Complexes between pilocarpine and cobalt(II), nickel(II), copper(II), and zinc(II) ions

The properties of pilocarpine as a ligand toward the halides of cobalt(II), nickel(II), copper(II), and zinc(II) were investigated. Pilocarpine behaved as a monodentate ligand, giving rise to compounds with the general formula methyl(pilocarpine)2X2. The coordinating geometry at the metal ion was pseudotetrahedral in every case. PMR studies showed that the pyridine-type nitrogen of the imidazole ring of pilocarpine was the donor atom of the ligand.     

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.     

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.     

Ni(II), Cu(II), and Zn(II) diethyldithiocarbamate complexes show various activities against the proteasome in breast cancer cells

A series of three complexes with diethyldithiocarbamate ligand and three different metals (Ni, Cu, Zn) was prepared, confirmed by X-ray crystallography, and tested in human breast cancer MDA-MB-231 cells. Zinc and copper complexes, but not nickel complex, were found to be more active against cellular 26S proteasome than against purified 20S proteasome core particle. One of the possible explanations is inhibition of JAMM domain in the 19S proteasome lid.     

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.     

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%.     

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.     

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.     

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.     

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.     

Distinctive accumulation patterns of Cd(II), Cu(II), and Cr(VI) in tissue of the South American teleost, pejerrey (Odontesthes bonariensis)

The time- and concentration-dependent accumulation patterns of three environmentally relevant metals, with different chemical and biological properties, were comparatively evaluated in tissue of South American fish, pejerrey (Odontesthes bonariensis). Six-month-old juvenile pejerrey were exposed to 1, 5, or 10 microgl(-1) of Cd(2+); 10, 50, or 100 microgl(-1) of Cu(2+); or 100, 500, or 1000 microgl(-1) of Cr(6+) during 16 days. Tested concentrations ranged from those that caused no significant accumulation to those that induced growth reduction or even mortality (Cd and Cu). Concentration-dependent accumulation of Cd and Cr presented similar patterns, characterized by a linear and exponential relationship in the gill and liver, respectively, with a greater slope at longer exposure times. Differently, essential Cu showed a linear relationship in both tissues, and no slope increase was observed in the gill. The gill time-dependent accumulation pattern of Cd exhibited relatively long times to half-saturation (t(1/2(1))=36.6 days) and high-saturation values (S((1))=205.4 nmolg(-1)). The opposite pattern was observed for Cu (t(1/2(100))=0.6 days; S((100))=24.4 nmolg(-1)), while Cr showed an intermediate position (t(1/2(1000))=2.8 days; S((1000))=50.2 nmolg(-1)). In the liver, times to half saturation for the three metals were as follows: Cd=4.7 days; Cu=2.5 days; Cr=1.6 days. Conversely, different saturation concentrations were observed among metals, Cu (S((100))=102) presenting the highest values, Cd (S((10))=4.4) the lowest, and Cr presenting an intermediate position (S((1000))=24.7). Bioconcentration of non-essential Cd was high in the gill (2000-fold) and low in the liver (50-fold). On the other hand, the essential element Cu was poorly retained by the gill (15-fold) and accumulated mainly in the liver (50-fold). Differently, Cr was quickly and evenly accumulated by both organs, but barely bioconcentrating (2.5- and 1.5-fold levels as compared to the original in the gill and liver, respectively). The ratio of gill/liver concentration in exposed fish clearly differed from that of non-exposed fish, and was characteristic for each metal (Cd>1; Cu<1; Cr<9), representing a potential tool to assess exposure. The accumulation patterns of studied metals in the tissue of pejerrey corresponded more with those reported for sensitive than for tolerant fish species. Distinctive tissue accumulation patterns in relation to growth reduction and non-acute lethality suggests different target tissues for sub-chronic effects, and would partially explain differences in the relative toxicity of these metals.