Antibacterial cobalt(II), nickel(II) and zinc(II) complexes of nicotinic acid-derived Schiff-bases

Nicotinic acid derived Schiff bases and their transition metal [cobalt(II), nickel(II) and zinc(II)] complexes have been prepared and characterized by physical, spectral and analytical data. The Schiff bases act as deprotonated tridentate ligands for the complexation of the above mentioned metal ions. These complexes, possessing the general formula [M(L)2] [where M = Co(II), Ni(II) and Zn(II) and L = HL1-HL4] showed an octahedral geometry of the metal ions. For determining the effect of metal ions upon chelation, the Schiff bases and their complexes have been screened for antibacterial activity against several pathogenic strains of Escherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa. The new metal derivatives reported here were more bactericidal against one or more bacterial species as compared to the uncomplexed Schiff bases.     

EPR non-detectable copper in pyridoxal biogenic amine Schiff base complexes.

Schiff bases formed with octopamine, pyridoxal and pyridoxal phosphate react with copper ions to give various pH-dependent species. The outstanding feature of these complexes is their absence of EPR spectra at physiological pH values. We propose dimeric dipolar coupled structures for the EPR non-detectable copper complexes, involving hydroxyde anions and vitamin B-6 Schiff bases. These results establish that EPR non-detectable copper in enzymes may arise from dipolar coupling between metal ions involved in Schiff base type complexes.     

Synthesis and characterization of a series of new mixed ligand complexes of manganese(III), iron(III), nickel(II), copper(II) and zinc(II) with schiff bases of N,N-diethylamino-dithiocarbamate as ligands

Twenty new bioactive complexes of Mn(III), Fe(III), Ni(II), Cu(II) and Zn(II) have been prepared containing Schiff bases of N,N-diethylaminodithio- carbamate as ligands. These complexes have been characterized by elemental analyses, IR and UV-Vis spectroscopy as well as by magnetic susceptibility measurements. The spectra of the complexes suggest that the ligands are coordinated to the metal ions via the sulfur atoms of the dithiocarbamato group.     

Biological activity of some schiff bases and their metal complexes

Schiff bases derived from salicylaldehyde and 2-substituted aniline and their metal chelates with Cu(II), Ni(II), and Co(II) ions were synthesized and screened for the antiinflammatory and antiulcer activity. The compound salicylidene anthranilic acid (SAA) was found to possess the antiinflammatory and antiulcer activity. The copper complexes showed an increased antiulcer activity. The SAA is perhaps acting by influencing prostaglandin biosynthesis.     

Antibacterial cobalt (II), copper (II), nickel (II) and zinc (II) complexes of mercaptothiadiazole--derived furanyl, thienyl, pyrrolyl, salicylyl and pyridinyl Schiff bases

A series of Co (II), Cu (II), Ni (II) and Zn (II) complexes of mercaptothiadiazole-derived furanyl, thienyl, pyrrorlyl, salicylyl and pyridinyl Schiff bases were synthesized, characterized and screened for their in vitro antibacterial activity against four Gram-negative, Escherichia coli, Pseudomonas aeruginosa, Salmonella typhi and Shigella fexneri, and two Gram-positive; Bacillus subtilis and Staphylococcus aureous bacterial strains. The results of these studies show the metal complexes to be more antibacterial as compared to the prepared un-complexed Schiff bases.     

Antibacterial Schiff bases of oxalyl-hydrazine/diamide incorporating pyrrolyl and salicylyl moieties and of their zinc(II) complexes

Schiff bases derived from oxaldiamide/oxalylhydrazine and pyrrol-2-carbaldehyde, or salicylaldehyde respectively, as well as their Zn(II) complexes have been prepared and tested as antibacterial agents. These Schiff bases function as tetradentate ligands, forming octahedral Zn(II) complexes. The ketonic form for the diamide derived Schiff base and the enolic form of the hydrazide derived Schiff base were the preferred tautomers for coordination of the metal ions. The title compounds and their Zn(II) derivatives were evaluated for antibacterial activity against several bacterial strains which easily develop resistance to classical antibiotics, such as Escherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa. Some of them showed promising biological activity in inhibiting the growth of such organisms.     

Independent and mutual interactions of copper(II) and zinc(II) ions with phytic acid

The interactions of phytic acid with Cu(II) and Zn(II) ions were examined as functions of metal ion concentrations and pH. Cu(II) ion-selective potentiometric and electron spin resonance (ESR) experiments provide strong evidence for the binding of Cu(II) ions to the phytic acid molecule at low pH (2.4–3.4) values. The relative stabilities of the copper and zinc phytates at low pH values were found to be very similar. For systems with metal ion:phytic acid molar ratios of 1:1–4:1 and 5:1–6:1 and pH values in the 3.4–5.9 and 3.4–5.0 ranges, respectively, Zn(II) ions were found to form complexes with phytic acid that were more stable than those of Cu(II) ions with phytic acid. The phytic acid molecule, however, was found to accommodate Cu(II) ions more readily than Zn(II) ions. For example, in systems containing equal amounts of Cu(II) and Zn(II) ions, 2 Zn(II) ions and 2, 3, 4, or 4.5 Cu(II) ions were found per phytic acid molecule depending upon metal ion:phytic acid molar ratios in the systems and pH. Total metal ion:phytic acid molar ratios and pH affected resultant metal ion solubilities and were factors influencing the effects of Zn(II) and Cu(II) ions on the binding of each other by phytic acid. Zn(II) and Cu(II) ions were observed to potentiate the binding of each other by phytic acid in some systems and compete with each other for phytate binding sites in others.     

Carbonic Anhydrase Inhibitors. Schiff Bases of some Aromatic Sulfonamides and Their Metal Complexes: Towards More Selective Inhibitors of Carbonic Anhydrase Isozyme IV

Abstract

Reaction of three aromatic sulfonamides possessing a primary amino group, i.e., sulfanilamide, homosulfanilamide and p-aminoethyl-benzenesulfonamide with heterocyclic and aromatic aldehydes afforded a series of Schiff bases. Metal complexes of some of these Schiff bases with divalent transition ions such as Zn(II), Cu(II), Co(II) and Ni(II) have also been obtained. The new compounds were assayed as inhibitors of three isozymes of carbonic anhydrase (CA). Several of the new compounds showed a modest selectivity for the membrane-bound (bovine) isozyme CA IV (bCA IV) as compared to the cytosolic human isozymes hCA I and II, in contrast to classical inhibitors which generally possess a 17-33 times lower affinity for bCA IV. This greater selectivity toward bCA IV is due mainly to a slightly decreased potency against hCA II relative to classical inhibitors. However, metal complexes of these Schiff bases possessed an increased affinity for hCA II, being less inhibitory against bCA IV. The first type of compounds reported here (i.e., the Schiff bases of aromatic sulfonamides with heterocyclic aldehydes) might thus lead to the development of low molecular weight isozyme specific CA IV inhibitors. The difference in affinity for the three isozymes of the inhibitors reported by us here is tentatively explained on the basis of recent X-ray crystallographic studies of these isozymes and their adducts with substratesiinhibitors     

Antibacterial Schiff Bases of Oxalyl-hydrazine/diamide Incorporating Pyrrolyl and Salicylyl Moieties and of Their Zinc(II) Complexes

Schiff bases derived from oxaldiamide/oxalylhydrazine and pyrrol-2-carbaldehyde, or salicylaldehyde respectively, as well as their Zn(II) complexes have been prepared and tested as antibacterial agents. These Schiff bases function as tetradentate ligands, forming octahedral Zn(II) complexes. The ketonic form for the diamide derived Schiff base and the enolic form of the hydrazide derived Schiff base were the preferred tautomers for coordination of the metal ions. The title compounds and their Zn(II) derivatives were evaluated for antibacterial activity against several bacterial strains which easily develop resistance to classical antibiotics, such as Escherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa. Some of them showed promising biological activity in inhibiting the growth of such organisms.     

Differential pulse polarography: a method for the direct study of biosorption of metal ions by live bacteria from mixed metal solutions

The technique of differential pulse polarography is shown here to be applicable to the monitoring directly the biosorption of metal ions from solution by live bacteria from mixed metal solutions. Biosorption of Cd(II), Zn(II) and Ni(II) by P. cepacia was followed using data obtained at the potential which is characteristic of the metal ion in the absence and presence of cells. Hepes buffer (pH 7.4, 50 mM) was used as a supporting electrolyte in the polarographic chamber and metal ion peaks in the presence of cells of lower amplitude were obtained due to metal-binding by the cells. Well defined polarographic peaks were obtained in experiments involving mixtures of metal ions of Cd(II)-Zn(II), Cu(II)-Zn(II), Cu(II)-Cd(II) and Cd(II)-Ni(II). Biosorption of Cd(II), Zn(II) increased with solution pH. The method was also tested as a rapid technique for assessing removal of metal ions by live bacteria and the ability of the polarographic technique in measuring biosorption of metal ions from mixed metal solutions is demonstrated. Cu(II) was preferentially bound and removal of metals was in the order Cu(II) > Ni(II) > Zn(II), Cd(II) by intact cells of P. cepacia. This revised version was published online in August 2006 with corrections to the Cover Date.     

The oxidation of Schiff bases of pyridoxal and pyridoxal phosphate with amino acids by manganous ions and peroxidase

1. Oxygen was taken up rapidly when pyridoxal or pyridoxal phosphate was added to mixtures of pea-seedling extracts and Mn(2+) ions. 2. The increases in total oxygen uptake were proportional to the pyridoxal or pyridoxal phosphate added and were accompanied by the disappearance of these compounds. 3. In addition to Mn(2+) ions, the reactions depended on two factors in the extracts, a thermolabile one in the non-diffusible material and a thermostable one in the diffusate; these factors could be replaced in the reactions by horse-radish peroxidase (donor-hydrogen peroxide oxidoreductase, EC 1.11.1.7) and amino acids respectively. 4. When pyridoxal phosphate was added to mixtures of amino acids and Mn(2+) ions oxygen uptake was rapid after a lag period of 30-90min.; the lag period was shortened to a few minutes by peroxidase, particularly in the presence of traces of p-cresol, or by light. 5. When pyridoxal replaced pyridoxal phosphate relatively high concentrations were required and peroxidase had only a small activating effect. 6. Pyridoxal or pyridoxal phosphate disappeared during the reactions and carbon dioxide and ammonia were formed. 7. With phenylalanine as the amino acid present, benzaldehyde was identified as a reaction product. 8. It is suggested that the reactions are oxidations of the Schiff bases formed between pyridoxal or pyridoxal phosphate and amino acids, mediated by a manganese oxidation-reduction cycle, and resulting in oxidative decarboxylation and deamination of the amino acids.     

Construction a hybrid biosorbent using Scenedesmus quadricauda and Ca-alginate for biosorption of Cu(II), Zn(II) and Ni(II): kinetics and equilibrium studies

The potential use of the immobilized fresh water algae (in Ca-alginate) of Scenedesmus quadricauda to remove Cu(II), Zn(II) and Ni(II) ions from aqueous solutions was evaluated using Ca-alginate beads as a control system. Ca-alginate beads containing immobilized algae were incubated for the uniform growth at 22 degrees C for 5d ays. Adsorption of Cu(II), Zn(II) and Ni(II) ions on the immobilized algae showed highest values at around pH 5.0. Adsorption of Cu(II), Zn(II) and Ni(II) ions on the immobilized algae increased as the initial concentration of metal ions increased in the medium. The maximum adsorption capacities of the immobilized algal biosorbents for Cu(II), Zn(II) and Ni(II) were 75.6, 55.2 and 30.4 mg/g (or 1.155, 0.933 and 0.465 mmol/g) biosorbent, respectively. When the heavy metal ions were in competition, the amounts of adsorbed metal ions were found to be 0.84 mol/g for Cu(II), 0.59 mol/g for Ni(II) and 0.08 mol/g for Zn(II), the immobilised algal biomass was significantly selective for Cu(II) ions. The adsorption-equilibrium was also represented with Langmuir, Freundlich and Dubinin-Radushkevich adsorption isotherms. The adsorption of Cu(II), Zn(II) and Ni(II) ions on the immobilized algae followed second-order kinetic.     

Antibacterial Co(II), Cu(II), Ni(II) and Zn(II) complexes of thiadiazole derived furanyl,thiophenyl and pyrrolyl Schiff bases

2-Amino-1,3,4-thiadiazole undergoes a condensation reaction with furane-, thiophene- and pyrrole-2-carboxaldehyde to form tridentate NNO, NNS and NNN donor Schiff bases. These Schiff bases were further used to obtain complexes of the type [M(L)2]X, where M = Co(II), Cu(II), Ni(II) or Zn(II), L = L1, L2 or L3 and X = Cl2. The new compounds described here have been characterized by their physical, spectral and analytical data, and have been screened for antibacterial activity against several bacterial strains such as Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa. The antibacterial potency of the Schiff bases increased upon chelation/complexation in comparison to the uncomplexed Schiff bases against the tested bacterial species thus, opening new approaches to find new ways in the fight against antibiotic-resistant strains.     

Antibacterial Co(II), Cu(II), Ni(II) and Zn(II) Complexes of Thiadiazole Derived Furanyl,Thiophenyl and Pyrrolyl Schiff Bases

2-Amino-1,3,4-thiadiazole undergoes a condensation reaction with furane-, thiophene- and pyrrole-2-carboxaldehyde to form tridentate NNO, NNS and NNN donor Schiff bases. These Schiff bases were further used to obtain complexes of the type [M(L) 2] X, where M=Co(II), Cu(II), Ni(II) or Zn(II), L=L 1, L 2 or L 3 and X=Cl 2. The new compounds described here have been characterized by their physical, spectral and analytical data, and have been screened for antibacterial activity against several bacterial strains such as Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa. The antibacterial potency of the Schiff bases increased upon chelation/complexation in comparison to the uncomplexed Schiff bases against the tested bacterial species thus, opening new approaches to find new ways in the fight against antibiotic-resistant strains.     

Antimicrobial metal-based thiophene derived compounds

A novel series of thiophene derived Schiff bases and their transition metal- [Co(II), Cu(II), Zn(II), Ni(II)] based compounds are reported. The Schiff bases act as tridentate ligands toward metal ions via azomethine-N, deprotonated-N of ammine substituents and S-atom of thienyl moiety. The synthesized ligands along with their metal complexes were screened for their in vitro antibacterial activity against six bacterial pathogens (Escherichia coli, Shigella flexneri, Pseudomonas aeruginosa, Salmonella typhi, Staphylococcus aureus and Bacillus subtilis) and for antifungal activity against six fungal pathogens (Trichophytonlongifusus, Candida albicans, Aspergillus flavus, Microsporum canis, Fusarium solani and Candida glabrata). The results of antimicrobial studies revealed the free ligands to possess potential activity which significantly increased upon chelation.     

Study of the biosorption of different heavy metal ions onto Kraft lignin

The ability of Kraft lignin, a waste product of paper production, for removing copper, zinc, cadmium and chromium ions from water was investigated. The studies were conducted by a batch method to determine equilibrium parameters. The adsorbed heavy metal ions followed the order: Cr(VI) ? Cd(II) > Cu(II) > Zn(II). The influence of other ions such as Ni(II), Cd(II) and Pb(II), on Cu(II) adsorption by Kraft lignin was evaluated. Obtained results support the idea that adsorption behaviour of heavy metal ions have to be perceived from the aspect of possible influence of interfering ion species.     

Metal-based biologically active azoles and β-lactams derived from sulfa drugs

Metal complexes of Schiff bases derived from sulfamethoxazole (SMZ) and sulfathiazole (STZ), converted to their β-lactam derivatives have been synthesized and experimentally characterized by elemental analysis, spectral (IR, ¹H NMR, ¹³C NMR, and EI-mass), molar conductance measurements and thermal analysis techniques. The structural and electronic properties of the studied molecules were investigated theoretically by performing density functional theory (DFT) to access reliable results to the experimental values. The spectral and thermal analysis reveals that the Schiff bases act as bidentate ligands via the coordination of azomethine nitrogen to metal ions as well as the proton displacement from the phenolic group through the metal ions; therefore, Cu complexes can attain the square planner arrangement and Zn complexes have a distorted tetrahedral structure. The thermogravimetric (TG/DTG) analyses confirm high stability for all complexes followed by thermal decomposition in different steps. In addition, the antibacterial activities of synthesized compounds have been screened in vitro against various pathogenic bacterial species. Inspection of the results revealed that all newly synthesized complexes individually exhibit varying degrees of inhibitory effects on the growth of the tested bacterial species, therefore, they may be considered as drug candidates for bacterial pathogens. The free Schiff base ligands (1–2) exhibited a broad spectrum antibacterial activity against Gram negative Escherichia coli, Pseudomonas aeruginosa, and Proteus spp., and Gram positive Staphylococcus aureus bacterial strains. The results also indicated that the β-lactam derivatives (3–4) have high antibacterial activities on Gram positive bacteria as well as the metal complexes (5–8), particularly Zn complexes, have a significant activity against all Gram negative bacterial strains. It has been shown that the metal complexes have significantly higher activity than corresponding ligands due to chelation process which reduces the polarity of metal ion by coordinating with ligands.     

DNA structural transitions induced by divalent metal ions in aqueous solutions

Using methods of IR spectroscopy, light scattering, gel-electrophoresis DNA structural transitions are studied under the action of Cu2+, Zn2+, Mn2+, Ca2+ and Mg2+ ions in aqueous solution. Cu2+, Zn2+, Mn2+ and Ca2+ ions bind both to DNA phosphate groups and bases while Mg2+ ions-only to phosphate groups of DNA. Upon interaction with divalent metal ions studied (except for Mg2+ ions) DNA undergoes structural transition into a compact form. DNA compaction is characterized by a drastic decrease in the volume occupied by DNA molecules with reversible formation of DNA dense particles of well-defined finite size and ordered morphology. The DNA secondary structure in condensed particles corresponds to the B-form family. The mechanism of DNA compaction under Mt2+ ion action is not dominated by electrostatics. The effectiveness of the divalent metal ions studied to induce DNA compaction correlates with the affinity of these ions for DNA nucleic bases: Cu2+>Zn2+>Mn2+>Ca2+>Mg2+. Mt2+ ion interaction with DNA bases (or Mt2+ chelation with a base and an oxygen of a phosphate group) may be responsible for DNA compaction. Mt2+ ion interaction with DNA bases can destabilize DNA causing bends and reducing its persistent length that will facilitate DNA compaction.     

Determination of photostability and photodegradation products of moxifloxacin in the presence of metal ions in solutions and solid phase. Kinetics and identification of photoproducts

Photostability of moxifloxacin (MOXI) after UVA irradiation in solutions and solid phase, with and without participation of Cu(II), Zn(II), Al(III), and Fe(III) was tested. The studies were carried out by the TLC-densitometric method and LC-MS/MS method. Elaborated and validated chromatography-densitometric method was used for assaying. It was shown that the number and type of photoproducts depend on the environment and type of the metal ion. The studied ions enhanced the degradation of MOXI in solutions, and the influence of Cu(II) and Fe(III) ions was higher than that of Zn(II) and Al(III) ions. In solid phase, in contrast to solutions, all metal ions decreased the photodegradation, however the influence of ions, Al(III) and Zn(II), was weaker than that of Cu(II) and Fe(III) ions. Identification of the degradation products performed with LC-MS/MS and (1)H NMR identified them as: 1-cyclopropyl-6-fluoro-7-amino-8-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid, 1-cyclopropyl-6-fluoro-8-methoxy-4-oxo-7-(2-oxo-octahydro-6H-pyrrolo[3,4-b]pyridine-6-yl)-1,4-dihydroquinoline-3-carboxylic acid, 7-[3-hydroxyamino-4-(2-carboxyethyl)pyrrolidin-1-yl]-1-cyclopropyl-6-fluoro-8-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid.     

Influence of metal ions on thermal aggregation of bovine serum albumin: Aggregation kinetics and structural changes

Metal ions are implicated in protein aggregation processes of several neurodegenerative pathologies. In this work the effects of Cu(II) and Zn(II) ions on heat-induced structural modifications of bovine serum albumin (BSA) were studied, with the aim of delineating the role of these ions in the early stages of proteins aggregation kinetics. A joint application of different techniques was used. The aggregate growth was followed by dynamic light scattering measurements, whereas the conformational changes occurring in the protein structure were monitored by Raman and IR spectroscopy. Both in absence and in presence of metal ions, heating treatment gave rise to β-structures to the detriment of α-helix conformation of BSA. The temperature of protein unfolding was not sensitively affected by the presence of Zn(II) or Cu(II) ions; on the contrary, only Zn(II) ions slightly promoted the heat-induced aggregation of the protein, since bigger aggregates were formed in their presence. The different efficacy of the Cu(II) and Zn(II) ions in promoting the BSA aggregation were highlighted by Raman measurements, assessing the role of His residues in metal binding. A distinct polypeptide folding of the two metal-BSA systems takes place, since the predominant mode of metal binding depends on metal. In particular, in Zn-BSA the metal coordination involves the imidazole N_τ atom of His which can promote inter-molecular cross-linking.