Solvent effects on the stability of nifuroxazide complexes with cobalt(II), nickel(II) and copper(II) in alcohols

A spectrophotometric study of the complexation of nifuroxazide with cobalt(II), nickel(II) and copper(II) was carried out in different alcohols. The formation of a complex in each case is reported and their stability constants have been calculated. For a given solvent, the stability of the complexes increases from cobalt to copper. In the case of copper(II), the stability varies as an inverse function of the dielectric constant of the solvent. A possible structure of the complex is proposed.     

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).     

Copper(II) Schiff-base complexes and apoglobin stability.

N,N'-Propylene-bis-(N-salicylidene)copper(II) (Cu(Salprn)) explicitly stabilizes apomyoglobin. The optical spectrum of this copper(II) Schiff-base complex of apomyoglobin arises from the electronic excitations of pi *-O-Salprn-->dx2-y2 and N-Salprn-->dx2-y2. Shifts of these transitions with respect to those of the parent complex may be a consequence of hydrophobic solvatochromism or binding of an additional ligand. ESR parameters imply no change in the identity of the first coordination sphere around the copper, while hydrophobic solvatochromism cannot be excluded. Combination of copper(II) Schiff-base complex with apomyoglobin does not inhibit the ability of apomyoglobin to extract hemin from the main component of Glycera dibranchiata hemoglobin. Hemin replaces the copper complex, and the value of the apparent first-order rate constant varies with time. The mechanism involves dissociative and associative interchange pathways. Values of rate constants for transfer of hemin to copper(II) Schiff-base apomyoglobin complex, as well as the change of concentration with time are evaluated.     

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.     

The complex formation of copper(II) with GHL and HSA

The formation constants for complexes of copper(II) with GHL have been determined by means of pH titrations and ESR spectroscopy in aqueous solutions. GHL has an extremely high affinity for copper(II) and forms very stable 1:1 complexes and a comparatively weak 1:2 complex. The ? amino group of GHL seems not to be involved in complex formation as can be deducted from both equilibrium constants and ESR spectroscopy. The ternary system copper(II)-GHL-HSA was investigated by ESR spectroscopy and optical absorption spectroscopy in aqueous solution at physiological pH (7.4). At equimolar concentrations, copper(II), HSA and GHL form a ternary complex.     

Unusual dinuclear copper(II) and nickel(II) complexes of a novel Schiff base deriving from 2-aminoethanol

It is generally accepted that copper(II) complexes involving 2-aminoethanol or a Schiff base deriving from this aminoalcohol display a tetranuclear structure with a Cu₄O₄ ‘cubane’ core. Using a Schiff base obtained by reacting 2′-aminoacetophenone with 2-aminoethanol, we have prepared copper(II) and nickel(II) complexes whose properties are fully consistent with a dinuclear structure. The copper complex is characterized by a low antiferromagnetic interaction.     

Synthesis and structural analysis of copper(II) cysteine complexes

This report describes the synthesis and structural analysis of stable copper(II) cysteine complexes. Pale pink copper(II) cysteine complexes were synthesized in mole ratios of 1:2, 1:4, and 1:6 of copper(II):cysteine in ethanol. Infrared spectroscopy and X-ray absorption spectroscopy confirmed that copper(II) binding occurred via the thiol ligand of cysteine. XANES analysis showed that the oxidation state of copper remained as copper(II) and the local atomic geometry was similar in all of the cysteine complexes. The EXAFS data indicate that the copper(II) cysteine complexes are forming ring type structures with sulfur ligands from the cysteines acting as bridging ligands. X-ray diffraction revealed that the copper(II) cysteine complexes formed monoclinic cells with maximum crystallinity found in the 1:4 copper(II):cysteine complex.     

Copper(II)ethylenediaminetetraacetate does disproportionate superoxide

The superoxide dismutase (SOD) mimetic reactivity of Cu(II)EDTA was studied in the pH range of 6.0 to 8.0. Cu(II)EDTA disproportionated superoxide without inhibiting superoxide production by xanthine oxidase, as a result of bonding sites becoming available on the copper complex with increasing acidity. This disproportionation by Cu(II)EDTA is offered as evidence that the addition of EDTA to biological preparations for the purpose of complexing copper and thereby inhibiting copper-dependent superoxide disproportionation and promoting superoxide-dependent reactions is not a valid practice.     

Tris-ruthenium(II)/copper(II) multimetallic porphyrin: Synthesis, characterization, DNA binding and supercoiled DNA photocleavage studies

The porphyrin, meso-5-(pentafluorophenyl)-10, 15, 20-tris(4-pyridyl)porphyrin has been used to synthesize two new metalloporphyrin complexes. Insertion of copper(II) into the porphyrin center gives the copper(II) porphyrin. Coordination of three [Ru(bipy)₂Cl]⁺ moieties (where bipy = 2,2′-bipyridine) to the pyridyl nitrogens of the copper(II) porphyrin gives the target complex. Electronic transitions associated with the copper(II) porphyrin and the triruthenium copper(II) porphyrin include an intense Soret band and a less intense Q-band in the visible region of the spectrum. An intense π-π∗ transition in the UV region associated with the bipyridyl groups and a metal to ligand charge transfer (MLCT) band appearing as a shoulder to the Soret band are observed for the ruthenated copper(II) porphyrin. Electrochemical properties associated with the multimetallic complex include a redox couple in the cathodic region with E_1/2 = −0.86 V versus Ag/AgCl attributed to the porphyrin and a redox couple in the anodic region E_1/2 = 0.88 V versus Ag/AgCl due to the Ru^III/II couple. DNA titrations indicate the triruthenium copper(II) porphyrin interacts with DNA potentially through a groove binding mechanism. Irradiation of aqueous solutions of the target complex and supercoiled DNA at a 10:1 base pair to complex ratio with visible light above 400 nm indicates that the complex causes nicking of the DNA helix.     

Synthesis, structural and corrosion inhibition studies on cobalt(II), nickel(II), copper(II) and zinc(II) complexes with 2-acetylthiophene benzoylhydrazone

Cobalt(II), nickel(II), copper(II) and zinc(II) complexes with 2-acetylthiophene benzoylhydrazone have been synthesized and characterized by elemental analyses, magnetic susceptibility measurements, electronic, IR, NMR and ESR spectral techniques. The molecular structures of ligand and its copper(II) complex have been determined by single crystal X-ray diffraction technique. The Cu(II) complex possesses a CuN₂O₂ chromophore with a considerable delocalization of charge. The structure of the complex is stabilized by intermolecular π–π stacking and C–H?π interactions. Hatbh acts as a monobasic bidentate ligand in all the complexes bonding through a deprotonated C–O⁻ and >CN groups. Electronic spectral studies indicate an octahedral geometry for the Ni(II) complex while square planar geometry for the Co(II) and Cu(II) complexes. ESR spectrum of the Cu(II) complex exhibits a square planar geometry in solid and in DMSO solution. The trend g_|| > g_⊥ > 2.0023 indicates the presence of an unpaired electron in the d_x²-y² orbital of Cu(II). The electro-chemical study of Cu(II) complex reveals a metal based reversible redox behavior. The Ni(II) complex shows exothermic multi-step decomposition pattern of the bonded ligand. The ligand and its most of the metal complexes show appreciable corrosion inhibition properties for mild steel in 1 M HCl medium. [Co(atbh)₂] complex exhibited the greatest impact on corrosion inhibition among the other compounds.     

Spectroscopic studies on the copper(II) complexes of carnosine

Carnosine complexes with copper(II) ions were studied with magnetic resonance techniques over a wide range of ligand to metal ratios at various pH values. Water proton relaxation rates increased with decreasing carnosine to copper ratios until a molar ratio of 48 was reached. Over the ratio range of 48–2 carnosine molecules per copper ion, the relaxation rate decreased so that in the 2:1 carnosine-copper(II) complex, the water-copper(II) distance was estimated to be 1.92 Å. Proton NMR studies revealed the broadening of imidazole proton lines at high mole ratios followed by other histidyl protons as the ratio decreased. The β-alanyl methylene protons were the last to be broadened by the addition of copper(II) ions. Carbon to copper(II) distances were determined for the carnosine to copper mole ratios of 500:1 and 5000:1. EPR spectra obtained at 93°K revealed the probable existence of four carnosine imidazoles as the sole coordinated ligands to copper(II) at high dipeptide-to-metal ratios (>10). At mole ratios below four, nuclear hyperfine lines characteristic of both monomeric and dimeric carnosine-copper(II) forms were observed. These results reveal that imidazole from carnosine is the sole ligand contributed to copper(II) for coordination over the pH range 5 to 7 at high carnosine to copper(II) ratios     

DNA-copper (II) complex and the DNA conformation

Spectrophotometric, sedimentation, infrared, optical rotatory dispersion (ORD), and circular dichroism (CD) methods have been used to demonstrate the structural changes in DNA induced by the interaction of copper(II) with bases and to elucidate the complex binding sites. As shown by the electrolyte-induced reversion (addition of salts) of temperature-denatured copper DNA the effectiveness of re-formation of the double-stranded structure depends on the temperature, copper(II) ion concentration, and on the base composition of the DNA. Exposure of heat-denatured copper DNA to higher temperatures decreases the reversion effect on addition of electrolyte. The results indicate that a greater fraction with a cooperative transition appears on heating DNA to 80 or 100°C at a Cu²⁺/DNA-P ratio of 2 : 1 than at a Cu²⁺/DNA-P ratio of 1 : 1. With AT-rich copper DNA, reversion to the native DNA structure was not observed. Selective methylation of guanine residues in DNA also affects the electrolyte-induced reversion, indicating the importance of GC pairs for copper(II) binding and the reversion to the native structure. Temperature-denatured copper DNA shows an increased sedimentation coefficient Which decreases again after electrolyte-induced reversion. This change in s is reduced by selective methylation of DNA. Complex formation between copper(II) and the bases is accompanied by a conformational change of the DNA double-helical structure as demonstrated by ORD and CD experiments. The ORD profile of GC-rich DNA is much more affected by copper(II) than that of AT-rich ones. Even at very low copper(II) concentrations, e.g., at 0.02 and 0.2 Cu²⁺/DNA-P, the ORD and CD measurements exhibit conformational changes of the DNA secondary structure at room temperature. By comparing the infrared spectra of deoxynucleosides with that of DNA of different GC content it has been shown that both guanine and cytosine are involved in the formation of the complex of copper(II) with DNA. N-7 and O at C-6 in guanine and N-3 as well as O of C-2 in cytosine are discussed as the most probable binding sites in DNA. A binding model for the coordination of the copper(II) ion between guanine and cytosine of the opposite strands is suggested. The results are in good agreement with the assumptions and predictions made by Eichhorn and Clark about the complexing of copper(II) with DNA. The recent proposal made by Schreiber and Daune about an interaction of the type guanine–Cu²⁺–guanine cannot be excluded as an additional kind of coordination of copper(II) in DNA.     

Spectroscopic studies on the copper(II)—Inosine system

Interactions of inosine derivatives with copper(II) were studied in the pH range 1.4–13 in 50% H₂O-50% DMSO solution. The distinct pH dependence of the optical spectra observed in copper(II)-inosine complexes are correlated to their respective EPR changes as a function of pH. It was concluded that a simple 1:1 complex of copper(II)-inosine is formed in the pH range 1.4–5.0 and bis complexes are present in the pH 5.0–6.2 region solutions of inosine and Cu(II). From pH 6.2 to 7.8 a diamagnetic, hydroxybridged complex dominates. At pH 7.8–9.2 an insoluble, oxybridged species is formed in addition to the soluble paramagnetic Cu(NI)₄ complex. Starting from pH 9.1 the N-polymeric complex is formed which is stable up to pH 12.5, and above pH 12.5 the only species is the Cu(ribose)₂ complex.     

Copper(II) and zinc(II) complexes of the peptides Ac-HisValHis-NH2 and Ac-HisValGlyAsp-NH2 related to the active site of the enzyme CuZnSOD

Copper(II) and zinc(II) complexes of the peptides Ac-HisValHis-NH2 and Ac-HisValGlyAsp-NH2 related to the active site of the enzyme CuZnSOD were studied by potentiometric and spectroscopic (UV-Vis, CD and EPR) techniques. The results reveal that both ligands have effective metal binding sites, but the tripeptide is a much stronger complexing agent than the tetrapeptide. The formation of a macrochelate via the coordination of the imidazolyl residues is suggested in the copper(II)-Ac-HisValHis-NH2 system in the acidic pH range, while a 4N complex predominates at physiological pH. The interaction of Ac-HisValHis-NH2 with zinc(II) results in the formation of a precipitate indicating polynuclear complex formation. Both copper(II)-Ac-HisValHis-NH2 and copper(II)-HisValHis systems exhibit catalytic activity toward the dismutation of superoxide anion at physiological pH, but the saturated coordination sphere of the metal ions in both systems results in low reactivity as compared to the native enzyme.     

A new dinuclear biphenylene bridged copper(II) complex: DNA cleavage under hydrolytic conditions

The dinucleating ligand, tpbpd (tetrapyridyl biphenylenediamine) forms a dicopper complex with practically no electronic coupling between the two copper (II) centres. The EPR spectrum of the complex is consistent with coordination of each copper ion to two nitrogens of the binuclear ligand. Cyclic voltammogram of the complex also reveals that the two copper (II) centres have identical ligating environment. This dimeric copper (II) complex is found to be a very efficient catalyst for the cleavage of plasmid DNA in the absence of any added cofactor. The amount of conversion of supercoiled form (Form I) of plasmid to the open circular form (Form II) depends on the concentration of the complex as well as the duration of incubation of the complex with DNA. The maximum rate of conversion of the supercoiled form to the nicked circular form at pH 7.5 in the presence of 150 microM of the complex is found to be 1.8 x 10(-3) s(-1).     

Enhancement of cytotoxicity of bleomycin by dithiocarbamates: formation of bis(dithiocarbamato) cu(II).

Properties of the reactions of dithiocarbamates and their Cu(II) or Fe(III) complexes with Ehrlich cells were determined and related to their effects on the inhibition of cell proliferation caused by bleomycin and Cu bleomycin. In complete culture medium containing Eagle's minimal essential medium plus Earles salts and 2.5% fetal calf serum, dimethyl- and diethyldithiocarbamates and their copper complexes inhibit cell proliferation and cause cell death. The copper complexes are more effective agents. Ferric tris-diethyldithiocarbamate is also a cytotoxic species. In contrast, when cells are exposed to dimethyldithiocarbamate or its copper complex in Ringer's buffer under metal-restricted condition, washed, and then placed in complete medium, the copper complex is much more active in inhibiting cell growth. The difference is magnified when dihydroxyethyldithiocarbamate and N-methylglucamine dithiocarbamate and their copper complexes are compared in complete media. Incubation of bleomycin or copper bleomycin with Ehrlich cells in Ringer's buffer with or without dimethyldithiocarbamate or bis-dimethyldithiocarbamato Cu(II) leads to no enhancement of cytotoxicity from combinations of agents, except when the two copper complexes are present. Diethyl- or dimethyldithiocarbamate readily extracts copper from Cu(II)bleomycin and iron from Fe(III)bleomycin when ethylacetate is present to remove the tris-dithiocarbamato Fe(III) complex from aqueous solution. When bis-dimethyldithiocarbamato Cu(II) is incubated with Ehrlich cells, copper is released from the complex and bound to high molecular weight and metallothionein fractions. A reductive mode of dissociation of the copper complexes in cells is supported by ESR experiments. Reactions of diethyl- and dimethyldithiocarbamato Cu(II) with thiol compounds demonstrates one possible mechanism of reduction of these complexes.     

Electrochemical study of the complexes of aspartame with Cu(II), Ni(II) and Zn(II) ions in the aqueous medium

The voltammetric behaviours of aspartame in the presence of some metal ions (Cu(II), Ni(II), Zn(II)) were investigated. In the presence of aspartame, copper ions reduced at two stages with quasi-reversible one-electron and, with increasing the aspartame (L) concentration, Cu(II)L(2) complex reduces at one-stage with irreversible two-electron reaction (-0.322 V). Zn(II)-aspartame complex (logbeta=3.70) was recognized by a cathodic peak at -1.320 V. Ni(II)-aspartame complex (logbeta=6.52) is reduced at the more positive potential (-0.87 V) than that of the hydrated Ni(II) ions (-1.088 V). In the case of the reduction of Ni(II) ions, aspartame serves as a catalyst. From electronic spectra data of the complexes, their stoichiometries of 1:2 (metal-ligand) in aqueous medium are determined. The greatness of these logarithmic values is agreement with Irwing-Williams series (NiZn).     

Synthesis and characterization of a new binucleating schiff base macrocycle and its nickel(II) and copper(II) complexes

A new binucleating ligand, m-xyl-bis(3-bae)) and its copper(II) and nickel(II) complexes have been prepared and characterized by various physical techniques. Data for the complexes indicate that they both have square-planar geometries. High resolution ¹H and ¹³C NMR confirm the square-planar geometry of the binuclear nickel(II) complex is maintained in non-coordinating solvents. The magnetic moment of the copper(II) complex is typical of square-planar complexes and the EPR spectrum in solution indicates the absence of any magnetic coupling between metal centers. In addition, both metal complexes display irreversible electrochemical behavior on various electrode surfaces.     

Spontaneous resolution of binary copper(II) complexes with racemic dipeptides: crystal structures of glycyl-L-alpha-amino-n-butyrato copper(II) monohydrate, glycyl-D-valinato copper(II) hemihydrate, and glycyl-L-valinato copper(II) hemihydrate

Copper(II) complexes with glycyl-DL-alpha-amino-n-butyric acid (H2gly-DL-but), glycyl-DL-valine (H2gly-DL-val), glycyl-DL-norleucine (H2gly-DL-norleu), glycyl-DL-threonine (H2gly-DL-thr), glycyl-DL-serine (H2gly-DL-ser), glycyl-DL-phenylalanine (H2gly-DL-phe), and glycyl-L-valine (H2gly-L-val), have been prepared and characterized by IR, powder diffuse reflection, CD and ORD spectra, and magnetic susceptibility measurements, and by single-crystal X-ray diffraction. The crystal structures of the copper complex with H2gly-DL-but, the copper complex with H2gly-DL-val, and [Cu(gly-L-val)]n.0.5nH2O have been determined by a single-crystal X-ray diffraction method. As for the structure of the copper complex with H2gly-DL-but, the configuration around the asymmetric carbon atom is similar to that of [Cu(gly-L-val)]n.0.5nH2O. Therefore it is concluded that the copper complex with H2gly-DL-but is [Cu(gly-L-but)]n.nH2O. On the contrary, as for the structure of the copper complex with H2gly-DL-val, the configuration around the asymmetric carbon atom is different from that of [Cu(gly-L-val)]n.0.5nH2O. Therefore it is concluded that the copper complex with H2gly-dl-val is [Cu(gly-D-val)]n.0.5nH2O. So during the crystallization of the copper(II) complexes with H2gly-DL-but and H2gly-DL-val, spontaneous resolution has been observed; the four complexes have separated as [Cu(gly-D-but)]n.nH2O, [Cu(gly-L-but)]n.nH2O, [Cu(gly-D-val)]n.0.5nH2O, and [Cu(gly-L-val)]n.0.5nH2O, respectively. [Cu(gly-L-but)]n.nH2O is orthorhombic with the space group P2(1)2(1)2(1). [Cu(gly-D-val)]n.0.5nH2O and [Cu(gly-L-val)]n.0.5nH2O are monoclinic with the space group C2. In these complexes, the copper atom is in a square-pyramidal geometry, ligated by a peptide nitrogen atom, an amino nitrogen atom, a carboxyl oxygen atom, and a carboxyl oxygen atom and a peptide oxygen atom from neighboring molecules. So these complexes consist of a two-dimensional polymer chain bridged by a carboxyl oxygen atom and a peptide oxygen atom from neighboring molecules. The axial oxygen atom is located above the basal plane and the side chain of an amino acid is located below it. These polymer chains consist of only one or the other type of optical isomers; no racemic dipeptides are found. Therefore, spontaneous resolution has been observed in the crystallization of copper(II) complexes with H2gly-DL-but and H2gly-DL-val. The crystal structure of [Cu(gly-D-val)]n.0.5nH2O agrees almost completely with that of [Cu(gly-L-val)]n.0.5nH2O, except for the configuration around the asymmetric carbon atom.     

A new copper(II) complex of unsymmetrical tetradentate ligand generated in situ: synthesis and molecular structure

A new copper(II) complex with tetradentate unsymmetrical ligand was prepared by one-pot condensation of methyl-2-pyrrole carboxylate, diethylenetriamine and copper(II) sulfate. The complex was characterized by elemental analysis, electronic and IR spectral, as well as X-ray crystal structure determination. The X-ray structure of the molecule reveals the copper(II) center is in a square planar environment through coordination by two nitrogen atoms of the amine, one amide nitrogen atom and one nitrogen atom of the pyrrole moieties, respectively. The copper(II) complex is neutral due to deprotonation of the amide and pyrrole groups.