate and N-phenylpiperazinedithiocarbamate) have been prepared and characterized through elemental analyses, conductivity measurements, spectral (electronic and IR) studies, magnetic moment measurements at different temperatures, e.p.r. techniques and thermal analyses (TG and DTG). The dithioligands exhibit bidentate behaviour in all the complexes. The magnetic moments studies suggest that there is no significant interaction between copper ions, and the e.p.r. data provide parameters typical of sulphur coordination in planar CuS₄ chromophores.     

In vitro advanced antimycobacterial screening of cobalt(II) and copper(II) complexes of fluorinated isonicotinoylhydrazones

The in vitro antimycobacterial activity of cobalt(II) and copper(II) complexes of some fluorinated isonicotinoylhydrazones was evaluated in a TB-infected macrophage model; all metalcomplexes exhibited excellent activity against Mycobacterium tuberculosis Erdman growing within macrophages, at concentrations much lower than in culture media. Moreover complexes 1b and 2a displayed EC(99) values lower than that of the parent-drug, isoniazid. In addition, all tested metalchelates significantly inhibited the growth of single-drug-resistant M. tuberculosis strains; complexes 1a and 2a also possessed moderate activity against Mycobacterium avium complex.     

Copper (II) and cobalt (II) complexes of chiral tetrathiafulvalene-oxazoline (TTF-OX) and tetrathiafulvalene-thiomethyl-oxazoline (TTF-SMe-OX) derivatives

Synthesis and single crystal X-ray structures of the first paramagnetic transition metal complexes containing chiral ethylenedithio-tetrathiafulvalene-oxazoline (EDT-TTF-OX) 1a-c and ethylenedithio-tetrathiafulvalene-thiomethyloxazoline 2 (EDT-TTF-(SMe)OX) ligands based on copper (II) and cobalt (II) are described. The racemic [EDT-TTF-OX][Cu(hfac)₂] complex 3a crystallizes in the triclinic centrosymmetric space group , whereas the enantiopure counterparts 3b-c crystallize in the triclinic non-centrosymmetric space group P1. Cu(II) adopts a distorted square pyramidal coordination geometry, a much weaker Cu?S_TTF interaction also being identified. The same coordination pattern around Cu(II) is observed in the complex [(rac)-EDT-TTF-(SMe)OX][Cu(hfac)₂] (4) in spite of the bidentate nature of the redox active ligand. DFT theoretical calculations afforded two equilibrium configurations for a corresponding model complex, in which the metal centre establishes secondary coordination either with one S_TTF or with the SMe group. The same ligand coordinates the cobalt (II) to afford the octahedral complex [(rac)-EDT-TTF-(SMe)OX][Co(hfac)₂] (5). In all these novel complexes, the paramagnetic centres are structurally and magnetically isolated. Cyclic voltammetry measurements show the stability of the radical cation species.