Browsing by Subject "Copper"

Now showing 1 - 11 of 11
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    Characterization of glycosylphoshatidylinositol-anchored ceruloplasmin in multiple redent organs following dietary copper deficiency.
    (2010-10) Mostad, Elise June
    Copper is a necessary metal cofactor in many enzymes that catalyze key reactions in both prokaryotes and eukaryotes. Ceruloplasmin (Cp) is a copper-dependent enzyme that acts as a ferroxidase, oxidizing FeII to FeIII for systemic iron mobilization. Cp is expressed as both a secreted plasma (sCp) enzyme and a membrane-bound glycosylphosphatidylinositol- anchored (GPI-Cp) splice variant enzyme. sCp is the most abundant copper-binding protein in mammalian plasma. The ferroxidase activity of Cp is essential for iron mobilization, as Cp null humans and mice exhibit selective tissue-specific iron overload. Dietary copper deficient (CuD) rodents have near total loss of Cp activity, severe loss of Cp protein, and anemia. The impacts of dietary copper deficiency on GPICp has not been previously evaluated. Studies were conducted in Holtzman and Sprague- Dawley rats, albino mice, and Cp -/- mice, to investigate the copper-iron interaction and further characterize GPI-Cp. Purified membrane extracts of these rodent tissues detected immunoreactive Cp protein, especially enriched in spleen and kidney, but not in membranes from Cp -/- mice. Immunoreactive Cp protein was released with phosphotidylinositol-specific phospholipase C treatment and released protein exhibited ferroxidase activity. These data suggest that the membrane-bound Cp immunoreactivity detected is GPI-anchored. Following perinatal and postnatal copper restriction, GPI-Cp was markedly lower in spleen and modestly lower in liver of CuD rats and mice, compared to copper-adequate (CuA) rodents. Livers of CuD mice contained elevated liver non-heme iron (NHI), while spleen NHI was lower in CuD than CuA rats, and not different in CuD mice, implying that lower GPI-Cp was not correlated with augmented NHI levels in CuD rodent spleens. Spleen and liver membranes of CuD rats expressed augmented levels of ferroportin, the iron efflux transporter, which may compensate for the loss of GPI-Cp in iron efflux. Copper deficient rats and mice both develop severe anemia but only in rats is plasma iron lower than normal, consistent with impaired Cp function. As multicopper oxidases like Cp are thought to be the major metabolic link between copper and iron, additional research is needed to determine the impact, if any, of lower GPI-Cp on iron flux and the development of anemia when copper is limiting.
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    The incorporation of nitrosocyanin copper binding loop into azurin.
    (2010-07) Schenewerk, Audrey Rose
    Metalloprotein design and engineering can be used to probe our understanding of active site structure and function. Loop-directed mutagenesis has been used in the metalloprotein field to change the copper binding loops from a number of members of the cupredoxin family into other protein scaffolds. We report the replacement of a ten amino acid loop that supports the copper binding site in the blue copper protein azurin with the red copper binding loop from the protein nitrosocyanin. Azurin is an electron transfer protein while the role of nitrosocyanin is unknown, yet believed to be catalytic. In addition to the loop, we added a carboxylic acid residue into the copper binding site which fully models the site of nitrosocyanin. Synthesis, expression, and UV-visible absorption and EPR spectra for this series of azurin variants will be reported.
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    Low Temperature Gaseous Chlorination for Sulfur Oxide Free Extraction of Copper from Chalcopyrite Concentrates
    (University of Minnesota Duluth, 2002) Iwasaki, Iwao; Fu, N. X; Tabaian, S. H; Tamagawa, T.; Kobayashi, M
    Laboratory investigations of gaseous chlorination-selective oxidation process on primary copper sulfide concentrates are described for producing copper chlorides, elemental sulfur and ferric oxide. The copper chlorides can then be leached, purified and electrolyzed to produce metallic copper and chlorine regenerated for recycle. When a process, originally proposed on a pyrite concentrate analyzing 2.5%Cu using a two-stage reactor, was applied to a Cu, Ni sulfide concentrate analyzing 9%Cu, the process had to be modified to a three-stage reactor by adding a sulfur chloride conversion unit. In this manner, operational problems associated with the formation of Cu-Fe chloride eutectics and sulfur chlorides could be circumvented. When the process was extended to a 29%Cu chalcopyrite concentrate, the use of excess oxygen was found to be necessary to stabilize the operation of the oxidation reactor. A flowsheet was further modified to separate the chlorination and selective oxidation units with separate flow paths of fluidizing gases, thereby preventing the oxidation of sulfide feed in the chlorination reactor. Leaching of selectively-oxidized samples produced solutions analyzing Cu concentrations in excess of 100 g/L with Fe/Cu ratios of less than 0.03 and with Cu extractions of over 99%. Leach residues were readily filterable with cake moisture contents of 20 to 25%.
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    Metallurgical Testing of Copper-Nickel Bearing Material from the Duluth Gabbro Progress Summary
    (University of Minnesota Duluth, 1998-06) Benner, Blair R
    This report summarizes the progress of metallurgical testing of copper-nickel bearing material from the Duluth gabbro to date and outlines the plan for the ongoing test program being funded under the University of Minnesota Permanent Trust Fund (PUTF).
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    Micronutrient interactions affecting the developing rat brain
    (2013-06) Bastian, Thomas William
    Micronutrient deficiencies affect billions of people worldwide and often coexist in developing countries due to consumption of diets lacking nutrient diversity. Thus, it is important to consider how micronutrients such as copper (Cu), iron (Fe), and iodine interact physiologically. Cu, Fe, and iodine/thyroid hormone (TH) deficiencies lead to similar brain development deficits, suggesting these micronutrient deficiencies share a common mechanism contributing to the observed derangements. Previous studies in rodents and humans indicate that Cu and Fe deficiencies during adolescence or adulthood lead to impaired TH status. However, prior to this thesis research, relationships between Fe or Cu deficiencies and thyroidal status had not been assessed in the most vulnerable population, the developing fetus/neonate. My first two studies showed that Fe deficiency lowers newborn rat circulating and brain TH concentrations and alters TH-regulated brain gene expression. In a third study, Fe deficiency exacerbated the effect of mild TH insufficiency on neonatal thyroidal status and brain TH-responsive gene expression. Together, these novel findings suggest that impaired neonatal thyroidal status may contribute to some of the brain developmental abnormalities associated with fetal/neonatal Fe deficiency. Fe deficiency also has significant impacts on the developing brain independent of effects on thyroid function. In humans, Fe deficiency often results in anemia, reduced blood oxygen carrying capacity. Decreased oxygen delivery to the brain can induce a compensatory increase in blood vessel outgrowth. My final study demonstrated, for the first time, that Fe deficiency anemia increases blood vessel growth in the neonatal rat brain. The functional contribution of increased vasculature to the developing Fe-deficient brain is unknown but could be adaptive, maladaptive, or both. In summary, my thesis research exploring micronutrient interactions during brain development has identified two novel potential contributors to the brain developmental derangements associated with Fe deficiency: impaired neonatal thyroid function and increased neonatal brain vasculature.
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    NRRI Library to House Materials Related to Copper-Nickel Study
    (1989) Sandy, John H; Miller, Patricia
    This article describes a large collection of published materials, including journal articles, technical reports, theses, and other sources used by authors in writing and compiling a major report on the copper-nickel deposits and related environment in northern Minnesota. The collection was originally stored at the Environmental Conservation Library at the Minneapolis Public Library before being transferred to the Natural Resources Library at the Natural Resources Research Institute, University of Minnesota Duluth.
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    NRRI Now (1989 Winter)
    (University of Minnesota Duluth, 1989) University of Minnesota Duluth. Natural Resources Research Institute; Sandy, John H; Miller, Patricia
    Includes an article on page 12 “NRRI Library to House Materials Related to Copper-Nickel Study” by John H. Sandy and Patricia Miller. This article describes a large collection of published materials, including journal articles, technical reports, theses, and other sources used by authors in writing and compiling a major report on the copper-nickel deposits and related environment in northern Minnesota. The collection was originally stored at the Environmental Conservation Library at the Minneapolis Public Library before being transferred to the Natural Resources Library at the Natural Resources Research Institute, University of Minnesota Duluth.
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    Probing the Effects of Ligand Electronic Variation on the Hydrogen Atom Transfer Reactivity of the Copper(III)-Hydroxide Core
    (2016-11) Yee, Gereon
    Thermochemical and rate measurements were performed on copper(III)-hydroxide variants in order to understand the influence of the supporting ligand on the reactive nature of the copper(III)-hydroxide core ([CuOH]2+) in hydrogen atom transfer (HAT) reactions. The thermodynamic and kinetic behaviors of the [CuOH]2+ moiety in reactions with C-H containing substrates were shown to be sensitive to electronic modifications made to the supporting pyridine dicarboxamide ligand framework, as evaluated by electrochemical, pKa, and bond dissociation enthalpy (BDE) measurements, and through determination of second-order rate constants, activation parameters, and kinetic isotope effects (KIEs). Likewise, the analogous reactions with phenolic substrates were also shown to obey a similar correlation between reaction rate and thermodynamic driving force, even displaying a change in mechanism when the thermodynamics of HAT and proton transfer (PT) become similar. The results presented in this dissertation are explored within the broader scope of understanding both the macroscopic relationship between reaction rate and driving force for HAT reactions, as well as more nuanced aspects of these reactions such as proton tunneling, changes in mechanism, and the role of charge. Implications for ligand design elements are also drawn within the context of pyridine dicarboxamide supported copper(III) complexes, which may be generalizable to the design of transition metal complexes as a whole.
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    Reactions of copper complexes with dioxygen and oxo transfer reagents: toward elusive copper-oxyl species.
    (2010-06) Hong, Sungjun
    The binding and activation of dioxygen by Cu ions is central to the function of numerous biological systems. Among the enzymes activate dioxygen for the functionalization of organic substrates, those catalyzed by the mononuclear copper enzymes dopamine β-monooxygenase (DβM) and peptidylglycine α-hydroxylating monooxygenase (PHM) are less understood. Despite extensive research on these enzymes, the exact nature of the active species responsible for substrate functionalization is not resolved, with two provocative proposals involving either a CuII-superoxo or a mononuclear CuII-oxyl species having been put forth. The goal of this research is to understand the reaction catalyzed by the PHM and DβM enzymes on a fundamental chemical level via a small molecule synthetic model approach, with particular emphasis on generating and/or characterizing a Cu-oxygen species that is capable of performing similar reactions to those seen in the DβM and PHM enzymes. Chapter 1 contains a general overview of dioxygen activation in biological systems and gives a review of the structure and proposed catalytic mechanisms of DβM and PHM, followed by a summary of recent synthetic efforts toward mononuclear Cu/O2 adducts and Cu-oxyl species. Chapter 2 describes the synthesis and characterization of the copper(I) complexes of the electron-deficient β-diketiminate and analogous 4- nitroformazan supporting ligands, and their O2-reactivity studies, portions of which have been previously reported.1 Chapter 3 describes a bio-inspired synthetic route toward a mononuclear Cu-oxyl species that involves decarboxylation of copper(I)-α- ketocarboxylate complexes by dioxygen; portions of the work have been communicated previously.2 Chapter 4 then describes results obtained from reactions of copper(I) complexes of bidentate N-donor ligands with pyridine- and trimethylamine N-oxides or PhIO. Portions of this work were previously reported.3
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    Synthesis and reactivity of high-valent copper complexes and the design of copper monooxygenase model complexes
    (2022-02) Bouchey, Caitlin
    Copper plays a vital role in various enzymatic and catalytic transformations. Specifically, copper-oxygen and high-valent copper species are implicated as intermediates in oxidations by metalloenzymes and catalysts. In order to study the nature and the role of copper in these transformations, copper model complexes have been sought after and investigated for their properties and reactivities. This thesis describes several such copper model complexes. Chapter 1 outlines the biological precedence of copper-oxygen complexes in a monooxygenase enzyme and a class of copper complexes that mimic the monooxygenase active site. Additionally, the literature relevant to high-valent copper complexes discussed herein is reviewed. In chapter 2, the development of two biomimetic, monoanionic ligands and their copper complexes is discussed. The characterization of the ligands and complexes and efforts to access copper-oxygen complexes bearing the monoanionic ligands are shown. Chapter 3 details the generation of a new high-valent copper-nitrite complex and its oxidative proton-coupled electron transfer (PCET) and anaerobic phenol nitration reactivity. Mechanistic considerations for the unusual anaerobic phenol nitration are made. Lastly, chapter 4 describes the synthesis and characterization of two copper-amidate complexes and the generation of their high-valent counterparts. The PCET reactivity of the high-valent copper-amidate complexes are contrasted with each other and previous high-valent copper-oxygen complexes. The results from the projects described herein provide insights into copper coordination chemistry, electronic structure, and reactivity, which helps augment the knowledge of copper enzymes and catalysts.
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    Synthesis of Metal-Metal Bond Containing Complexes with Multiple Open Coordination Sites and Multi-electron Redox Capabilities
    (2015-12) Eisenhart, Reed
    This dissertation focuses on the synthesis and characterization of compounds containing metal-metal bonds between first row transition metals. More specifically, this research focused on creating metal-metal bond containing complexes with multiple open coordination sites or redox active metal pairs capable of mediating multi-electron redox processes. This thesis covers three related studies. In the first study, heterobimetallic complexes that pair cobalt and copper were synthesized and characterized by a suite of physical methods. A covalent cobalt-copper bond is present in the oxidized [CoCu]4+ state, and the bond is broken upon reduction to [CoCu]3+ state. The reduced state has up to three open coordination sites. Cyclic voltammetry shows that the cobalt-copper unit is capable of two-electron redox changes. In the second study, a complex containing a chromium-chromium triple bond is investigated. The [CrCr]4+ unit is capable of two closely separated oxidations as studied by cyclic voltammetry, UV-Vis, and EPR spectroscopy. In the third study, new ligand designs for coordinatively unsaturated bimetallic compounds are described. Investigations into the metalation of these multifunctional ligands are detailed. A set of isolated monometallic complexes were characterized and they were investigated for the ability to bind a second metal.