Studies on biologically active complexes of cobalt(II) and nickel(II) with dithiooxamide-derived ligands.

A number of cobalt(II) and nickel(II) complexes with novel dithiooxamide ligands derived from precursors such as benzonitrile, benzosulfonamide, benzaldehyde, benzoic acid, and phenol have been synthesized and characterized on the basis of their elemental analysis molar conductance, magnetic moment, H NMR and electronic and IR spectral data. These ligands and their complexes have been screened for their antibacterial activities against bacterial species Staphylococcus aureus, Streptococcus pneumoniae, Escherichia coli, and Tuberculi bacilli. The studies indicate that in comparison to the ligands their metal complexes are more potent and antibacterial.     

Studies of interactions between platinum(II) complexes and some biologically relevant molecules

The reactions of Pt(II) complexes, cis-[Pt(NH3)2Cl2], [Pt(terpy)Cl]+, [Pt(terpy)(S-cys)]2+, and [Pt(terpy)(N7-guo)]2+, where terpy=2,2':6',2'-terpyridine, S-cys=L-cysteine, and N7-guo=guanosine, with some biologically relevant ligands such as guanosine-5'-monophosphate (5'-GMP), L-cysteine, glutathione (GSH) and some strong sulfur-containing nucleophiles such as diethyldithiocarbamate (dedtc), thiosulfate (sts), and thiourea (tu), were studied in aqueous 0.1 M Hepes at pH of 7.4 using UV-vis, stopped-flow spectrophotometry, and 1H NMR spectroscopy.     

The syntheses and properties of cobalt(II), nickel(II) and copper(II) complexes with some heterocyclic dithiocarbamates

New cobalt(II), Nickel(II) and copper(II) dithiocarbamato complexes of the type M(Rdtc)₂ (Rdtc = 4-phenylpiperidinedithiocarbamate and N-phenylpiperazinedithiocarbamate) have been prepared and characterized through elemental analyses, conductivity measurements, spectral (electronic and IR) studies, magnetic moment measurements at different temperatures, e.p.r. techniques and thermal analyses (TG and DTG). The dithioligands exhibit bidentate behaviour in all the complexes. The magnetic moments studies suggest that there is no significant interaction between copper ions, and the e.p.r. data provide parameters typical of sulphur coordination in planar CuS₄ chromophores.     

Squarato-metal(II) complexes. 1: Structural and magnetic characterization of squarato-bridged dinuclear nickel(II) and copper(II) complexes

A new series of dinuclear squarato-bridged nickel(II) and copper(II) complexes [Ni₂(2,3,2-tet)₂(μ_1,3-C₄O₄)(H₂O)₂](ClO₄)₂ (1), [Ni₂(aepn)₂(μ_1,3-C₄O₄)(H₂O)₂](ClO₄)₂ (2), [Cu₂(pmedien)₂(μ_1,3-C₄O₄)(H₂O)₂](ClO₄)₂.4H₂O (3) and [Cu₂(DPA)₂(μ_1,2-C₄O₄)(H₂O)₂](ClO₄)₂ (4) where is the dianion of 3,4-dihydroxycyclobut-3-en-1,2-dione (squaric acid), 2,3,2-tet = 1,4,8,11-tetraazaundecane, aepn = N-(2-aminoethyl)-1,3-propanediamine, pmedien = N,N,N′,N″,N″-pentamethyldiethylenetriamine and DPA = di(2-pyridylmethyl)amine were synthesized and structurally characterized by X-ray crystallography. The spectral and structural characterization as well as the magnetic behaviour of these complexes is reported. In this series, structures consist of the groups as counter ions and the bridging the two M(II) centers in a μ-1,3- (1-3) and in a μ-1,2-bis(monodentate) (4) bonding fashions. The coordination geometry around the Ni(II) ions in 1 and 2 is six-coordinate with distorted octahedral environment achieved by N atoms of the amines and by one or two oxygen atoms from coordinated water molecules, respectively. In the Cu(II) complexes 3 and 4, a distorted square pyramidal geometry is achieved by the three N-atoms of the aepn or DPA and by an oxygen atom from a coordinated water molecule. The electronic spectra of the complexes in aqueous solutions are in complete agreement with the assigned X-ray geometry around the M(II) centers. The complexes show weak antiferromagnetic coupling with ∣J∣ = 1.8-4.2 cm⁻¹ in the μ-1,3- bridged squarato compounds 1-3, and J = −16.1 cm⁻¹ in the corresponding μ-1,2- bridged squarato complex 4. The magnetic properties are discussed in relation to the structural data.     

Reversal by nickel(II) of inhibitory effects of some scavengers of active oxygen species upon hydroxylation of 2'-deoxyguanosine in vitro.

Effects of ethanol (EtOH), mannitol (Man), L-histidine (His) and glutathione (GSH) on the oxidation of 2'-deoxyguanosine (dG) to its 8-hydroxy derivative (8-OH-dG) with H2O2 plus L-ascorbic acid (Ascb) in the absence and presence of Ni(II) were investigated in order to unveil the nature of active oxygen species involved in that oxidation. In the absence of Ni(II), production of 8-OH-dG was inhibited by His much greater than GSH greater than or equal to GSSG (oxidized glutathione) much greater than EtOH, but not by Man. The latter tended to enhance the production of 8-OH-dG. In the presence of Ni(II), the inhibition by His, GSH and GSSG, but not EtOH, was prevented. The results indicate involvement of a 'crypto-hydroxyl' radical as the dG oxidizing species in both the absence and presence of Ni(II). Also, the results provide evidence that Ni(II) complexes with His, GSH and GSSG may lack antioxidant capacity. Moreover, the Ni(II) complex with His was found capable of enhancing 8-OH-dG production by the Ascb+H2O2 system to a greater extent than Ni(II) alone. Likewise, although to a lesser extent, the formation of 8-OH-dG was enhanced by the combination of Ni(II) and Man which do not form complexes at pH 7.4. Since His is a major Ni(II) carrier in animal tissues, the dG oxidation enhancing capacity of the Ni(II) complex with His may contribute to the toxic and carcinogenic effects of Ni(II).     

Macrocyclic nickel(II) complexes: Spectroscopic studies and crystal structure of bis(difluoroboron-alpha-furilglyoximato)nickel(II)

Bis (difluoroboron - α - furilglyoximato) nickel (II), C₂₀H₁₂O₈N₄B₂F₄Ni, was prepared by cyclization of its hydrogen-bonded precursor with BF₃·OEt₂. The compound crystallizes in the space group P2₁/_c with a = 11.162(2), b = 5.569(2), c = 19.527(3) Å, β = 100.08(1)°, U = 1195.1(3) ų, and Z = 2. The structure was refined to an R value of 0.033 using 2371 unique reflections collected with a CAD4-SDP diffractometer system. Unlike the corresponding planar macrocyclic as well as hydrogen-bonded dimethylglyoximates, the title compound neither dimerizes not exhibits columnar stacked structure. The 14-member macrocycle is planar except the B atoms, and no metal-metal interactions are observed in this compound. The complexation and cyclization reactions were investigated using spectral data. The structure is compared with other macrocyclic complexes.     

ESR an optical absorption studies on the copper(II) interaction with small peptides containing aromatic amino acids.

The interaction of Cu(II) with di- and tripeptides each containing phenylalanine, tryptophan or histidine in the amino acid chain has been investigated by means of electron spin resonance (ESR) and optical absorption spectroscopy. Cu(II) complexes of dipeptides and tripeptides exhibit different magnetic and optical parameters. Dipeptide complexes have larger gparallel-values and smaller A parallel values than tripeptide complexes. When compared to dipeptide complexes, the d-d band of the central metal ion is blue shifted for tripeptide complexes. There are no significant difference in the behavior of Cu(II) peptide complexes containing phenylalanine or tryptophan. Complexes of histidine containing peptides, however, show modified spectra caused by the participation of the imidazole nitrogen in the coordination to Cu(II). The imidazole nitrogen seems to coordinate in-plane with other coordinating atoms or in an axial position depending on the kind of peptide.     

N.m.r. studies of the structures and bonding of some cobalt(II) and nickel(II) complexes of carboxylic acids

Some octahedral complexes of types ML₄T₂ and ML₂T₂, where M = Co^II, Ni^II, L = γ-picoline and T = C₂F₅CO₂, C₃F₇CO₂ and CHCl₂CO₂, have been studied by ¹H and ¹⁹F n.m.r. spectroscopy. The complexes exist in solution in both cis and trans isomeric forms, interconversion of the two forms being slow at ambient temperature in the case of the Ni^II complexes. The appreciable isomeric distinction shown in the ¹⁹F spectra of the acid ligands in contrast to the ¹H spectra of the γ-picoline ligands is attributed to a sizeable π-contact interaction of the acid ligands, particularly when they act as bidentate ligands.     

Orientational and motional properties of copper (II) complexes of dibenzotetraaza [14]annulenes in lipid bilayers: an ESR study.

ESR studies of two copper(II) complexes of substituted dibenzotetraaza [14]annulenes, CuL and CuLA, in dimyristoylphosphatidylcholine (DMPC) and egg yolk phosphatidylcholine (EYPC) are reported. Our data show that both complexes partition into the membranes and that the rotational motion of CuL is faster than CuLA. Analysis of the ESR spectra of these complexes in DMPC vesicles indicate that the Cu-motion parameter, which is a measure of the degree of resolution of the nitrogen hyperfine structure, changes abruptly at the main phase transition. At 1 mole %, both complexes lowered the fluid/gel phase transition temperature by 2 degrees C as measured by the Cu-motion parameter. A gradual change of the Cu-motion parameter is observed in EYPC liposomes over the same temperature range. ESR spectra of both CuL and CuLA in oriented membranes reveal that both complexes are well oriented with the plane of the complex perpendicular to the bilayer surface.     

Structural and spectroscopic comparison of five-coordinate cobalt(II) and nickel(II) thiolato complexes with the related four-coordinate complexes

Five-coordinate thiolato complexes, [L1M(SMeIm)] (M = Co and Ni) (L1 = hydrotris(3,5-diisopropyl-1-pyrazolyl)borate anion and HSMeIm = 2-mercapto-1-methylimidazole), were synthesized. These complexes were compared with the corresponding Cu(II) and Zn(II) complexes with the same ligands and were also compared with the related four-coordinate complexes [L1M(SC₆F₅)] (HSC₆F₅ = pentafluorobenzenthiol). All the complexes were characterized by X-ray crystallography and UV-Vis absorption, IR, ¹H NMR, and other spectroscopic techniques. All five-coordinate thiolato complexes, [L1M(SMeIm)] (M = Co, Ni, and Cu), form a distorted square pyramidal structure with a high spin state, and only [L1Zn(SMeIm)] takes a four-coordinate structure with a distorted tetrahedral configuration. The N21-M-S bond angles of the obtained five-coordinate complexes were proportional to the corresponding d value, which comes from between the equatorial basal plane with N4S ligand donor sets and metal ion. These observations and M-S bond distances affect on UV-Vis and far-IR spectral behavior.     

Decomposition of reactive oxygen species by copper(II) bis(1-pyrazolyl)methane complexes

Two bis(1-pyrazolyl)alkane ligands, bis(3,5-dimethyl-1-pyrazolyl)methane and bis(4-iodo-3,5-dimethyl-1-pyrazolyl)methane, and their copper(II) complexes, bis(3,5-dimethyl-1-pyrazolyl)methanedinitratocopper(II) [CuL₁(NO₃)₂] and bis(4-iodo-3,5-dimethyl-1-pyrazolyl)methanedinitratocopper(II) [CuL₂(NO₃)₂]·2H₂O, were prepared. Physiochemical properties of the copper(II) complexes were studied by spectroscopic (UV–vis, IR, EPR) techniques and cyclic voltammetry. Spectroscopic analysis revealed a 1:1 stoichiometry of ligand:copper(II) ion and a bindentate coordination mode for the nitrate ions in both of the complexes. According to experimental and theoretical ab initio data, the copper(II) ion is located in an octahedral hexacoordinated environment. Both complexes were able to catalyze the dismutation of superoxide anion () (pH 7.5) and decomposition of H₂O₂ (pH 7.5) and peroxynitrite (pH 10.9). In addition, both complexes exhibited superoxide dismutase (SOD) like activity toward extracellular and intracellular reactive oxygen species produced by activated human neutrophils in whole blood. Thus, these complexes represent useful SOD mimetics with a broad range of antioxidant activity toward a variety of reactive oxidants.     

Stability constants of thiocyanato complexes of cobalt(II), nickel(II) and copper(II) in methanol.

A spectrophotometric study of cobalt(II), nickel(II) and copper(II) thiocyanato complexes was carried out in methanol at 25 degrees C and at a constant ionic strength of 1 M. Under the experimental conditions, two mononuclear complexes are identified with each of the three metal ions. Their stability constants are determined with a recent PC program SIRKO and the calculated values are: for cobalt, log beta 1 = 1.6, log beta 2 = 2.7; for nickel, log beta 1 = 1.8, log beta 2 = 3.0; and for copper, log beta 1 = 3.0, log beta 2 = 3.6.     

Interaction of hexacyanoferrate(III) with some copper(II) complexes

The interaction between hexacyanoferrate(III) and some copper complexes of different geometry was studied. In solution, and in the presence of coordination unsaturation of copper, 1:1 and 2:1 Cu:Fe adducts formed and were characterized by the absence of any copper electron paramagnetic resonance (EPR) signal. The magnetic susceptibility of the 1:1 adducts is essentially equal to the sum of those due to the parent compounds. Solid state studies confirm the solution data. In the light of the present results the absence of the EPR signal of [Fe(CN)₆]^3?-treated galactose oxidase is discussed.     

Metal complexes of the schiff bases 2-pyridinylhydrazine and 2-quinolinyl-hydrazine with 2-pyridinecarboxaldehyde N-oxide,including some N-oxide-bridged antiferromagnetic complexes of cobalt(II) and nickel(II)

Metal complexes of 2-pyridine carboxaldehyde 2′-pyridinylhydrazone 1-oxide (poph) and 2-pyridinecarboxaldehyde 2′-quinolinylhydrazone 1-oxide (poqh) are reported with copper(II), nickel(II), cobalt(II), iron(II) and manganese(II). Each ligand appears to function as an ONN donor, via the pyridine N-oxide oxygen, the imine nitrogen, and a pyridine or quinoline nitrogen. The complexes have been characterised by magnetic susceptibility measurements to liquid nitrogen temperature, and also by electronic, infrared, X-ray powder diffraction, and Mössbauer spectra. No magnetic interaction was detected with the copper(II) complexes. All the complexes of metal nitrates appear to be monomers.The complexes of poph with the halides and thiocyanates of nickel(II) and cobalt(II) appear to be six-coordinate and N-oxide-bridged; they exhibit varying degress of antiferromagnetic interaction and the magnetic data for the nickel(II) complexes have been fitted to various models. In contrast, the bulky ligand poqh produces halide-bridged six-coordinate nickel(II) complexes and monomeric five-coordinate cobalt(II) complexes.This behaviour by poqh resembles that of the related NNN ligands paphy and paqhy, which are the Schiff bases of 2-pyridinecarboxaldehyde with 2-pyridinylhydrazine and 2-quinolinylhydrazine, respectively.     

Unusual phenomenon in the chemistry of orthometalated ruthenium (II) complexes

Yellow cyclometalatated ruthenium (II) complexes [Ru(o-X-2-py)(MeCN)₄]PF₆ (1, X = C₆H₄ (a) or 4-MeC₆H₃ (b)) react readily with 1,10-phenanthroline (LL) in MeCN to give brownish-red species cis-[Ru(o-X-2-py)(LL)(MeCN)₂]PF₆ in high yields. The same reaction of the same complexes under the same conditions with 2,2′-bipyridine results in a significant color change from yellow to brownish-orange suggesting a formation of new species. Surprisingly, X-ray structural studies of these two complexes showed that they are structurally indistinguishable from the starting complexes 1. Referred to as complexes 4a,b, the new compounds are slightly more stable in the air though their spectral characteristics in solution are similar to 1a,b. The diffuse reflectance spectroscopy is so far the only technique that indicated differences between 1 and 4.     

Synthesis, physico-chemical characterization and antimicrobial activity of cobalt(II), nickel(II), copper(II), zinc(II) and cadmium(II) complexes with some acyldihydrazones

Complexes of the type [M(bssdh)]Cl and [M(dspdh)]Cl, where M = Co(II), Ni(II), Cu(II), Zn(II) and Cd(II); Hbssdh = benzil salicylaldehyde succinic acid dihydrazone, Hdspdh = diacetyl salicylaldehyde phthalic acid dihydrazone have been synthesized and characterized with the help of elemental analyses, electrical conductance, magnetic susceptibility measurements, electronic, ESR and IR spectra and X-ray diffraction studies. Magnetic moment values and electronic spectral transitions indicate a spin free octahedral structure for Co(II), Ni(II) and Cu(II) complexes. IR spectral studies suggest that both the ligands behave as monobasic hexadentate ligands coordinating through three > C = O, two > C = N- and a phenolate group to the metal. ESR spectra of Cu(II) complexes are axial type and suggest d(x(2)-y(2)) as the ground state. X-ray powder diffraction parameters for [Co(bssdh)]Cl and [Co(dspdh)]Cl complexes correspond to an orthorhombic crystal lattice. The ligands as well as their metal complexes show a significant antifungal and antibacterial activity against various fungi and bacteria. The metal complexes are more active than the parent ligands.     

An ESR study of the Mn(II)-heavy meromyosin system.

The Mn(II)-heavy meromyosin system was studied by measuring the ESR spectrum of Mn(II). The temperature dependence of the line width parameter W(1, t) of a freshly prepared sample changes at around 7-10 degrees C, where W(1, t) is the reciprocal of the peak-to-peak height of the lowest magnetic field component of the hyperfine structure. It is shown that the change in the slope of W(1, t) at 7-10 degrees C is due to a change in the structure of Mn(II)-heavy meromyosin or a change in the interaction between Mn(II) and heavy meromyosin without ATP. This result is in accord with the recently reported observations that heavy meromysin ATPase activity showed different temperature dependence above and below 10 degrees C in the presence of Mn(II). The characteristics of the spectrum of the Mn(II)-heavy meromyosin system in the liquid state between 2 degrees C and 20 degrees C are compared with those of a frozen sample of Mn(II)-heavy meromyosin in a low temperature region (-50-0 degrees C) and with those of the lyophilized material. The forbidden transitions are observed, and hence the zero field splitting parameter can be obtained. It is 115 +/- 15 gauss at -50 degrees C, and decreases with increase of the temperature to 70 +/- 15 gauss at 20 degrees C.     

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.     

Strong protective action of Copper(II) N-substituted sulfonamide complexes against reactive oxygen species

Copper(II) complexes of N-benzothiazolsulfonamides, [Cu(N-2-(5,6-dimethylbenzothiazole)toluenesulfonamidate)(2)(dmso)(2)] (1), [Cu(N-2-(6-chlorobenzothiazole)benzenesulfonamidate)(2)(dmso)(2)] (2) and [Cu(N-2-(6-chlorobenzothiazole)toluenesulfonamidate)(2)(dmso)(2)] (3) with interesting protective properties against superoxide radicals have been prepared. The compounds have been characterized by X-ray diffraction and their chemical properties have been studied by spectroscopic methods. The crystal structure of 1 shows that the copper(II) is surrounded by two benzothiazole N atoms from the sulfonamide ligands and two O atoms from the dimethylsulfoxide molecules in a square planar arrangement. The coordination polyhedron around copper(II) in 2 and 3 is distorted square pyramidal being the metal ion linked to benzothiazole N and sulfonamidate O atoms of the ligand and to two dimethylsulfoxide O atoms. The three complexes have a strong protective action over Delta sod1 mutant of Saccharomyces cerevisiae against reactive oxygen radicals derived from respiration and against those generated by hydrogen peroxide and menadione.