Formation Of Copper Complexes Research Articles

CB-TE2A(+)·Cl(-)·3H2O: a short intermolecular hydrogen bond between zwitterionic bicyclo[6.6.2]tetraamine macrocycles.

1,4,8,11-Tetraazabicyclo[6.6.2]hexadecane-4,11-diacetic acid (CB-TE2A) is of much interest in nuclear medicine for its ability to form copper complexes that are kinetically inert, which is beneficial in vivo to minimize the loss of radioactive copper. The structural chemistry of the hydrated HCl salt of CB-TE2A, namely 11-carboxymethyl-1,8-tetraaza-4,11-diazoniabicyclo[6.6.2]hexadecane-4-acetate chloride trihydrate, C16H31N4O4(+)·Cl(-)·3H2O, is described. The compound crystallized as a positively charged zwitterion with a chloride counter-ion. Two of the amine groups in the macrocyclic ring are protonated. Formally, a single negative charge is shared between two of the carboxylic acid groups, while one chloride ion balances the charge. Two intramolecular hydrogen bonds are observed between adjacent pairs of N atoms of the macrocycle. Two intramolecular hydrogen bonds are also observed between the protonated amine groups and the pendant carboxylate groups. A short intermolecular hydrogen bond is observed between two partially negatively charged O atoms on adjacent macrocycles. The result is a one-dimensional polymeric zigzag chain that propagates parallel to the crystallographic a direction. A second intermolecular interaction is a hydrogen-bonding network in the crystallographic b direction. The carbonyl group of one macrocycle is connected through the three water molecules of hydration to the carbonyl group of another macrocycle.

Thermodynamic study of heteroligand complex formation of copper(II) and nickel(II) nitrilotriacetates with amino acids in solution

Ternary complexes of copper(II) and nickel(II) nitrilotriacetate (MNta) with arginine (Arg), serine (Ser), glycine (Gly), aspartic acid (Asp), and iminodiacetic acid (Ida) have been calorimetrically, potentiometrically, and spectrophotometrically studied in aqueous solution at 298.15 K and ionic strength 0.5 (KNO3). The thermodynamic parameters of mixed-ligand complex formation have been determined. The probable coordination modes of amino acid residues in the heteroligand complexes were discussed.

Complex formation of copper(II) with 2,6-dimercaptophenol and its derivatives in the presence of aminophenols

Complex formation of copper(II) with 2,6-dimercaptophenol and its derivatives in the presence of aminophenols

Neutral copper(I) complexes featuring phosphinesulfonate chelates.

The reaction of diphenylphosphinobenzenesulfonic acid with copper(i) oxide resulted in the formation of the new neutral dimeric copper(i) complex {Cu2(DPPBS)2·(MeOH)2}. X-ray diffraction studies revealed that the complex has a dimeric structure and a pyramidal trigonal geometry around the copper atom which contains coordinated methanol molecules at the copper centers. Cleavage of the dimer by reaction with various bipyrimidines enabled the preparation of the corresponding well-defined heterotopic mononuclear [Cu(P^O)(N^N)] and dinuclear {(P^O)Cu(N^N)Cu(P^O)} complexes. X-ray crystal structure determination shows these to have distorted tetrahedral geometries. Their absorption and emission properties were investigated experimentally and photophysical data were also confirmed by DFT and TD-DFT calculations. Owing to the methanol molecules, the neutral crystalline dimer {Cu2(DPPBS)2·(MeOH)2} displays green reversible photoluminescence upon UV irradiation in the solid state with an absolute luminescence quantum yield of 0.51.

Formation and decomplexation kinetics of copper(ii) complexes with cyclen derivatives having mixed carboxylate and phosphonate pendant arms.

The kinetic properties of Cu(ii) complexes of H4dota and its analogues with one (H5do3ap), two in the 1,7-position (trans-H6do2a2p), three (H7doa3p) and four (H8dotp) phosphonic acid pendant arms were investigated. The formation of a Cu(ii) complex with H4dota, trans-H6do2a2p and H8dotp at a slightly acidic pH is faster for the phosphonic acid derivatives than for H4dota, but with no simple dependence on the number of -CH2PO3H2 substituents (trans-H6do2a2p > H8dotp > H4dota; pH 4-6). Relative differences in the reactivity among the differently protonated species (HnL(x-)) of the same ligand are successively decreased with the more phosphonic acid groups in the ligand. The faster complexation is probably caused by the higher ability of phosphonates to bind the metal ion and/or to assist in the transfer of protons from the ring amine groups to the bulk water. The acid-assisted decomplexation kinetics of the complexes was followed in highly acidic solutions ([H(+)] = 0.01-5 M) and at different temperatures (15-70 °C) to determine the activation parameters of the reaction. The kinetic inertness of the Cu(ii) complexes follows the order: H4dota > H5do3ap > trans-H6do2a2p > H7doa3p > H8dotp. To obtain information on the influence of additional pendant arms, analogous data were obtained for trans-H2do2a. The ligand is less reactive than H4dota, but the kinetic inertness of its Cu(ii) complex is similar to that of the H4dota complex. As it was considered that the published thermodynamics data on the Cu(ii)-H8dotp system are probably incorrect, the system was re-investigated. It showed a very high stability for the [Cu(dotp)](6-) species and the easy formation of several Cu2L species in the presence of an excess of the metal ion. Also, the structure of the (H6doa3p)(-) anion in the solid state was determined. These experimental data demonstrate that the substitution of acetic acid pendant arms by methylphosphonic acid ones in H4dota-like ligands increases the rate of complexation but significantly decreases the kinetic inertness of the Cu(ii) complexes.

Complex formation of β-brominated tetraphenylporphyrins and metal exchange of their cadmium complexes with d-metal salts in dimethylformamide

Complex formation of zinc and copper(II) acetates with tetraphenylporphyrin, 2-bromo-5,10,15,20-tetraphenylporphyrin, 2,3,12,13-tetrabromo-5,10,15,20-tetraphenylporphyrin, and 2,3,7,8,12,13,17,18-octabromo-5,10,15,20-tetraphenylporphyrin in N,N-dimethylformamide has been studied. The rate constants determined in the study of the complex formation and the metal exchange reactions have been compared.

Cyclam Derivatives with a Bis(phosphinate) or a Phosphinato–Phosphonate Pendant Arm: Ligands for Fast and Efficient Copper(II) Complexation for Nuclear Medical Applications

Cyclam derivatives bearing one geminal bis(phosphinic acid), -CH2PO2HCH2PO2H2 (H2L(1)), or phosphinic-phosphonic acid, -CH2PO2HCH2PO3H2 (H3L(2)), pendant arm were synthesized and studied as potential copper(II) chelators for nuclear medical applications. The ligands showed good selectivity for copper(II) over zinc(II) and nickel(II) ions (log KCuL = 25.8 and 27.7 for H2L(1) and H3L(2), respectively). Kinetic study revealed an unusual three-step complex formation mechanism. The initial equilibrium step leads to out-of-cage complexes with Cu(2+) bound by the phosphorus-containing pendant arm. These species quickly rearrange to an in-cage complex with cyclam conformation II, which isomerizes to another in-cage complex with cyclam conformation I. The first in-cage complex is quantitatively formed in seconds (pH ≈5, 25 °C, Cu:L = 1:1, cM ≈ 1 mM). At pH >12, I isomers undergo nitrogen atom inversion, leading to III isomers; the structure of the III-[Cu(HL(2))] complex in the solid state was confirmed by X-ray diffraction analysis. In an alkaline solution, interconversion of the I and III isomers is mutual, leading to the same equilibrium isomeric mixture; such behavior has been observed here for the first time for copper(II) complexes of cyclam derivatives. Quantum-chemical calculations showed small energetic differences between the isomeric complexes of H3L(2) compared with analogous data for isomeric complexes of cyclam derivatives with one or two methylphosphonic acid pendant arm(s). Acid-assisted dissociation proved the kinetic inertness of the complexes. Preliminary radiolabeling of H2L(1) and H3L(2) with (64)Cu was fast and efficient, even at room temperature, giving specific activities of around 70 GBq of (64)Cu per 1 μmol of the ligand (pH 6.2, 10 min, ca. 90 equiv of the ligand). These specific activities were much higher than those of H3nota and H4dota complexes prepared under identical conditions. The rare combination of simple ligand synthesis, very fast copper(II) complex formation, high thermodynamic stability, kinetic inertness, efficient radiolabeling, and expected low bone tissue affinity makes such ligands suitably predisposed to serve as chelators of copper radioisotopes in nuclear medicine.

Metal-binding effects of sirtuin inhibitor sirtinol

Sirtinol, a Schiff base derived from 2-hydroxy-1-naphthaldehyde, is an inhibitor of sirtuin proteins, a family of deacetylases active in gene regulation and relevant to the study of cancer growth. The formation of copper(II) and zinc(II) complexes of sirtinol is investigated by spectroscopic and structural methods. The molecular structure of this protein inhibitor allows for coordination of first-row transition metals in both tridentate and bidentate fashion. In addition, assays in cultured breast cancer cells reveal that CuII(sirtinol−H)2 and previously reported FeIII(sirtinol−H)(NO3)2 present enhanced cytotoxicity when compared to the free ligand, and that the ferric complex causes an increase in intracellular oxidative stress. Transition metal coordination in the biological milieu could therefore contribute additional effects to the biological profile of sirtinol.

Influence of copper layer on epoxy acrylate based solder mask surface chemistry and the effect on epoxy adhesion

The influence of the presence of copper on the network formation and the surface chemistry of an epoxy acrylate based solder mask system were investigated, with regards to the application of solder masks on copper layer. The presence of copper within the bulk volume of the solder mask was characterized by utilizing scanning electron microscopy/focused ion beam and energy dispersive X-ray analysis. The copper originates from the copper layer underneath and decreases towards the surface. Differences in the network structure were analyzed by applying infrared spectroscopy in attenuated total reflection mode, which showed no changes in the network structure due to a copper layer underneath. The surface chemistry of two solder masks with different curing agents, amine and anhydride, was investigated for differences caused by changes in the curing behavior depending on copper complex formation. Surface chemistry was analyzed by applying X-ray photoelectron spectroscopy and time of flight secondary ion mass spectrometry. Measurable differences in the surface chemistry with regards to copper content are generated due to the copper layer underneath. However, through the optical contact angle method and pull-off test, no differences concerning wetting or adhesion behavior between the solder mask and an epoxy adhesive were observed.

Effect of Copper on Fatty Acid Profiles in Non- and Semifermented Teas Analyzed by LC-MS-Based Nontargeted Screening.

Unsaturated fatty acids are well-known precursors of aroma compounds, which are considered important for green tea quality. Due to the known copper-induced oxidation of unsaturated fatty acids and the broad variability of the amount of copper present in tea infusions, this paper investigates the influence of copper, added at a nontoxic concentration (300 μM) to non- and semifermented teas, on the degradation of fatty acids and fatty acid hydroperoxides thereof. The abundance of fatty acids in green and oolong tea was determined by means of a nontargeted approach applying high-resolution MS/MS. As a result, most of the fatty acids in green and oolong tea were already oxidized prior to copper addition. Addition of 300 μM CuSO4 to the oolong tea sample resulted in a decrease of 13-hydroperoxy-9Z,11E-octadecadienoic acid, an important flavor precursor, from 0.12 ± 0.02 to 0.05 ± 0.01 μM (p = 0.035), and other oxidized fatty acids decreased as well. However, copper-induced degradation of oxidized fatty acids was less pronounced in green tea compared to oolong tea, most likely due to the formation of copper complexes with low-molecular-weight compounds as evidenced by electron paramagnetic resonance spectroscopy.

Effect of temperature on the enthalpies of formation of copper(II) complexes with L-Aspartic acid in aqueous solutions

Complex formation of L-aspartic acid (H2Asp) with Cu2+ ion was studied by calorimetry at 298.15, 308.15, and 318.15 K and ionic strength of 0.50, 0.75, and 1.00 (KNO3). The thermodynamic parameters (ΔrG°, ΔrH°, ΔrS°, and ΔrC°p) of reactions of formation of CuAsp22- and were calculated. The results were compared to the corresponding data for the related compounds and a hypothesis about the ligand coordination mode in these complexes was put forward.

Thermodynamics of the formation of copper(II) complexes with L-histidine in aqueous solution

Thermodynamics of the formation of copper(II) complexes with L-histidine in aqueous solution

Usage of X-ray absorption spectroscopy and extractive fractionation in studies of the Cu (II) and Zn (II) ions in soils

XANES spectroscopy is an effective method for the study of bonds between metals and soil components. The study of structural organization in different soil samples and soil phases saturated with Cu 2+ and Zn 2+ ions by using XANES allowed determining the mechanism of their interaction with soil phases and all the chemical bindings taken place in the course of this process. Changes in the structure of the metal ion, in particular breakdown of the symmetry of electron orbits of atoms, take place due to interaction with soil components. Application of this method demonstrated that the state of copper and zinc introduced in chernozem as oxides did not change after one year of incubation. Copper is absorbed after being introduced as soluble salts, and copper ions are incorporated in the octahedral and tetrahedral sites of minerals and bonded with humic materials at the expense of covalent bond and the formation of coordination humate copper complexes. Zinc included into octahedric structures of layered minerals and hydro(oxides) can be inner-and outer-sphere adsorbed. It is shown that the action of the metal bound to soil components becomes weakened in case of increasing the Cu and Zn load (from 2000 to 10000 mg/kg) especially applied in the form of soluble salts. Extractive fractionation of metal compounds in chernozem samples, artificially contaminated with copper and zinc salts serves as evidence of absorbing the applied Cu 2+ ions by the soil organic matter and Zn 2+ ions – by silicates, carbonates, and Fe-Mn oxides.

Synthesis, spectroscopic and DNA interaction studies on bis(1-amidino-O-2-alkoxyethylurea)Cu(II)nitrate where alkoxy = methoxy, ethoxy or butoxy

Three new copper(II) complexes, bis(1-amidino-O-2-alkoxyethylurea)Cu(II)nitrate, where alkoxy=methoxy (1), ethoxy (2) or butoxy (3) have been synthesized and characterized. Electron paramagnetic resonance (EPR) spectra of complexes 2 and 3 gave half-field signal (ΔMs=±2) ca. 1600 G, in addition to fine structure due to zero field splitting (ZFS) characteristics of the S=1 system suggesting the formation of binuclear copper(II) complexes. Single crystal X-ray diffraction studies of complex 1 revealed that the copper atoms have tetra-coordinated square planar environments formed by two N atoms derived from two different ligands. The interaction of the copper(II) complexes with DNA were investigated by absorption spectroscopy, fluorescence spectroscopy, viscosity measurements and thermal denaturation studies. The values of binding constant (Kb) and the apparent binding constant (Kapp) calculated from the absorption and fluorescence spectral studies suggest that the binding strength of the three complexes are in the order 3>2>1. The three complexes interact with CT-DNA primarily by partial or non-intercalative modes.

Synthesis and structural investigation of R2Si (R = Me, Ph) bridged di-N-heterocyclic carbenes.

Functionalization of the C4 carbon of an imidazol-derived N-heterocyclic carbene (NHC) may allow fine-tuning of the electronic and steric properties of the C2 carbene center. A facile route to silyl-functionalized di-N-heterocyclic carbenes (Di-NHCs) is described. Treatment of the polymeric lithiated NHC, {Li(IPrH)}n (1) (Li(IPrH) = {(N-2,6-iPr2C6H3)2CHCLi}C:) with a dichlorosilane affords monomeric silyl-functionalized Di-NHCs, R2Si(IPrH)2 (R = Ph, 2; Me, 3). Interestingly, silyl-functionalized mono-NHC, Ph2(Cl)Si(IPrH) (4) with a pendant chloro-substituent can also be exclusively isolated maintaining the reactants 1 and Ph2SiCl2 ratio. NHCs 2 and 4 readily form copper complexes, Ph2Si{(IPrH)CuCl}2 (5) and Ph2(Cl)Si{(IPrH)CuCl} (6), on reaction with CuCl. Straightforward conversion of an NHC to a Di-NHC (2 or 3) via C4 functionalization is reported for the first time. Molecular structures of 2, 4, 5 and 6 have been established by single crystal X-ray diffraction studies.

Copper-chelating azides for efficient click conjugation reactions in complex media.

The concept of chelation-assisted copper catalysis was employed for the development of new azides that display unprecedented reactivity in the copper(I)-catalyzed azide-alkyne [3+2] cycloaddition (CuAAC) reaction. Azides that bear strong copper-chelating moieties were synthesized; these functional groups allow the formation of azide copper complexes that react almost instantaneously with alkynes under diluted conditions. Efficient ligation occurred at low concentration and in complex media with only one equivalent of copper, which improves the biocompatibility of the CuAAC reaction. Furthermore, such a click reaction allowed the localization of a bioactive compound inside living cells by fluorescence measurements.

Complex Formation of Nickel(II) and Copper(II) with Barbituric Acid

Equilibrium studies have been carried out on complex formation of M2+ ions (M = Ni and Cu) with L = barbituric acid (BA) in aqueous solution at 25.0±0.1°C and with an ionic strength of I=0.10 M (KNO3) in aqueous medium. The basicity of the ligand was also assessed by the determination of the dissociation constants of the ligand. The experimental pH titration data were analyzed with the help of the BEST computer program in order to evaluate the stability constants of the various species formed. The stability constants of the binary systems decrease in the order of Cu(II) > Ni(II). Distribution diagrams for the species were drawn showing the concentrations of individual species as a function of pH by the SPE software program.

Synthese und Koordinationsverhalten neuer Schiffscher Basen aus 3-Formylacetylaceton und natürlichenL-Aminosäuren

Three novel chiral Schiff Base ligands (H2L) were prepared from the condensation reaction of 3-formyl acetylacetone with the amino acids L-alanine, L-phenylalanine, and L-threonine. X-ray single crystal analyses revealed that the Schiff Base compounds exist as enamine tautomers in the solid state. The molecular structure of the compounds is stabilized by an intramolecular hydrogen bridge between the enamine NH function and a carbonyl oxygen atom of the pentandione residue. Treatment of the ligands H2L with copper(II) actetate in the presence of pyridine led to the formation of copper complexes [CuL(py)]. In each of the complexes the copper atoms adopt a distorted square-pyramidal coordination. Three of the basal coordination sites are occupied by the doubly deprotonated Schiff Bases L2– which act as tridentate chelating O, N, O-ligands. The remaining coordination sites are occupied by a pyridine ligand at the base and a carboxyl oxygen atom of a neighboring complex at the apical position. The latter coordination is responsible for a catenation of the complexes in the solid state.

PET imaging of tumours with a64Cu labeled macrobicyclic cage amine ligand tethered to Tyr3-octreotate

The use of copper radioisotopes in cancer diagnosis and radionuclide therapy is possible using chelators that are capable of binding Cu(II) with sufficient stability in vivo to provide high tumour-to-background contrast. Here we report the design and synthesis of a new bifunctional chelator, 5-(8-methyl-3,6,10,13,16,19-hexaaza-bicyclo[6.6.6]icosan-1-ylamino)-5-oxopentanoic acid (MeCOSar), that forms copper complexes of exceptional stability by virtue of a cage amine (sarcophagine) ligand and a new conjugate referred to as SarTATE, obtained by the conjugation of MeCOSar to the tumour-targeting peptide Tyr(3)-octreotate. Radiolabeling of SarTATE with (64)Cu(II), a radioisotope suitable for positron emission tomography (PET), was fast (~20 min), easily performed at room temperature and consistently resulted in high radiochemical purity (>99%). In vitro and in vivo evaluation of (64)CuSarTATE demonstrated its high selectivity for tumour cells expressing somatostatin receptor 2 (sstr2). Biodistribution and PET imaging comparisons were made between (64)CuSarTATE and (64)Cu-labeled DOTA-Tyr(3)-octreotate ((64)CuDOTATATE). Both radiopharmaceuticals showed excellent uptake in sstr2-positive tumours at 2 h post-injection. While tumour uptake of (64)CuDOTATATE decreased significantly at 24 h, (64)CuSarTATE activity was retained, improving contrast at later time points. (64)CuSarTATE accumulated less than (64)CuDOTATATE in the non-target organs, liver and lungs. The uptake of (64)CuSarTATE in the kidneys was high at 2 h but showed significant clearance by 24 h. The new chemistry and pre-clinical evaluation presented here demonstrates that MeCOSar is a promising bifunctional chelator for Tyr(3)-octreotate that could be applied to a combined imaging and therapeutic regimen using a combination of (64)Cu- and (67)CuSarTATE complexes, owing to improved tumour-to-non-target organ ratios compared to (64)CuDOTATATE at longer time points.

Understanding the relationship between trace mineral forms and digestive pH conditions. Part I—Copper

Understanding the chemical nature of trace-metal elements in an aqueous solution is pivotal to interpreting absorption and nutritional studies in production animals. To characterize copper(II)-ion solution chemistry, a series of aqueous titrations with strong base were performed on 1:1- and 1:2-molar-ratio mixtures of copper(II) nitrate and 5 weak organic acids commonly found in commercial trace-metal products. Three amino acids, glycine, lysine, and methionine, and 2 weak organic acids, propionic and 2-hydroxy-4-(methyl-thio)-butyric, were included. Based on the volume of NaOH and the pH measured after each addition, descriptions of the chemical forms of the copper(II) ions in solutions of varying acidities were developed. The forms fell into 4 groupings: free copper(II) ions and organic-acid molecules; mixtures of copper(II) ions, organic-acid molecules, and copper–organic acid complexes; mixtures of organic-acid complexes and hydroxyl complexes; and copper(II) precipitates. As the various copper and ligand solution combinations changed from an acid (stomach conditions) to a basic (intestine conditions) environment, there was either the formation of insoluble metal ion precipitates that indicated a loss of the soluble metal ions available for absorption, or there was the formation of stable and soluble copper(II) complexes that prevented precipitation but also reduced the free metal ion available for absorption.