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     

Coordination modes of N-(2-hydroxyphenyl)methyl-bis-(2-pyridylmethyl)amine with copper (I) and (II) halides

The title ligand, N-(2-hydroxyphenyl)methyl-bis-(2-pyridylmethyl)amine, was prepared via a condensation-reduction synthetic route. The compounds, CuCl(C₁₉H₁₉N₃O) and [CuBr(C₁₉H₁₉N₃O)]⁺Br⁻ · 3H₂O, were readily synthesized from the reaction of CuCl or CuBr₂ and the ligand in acetonitrile. The title copper(I) compound is an O-H ? Cl hydrogen-bonded linear chain of tetrahedrally coordinated copper centers, and the title copper(II) compound exists as two strongly tetragonally distorted dibromide bridged metal cations in a dimer with the phenol hydroxyl groups weakly bound in a trans-fashion to one of the bridging bromides. In the copper(I) complex the phenoxy group acts only as a hydrogen bond donor, whereas in the copper(II) complex it acts both as a ligand and a hydrogen bond donor.     

Binuclear copper(II) complexes of some potentially sexadentate phthalazine hydrazone ligands

Binuclear copper(II) complexes of three potentially sexadentate phthalazine hydrazone ligands, obtained by reacting 1,4-dihydrazinophthalazine with an appropriate aldehyde, are reported, in which variable terminal donor substituents include the phenol (DPSI), N-methyl imidazole (DPIM) and pyridine (PHP) groups. For the phenol substituted ligand (DPSI) the phenol residues are sufficiently acidic that in most cases this ligand behaves as a dianion. Hydroxy bridged structures are proposed in almost all cases based on analytical, infrared and magnetic data. Reduced magnetic moments are observed for all compounds indicating anti-ferromagnetically coupled copper(II) centres and in six cases magnetic moments of < 0.5 BM are observed. The copper(II) centres appear to have distorted square planar stereochemistries in the systems which involve two metals bound to each ligand. In one case involving the copper chloride complex of DPIM a polynuclear system is proposed involving three metals per ligand.     

Copper(II) complexes of carnosine, glycylglycine, and glycylglycine-imidazole mixtures

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     

Comparative solvolytic stabilities of copper(II) nanoballs and dinuclear Cu(II) paddle wheel units

The self-assembly of copper(II) ions and 5-(2-(2-hydroxyethoxy)ethoxy)benzene-1,3-dicarboxylic acid (2) leads to hollow nanoballs in which 12 dinuclear copper(II) paddle wheel units are interconnected via 24 ligands, as determined by single crystal X-ray structure analysis. The nanoball dissociates in aqueous solutions, and in the presence of an excess of ligand it transforms into a three-dimensional network, but is stable in organic solvents. The thermodynamic stability of the nanoball against dissociation in aqueous solution is studied and compared to simple copper(II) paddle wheel complexes. The results reveal enhanced thermodynamic stability of the nanoball as compared to discrete copper(II) paddle wheel complexes due to chelate effects and positive cooperativity.     

Copper(II) assisted hydrolysis of 2,4,6-tris(pyrazol-1-yl)-1,3,5-triazine. Crystal and molecular structure of catena-[CuL(H2O)Cl]n (L = 2,4-dione-1,3,5-(1H)-triazin-1-amido)

This article describes the partial hydrolysis of the multidentate ligand 2,4,6-tris(pyrazol-1-yl)-1,3,5-triazine in the presence of copper(II), to give the anionic ligand 2,4-dione-1,3,5-(1H)-triazin-1-amido, which was isolated as the cupric complex catena-[CuL(H₂O)Cl]_n, where L is the amido ligand. No other hydrolysis products were isolated or identified.The complex defines a zigzag 1D covalent chain, along the b cell axis, through apical copper-oxygen bonds (Cu-N-C-O···Cu bridges).     

Copper(II) interaction with 3,5-diisopropylsalicylic acid (Dips): new insights on its role as a potential *OH inactivating ligand

The purpose of this study was to identify the low molecular mass complexes formed between copper(II) and 3,5-diisopropylsalicylic acid (Dips) in physiological conditions. Copper(II)-Dips complex equilibria were determined using glass electrode potentiometry and their solution structures checked by UV-visible (UV-vis) spectrophotometry. Because of the low solubility of Dips in water, the equilibria were investigated in different water/ethanol mixtures. Formation constants were extrapolated to 100% water and then compared with the values obtained for the other anti-inflammatory drugs previously studied. Given the prime role of histidine as the copper(II) ligand in blood plasma, copper(II)-histidine-Dips ternary equilibria were studied under similar experimental conditions. Computer simulations of copper(II) distribution relative to different biofluids, gastrointestinal (g.i.) fluid and blood plasma, show that like salicylic and anthranilic acids, Dips favors g.i. copper absorption, but cannot exert any significant influence on plasma copper distribution. Moreover, Dips can mobilize increasing fractions of copper(II) as the pH decreases. In conclusion, Dips seems to correspond to the notion of *OH-inactivating ligand (OIL) as determined for anthranilic acid.     

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), cobalt(II) and nickel(II) complexes of alkyl-substituted tris(2-benzimidazolylmethyl)amines and their ternary copper(II) systems containing several thiolates

Copper(II), cobalt and nickel(II) complexes of tris(benzimidazolylmethyl)amine(1) and of its methyl(2), isobutyl(3) or isopropyl(4)-substituted derivatives of one of the backbone methylene groups were prepared and characterized. The ligands (1)–(3) afforded trigonal bipyramidal copper(II) complexes, whereas ligand (4) gave a tetrahedrally distorted tetragonal one because of the steric hindrance arising from the isopropyl group. All the cobalt(II) complexes prepared were supposed to be tetrahedral or pseudotrigonal bipyramidal, and all the nickel(II) complexes to be slightly tetrahedrally distorted octahedral. Ternary copper(II) systems containing several thiolates as the third component exhibited intense blue, brown or green color under a reduced temperature by virtue of the charge transfer bands, S^? → Cu.     

Spectroscopy of Cu(II)-PcoC and the multicopper oxidase function of PcoA,two essential components of Escherichia coli pco copper resistance operon

The plasmid-encoded pco copper resistance operon in Escherichia coli consists of seven genes that are expressed from two pco promoters in response to elevated copper; however, little is known about how they mediate resistance to excess environmental copper. Two of the genes encode the soluble periplasmic proteins PcoA and PcoC. We show here that inactivation of PcoC, and PcoA to a lesser extent, causes cells to become more sensitive to copper than wild-type nonresistant strains, consistent with a tightly coupled detoxification pathway. Periplasmic extracts show copper-inducible oxidase activity, attributed to the multicopper oxidase function of PcoA. PcoC, a much smaller protein than PcoA, binds one Cu(II) and exhibits a weak electronic transition characteristic of a type II copper center. ENDOR and ESEEM spectroscopy of Cu(II)-PcoC and the (15)N- and Met-CD(3)-labeled samples are consistent with a tetragonal ligand environment of three nitrogens and one aqua ligand "in the plane". A weakly associated S-Met and aqua are likely axial ligands. At least one N is a histidine and is likely trans to the in-plane aqua ligand. The copper chemistry of PcoC and the oxidase function of PcoA are consistent with the emerging picture of the chromosomally encoded copper homeostasis apparatus in the E. coli cell envelope [Outten, F. W., Huffman, D. L., Hale, J. A., and O'Halloran, T. V. (2001) J. Biol. Chem. 276, 30670-30677]. We propose a model for the plasmid system in which Cu(I)-PcoC functions in this copper efflux pathway as a periplasmic copper binding protein that docks with the multiple repeats of Met-rich domains in PcoA to effect oxidation of Cu(I) to the less toxic Cu(II) form. The solvent accessibility of the Cu(II) in PcoC may allow for metal transfer to other plasmid and chromosomal factors and thus facilitate removal of Cu(II) from the cell envelope.     

1,4-Di(1,2,3,4-tetrazol-2-yl)butane as a precursor of new 2D and 3D coordination polymers of Cu(II)

A series of new coordination polymers of Cu(II) have been prepared in a reaction between copper(II) perchlorate or tetrafluoroborate salt and a novel ligand 1,4-di(1,2,3,4-tetrazol-2-yl)butane (bbtz). The compounds were characterised by an elemental analysis, TG measurements, IR, EPR and UV-Vis spectroscopy. Crystal structures of bbtz and five complexes of Cu(II) were determined by a single crystal X-ray diffraction measurement performed at 100 K. The composition and architecture of the obtained complexes strongly depend on the reaction conditions especially on the kind of solvent. Investigated complexes are composed of polymeric macrocations and non-coordinated anions. In all cases the bbtz molecules act as the bidentate ligand coordinated to metal(II) ions via N4, N4^′ nitrogen atoms from tetrazole rings. The complexes {[Cu(bbtz)₂(MeOH)₂]X₂}_∞ (X=ClO₄⁻, BF₄⁻) crystallise from methanol as 2D coordination polymers. In these compounds central metal ions are coplanar linked by molecules of bbtz and a coordination sphere is completed by axially coordinated solvent molecules. The complexes {[Cu(bbtz)₃]X₂}_∞ (X=ClO₄⁻, BF₄⁻) were synthesised in EtOH/H₂O solvent system and posses a common network topology. In this group of complexes each central atom is linked by ligand molecules to six other in plane arranged central atoms resulting in 2D networks. Reactions between Cu(II) salts and bbtz performed in absolute ethanol resulted in the formation of the next type of product. In {[Cu(bbtz)₃](ClO₄)₂·2EtOH}_∞ neighboured copper(II) ions are linked by ligand molecules in the three directions what leads to the formation of 3D net. A crystal of this complex is composed of two mutually interpenetrated 3D networks.     

Potentiometric and spectroscopic studies on the solution molecular structures of copper(II)-[S]-2-[N-(2′-hydroxybenzyl)aminomethyl]pyrrolidine complexes, potential non-steroidal anti-inflammatory agents (NSAIDs)

The purpose of this study was to investigate the complexes formed by copper(II) with potential non-steroidal anti-inflammatory agents (NSAIDs) under physiological conditions. A former study suggested that 2-benzylaminomethylpyrrolidine ligands could be good candidates as potential OIL (OH-inactivating ligand) when complexed to copper(II). In order to assess the chemical behavior as OIL, [S]-2-[N-(2′-hydroxybenzyl)aminomethyl]pyrrolidine (OHbamp) was synthesized and bound to copper(II). Physico-chemical properties were determined at 37 °C in 0.15 M NaCl using glass electrode potentiometry, UV-Vis and circular dichroism spectroscopies, before and after copper(II) complexation. [Cu(OHbamp)(H₂O)₃]⁺ was the main complex found at both physiological and inflammatory pH values, showing appreciable stability at pathological pH compared to copper(II) complexes of histidine, the predominant low-molar-mass ligand of copper(II) in blood plasma. However, neutral species such as [Cu(OHbamp)₂(H₂O)₂] and [Cu(OHbamp)(OH)(H₂O)₃] are predominant only above pH 8, preventing a significant amount of drug from diffusing through membranes at inflammatory pH. In conclusion, copper(II)-OHbamp system does not meet all the requirements to be an OIL. Nevertheless, these results allow us to better identify the chemical features needed for a good OIL candidate.     

Spectroscopic and structural studies of 6-(1-methylbenzimidazol-2-yl)-1H-pyridin-2-one and of an unusual T4(2)7(2)6(2)7(2) water tape stabilized by the copper(II) coordination polymer

The solid-state structures of 6-(1-methylbenzimidazol-2-yl)-1H-pyridin-2-one (HL) and the copper(II) complex [Cu(L⁻)₂(OH₂)]·2H₂O (1) are established by X-ray crystallography and also by means of physicochemical and spectroscopic methods. The molecules of HL form a self-complementary head-to-tail hydrogen-bonded dimer through C-H?N and C-H?O contacts to give an infinite 1D chain. The copper(II) complex (1) is five-coordinate with distorted trigonal-bipyramidal (TBP) geometry of the N₄O donor atoms. The electronic and EPR data are in agreement with the X-ray structure of 1, showing that HL coordinates to copper(II) centre as a mono-anionic ligand through deprotonated pyridone N atom and the tertiary benzimidazole nitrogen atom to form a neutral complex in which the water molecule occupies the fifth position. The 1D water tape, T4(2)7(2)6(2)7(2) is anchored to the host through hydrogen bonds between coordinated water molecule [O(3w)] as acting double H-donor, pyridone carbonyl groups [O(2) and O(1)] as double H-acceptor and the lattice water molecules [O(4w) and O(5w)] as double H-donor and single H-acceptor).     

Synthesis, characterization, and crystal structures of hydrotris(2-mercapto-1-imidazolyl)borate-based zinc(II) and copper(I) complexes

The reaction of the tripod ligand hydrotris(2-mercapto-1-imidazolyl)borate Tm^xylyl with zinc(II) perchlorate in methanol afforded the mononuclear complex of the type [Tm^xylyl-Zn(mim^xylyl)]ClO₄ (1). Whereas under the same conditions, the reaction with copper(II) perchlorate gives rise to the simultaneous formation of the dinuclear copper(I) complex [Tm^xylylCu]₂ (2). The chemical formulae of the complexes have been characterized by elemental chemical analysis, IR-NMR spectroscopies, and single crystal X-ray methods. In complex 1, the zinc(II) atom displays a distorted tetrahedral environment. While in complex 2, the Tm^xylyl ligand bridges the two copper(I) atoms in an asymmetric manner with trigonal geometry. The inverted conformation of the ligand Tm^xylyl at the boron center, allows the B-H units to be directed towards the copper centers. The greater reactivity of the borohydride groups towards metal centers enhances the reduction of Cu(II) to Cu(I). The obtained kinetic results for the methylation reactions of 1 and 2 indicate that these bound thione complexes are less suitable to electrophilic attack than the thiolate ligand.     

Application of saccharose as copper(II) ligand for electroless copper plating solutions

Saccharose, forming sufficiently stable complexes with copper(II) ions in alkaline solutions, was found to be a suitable ligand for copper(II) chelating in alkaline (pH>12) electroless copper deposition solutions. Reduction of copper(II)-saccharose complexes by hydrated formaldehyde was investigated and the copper deposits formed were characterized. The thickness of the compact copper coatings obtained under optimal operating conditions in 1h reaches ca. 2 microm at ambient temperature. The plating solutions were stable and no signs of Cu(II) reduction in the bulk solution were observed. Results were compared with those systems operating with other copper(II) ligands.     

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.     

Spectroscopic,structural and antibacterial properties of copper(II) complexes with bio-relevant 5-methyl-3-formylpyrazole N(4)-benzyl-N(4)-methylthiosemicarbazone

The coordination behaviour of the title ligand, 5-methyl-3-formylpyrazole N(4)-benzyl-N(4)-methylthiosemicarbazone(HMPz4BM), is reported with solid state isolation of copper(II) complexes, [Cu(HMPz4BM)X₂] (X = Cl, Br, NO₃, ClO₄ and BF₄) which have been spectroscopically and structurally characterised. I.r. data for the free ligand and its Cu(II) complexes indicate that HMPz4BM exhibits a neutral NNS tridentate function via the pyrazolyl nitrogen(tertiary), azomethine nitrogen and thione sulphur. Electronic spectral data are suggestive of a square pyramidal environment for the seemingly pentacoordinated Cu(II) species. E.s.r parameters (RT and LNT) of the reported copper(II) complexes are indicative of a dx_x2–y2 ground state for the reported species. Cyclic voltammograms of Cu(II) complexes show a quasireversible Cu^II/Cu^III couple and also an irreversible Cu^II/Cu^I couple. X-ray crystallography of a representative species, [Cu(HMPz4BM)(NO₃)₂] (C2/c, monoclinic ), has unambiguously documented the conjectural findings from i.r. data that coordinating sites of the title ligand are pyrazolyl (tertiary)nitrogen, azomethine nitrogen and the thione sulphur (NNS); and the oxygen of one of the nitrate ions has occupied the basal plane; the fifth coordination position has been occupied by the oxygen of another nitrate ion in a square pyramidal geometry. The antibacterial properties of the ligand and its copper(II) complexes studied on microorganism, Staphylococcus aureus have pointed out that most of the complexes have higher activities than that of the free ligand.     

Preparation,characterization and crystal structures of manganese(II), iron(III) and copper(II) complexes of the bis[di-1,1-(2-pyridyl)ethyl]amine (BDPEA) ligand; evaluation of their DNA cleavage activities

The synthesis of a new tetrapyridyl ligand, bis[di-1,1-(2-pyridyl)ethyl]amine (BDPEA), is described. Complexation of this ligand with manganese(II), iron(III) or copper(II) chlorides afforded mononuclear complexes: Mn(BDPEA)Cl2 (1) [Fe (BDPEA)Cl2]Cl (2) and [Cu(BDPEA)Cl]Cl (3). In all cases, BDPEA is coordinated to the metal center by three pyridine nitrogen atoms and the secondary amine. The geometrical environments around the metals in Mn(BDPEA)Cl2 and [Fe(BDPEA)Cl2]Cl are best described as distorted octahedrals and in [Cu (BDPEA)Cl]Cl as a slightly distorted square pyramid. The DNA cleavage activities of manganese(II), iron (III) or copper(II) complexes of both BDPEA and another tetrapyridyl ligand, bis[di(2-pyridyl) methyl]amine (BDPMA), in the presence of an oxidant (H2O2) or a reducing agent (ascorbate) with air, are reported. The iron(III) complexes exhibited significantly enhanced efficiencies, compared to copper(II) complexes. [Fe(BDPEA)Cl2]Cl is found to be the most active DNA cleaver, in agreement with a better stability of BDPEA in oxidizing conditions.     

Inactivation of thiostrepton by copper(II)

Summary Among the various bivalent metal ions tested, only copper(II) was found to bind to thiostrepton (M _rr 1650) in a stoichiometric ratio of 4:1. The binding of four copper ions to a thiostrepton molecule resulted in (a) irreversible loss in biological activity and (b) a change in the ultraviolet absorption spectrum of the antibiotic. Potentiometric titration of thiostrepton in the presence of copper(II) revealed dissociation of the antibiotic with a loss of 11 protons/molecule. Based on the preferential ability of copper(II) to bind to thiostrepton in the presence of some copper-complexing compounds containing similar ligand groups to the antibiotic, the possible co-ordinating atoms of the thiostrepton molecule involved in binding to the metal ion are discussed.     

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.