Synthesis, spectroscopic, thermal and antimicrobial studies of Co(II), Ni(II), Cu(II) and Zn(II) complexes with Schiff base derived from 4-amino-3-mercapto-6-methyl-5-oxo-1,2,4-triazine

Coordination complexes of Co(II), Ni(II), Cu(II) and Zn(II) with Schiff base derived from syringaldehyde and 4-amino-3-mercapto-6-methyl-5-oxo-1,2,4-triazine have been synthesized. These complexes have been characterized by elemental analysis, magnetic moment, spectroscopic (IR, Electronic, ¹H NMR, ESR) and thermogravimetric analysis. Magnetic and spectral data suggest octahedral geometry for Co(II), Ni(II) and Zn(II) complexes and square planar for Cu(II) complexes. The presence of coordinated water in metal complexes was confirmed by thermal and IR data. The Schiff base and its metal complexes have been screened for antibacterial (Pseudomonas aeruginosa, Bacillus subtilis, Escherichia coli, Staphylococcus aureus) and antifungal activities (Aspergillus niger, A. flavus). A comparison is made between activities of complexes with Schiff base and with the standard antibiotics.     

First divalent metal complexes of the polyether ionophore Monensin A: X-Ray structures of [Co(Mon)2(H2O)2] and [Mn(Mon)2(H2O)2] and their bactericidal properties

The complexation of carboxylic acid Monensin A (MonH, 1a) with CoCl2.6H2O and MnCl2.4H2O leads to the formation of mononuclear complexes [Co(Mon)2(H2O)2], 2a and [Mn(Mon)2(H2O)2], 2b, respectively. The unique crystal structures of 2a and 2b were determined by X-ray crystallography. The complexes crystallize in the monoclinic space group P2 1 with an octahedrally coordinated transition metal center forming the crystallographically centrosymmetric chromophore CoO6 or MnO6, respectively. Two molecules of Monensin A act bidentately through their carboxylate moiety and a hydroxyl group, and two water molecules are additionally trans-coordinated. Although the transition metal ions are not bound into the cavity of the ligand, the unusual bidentate coordination mode of the ionophore induces its "pseudo-cyclization" forming 22-membered cycles further stabilized by a number of H-bonds. The complexes are the first example of divalent metal complexes of the monovalent polyether ionophore. The parallel study on the complexation ability of the potassium complex of Monensin A (MonK, 1b) towards Co(II) and Mn(II) showed the formation of the isostructural complexes 2a and 2b accompanied by loss of the potassium ion due to the new coordination mode of the ligand. The biological tests performed with the antibiotic MonH and the corresponding metal(II) complexes show greatly enhanced antimicrobial activity of complexes 2a-b against Gram(+)-bacteria.     

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.     

Lipophilicity of kinetically labile metal complexes through the example of antidiabetic Zn(II) and VO(IV) compounds

The lipophilic character of several carrier ligands of antidiabetic Zn(II) and VO(IV) metal complexes were characterized by the traditional saturation shake flask method based on n-octanol/water partitioning. The transfer of the neutral ligand species to the organic phase was followed by UV spectrophotometry at various pH and the partition and distribution coefficients were calculated with the help of the proton dissociation constants and the spectra of the individual ligand species. Partition and distribution coefficients of the Zn(II) and VO(IV) complexes were determined by analysis of the metal ion content of the aqueous phases before and after separation by ICP-AES, their UV spectra and the corresponding concentration distribution curves. Results revealed the fairly hydrophilic character both the carrier ligands and their neutral Zn(II) and VO(IV) complexes. A quasi-linear relationship was found between logP of the ligands and that of the metal species in the case of the ligands studied with the exception of the picolinates. Importance of the knowledge of the chemical speciation (i.e. stoichiometry and stability constants) was also highlighted for the characterization of the lipophilic character of the kinetically labile metal complexes.     

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 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.     

Synthesis,characterization, and anti-rheumatic potential of phthalazine-1,4-dione and its Cu(II) and Zn(II) complexes

Two new metal complexes derived from the reaction of 2-[(2-hydroxybenzoyl) 2,3,4a,5,10,10a-hexahydro-5,10[1′,2′]-benzenobenzo[g]phthalazine-1,4-dione] (HBPD) with Cu(II) and Zn(II) have been synthesized and characterized by using elemental analysis, spectral analysis (UV–Vis, IR, ¹H NMR, ¹³C NMR), conductance, thermal analysis, and magnetic moments. The in vivo collagen-adjuvant arthritis model in rats revealed a significant antioxidant, analgesic, and anti-rheumatic effects for HBPD and its copper and zinc complexes in comparison with standard piroxicam. The results showed that, the investigated Cu and Zn complexes have higher anti-inflammatory activity than the free ligand.     

Synthesis, spectroscopy, and antibacterial activity of some transition metal complexes with tridentate (ONS) and bidentate (NN) donor Schiff bases

The complexes of a series of transition metal ions including Mn(II), Co(II), Ni(II), Cu(II), Zn(II), and Cd(II) with salicylidene-o-aminothiophenol and bis(benzylidene)ethylenediamine or bis(acetophenone)ethylenediamine have been synthesized and characterized by elemental analyses, infrared spectra, reflectance spectra, magnetic measurements, and thermogravimetric analyses. All complexes have been screened for their antibacterial activity against bacterial strains using the disc diffusion technique. It is established that the complexes possess moderate antibacterial activity against Salmonella typhimurium, Escherichia coli, and Serratia marcescens, the effect being higher as compared to the action of individual ligands, metal chlorides, and control (DMSO), but lower than the action of the reference drug tetracycline. Published in Khimiko-Farmatsevticheskii Zhurnal, Vol. 40, No. 10, pp. 24–27, October, 2006.     

Preparation and properties of selected Zn(II)-peptide complexes in suspension

The preparation and properties of low soluble, suspended Zn(II) complexes containing the selected peptides: tyroliberin (TRH), gonadorelin (GnRH), dalarelin and corticothropin (ACTH) were studied. The amount of Zn(II) bound by 1 muM of the selected peptide (n) was defined, as well as affinity of Zn(II) to the peptide (Ka) and the durability of the created complex Zn(II)-peptide (Kd). ACTH associated the highest amount of Zn(II), and GnRH the lowest one: 1 microM of ACTH complexed 0.81 microM +/- 0.03 Zn(II), the same quantity of GnRH-0.52 microM +/- 0.07 and TRH and dalarelin associated 0.75+/-0.03 and 0.79+/-0.02 microM of Zn(II), respectively. The closest affinity was stated between Zn(II) and GnRH (Ka=157.692+/-21.300 microM(-1)), the smallest-towards ACTH (Ka=1.136+/-0.042 microM(-1)). The lower amount of Zn(II) associated by the studied peptide, the higher was its affinity versus this metal (r=-0.942). The analysis of the kinetics of the Zn(II)-peptide linkage revealed that the most stable complexes with this metal were formed by GnRH (Kd=0.006+/-0.001 microM(-1)) and by dalarelin (Kd=0.020+/-0.001 microM(-1)). Zn(II) with GnRH complexes are about 147 times more durable than ACTH (Kd=0.880+/-0.033 microM(-1)) ones. It was established that the Zn(II)-peptide complexes were more stable in the case of lower molecular weight of the peptide (r=0.963), and the inferior number of the amino acid residues accessible in the peptide (r=0.967).     

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.     

Chiral mixed ligand Co(II) and Ni(II) complexes: synthesis and biological activity

Chiral mixed ligand (CML) transition metal complexes of the type MQL.2H2O, where M is Co(II)/Ni(II), Q is deprotonated 8-hydroxyquinoline and L is a deprotonated chiral saccharide such as (+)-glucose and (-)-fructose, have been synthesized. The metal complexes have been characterized on the basis of elemental analysis and various physicochemical techniques such as molar conductance, specific rotation measurements, magnetic, spectral and thermal studies. The cup-plate method has been used to study the antibacterial activity of the compounds against some of the pathogenic bacteria such as C. diphtheriae, E. coli, S. typhi, S. dysenteriae, S. aureus and V. cholerae. The antifungal activity of the complexes against some of the pathogenic fungi such as Candida albicans and Aspergillus niger has been studied by the tube dilution method. The results have been compared against those of controls, which were screened simultaneously. The complexes have been screened for acute oral toxicity in albino rats. The method of Litchfield and Wilcoxon has been used to determine the LD50 values.     

Antitumor activity of bis(diphenylphosphino)alkanes, their gold(I) coordination complexes, and related compounds

Bisphosphines related to bis(diphenylphosphino)ethane (dppe) and their gold complexes are described that are active in a spectrum of transplantable tumor models. When administered ip on days 1-5 at its maximally tolerated dose (MTD) of 40 mumol/kg, dppe reproducibly gives 100% increase in life span (ILS) in mice bearing ip P388 leukemia. Coordination of chlorogold(I) to each phosphine in dppe gave a complex that had similar activity but at a much lower dose level than dppe; the MTD for the gold(I) complex was 7 mumol/kg. Among other metal complexes of dppe, the Au(III) complex was active (greater than 50% ILS) whereas Ag(I), Ni(II), Pt(II), Pd(II), and Rh(I) complexes were inactive. Among dppe analogues, replacement of phenyl groups with ethyl or benzyl groups resulted in inactivity for both ligands and the corresponding gold complexes whereas substitution with cyclohexyl or heterocyclic ring systems yielded ligands and/or gold complexes with antitumor activity. Among substituted-phenyl dppe and dppe(AuCl)2 analogues, 3-fluoro, 4-fluoro, perdeuterio, 4-methylthio, and 2-methylthio analogues were active; 4-methyl, 3-methyl, 4-methoxy, 4-dimethylamino, and 4-trifluoromethyl analogues were marginal or inactive. Analogues in which the ethane bridge of dppe or dppe(AuCl)2 was varied between one and six carbons, unsaturated or substituted, revealed that activity was maximal with ethane or cis-ethylene. Compounds with good P388 activity were also active in other animal tumor models.     

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.     

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.     

Synthesis,characterization and antimicrobial activity of some mixed ligand Co(II) and Ni(II) complexes

Mixed ligand Co(II) and Ni(II) complexes have been synthesized by using 8-hydroxyquinoline as primary ligand and N- and/or O- donor ligands such as tartaric acid/phenylalanine as secondary ligands. The metal complexes have been characterized on the basis of elemental analysis, electrical conductance, room temperature magnetic susceptibility measurements, spectral and thermal studies. The electrical conductance studies of the complexes in methanol solution at 10(-3) M concentration indicate their non-electrolytic nature. Room temperature magnetic susceptibility measurements are indicative of an octahedral geometry for Co(II) and Ni(II) complexes. Electronic spectra of the complexes show intra-ligand, charge transfer and the crystal field transitions, which are supportive of the proposed octahedral geometries of the complexes. The thermal analysis data of the complexes indicate the presence of crystallization water. The antibacterial and antifungal activities of the complexes have been studied again some of the pathogenic bacteria and fungi. The cup-plate method has been used to study the antibacterial activity of the compounds against C. diphtheriae, E. coli, S. typhi, S. dysentariae, S. aureus and V. cholerae. The results have been compared against those of controls, which were screened simultaneously. The activity is measured by measuring the diameter of the inhibited zone in millimeters (mm). The antifungal activity of the complexes against Candida albicans and Aspergillus niger has been studied by the tube dilution method. The complexes have been screened for acute oral toxicity in rats. The LD50 values have been determined by the method of Litchfield and Wilcoxon.     

Antiradiation compounds: XXI. Metal ion complexation of bis(methylthio) and methylthio amino derivatives of 1-methylquinolinium-2-dithioacetic acids

With the assumption that the radiation-protective ability (whole body protection of mice) of the bis(methylthio) and methylthio amino derivatives of the 1-methylquinolinium-2-dithioacetic acids may be due to complexation of copper or zinc ions in vivo, the ability of these compounds to form stable metal complexes has been observed. Metal ion stability constants have been determined for three of the compounds with Al(III), Cu(II), Fe(III), and Zn(II) ions, and stabilities somewhat larger than those for simple peptides were found. Structures of the Cu(II) and Fe(III) complexes are proposed, based on elemental analyses and infrared absorption. The Cu(II) complexes are 1:1 ligand:metal structures that precipitated as double salts with CuCl2, and the Fe(III) complexes are 2:1 structures in which the ligands incorporated an additional sulfur atom.     

Antimicrobial and antioxidant activities of new metal complexes derived from (E)-3-((5-phenyl-1,3,4-oxadiazol-2-ylimino)methyl)naphthalen-2-ol

(E)-3-((5-phenyl-1,3,4-oxadiazol-2-ylimino)methyl)naphthalen-2-ol (LH) has been synthesized and used as a ligand for the formation of V(IV), Cr(III), Mn(II), Co(II), Ni(II), and Cu(II) complexes. The chemical structures were characterized using different spectroscopic methods. The elemental analyses revealed that the complexes have the general formula [ML₂(H₂O)₂] [where M?=?Mn(II), Co(II), and Cu(II)], while the Cr(III) complex has the formula [CrL₂(H₂O)₂]Cl, V(IV) complex has the formula [VO₂L₂], and Ni(II) complex has the formula [NiL₂]. The molar conductance data revealed that all the metal chelates except the Cr(III) are non-electrolytes. From the magnetic susceptibility measurement and UV–Visible spectra, it is found that the structures of Cr(III), Mn(II), Co(II), and Cu(II) complexes are octahedral, V(IV), complex is square pyramid and Ni(II) complex is square planar. The stability of the prepared complexes was studied theoretically using density function theory. The total energy for the complexes was calculated and it was shown that the copper complex is the most stable. Complexes were tested against selected types of microbial organisms and showed significant activities. The free radical scavenging activity of metal complexes have been determined by their interaction with the stable DPPH-free radicals. All the compounds have shown encouraging antioxidant activities.     

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.     

Antimicrobial,DNA cleavage,and antioxidant properties of new series of metal(II) complexes derived from naphthofuran-2-carbohydrazide Schiff base: synthesis and physico-chemical studies

Metal complexes of the type [NiL₂Cl₂]·H₂O and ML₂Cl₂ [M = Co(II), Cu(II), Cd(II), Zn(II), and Hg(II)] where L = Schiff base, derived from condensation of naphthofuran-2-carbohydrazide and 2-chloro-3-formylquinoline have been synthesized. The chelation of the complexes have been inferred through elemental analyses, IR, electronic mass, ¹H NMR, ESR spectral data, magnetic and thermal studies. The measured low molar conductance values in DMF indicate the complexes to be non-electrolytic in nature. The cyclic voltammetric investigation suggested that, the Cu(II) complex is of single electron transfer quasi-reversible nature. The free ligand and its complexes have been evaluated for their in vitro antibacterial and antifungal activities by minimum inhibitory concentration method. The influence of DNA cleavage on all the complexes was analyzed by agarose gel electrophoresis method. The free ligand with its complexes has been studied for their antioxidant activity by DPPH method. The results of bioassay revealed that, the metal complexes are active than the free ligand and their biological activity increases on complexation.