Cytotoxic and antimicrobial activities of Cu(II), Co(II), Pt(II) and Zn(II) Complexes with N,O-chelating heterocyclic carboxylates

A series of Cu(II), Co(II), Pt(II) and Zn(II) coordination compounds has been prepared by the reaction of the metal chlorides with pyrazine-2-carboxylic acid, pyridine-2-carboxylic acid, imidazole-4-carboxylic acid, benzimidazole-2-carboxylic acid and 1-methylimidazole-2-carboxylic acid. The complexes were characterized by IR, UV-VIS, elemental analysis, and some by (1) H-NMR, X-ray crystallography, HPLC and LC/MS spectroscopy. All complexes consist of a 2:1 ratio of ligand to metal ion. IR and X-ray crystallography show that coordination is through the nitrogen and carboxylate oxygen donor atoms of the ligand to form chelating rings. DFT calculations predict that the trans-coordinated isomers are thermodynamically more stable than their cis-forms. Only one of five complexes studied by X-ray crystallography, Cu(II) complex of 1-methylimidazole-2-carboxylic acid showed a cis-configured metal ion center. HPLC analysis indicated that Pt(II) complex of 1-methylimidazole-2-carboxylic acid is dominated (>90%) by the trans-configured complex. All other complexes showed one isomer, presumably the trans-form. The cytotoxic activity was investigated in human cancer cell lines in vitro; only the Pt(II) complexes were active. The antimicrobial activity against four bacterial strains and one fungi was estimated by the MIC method and best results were found amongst the Co(II) complexes. These results indicate that trans-coordinated bischelating N,O-heterocyclic carboxylates of Pt(II) are an interesting new class of potential antitumor agents.     

Synthesis, characterization, antibiogram and DNA binding studies of novel Co(II), Ni(II), Cu(II), and Zn(II) complexes of Schiff base ligands with quinoline core

A series of Co(II), Ni(II), Cu(II), and Zn(II) complexes of Schiff base ligands L¹H₃ and L²H have been prepared. The ligands are synthesized by the condensation of 2-hydroxy-3-formylquinoline with salicyloylhydrazide and 2-hydrazinobenzothiazole in absolute ethanol. The prepared complexes were characterized by the analytical and spectral techniques. The stoichiometry of the complexes is found to be 1:1. The presence of coordinated and lattice water is confirmed by the TG and DTA studies. Subsequently all the prepared complexes were screened for antimicrobial activity against bacteria and fungi. The Cu(II) complexes have been found to be more active than the ligand. In addition the DNA binding/cleaving capacity of the compounds was analyzed by absorption spectroscopy, viscosity measurement, thermal denaturation, and gel electrophoresis methods.     

Synthesis and in vitro tuberculostatic activity of Co (II), Cu (II) and Ni (II) complexes of dialdehyde starch dithiosemicarbazone

Co (II), Cu (II) and Ni (II) complexes of starch dialdehyde dithiosemicarbazone (DASTSC) of low (approximately 15%) degree of oxidation were prepared and their tuberculostatic activity was tested in vitro against isoniazid-sensitive and isoniazid-resistant strains of Mycobacterium tuberculosis. In 10-week lasting tests the DASTSC complex with Ni (II) was tuberculostatic to a similar extent as was the free ligand, whereas the Co (II) and Cu (II) complexes inhibited the growth of M. tuberculosis more efficiently. It was also proved that the corresponding non-co-ordinated metal salts were inactive to both strains of M. tuberculosis.     

Synergistic antifungal action of 8-quinolinol and its bischelate with copper(II) and with mixed ligand chelates composed of copper(II), 8-quinolinol, and aromatic hydroxy acids

Antifungal studies were made of mixtures of minimal inhibitory concentrations (MICs) of 8-quinolinol and its bischelates with copper(II), zinc(II), and manganese(II) and with mixed ligand chelates composed of 8-quinolinol, copper(II) and a second ligand including salicylic acid, 3-hydroxy-2-naphthoic acid, 3,5-diiodosalicylic acid, and 4-bromo-3-hydroxy-2-naphthoic acid. Mixtures of the MICs of the bischelates of 8-quinolinol with copper(II) and zinc(II) and copper(II) and manganese(II), as well as 7-iodo-8-quinolinol and its bischelate with copper(II), and 8-quinolinol and 5-iodo-8-quinolinol were also studied against six fungi: Aspergillus niger, Aspergillus oryzae, Trichoderma viride, Myrothecium verrucaria, Mucor cirinelloides, and Trichophyton mentagrophytes. With the exceptions of the mixtures of 8-quinolinol and (8-quinolinolato)(3,5-diiodosalicylato)copper(II) and (8-quinolinolato)(4-bromo-3-hydroxy-2-naphthoato)copper(II) against M. cirinelloides, all of the test organisms were inhibited by 40% or less of each mixture containing 8-quinolinol. Bischelates of 8-quinolinol with copper(II) and zinc(II) and copper(II) and manganese(II) inhibited five fungi at 50% of the mixtures of the MICs. Mucor cirinelloides was not inhibited by bis(8-quinolinolato)copper(II), bis(8-quinolinolato)zinc(II), or by bis(7-iodo-8-quinolinolato)copper(II).(ABSTRACT TRUNCATED AT 250 WORDS)     

In vitro study of the interaction between omeprazole and the metal ions Zn(II), Cu(II), and Co(II)

The purpose of this study was to investigate the possibility of a chemical interaction between omeprazole (OM) and the metal ions Zn(II), Cu(II), and Co(II). Using UV absorption spectroscopy and elemental analysis, it was demonstrated that all of the studied metals form complexes with OM. The spectral changes associated with the complexation reaction were used to obtain the stoichiometry and formation constants of the complexes. In all cases complexes were found to form in 1:2 metal to OM ratio. In the case of cobalt another complex species which appeared as a green precipitate was also evident. Copper was shown to form the complex with the formula Cu3(OM)2 in addition to Cu(OM)2. The complexation of cobalt and copper to OM was found to be time dependent and the time required for the completion of the reaction was determined (about 6 h). Apparent binding constants were also determined.     

Rapid and sensitive colorimetric determination of cobalt(II).

A highly selective and sensitive spectrophotometric determination of cobalt (II) was developed. 7-Nitroso-8-hydroxyquinoline-5-sulfonic acid sodium salt was used as the chromogenic reagent for color development. Although other metals form colored chelates with the ligand, it was possible to develop a selective method using McIlvaine's pH 8 citric acid-phosphate buffer. Under these conditions, iron(II), iron (III), copper (II), zinc (II), and manganese (II), minerals likely to be compounded with cobalt (II) in geriatric formulations, do not interfere with the precision of the method or the color development. Calcium (II) and magnesium (II) do not form colored chelates with the used ligand. Hormones, vitamins, and additives likely to be present along with the cobalt ion in pharmaceutical formulations do not interfere. The sensitivity is 0.37 mug of cobalt (II)/ml of sample solution.     

Spectroscopic,antiproliferative and antiradical properties of Cu(II), Ni(II), and Zn(II) complexes with amino acid based Schiff bases

Novel six Cu(II), Ni(II), and Zn(II) complexes with Schiff bases derived from 4-aminobenzoic acid with terephtaldehyde and amino acids (glycine, β-alanine). Structures have been proposed from elemental analysis, UV–Vis, IR, NMR, TGA, DTA, and magnetic measurements. Spectroscopic studies suggest that coordination occurs through azomethine nitrogen, hydroxyl group, and carbonyl oxygen of the ligands to the metal ions. The elemental analyses of the complexes where L is Schiff base ligands, are confined to the stoichiometry of the type M₂L₂(CH₃COO)₂ [M = Cu(II)]; and M₂L(CH₃COO)₂ [M = Ni(II) and Zn(II)]. The cytotoxicity activities of the compounds against human breast carcinoma MCF-7 cell line have been studied. Ligands and their Zn(II) compounds inhibited cell proliferation of MCF-7 cancer cell lines in a dose- and time-dependent manner. The free radical scavenging activity was measured by 1,1-diphenyl-2-picryl-hydrazil. Our results show that the synthesized compounds induced oxidative damage by increasing the lipid peroxidation in yeast since MDA formation was increased, and it could be concluded that the synthesized compounds caused oxidative stress. In addition, the antioxidant activities of the synthesized compounds were very much lower than those of standard antioxidants.     

Synthesis and properties of the monomethyl ester of meso-dimercaptosuccinic acid and its chelates of lead (II), cadmium(II), and mercury(II).

The monomethyl ester of meso-dimercaptosuccinic acid (MoMeDMSA) and its chelates with lead(II), cadmium(II), and mercury(II) have been synthesized. The mercury(II) chelate of MoMeDMSA is formed by the coordination of the two sulfur atoms in MoMeDMSA, whereas the lead(II) and cadmium(II) chelates are formed by the coordination of one sulfur and one oxygen atom. The solubilities of the chelates are pH dependent; the mercury(II) chelate dissolves when the uncoordinated carboxylic acid dissociates, but the lead(II) and cadmium(II) chelates are solubilized only after the uncoordinated mercapto group is dissociated. The cadmium(II) chelate is dimeric and the lead(II) and mercury(II) chelates are monomeric at the concentrations and conditions used in this study. The acid dissociation constants of the chelating agent and the uncoordinated groups in its metal chelates have been determined in 50% v/v methanol-water. These acid-base properties in addition to the polarity of the chelating agent contribute to the effectiveness in the in vivo mobilization of intracellular in vivo deposits of cadmium. The biliary excretion of cadmium in rats increased by a factor of 173 upon administration of the relatively toxic, nonpolar dimethyl ester of DMSA whereas the administration of the less toxic, more polar monomethyl ester increased the biliary excretion of cadmium by a factor of 63. On the other hand, meso-DMSA which is highly polar and less toxic is known to be without effect on biliary excretion of cadmium. The monomethyl DMSA, therefore, appears to have properties that are intermediate between those of DMSA and its dimethyl ester, as far as both chelating properties and biliary excretion of cadmium are concerned.     

Concurrent removal of Cr(III), Cu(II), and Pb(II) ions from water by multifunctional TiO2/Alg/FeNPs beads

The use of multifunctional materials for water remediation is a modern approach where adsorption phenomena and heterogeneous photocatalysis can be applied for the removal of pollutants. Since the ideal remediation system should be able to remove both organic and inorganic pollutants, a crucial aspect to consider is the knowledge of operational parameters affecting the removal process, especially when heavy metal ions are present in concoction as in real systems. Given the proven efficiency of multifunctional TiO₂/Alg/FeNPs magnetic beads for the removal of model organic pollutants, this study investigated the possibility to exploit such system also for the removal of mixed heavy metals (MHM), specifically Cr(III), Cu(II), and Pb(II) ions, under ultraviolet irradiation at a wavelength of 254 nm. After a preliminary screening on the optimal catalyst loading, operating parameters such as the initial concentration of metal ions, contact and irradiation time, and pH were investigated to optimize the removal of metal ions using response surface methodology (RSM) via Box–Behnken design. Starting from a MHM solution containing 44 ppm of each metal ion, the removal of Pb(II), Cr(III), and Cu(II) ions in the aqueous solution was nearly completed (>98.4%) for all three ions within 72 min of irradiation at almost neutral pH (pH = 6.8). The stability of TiO₂/Alg/FeNPs was confirmed by retrieving and reusing the beads in three consecutive cycles of heavy metals removal without observing significant changes in catalyst efficiency.     

Contrasting effects of metal ions on S-nitrosoglutathione, related to coordination equilibria: GSNO decomposition assisted by Ni(II) vs stability Increase in the presence of Zn(II) and Cd(II)

Complex formation between nitrosoglutathione (GSNO) and Zn(II), Cd(II), and Ni(II) ions was studied by potentiometry and spectroscopic techniques. GSNO forms simple ML and ML2 type complexes (L = GSNO) with these ions. The stability of GSNO in HEPES buffer solution, pH 7.4, increased in the presence of both Zn(II) and Cd(II), due to an indirect mechanism. A concentration-dependent destabilization of GSNO by Ni(II) ions was found to be linearly dependent on the NiL complex concentration. NiL forms ternary complexes readily. The NiLA- stoichiometry was found for l-His, and NiHLB3- and NiLB4- complexes were detected for GSSG as the second ligand. The formation of these complexes was found to inhibit GSNO decay, by limiting the concentration of the NiL complex. The mechanism of Ni(II)-assisted GSNO decomposition contains several steps, with a hypothetical ternary complex with GSH as a likely active form. These results provide experimental evidence for the stabilization of GSNO in solution by metal ions, which may provide an additional level of control and/or impairment of cellular redox signaling. The Ni(II)-dependent destabilization of GSNO may constitute a novel epigenetic mechanism in nickel carcinogenesis.     

DNA cleavage and antimicrobial investigation of Co(II), Ni(II), and Cu(II) complexes with triazole Schiff bases: synthesis and spectral characterization

The Co(II), Ni(II), and Cu(II) complexes with Schiff bases derived from 3-substituted-4-amino-5-mercapto-1,2,4-triazole and fluvastatin have been synthesized. Schiff bases exhibited thiol–thione tautomerism and coordinated to metal ion through azomethine nitrogen and thiolate sulphur atoms. Square planar geometry for all the metal complexes of the type ML₂ has been proposed in the light of analytical, spectral (IR, UV–Vis., ESR, and FAB-mass), magnetic, and thermal studies. The antimicrobial studies of Schiff bases and their metal complexes against various antibacterial (Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa and Bacillus subtilis) and antifungal (Aspergillus niger, and Pencillium Chrysogenum) species by Minimum Inhibitory Concentration method revealed that, the metal complexes possess more healing antibacterial activity than the Schiff bases. Co(II), Ni(II), and Cu(II) complexes cleave the DNA isolated from A. niger.     

Simultaneous determination of zinc(II), manganese(II) and iron(II) in pharmaceutical preparations

The applicability of derivative spectrophotometry for simultaneous determination of zinc(II), manganese(II) and iron(II) in the form of PAR complexes was presented and discussed. Beer's law was obeyed in range 0.025-13 ppm for zinc 1-20, for manganese and 0.025-0.2 for iron ion. The elaborated method was applied successfully for determination of mentioned ions in pharmaceutical preparation without previous separation. The error of the determination did not exceed +/-3%.     

Synthesis, characterization, and comparative in vitro cytotoxicity studies of platinum(II), palladium(II), and gold(III) methylsarcosinedithiocarbamate complexes

This work reports on the synthesis, characterization, and in vitro cytotoxic activity of some new platinum(II), palladium(II), and gold(III) derivatives of methylsarcosinedithiocarbamate and its S-methyl ester, to study their behavior as potential antitumor agents. The biological activity of these compounds, as determined by growth inhibition and apoptosis induction, has been investigated in both human leukemic promyelocites HL60 and human squamous cervical adenocarcinoma HeLa cell lines, and their activity has been compared to the well-known platinum-based anticancer agent cisplatin. On the basis of these experimental results, [Pd(MSDT)X]n (MSDT = methylsarcosinedithiocarbamate; X = Cl, Br) complexes show a strong dose-dependent growth inhibition of both HL60 and HeLa cells, with IC(50) values slightly higher than those recorded for cisplatin; moreover, [Au(MSDT)X(2)] activity appears significantly higher or, at least, comparable to that of the reference drug. Exposure of both cell lines to [Pd(MSDT)X]n and [Au(MSDT)X(2)] complexes induces apoptosis, as determined by an Apo2.7 assay.     

Column solid phase extraction of iron(III), copper(II), manganese(II) and lead(II) ions food and water samples on multi-walled carbon nanotubes

A column solid phase extraction method for preconcentration of Fe(III), Cu(II), Mn(II) and Pb(II) on multi-walled carbon nanotubes (MWNTs) has been established. The adsorption was achieved quantitatively on carbon nanotube at pH 9.0, then the retained analyte contents on the column were quantitatively eluted with 1 M HNO₃ in acetone. The effects of analytical parameters including pH of the solution, eluent type, sample volume, flow rates of eluent, matrix ions, etc. were investigated for optimization of the presented procedure. The preconcentration factor was calculated as 20. The detection limits for the understudy analyte ions were found in the range of 3.5 μg/L (Mn)–8.0 μg/L (Pb). The validation of the presented procedure was checked by the analysis of TMDA 54.4 fortified lake water and HR-1 River Sediment certified reference materials. The method was applied to the determination of analyte ions in environmental samples.     

Metal binding by pharmaceuticals. Part 5. Interaction of Cd(II), Ni(II) and Pb(II) with the intracellular hydrolysis products of the anti-tumour agent ICRF 159 and its inactive homologue ICRF 192

Formation constants for the cadmium(II), nickel(II) and lead(II) complexes of DL-NN'-dicarboxamidomethyl-NN'-dicarboxymethyl-1,2-diaminopr opane (ICRF 198) and the 1,2-diaminobutane homologue (ICRF 226) have been measured potentiometrically at 37 degrees C and I = 150 mmol dm-3 [NaCl]. In all titrations a competing ligand, known to complex strongly with the metal ion, and having its formation constants predetermined, was employed. The constants are used in computer simulation models to assess the relative efficacy of the agents in mobilizing these metals from plasma proteins into low-molecular-weight complexes and the results are compared to those for known chelating agents. It is shown that the lead mobilizing potential of the agents is greater than either EDTA or D-penicillamine; they are, however, less adept in the removal of cadmium and nickel than other established agents.     

Crystallochemistry of copper (II) and zinc (II) chelates by nonsteroidal antiinflammatory drugs

Copper(II) and zinc(II) chelates by some non-steroidal antiinflammatory drugs NSAIDs (niflumic acid, indomethacin) and 3,5-diisopropylsalicylic acid (DIPS) were characterized by single X-ray diffraction methods. Copper(II) complexes by these two types of chelates are binuclear compounds, with Cu(2)(DIPS)(4)L(2) or Cu(2)(AINS)(4)L(2) formula (L=axial non-NSAID ligand such as diethylether, dimethylsulfoxide DMSO). In zinc(II) complex by DIPS, the metal ion is tetrahedrally coordinated and the corresponding compound is mononuclear with Zn(DIPS)(2)(DMSO)(2) formula. These copper(II) and zinc(II) complexes were found to be more active than their parent drugs from the antiinflammatory and anticonvulsant properties. It was pointed out that the Cu(2)(DIPS)(4)L(2) complexes (L=diethylether, N,N-dimethylformamide) exhibited no rotorod toxicity when examined for anticonvulsant activity using the seizure produced by maximal electroshock, following oral administration to rats.     

Pod razor (Ensis siliqua) shell powder as cost-effective biomineral for removal of nickel(II), copper(II) and zinc(II) from artificially contaminated industrial wastewater

The removal of Ni(II), Cu(II) and Zn(II) from aqueous model solutions and real wastewater samples by using pod razor (Ensis siliqua) shell powder has been investigated under several conditions such as heavy metal concentrations, pH, contact time, powder dosage. It was found that the removal of heavy metals was dependent on the dose of the biomineral and contact time. The results showed that this low-cost material can be fruitfully used for the removal of heavy metal ions such as Ni(II), Cu(II) and Zn(II) below concentration of 200 mg/L applying a shell powder dose of 1.2–4 g/L. The minimal dose for removal of Cu(II) and Zn(II) from industrial wastewater was found to be 1.2 g/L, while for Ni this value amounted to 1.6 g/L. The contact time necessary for quantitative removal was found to be 30–60 min and the optimum initial pH range was between 4 and 5.     

Synthesis and Characterization of Cr(III), Mn(III), Fe(III), VO(IV), Zr(IV) and UO2(VI) Complexes of Schiff Base Derived from Isonicotinoyl Hydrazone

2-hydroxy-5-chloro-3-nitroacetophenone isonicotinoyl hydrazone as a Schiff base ligand and its complexes with Cr(III), Mn(III), Fe(III), VO(IV), Zr(IV) and UO₂(VI) metal ions have been synthesized. The ligands as well as their metal complexes were well characterized using various physicochemical techniques such as elemental analyses, molar conductance measurements, magnetic measurements, thermal analysis, electronic and IR spectral studies. On the basis of these studies, square pyramidal stereochemistry for Mn(III) and VO(IV) complexes while octahedral stereochemistry for all the other complexes have been suggested. The complexes were found to be stable up to 60-70° and thermal decomposition of the complexes ended with respective metal oxide as a final product. The thermal data have been analyzed for kinetic parameters using Broido and Horowitz-Metzger methods. The synthesized Schiff base ligand and its complexes were also tested for their antimicrobial activity using various microorganisms.     

Determination of Se(IV), Cd(II) and Pb(II) ions in homeopathic drugs by inversion voltammetry method

The conditions for identification and quantification of Se(IV), Cd(II) and Pb(II) ions in homeopathic drugs by inversion voltammetry method with the use of EAGRAPH software were established. The studies proved that the method was of high sensitivity in established conditions. The detection limits were 0.66 microg/mL, 0.08 microg/mL and 0.12 microg/mL for Se(IV), Pb(II) and Cd(II) ions, respectively. This method was characterized by repeatability of measurements, a wide range of linearity and satisfactory percent recovery.     

Antimicrobial studies of hydrazone complexes of Hg(II) and Fe(II) divalent metal ions

The antibacterial, antifungal and antitubercular activities of Hg(II) and Fe(II) complexes of hydrazone were studied. All the complexes have been screened against Staphylococcus aureus, Salmonella typhi, Candida albicans, Aspergillus niger, Saccharomyces cerevisiae and Mycobacterium tuberculosis H37Rv and found to be more toxic than the parent ligand. The activity increased in the order [5-methyl-3-oximino-hexan-2-one-hydrazone]2 Fe(II) < [5-methyl-3-oximino-hexan-2-one-hydrazone]2 Hg(II) < 3-oximino-hexan-2-one-phenylhydrazone]2 Fe(II) < [5-methyl-3-oximino-hexan-2-one-phenylhydrazone]2 Hg(II) for antibacterial and antifungal activity.