Role Of Copper Research Articles

The activity of ascorbic acid and catechol oxidase, the rate of photosynthesis and respiration as related to plant organs, stage of development and copper supply

Some experiments were performed to investigate the physiological role of copper in oat and sunflower and to recognize some effects of copper deficiency. Oat and sunflower plants were grown in pots on a peat soil under copper deficiency conditions (–Cu) or with the optimal copper supply (+Cu). In plants the following measurements were carried out: 1) the activity of ascorbic acid oxidase (AAO) and of catechol oxidase (PPO) in different plant organs and at different stages of plant development, 2) the activity and the rate of photosynthesis, 3) the activity of RuDP-carboxylase, 4) the intensity of plant respiration. The activity of AAO and of PPO, and also the rate and the activity of photosynthesis were significantly lower under conditions of copper deficiency. The activity of both discussed oxidases depended on: 1) the plant species, 2) plant organs, 3) stage of plant development. Copper deficiency caused decrease of the respiration intensity of sunflower leaves but it increased to some extent the respiration of oat tops. Obtained results are consistent with the earlier suggestion of the authors that the PPO activity in sunflower leaves could be a sensitive indicator of copper supply of the plants, farther experiments are in progress.

ChemInform Abstract: Another Role of Copper in the Simmons—Smith Reaction: Copper‐Catalyzed Nucleophilic Michael‐Type Cyclopropanation of α,β‐Unsaturated Ketones.

AbstractCyclopropanation of unsaturated ketones [(I), (IV), and (VI)] using the Furukawa procedure in the presence of Cu(OTf)2 leads to better product yields than Simmons—Smith conditions in some cases.

First-Principles Study of C2 Oxygenates Synthesis Directly from Syngas over CoCu Bimetallic Catalysts

Density functional theory (DFT) calculations were used to study C2 oxygenate from syngas over bimetallic Co/Cu catalysts. The thermodynamics and kinetics for all possible elementary steps involved in the formation of C2 oxygenate from syngas have been investigated on both pure and Cu-doped Co(0001) surfaces. By comparing the results on two surfaces, the role of copper in improving the selectivity toward C2 oxygenates has been identified as two aspects: (1) controlling the Co ensemble size and blocking the active sites for C–O bond cleavage, which results in inhibition of CHx coupling to hydrocarbons; (2) providing undissociated CO/HCO as well as reducing the barriers for HCO insertion toward the formation of oxygenate precursors. With the combination of the mechanistic study and the charge analysis on the bimetallic surface, we conclude that the nature of the copper promotion is mainly a geometric effect rather than an electronic effect.

The role of copper and the copper-related protein CUTA in mediating APP processing and Aβ generation

One major pathologic hallmark and trigger of Alzheimer's disease (AD) is overproduction and accumulation of β-amyloid (Aβ) species in the brain. Aβ is derived from β-amyloid precursor protein (APP) through sequential cleavages by β- and γ-secretases. Abnormal copper homeostasis also contributes to AD pathogenesis. Recently, we find that a copper-related protein, CutA divalent cation tolerance homolog of Escherichia coli (CUTA), interacts with the β-secretase β-site APP cleaving enzyme 1 (BACE1) and inhibits APP β-processing and Aβ generation. Herein, we further found that overexpression of CUTA increases intracellular copper level, whereas copper treatments promote CUTA expression. We also confirmed that copper treatments promote APP expression and Aβ secretion. In addition, copper treatments promoted the increase of Aβ secretion induced by CUTA downregulation but had no effect on CUTA-β-site APP cleaving enzyme 1 interaction. On the other hand, CUTA overexpression ameliorated copper-induced Aβ secretion but had no effect on APP expression. Moreover, we found that Aβ treatments can reduce both CUTA and copper levels in mouse primary neurons. Consistently, both CUTA and copper levels were decreased in the hippocampus of APP/PS1 AD mouse brain. Together, our results reveal a reciprocal modulation of copper and CUTA and suggest that both regulate Aβ generation through different mechanisms, although Aβ mutually affects copper and CUTA levels.

Role of copper in regression of cardiac hypertrophy.

Pressure overload causes an accumulation of homocysteine in the heart, which is accompanied by copper depletion through the formation of copper-homocysteine complexes and the excretion of the complexes. Copper supplementation recovers cytochrome c oxidase (CCO) activity and promotes myocardial angiogenesis, along with the regression of cardiac hypertrophy and the recovery of cardiac contractile function. Increased copper availability is responsible for the recovery of CCO activity. Copper promoted expression of angiogenesis factors including vascular endothelial growth factor (VEGF) in endothelial cells is responsible for angiogenesis. VEGF receptor-2 (VEGFR-2) is critical for hypertrophic growth of cardiomyocytes and VEGFR-1 is essential for the regression of cardiomyocyte hypertrophy. Copper, through promoting VEGF production and suppressing VEGFR-2, switches the VEGF signaling pathway from VEGFR-2-dependent to VEGFR-1-dependent, leading to the regression of cardiomyocyte hypertrophy. Copper is also required for hypoxia-inducible factor-1 (HIF-1) transcriptional activity, acting on the interaction between HIF-1 and the hypoxia responsible element and the formation of HIF-1 transcriptional complex by inhibiting the factor inhibiting HIF-1. Therefore, therapeutic targets for copper supplementation-induced regression of cardiac hypertrophy include: (1) the recovery of copper availability for CCO and other critical cellular events; (2) the activation of HIF-1 transcriptional complex leading to the promotion of angiogenesis in the endothelial cells by VEGF and other factors; (3) the activation of VEGFR-1-dependent regression signaling pathway in the cardiomyocytes; and (4) the inhibition of VEGFR-2 through post-translational regulation in the hypertrophic cardiomyocytes. Future studies should focus on target-specific delivery of copper for the development of clinical application.

Promoting χ-Fe5C2(100)0.25 with copper – a DFT study

The role of copper in iron based Fischer–Tropsch catalysts was investigated using DFT with χ-Fe5C2(100)0.25 as a model surface. The presence of atomic copper on the iron-rich χ-Fe5C2(100)0.25-surface is more favorable than its presence in surface. Nevertheless, the segregation of copper from the surface yielding fcc-Cu remains an exergonic process. Carbon monoxide at a coverage of 2.2 CO per nm2 stabilizes atomic copper on this surface. The presence of copper results in the redshift in the stretching frequency of adsorbed CO. The mobility of copper atoms was investigated on χ-Fe5C2(100)0.25 in the presence of CO. The hopping frequency is reduced due to the presence of CO, although never enough to avoid formation of fcc-Cu on a shorter time scale than typically required for the formation of hydrocarbons in the Fischer–Tropsch synthesis.

Effects of copper on the preparation and characterization of Na–Ca–P borate glasses

Glasses in the system Na2O–CaO–B2O3–P2O5: CuO have been prepared by melt quenching at 1200°C and rapidly cooling at room temperature. The structural, optical and thermal properties have been investigated using X-ray diffraction (XRD), ultraviolet–visible (UV–VIS) spectroscopy, thermogravimetric-differential thermal analysis (TG-DTA), Fourier transform infrared (FTIR) spectroscopy, high resolution scanning electron microscopy (HRSEM) with energy dispersive X-ray (EDX) spectroscopy and high resolution transmission electron microscope (HRTEM) with energy dispersive X-ray (EDAX). The amorphous and crystalline nature of these samples was verified by XRD. Glass transition, crystallization and thermal stability were determined by TG-DTA investigations. Direct optical energy band gaps before and after doping with different percents of copper oxide were evaluated from 4.81eV to 2.99eV indicated the role of copper in the glassy matrix by UV spectra. FTIR spectrum reveals characteristic absorption bands due to various groups of triangular and tetrahedral borate network. Due to the amorphous nature, the particles like agglomerates on the glass surface were investigated by the HRSEM analysis. The crystalline nature of the samples in XRD is confirmed by SAED pattern using HRTEM.

Pentafluorosulfanylbenzene chemistry: Role of copper in the Sheppard reaction, direct fluorination of aromatic sulfenyl chlorides, and several potentially energetic SF5-benzenes

In honor of the awardee Dr. Teruo Umemoto and his significant advances in the preparation of pentafluorosulfanylbenzenes [1], we will first overview our results aimed at understanding the importance of copper (and other coinage metals) in W.A. Sheppard's original synthesis of SF5-benzenes [2] as well as a new route to SF5-benzenes involving the direct fluorination of aromatic sulfenyl chlorides (Ar–S–Cl). Further nucleophilic substitution chemistry of the active halogen atom in 1-chloro-2,6-dinitrobenzene-4-pentafluorosulfanylbenzene will be presented, including chemistry aimed at potentially energetic materials such as an SF5-analog of picric acid.

The many "faces" of copper in medicine and treatment.

Copper (Cu) is an essential microelement found in all living organisms with the unique ability to adopt two different redox states—in the oxidized (Cu2+) and reduced (Cu+). It is required for survival and serves as an important catalytic cofactor in redox chemistry for proteins that carry out fundamental biological functions, important in growth and development. The deficit of copper can result in impaired energy production, abnormal glucose and cholesterol metabolism, increased oxidative damage, increased tissue iron (Fe) accrual, altered structure and function of circulating blood and immune cells, abnormal neuropeptides synthesis and processing, aberrant cardiac electrophysiology, impaired myocardial contractility, and persistent effects on the neurobehavioral and the immune system. Increased copper level has been found in several disorders like e.g.: Wilson’s disease or Menke’s disease. New findings with the great potential for impact in medicine include the use of copper-lowering therapy for antiangiogenesis, antifibrotic and anti-inflammatory purposes. The role of copper in formation of amyloid plaques in Alzheimer’s disease, and successful treatment of this disorder in rodent model by copper chelating are also of interest. In this work we will try to describe essential aspects of copper in chosen diseases. We will represent the evidence available on adverse effect derived from copper deficiency and copper excess. We will try to review also the copper biomarkers (chosen enzymes) that help reflect the level of copper in the body.

The cytotoxicity of the anticancer drug elesclomol is due to oxidative stress indirectly mediated through its complex with Cu(II)

Elesclomol is an anticancer drug that is currently undergoing clinical trials. Elesclomol forms a strong 1:1 complex with Cu(II) and may exert its anticancer activity through the induction of oxidative stress and/or its ability to transport copper into the cell. A UV–vis spectrophotometric titration showed that Cu(I) also formed a 1:1 complex with elesclomol. Ascorbic acid, but not glutathione or NADH, potently reduced the Cu(II)-elesclomol complex to produce hydrogen peroxide. Even though hydrogen peroxide mediated reoxidation of the copper(I) produced by ascorbic acid reduction has the potential to lead to hydroxyl radical formation, electron paramagnetic resonance spin trapping experiments, either with or without added hydrogen peroxide, showed that the ascorbic acid-reduced Cu(II)-elesclomol complex could not directly generate damaging hydroxyl radicals. Both Cu(II)-elesclomol and elesclomol potently oxidized dichlorofluorescin in K562 cells. The highly specific copper chelators tetrathiomolybdate and triethylenetetramine were found to greatly reduce the cytotoxicity of both elesclomol and Cu(II)-elesclomol complex towards erythroleukemic K562 cells, consistent with a role for copper in the cytotoxicity of elesclomol. The superoxide dismutating activity of Cu(II)-elesclomol was much lower than that of Cu(II). Depletion of glutathione levels in K562 cells by treatment with buthionine sulfoximine sensitized cells to both elesclomol and Cu(II)-elesclomol. In conclusion, these results showed that elesclomol indirectly inhibited cancer cell growth through Cu(II)-mediated oxidative stress.

The role of copper(II) and zinc(II) in the degradation of human and murine IAPP by insulin-degrading enzyme

Amylin or islet amyloid polypeptide (IAPP) is a 37-residue peptide hormone secreted from the pancreatic islets into the blood circulation and is cleared by peptidases in the kidney. IAPP aggregates are strongly associated with β-cell degeneration in type 2 diabetes, as demonstrated by the fact that more than 95% of patients exhibit IAPP amyloid upon autopsy. Recently, it has been reported that metal ions such as copper(II) and zinc(II) are implicated in the aggregation of IAPP as well as able to modulate the proteolytic activity of IAPP degrading enzymes. For this reason, in this work, the role of the latter metal ions in the degradation of IAPP by insulin-degrading enzyme (IDE) has been investigated by a chromatographic and mass spectrometric combined method. The latter experimental approach allowed not only to assess the overall metal ion inhibition of the human and murine IAPP degradation by IDE but also to have information on copper- and zinc-induced changes in IAPP aggregation. In addition, IDE cleavage site preferences in the presence of metal ions are rationalized as metal ion-induced changes in substrate accessibility.

Vibrational Spectroscopy of Small Hydrated CuOH+ Clusters

Coordinated copper hydroxide centers can play an important role in copper catalyzed water oxidation reactions. To have a better understanding of the interactions involved in these complexes, we studied the vibrational spectra of D2 tagged CuOH(+)(H2O)n clusters in the OH stretch region. These clusters are generated by electrospray ionization and probed via cryogenic ion vibrational spectroscopy. The results show that the copper center in the n = 3 clusters has a distorted square planar geometry. The coordination in CuOH(+)(H2O)n is therefore more akin to Cu(2+)(H2O)n with four ligands in the first solvation shell than Cu(+)(H2O)n with two ligands in the first solvation shell. There is also no evidence of any strong axial ligand interactions. The well-resolved experimental spectra enabled us to point out some discrepancies in the calculated spectra, which were found to be highly dependent on the level of theory used.

Role of copper and aluminum on the corrosion behavior of austenitic Fe–Mn–C TWIP steels in aqueous solutions and the related hydrogen absorption

Corrosion tests, isotopic tracing and surface analyses were used to study the corrosion behavior and the related hydrogen absorption of a Fe–18Mn–0.6C alloy in aqueous solutions. The influence of alloying elements was investigated. Copper addition leads to the formation of an oxide layer enriched in metallic copper, which favors H recombination and decreases H absorption in the alloy. Aluminum addition decreases the average corrosion rate by the formation of an oxide layer enriched in aluminum, thus decreasing the hydrogen absorption during the corrosion process. In this Al-enriched alloy, the presence of phosphorus increases the corrosion kinetics and promotes hydrogen absorption.

Role of copper and aluminum additions on the hydrogen embrittlement susceptibility of austenitic Fe–Mn–C TWIP steels

The role of alloying elements on the hydrogen embrittlement (HE) susceptibility of a Fe–18Mn–0.6C alloy was investigated by in situ tensile tests and characterized by the ductility loss associated with intergranular fracture. Under cathodic polarization an improvement of HE resistance is related to the SFE increase with Cu or Al additions reducing the stress–strain and H localization at grain boundaries, which prevents H-induced intergranular cracking. At rest potential, beneficial effects of Cu and Al are related to their influence on hydrogen absorption during the corrosion process. However, residual phosphorus strongly reduces the beneficial effect of aluminum.

Another Role of Copper in the Simmons–Smith Reaction: Copper-catalyzed Nucleophilic Michael-type Cyclopropanation of α,β-Unsaturated Ketones

Abstract Cyclopropanation was performed using the Furukawa procedure with CH2I2/Et2Zn and α,β-unsaturated ketones. The reaction was performed in the presence of a copper salt. The reactivity was highly dependent on the substrate structure, and cyclopropanated products were obtained in better yields than those achieved using the original Simmons–Smith conditions with a Zn–Cu couple in some cases. Stereospecificity was observed in a certain case; however, the synthesis of an asymmetric version with a chiral ligand was not successful.

Effect of minerals on the stability of gold in copper ammoniacal thiosulfate solutions — The role of copper, silver and polythionates

The effect of some typical oxide and sulfide minerals, as well as activated carbon, on synthetic gold thiosulfate leach solutions was examined. The presences of pyrite and goethite in a synthetic ore slurry have a significant effect on the adsorption and stability of gold, silver, copper and polythionates in ammoniacal thiosulfate solutions. Adsorption of tetrathionate in particular leads to significant gold and silver losses. The adsorption of copper on mineral surfaces inhibited gold and silver losses, even in the presence of tetrathionate. However, goethite was found to strongly adsorb copper(II). It is concluded that gold extraction from natural ores is lower than that obtained with cyanide, partly as a result of sorption or precipitation reactions. Furthermore, the presence of silver in solution catalyses the precipitation of a mixed copper/silver/gold sulfide in ammoniacal thiosulfate solutions containing tetrathionate.

Regulation of Copper Homeostasis and Biotic Interactions by MicroRNA 398b in Common Bean

MicroRNAs are recognized as important post-transcriptional regulators in plants. Information about the roles of miRNAs in common bean (Phaseolus vulgaris L.), an agronomically important legume, is yet scant. The objective of this work was to functionally characterize the conserved miRNA: miR398b and its target Cu/Zn Superoxide Dismutase 1 (CSD1) in common bean. We experimentally validated a novel miR398 target: the stress up-regulated Nodulin 19 (Nod19). Expression analysis of miR398b and target genes –CSD1 and Nod19- in bean roots, nodules and leaves, indicated their role in copper (Cu) homeostasis. In bean plants under Cu toxicity miR398b was decreased and Nod19 and CSD1, that participates in reactive oxygen species (ROS) detoxification, were up-regulated. The opposite regulation was observed in Cu deficient bean plants; lower levels of CSD1 would allow Cu delivery to essential Cu-containing proteins. Composite common bean plants with transgenic roots over-expressing miR398 showed ca. 20-fold higher mature miR398b and almost negligible target transcript levels as well as increased anthocyanin content and expression of Cu-stress responsive genes, when subjected to Cu deficiency. The down-regulation of miR398b with the consequent up-regulation of its targets was observed in common bean roots during the oxidative burst resulting from short-time exposure to high Cu. A similar response occurred at early stage of bean roots inoculated with Rhizobium tropici, where an increase in ROS was observed. In addition, the miR398b down-regulation and an increase in CSD1 and Nod19 were observed in bean leaves challenged with Sclerotinia scleortiorum fungal pathogen. Transient over-expression of miR398b in Nicotiana benthamiana leaves infected with S. sclerotiorum resulted in enhanced fungal lesions. We conclude that the miR398b-mediated up-regulation of CSD and Nod19 is relevant for common bean plants to cope with oxidative stress generated in abiotic and biotic stresses.

Genetic, metabolic and cellular factors influencing intracellular localization of the Wilson disease protein, ATP7B

Background Wilson disease (WD) is a disorder of copper accumulation in liver and brain caused by mutations in the coppertransporting ATPase ATP7B that affects 1 in 5000 live births. Under basal conditions, ATP7B protein localizes to the trans-Golgi network (TGN) but traffics to vesicles in response to high copper. The purpose of the study is to identify genetic, metabolic and regulatory factors that regulate ATP7B function and localization to maintain normal copper homeostasis in cells. The study is divided into three parts, (a) Role of copper in normal protein folding and its ER exit, (b) Role of regulatory phosphorylation of ATP7B in its trafficking from TGN to vesicles (c) Interaction of ATP7B with regulatory proteins in its trafficking route.

The role of copper(II) in the aggregation of human amylin.

Amylin is a 37-residue peptide hormone produced by the islet β-cells of pancreas and the formation of amylin aggregates is strongly associated with β-cell degeneration in type 2 diabetes, as demonstrated by more than 95% of patients exhibiting amylin amyloid upon autopsy. It is widely recognized that metal ions such as copper(II) have been implicated in the aggregation process of amyloidogenic peptides such as Aβ and α-synuclein and there is evidence that amylin self-assembly is also largely affected by copper(II). For this reason, in this work, the role of copper(II) in the aggregation of amylin has been investigated by several different experimental approaches. Mass spectrometric investigations show that copper(II) induces significant changes in the amylin structure, which decrease the protein fibrillogenesis as observed by ThT measurements. Accordingly, solid-state NMR experiments together with computational analysis carried out on a model amylin fragment confirmed the non-fibrillogenic nature of the copper(II) induced aggregated structure. Finally, the presence of copper(II) is also shown to have a major influence on amylin proneness to be degraded by proteases and cytotoxicity studies on different cell cultures are reported.

Propane dehydrogenation over Pt-Cu bimetallic catalysts: the nature of coke deposition and the role of copper.

This paper describes an investigation of the promotional effect of Cu on the catalytic performance of Pt/Al2O3 catalysts for propane dehydrogenation. We have shown that Pt/Al2O3 catalysts possess higher propylene selectivity and lower deactivation rate as well as enhanced anti-coking ability upon Cu addition. The optimized loading content of Cu is 0.5 wt%, which increases the propylene selectivity to 90.8% with a propylene yield of 36.5%. The origin of the enhanced catalytic performance and anti-coking ability of the Pt-Cu/Al2O3 catalyst is ascribed to the intimate interaction between Pt and Cu, which is confirmed by the change of particle morphology and atomic electronic environment of the catalyst. The Pt-Cu interaction inhibits propylene adsorption and elevates the energy barrier of C-C bond rupture. The inhibited propylene adsorption diminishes the possibility of coke formation and suppresses the cracking reaction towards the formation of lighter hydrocarbons on Pt-Cu/Al2O3, while a higher energy barrier for C-C bond cleavage suppresses the methane formation.