Tetrazole peptides as copper(II) ion chelators

The 1,5-disubstituted tetrazole ring a mimetic of the cis-amide bond is an unique element modifying the ability of peptides to chelate copper(II) ions. The position of the tetrazole ring system in the peptide backbone plays a critical role in the stabilization of the metallopeptide molecule. The insertion of a tetrazole between amide groups leads to enhancing the stability of the complex and to obtaining a very effective peptide chelating agent. These findings can provide important information for modeling biologically relevant peptide–metal binding sites. Some aspects of biological activity of tetrazole modified exogenous opioid peptides in the presence of copper(II) ions are also presented in this review.     

Quantum chemical insights into Alzheimer's disease: Curcumin's chelation with Cu(II), Zn(II), and Pd(II) as a mechanism for its prevention

We provide quantum chemical insights into curcumin's prevention of Alzheimer' disease through curcumin's scavenging of neurotoxic Cu(II), Zn(II), and Pd(II) transition metal ions that catalyze polymerization of amyloid‐β and promote misfolding of amyloid into neurotoxic conformations. We have employed high level quantum chemical computations to study the chelate complexes of curcumin with Cu(II), Zn(II), and Pd(II). Quantum chemically derived structures, IR spectra, and UV‐visible spectra of these complexes corroborate with the observed spectra, confirming that the primary site of chelation is the β‐diketone bridge through the loss of an enolic proton of curcumin. We have also obtained the various structural parameters such as the Mulliken charges on various centers, highest occupied, lowest unoccupied molecular orbitals—all of which confirm that curcumin forms chelate complexes and thus acts as a scavenger of these neurotoxic metal ions preventing Alzheimer's disease. We find that the open‐d‐shell Cu(II) and Pd(II) form nearly square planar complexes while the closed‐d‐shell Zn(II) forms a tetrahedral complex with curcumin. © 2016 Wiley Periodicals, Inc.     

Interactions of pyridinecarboxylic acid chelators with brain metal ions: Cu(II), Zn(II), and Al(III)

Abstract  

The interactions of Cu(II), Zn(II), and Al(III) with 1,6-dimethyl-4-hydroxy-3-pyridinecarboxylic acid (DQ716) and 2,6-dimethyl-3-hydroxy-4-pyridinecarboxylic acid (DT726), possible chelating agents in Alzheimer’s disease, were investigated in aqueous solution. The proton dissociation constants of the ligands, the stability constants, and the coordination modes of the metal complexes formed were determined by pH-potentiometric, UV–vis spectrophotometric, and ¹H NMR methods. The nitrogen of the pyridine ring changes the proton affinity of the carboxylate and phenolate moieties and these pyridine derivatives form stronger complexes with Cu(II), Zn(II), and Al(III) than salicylic acid. Interactions of the ligands with human serum albumin as their potential transporter in blood were investigated at physiological pH through ultrafiltration by UV–vis and fluorescence spectroscopy.     

Cork biomass as biosorbent for Cu(II), Zn(II) and Ni(II)

The removal of Cu(II), Zn(II) and Ni(II) from solutions using biosorption in cork powder is described. The adsorption isotherms were determined, along with the effect of different variables, such as the solid–liquid ratio, temperature and pH on the removal efficiency of the metals. The potentiometric titration curve of the cork biomass was determined and some zeta-potential studies were carried out. The effect of the pre-treatment by Fisher esterification on the biosorption properties of cork is also presented. It was concluded that the adsorption of the heavy metals was favoured by an increase in pH. The degree of heavy metal removal is directly related to the concentration of cork biomass, and the maximum sorption capacity of cork biomass for Cu(II), Zn(II) and Ni(II) was 0.63, 0.76 and 0.34 meq./g, respectively. It is shown that ion exchange plays a more important role in the sorption of Cu(II) and Ni(II) on cork biomass than in the sorption of Zn(II). The pre-treatment by Fisher esterification confirmed the important role of the carboxylic groups in binding of Cu(II) and Ni(II) and showed that they are the only binding sites for Zn(II).     

Designing Zn(II) and Cu(II) derivatives as probes for in vitro fluorescence imaging

New M(II) bis(thiosemicarbazonato) complexes (M = Ni(II), Cu(II) and Zn(II)) featuring allyl groups at the exocyclic nitrogens have been synthesised. The complexes were characterised in solution by spectroscopic methods and their solid state structures determined by single crystal X-ray diffraction using synchrotron radiation. The Zn(II) complex was found to be intrinsically fluorescent and soluble in biocompatible media. The uptake of this Zn(II) complex in HeLa, MCF-7 and IGROV cancer cells was monitored by fluorescence microscopies (epi- and confocal fluorescence imaging). The radiolabelling to (64)Cu(II) bis(thiosemicarbazonato) complex was performed cleanly by transmetallation from the corresponding Zn(II) species using (64)Cu(OAc)(2).     

Synthesis of azolyl carboximidamides as ligands for Zn(II) and Cu(II): application of the Zn(II) complexes as catalysts for the copolymerization of carbon dioxide and epoxides

A series of novel S,N-heterocyclic (thiazolyl) substituted carboximidamides 3 and 4 was synthesized in yields up to 82% from specific triazinium salts 1 and primary or secondary amines 2 which additionally bear pyridine or imidazole units. These carboximidamides are used as tailor-made ligands for the complexation of Cu(II) and Zn(II). The coordination behavior of 3 and 4 and the properties of the resulting metal complexes are affected a significant extent especially by the nature of these amine substituents. The most important structural feature of the novel complexes is that the ligation of the metal cations is achieved by a 1,3,5-triazapentadienyl anion system, compare the X-ray structure of the model complex Cu-4d. Analogous Zn(II) complexes 5, 6a, 6b, 6c, 7a, and 7b were obtained from carboximidamides 3, 4a, 4b, 4c, 4d, and 4e after reaction with diethylzinc. Interestingly, these Zn(II) complexes possess an intrinsic activity to catalyze the copolymerization of cyclohexene oxide and carbon dioxide to give polycarbonates 15 (TON up to 113; Turn Over Number: moles of substrate 14 consumed per moles of zinc. Molecular weights: up to 206.10(3) Da). Contaminations of 15 by polyethers are produced only in remarkably small amounts.     

One-dimensional oxalato-bridged Cu(II), Co(II), and Zn(II) complexes with purine and adenine as terminal ligands

The reaction of nucleobases (adenine or purine) with a metallic salt in the presence of potassium oxalate in an aqueous solution yields one-dimensional complexes of formulas [M(mu-ox)(H(2)O)(pur)](n) (pur = purine, ox = oxalato ligand (2-); M = Cu(II) [1], Co(II) [2], and Zn(II) [3]), [Co(mu-ox)(H(2)O)(pur)(0.76)(ade)(0.24)](n)(4) and ([M(mu-ox)(H(2)O)(ade)].2(ade).(H(2)O))(n) (ade = adenine; M = Co(II) [5] and Zn(II) [6]). Their X-ray single-crystal structures, variable-temperature magnetic measurements, thermal behavior, and FT-IR spectroscopy are reported. The complexes 1-4 crystallize in the monoclinic space group P2(1)/a (No. 14) with similar crystallographic parameters. The compounds 5 and 6 are also isomorphous but crystallize in the triclinic space group P (No. 2). All compounds contain one-dimensional chains in which cis-[M(H(2)O)(L)](2+) units are bridged by bis-bidentate oxalato ligands with M(.)M intrachain distances in the range 5.23-5.57 A. In all cases, the metal atoms are six-coordinated by four oxalato oxygen atoms, one water molecule, and one nitrogen atom from a terminal nucleobase, building distorted octahedral MO(4)O(w)N surroundings. The purine ligand is bound to the metal atom through the most basic imidazole N9 atom in 1-4, whereas in 5 and 6 the minor groove site N3 of the adenine nucleobase is the donor atom. The crystal packing of compounds 5 and 6 shows the presence of uncoordinated adenine and water crystallization molecules. The cohesiveness of the supramolecular 3D structure of the compounds is achieved by means of an extensive network of noncovalent interactions (hydrogen bonds and pi-pi stacking interactions). Variable-temperature magnetic susceptibility measurements of the Cu(II) and Co(II) complexes in the range 2-300 K show the occurrence of antiferromagnetic intrachain interactions.     

Synthesis and biological evaluation of Cu(II), Zn(II), and Ni(II) 3-(4-nitrophenyl)acrylic acid complexes with diamines as potential urease inhibitors

Five new Cu(II), Zn(II), and Ni(II) 3-(4-nitrophenyl)acrylic acid complexes were synthesized and evaluated for inhibitory activity on jack bean urease. All five complexes were structurally determined by single crystal X-ray analysis. Compared with the positive reference acetohydroxamic acid (IC₅₀?=?13.25?μM), Cu(II) complexes 3 and 4 showed the strongest inhibitory activity against jack bean urease (IC₅₀?=?1.23 and 1.17?μM). Ni(II) and Zn(II) complexes also exhibited inhibitory activities (IC₅₀?=?10.09–13.10?μM).     

Dehydration studies of Co(II), Cu(II) and Zn(II) methanesulfonates

The dehydration process of Co(II), Cu(II) and Zn(II) methanesulfonates was studied by thermogravimetry/derivative thermogravimetry (TG/DTG) and differential scanning calorimetry (DSC) techniques in dynamic N₂ atmosphere. The TG/DTG curves show that all of them contain four crystallization water molecules, which are lost in two steps. The peak temperature and dehydration enthalpies ΔH were measured from DSC curves for each compound. The effect of procedural variables on the TG and DSC curves was investigated. In this work, the procedural variables included heating rate, Al pan state (unsealed and sealed) and sample mass.     

The Binding of Cu(II) and Zn(II) Ions by Heparin

Abstract

A method is described for measuring the ion binding capacity of heparin. The method is based on the separation of the zinc or copper complex of heparin by gel permeation. It was found that the number of the cation per average molecule of heparin depends on the pH and on the initial concentration of metal cation in solution. The absorption spectrum of heparin-Cu complex is described. The molar absorptivity of this complex is determined, as is the complex formation constant.     

Syntheses and structures of isoindoline complexes of Zn(II) and Cu(II): an unexpected trinuclear Zn(II) complex

Deprotonation of the tridentate isoindoline ligand 1,3-bis[2-(4-methylpyridyl)imino]-isoindoline, 4'-MeLH, and reaction with hydrated zinc(II) perchlorate produces an unexpected trinuclear Zn(II) complex, [Zn(3)(4'-MeL)(4)](ClO(4))(2).5H(2)O (1), whereas reaction with hydrated copper(II) perchlorate in methanol produces the expected mononuclear product, [Cu(4'-MeL)(H(2)O)(2)]ClO(4) (2). X-ray diffraction shows that the trinuclear Zn(II) complex (1) contains a linear zinc backbone, and the arrangement of ligands about the outer chiral zinc(II) atoms is helical. The two terminal zinc ions exhibit approximate C(2) site symmetry, with tetrahedral coordination by two pyrrole and two pyridyl nitrogen atoms of the potentially tridentate isoindoline ligands. The central zinc ion exhibits approximate tetrahedral symmetry, with coordination by four pyridyl nitrogen atoms of four different isoindoline ligands. Pyridyl-pyrrole intramolecular pi-stacking interactions contribute to the stability of the trinuclear cation. The structure of the mononuclear copper(II) complex cation in 2 is best described as a distorted trigonal bipyramid. The isoindoline anion binds Cu(II) in both axial positions and one of the equatorial positions; water molecules occupy the other two equatorial positions.     

Phenoxyl radicals: H-bonded and coordinated to Cu(II) and Zn(II)

Two pro-ligands ((R)LH) comprised of an o,p-di-tert-butyl-substituted phenol covalently bonded to a benzimidazole ((Bz)LH) or a 4,5-di-p-methoxyphenyl substituted imidazole ((PhOMe)LH), have been structurally characterised. Each possesses an intramolecular O-H[dot dot dot]N hydrogen bond between the phenolic O-H group and an imidazole nitrogen atom and (1)H NMR studies show that this bond is retained in solution. Each (R)LH undergoes an electrochemically reversible, one-electron, oxidation to form the [(R)LH] (+) radical cation that is considered to be stabilised by an intramolecular O...H-N hydrogen bond. The (R)LH pro-ligands react with M(BF(4))(2).H(2)O (M = Cu or Zn) in the presence of Et(3)N to form the corresponding [M((R)L)(2)] compound. [Cu((Bz)L)(2)] (), [Cu((PhOMe)L)(2)] (), [Zn((Bz)L)(2)] and [Zn((PhOMe)L)(2)] have been isolated and the structures of .4MeCN, .2MeOH, .2MeCN and .2MeCN determined by X-ray crystallography. In each compound the metal possesses an N(2)O(2)-coordination sphere: in .4MeCN and .2MeOH the {CuN(2)O(2)} centre has a distorted square planar geometry; in .2MeCN and .2MeCN the {ZnN(2)O(2)} centre has a distorted tetrahedral geometry. The X-band EPR spectra of both and , in CH(2)Cl(2)-DMF (9 : 1) solution at 77 K, are consistent with the presence of a Cu(ii) complex having the structure identified by X-ray crystallography. Electrochemical studies have shown that each undergo two, one-electron, oxidations; the potentials of these processes and the UV/vis and EPR properties of the products indicate that each oxidation is ligand-based. The first oxidation produces [M(II)((R)L)((R)L )](+), comprising a M(ii) centre bound to a phenoxide ((R)L) and a phenoxyl radical ((R)L ) ligand; these cations have been generated electrochemically and, for R = PhOMe, chemically by oxidation with Ag[BF(4)]. The second oxidation produces [M(II)((R)L )(2)](2+). The information obtained from these investigations shows that a suitable pro-ligand design allows a relatively inert phenoxyl radical to be generated, stabilised by either a hydrogen bond, as in [(R)LH] (+) (R = Bz or PhOMe), or by coordination to a metal, as in [M(II)((R)L)((R)L )](+) (M = Cu or Zn; R = Bz or PhOMe). Coordination to a metal is more effective than hydrogen bonding in stabilising a phenoxyl radical and Cu(ii) is slightly more effective than Zn(II) in this respect.     

Metallomicellar Catalysis: Hydrolysis of Phosphodiester with Cu(II) and Zn(II) Complexes in Micellar Solution

Abstract

The effects of two metal complexes of 2,2′‐dipyridylamine (bpya) ligand, [(bpya)Cu]Cl₂ and [(bpya)Zn]Cl₂, in promoting the hydrolysis of bis(4‐nitrophenyl) phosphate (BNPP) have been kinetically investigated in Brij35 micellar solution and at 298 K, pH ranging from 6.41 to 8.6. In neutral micellar solution at 298 K, pH 7.02, the rate constants for the catalytic hydrolysis of BNPP by [(bpya)Cu]Cl₂ and [(bpya)Zn]Cl₂ are 1.2 × 10⁶ times and 1.5 × 10⁵ times higher than those for the spontaneous hydrolysis, respectively. Kinetic studies show that the active species in the catalytic hydrolysis of BNPP is the aquo‐hydroxy form, and the relative kinetic and thermodynamic parameters indicate that the mechanism of the reaction involves intramolecular nucleophilic attack on the metal center‐bound diester.     

Thermal decomposition of Co(II), Ni(II), Cu(II) and Zn(II) hippurates

The hippurates of Co(II), Ni(II), Cu(II) and Zn(II) were isolated from the solution, their quantitative composition and the way of coordination of metal — ligand were determined and the conditions and products of thermal decomposition during heating in air atmosphere up to 1273 K were studied. The complexes of Ni(II), Cu(II) and Zn(II) heated lose some water molecules and then decompose to MO. The hippurate of Co(II) heated loses some water molecules and then decomposes to CoO with intermediate formation Co₃O₄.

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Zusammenfassung Aus Lösung wurden die Co(II)-, Ni(II)-, Cu(II)- und Zn(II)-Salze der Hippursäure gewonnen, ihre quantitative Zusammensetzung sowie die Art der Koordination der Metall-Ligandenbindung bestimmt. Weiterhin wurden die Bedingungen und Produkte der thermischen Zersetzung beim Erhitzen in einer Luftatmosphäre bis 1273 K untersucht. Die Komplexe von Ni(II), Cu(II) und Zn(II) verlieren beim Erhitzen ein paar Moleküle Wasser und zersetzen sich anschlieend zu MO. Co(II)-hippurat gibt beim Erhitzen einige Moleküle Wasser ab und zersetzt sich dann über die Zwischenstufe Co₃O₄ zu CoO.

     

Syntheses and thermal reactivities of tetradentate metalloenediynes of Cu(II) and Zn(II)

The syntheses and Bergman cyclization temperatures of disubstituted tetradentate enediyne ligands based on a dibenzylethylenediamine backbone are reported relative to the corresponding Cu(II) and Zn(II) analogues. For these compounds, the R-groups dimethylamine (dma), pyridine (py), quinoline (quin), and 3-oxypyridine (pyO) have been symmetrically and asymmetrically incorporated at the alkyne termini positions directly (0:0) or via a methylene spacer (1:0, 0:1, 1:1). Electron paramagnetic resonance (EPR) reveals that all Cu(II) complexes are monomeric with near axial symmetry and g-values (g(x) approximately 2.04, g(y) approximately 2.09 g(z) approximately 2.25) representative of tetragonal Cu(II) geometries. The hyperfine splitting parameter A(z) values are approximately 170 x 10(-)(4) cm(-)(1), which is consistent with distorted 4-coordinate, or weakly 6-coordinate, structures. In contrast, solution conductivity measurements show that Zn(II) complexes with rigid py or quin ligands (e.g., py-py 0:0, py-quin 0:0) behave as 1:4 electrolytes indicative of dimeric, bridging enediyne structures. Consequently, these Zn(II) complexes have very high Bergman cyclization temperatures (>290 degrees C), while their less rigid, 1:1 analogues (<185 degrees C) and monomeric Cu(II) counterparts (110-136 degrees C) have markedly lower cyclization temperatures. The results underscore the important consequences metal center structure plays in influencing Bergman cyclization temperatures of metalloenediynes.     

Cu(II) and Zn(II) complexes with a fluoroquinolone antibiotic: Spectroscopic and X-ray absorption characterization

The synthesis of two complexes with the antibiotic flumequine, [Cu(Flumequine)₂(OH₂)₂] (1) and [Zn(Flumequine)₂(OH₂)₂]·H₂O (2) is reported. Their molecular structure was elucidated by combining various spectroscopic techniques. The EPR parameters combined with XAS data underline a tetragonal distorted octahedral geometry for the two complexes. The coordination occurs through the carbonyl and carboxylate oxygen atoms in the equatorial plane. The coordination sphere is completed by two water molecules in axial position.     

Crystal Structures and Characterizations of Bis(pyrrolidinedithiocarbamato)Cu（Ⅱ） and Zn(Ⅱ） Complexes

The structures of [Cu (S₂CN (CH₂)₄)₂] (1) and [Zn₂(S₂CN‐(CH₂)₄)₄] (2) have been determined by X‐ray crystallography analysis. They are all isomorphous and triclinic, space group of P1^?, with Z = 1. The lattice parameters of compound 1 is: a = 0.63483(2) nm, b = 0.74972(3) nm, c=0.78390(1) mn, α = 75.912(2)°, β = 78.634(2)° and γ = 86.845(2)°; compound 2: a = 0.78707(6) nm, b=0.79823(6) nm, c = 1.23246(9) nm, α = 74.813(2)°, β = 73.048(2)° and γ = 88.036(2)°. The copper atom is located on a crystallographic inversion center and zinc atom lies across centers of symmetry. The Cu(II) ion has a square‐planar geometry while Zn(II) has a distorted tetrahedral geometry. The thermal gravity (TG) data indicate that no structural transitions in the two compounds were abserved and the decomposition products can adsorb gas. Also they all have a high thermal stability.     

Crystal Structures and Characterizations of Bis(pyrrolidinedithiocarbamato) Cu(II) and Zn(II) Complexes

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