Biological and Clinical Aspects of Lanthanide Coordination Compounds

PubMed Central

Misra, Sudhindra N.; M., Indira Devi; Shukla, Ram S.

2004-01-01

The coordinating chemistry of lanthanides, relevant to the biological, biochemical and medical aspects, makes a significant contribution to understanding the basis of application of lanthanides, particularly in biological and medical systems. The importance of the applications of lanthanides, as an excellent diagnostic and prognostic probe in clinical diagnostics, and an anticancer material, is remarkably increasing. Lanthanide complexes based X-ray contrast imaging and lanthanide chelates based contrast enhancing agents for magnetic resonance imaging (MRI) are being excessively used in radiological analysis in our body systems. The most important property of the chelating agents, in lanthanide chelate complex, is its ability to alter the behaviour of lanthanide ion with which it binds in biological systems, and the chelation markedly modifies the biodistribution and excretion profile of the lanthanide ions. The chelating agents, especially aminopoly carboxylic acids, being hydrophilic, increase the proportion of their complex excreted from complexed lanthanide ion form biological systems. Lanthanide polyamino carboxylate-chelate complexes are used as contrast enhancing agents for Magnetic Resonance Imaging. Conjugation of antibodies and other tissue specific molecules to lanthanide chelates has led to a new type of specific MRI contrast agents and their conjugated MRI contrast agents with improved relaxivity, functioning in the body similar to drugs. Many specific features of contrast agent assisted MRI make it particularly effective for musculoskeletal and cerebrospinal imaging. Lanthanide-chelate contrast agents are effectively used in clinical diagnostic investigations involving cerebrospinal diseases and in evaluation of central nervous system. Chelated lanthanide complexes shift reagent aided 23Na NMR spectroscopic analysis is used in cellular, tissue and whole organ systems. PMID:18365075

Method for separating metal chelates from other materials based on solubilities in supercritical fluids

DOEpatents

Wai, Chien M.; Smart, Neil G.; Phelps, Cindy

2001-01-01

A method for separating a desired metal or metalloi from impurities using a supercritical extraction process based on solubility differences between the components, as well as the ability to vary the solvent power of the supercritical fluid, is described. The use of adduct-forming agents, such as phosphorous-containing ligands, to separate metal or metalloid chelates in such processes is further disclosed. In preferred embodiments, the extraction solvent is supercritical carbon dioxide and the chelating agent is selected from the group consisting of .beta.-diketones; phosphine oxides, such as trialkylphosphine oxides, triarylphosphine oxides and alkylarylphosphine oxides; phosphinic acids; carboxylic acids; phosphates, such as trialkylphosphates, triarylphosphates and alkylarylphosphates; crown ethers; dithiocarbamates; phosphine sulfides; phosphorothioic acids; thiophosphinic acids; halogenated analogs of these chelating agents; and mixtures of these chelating agents. In especially preferred embodiments, at least one of the chelating agents is fluorinated.

3-hydroxy-2(1H)-pyridinone chelating agents

DOEpatents

Raymond, K.N.; Xu, J.

1997-04-29

Disclosed is a series of improved metal chelating agents, which are highly effective upon both injection and oral administration; several of the most effective are of low toxicity. These chelating agents incorporate within their structure 1-hydroxy-2-pyridinone (1,2-HOPO) and 3-hydroxy-2-pyridinone (3,2-HOPO) moieties with a substituted carbamoyl group ortho to the hydroxy or oxo groups of the hydroxypyridinone ring. The electron-withdrawing carbamoyl group increases the acidity of the hydroxypyridinones. In the metal complexes of the chelating agents, the amide protons form very strong hydrogen bonds with its adjacent HOPO oxygen donor, making these complexes very stable at physiological conditions. The terminal N-substituents provides a certain degree of lipophilicity to the 3,2-HOPO, increasing oral activity. Also disclosed is a method of making the chelating agents and a method of producing a known compound, 3-hydroxy-1-alkyl-2(1H)pyridinone, used as a precursor to the chelating agent, safely and in large quantities. 2 figs.

3-hydroxy-2(1H)-pyridinone chelating agents

DOEpatents

Raymond, Kenneth N.; Xu, Jide

1997-01-01

Disclosed is a series of improved metal chelating agents, which are highly effective upon both injection and oral administration; several of the most effective are of low toxicity. These chelating agents incorporate within their structure 1-hydroxy-2-pyridinone (1,2-HOPO) and 3-hydroxy-2-pyridinone (3,2-HOPO) moieties with a substituted carbamoyl group ortho to the hydroxy or oxo groups of the hydroxypyridinone ring. The electron-withdrawing carbamoyl group increases the acidity of the hydroxypyridinones. In the metal complexes of said chelating agents, the amide protons form very strong hydrogen bonds with its adjacent HOPO oxygen donor, making these complexes very stable at physiological conditions. The terminal N-substituents provides a certain degree of lipophilicity to said 3,2-HOPO, increasing oral activity. Also disclosed is a method of making the chelating agents and a method of producing a known compound, 3-hydroxy-1-alkyl-2(1H)pyridinone, used as a precursor to the chelating agent, safely and in large quantities.

Synthesis of 4-substituted-trans-1,2-diaminocyclohexyl polyaminocarboxylate metal chelating agents for the preparation of stable radiometal antibody immunoconjugates for therapy and SPECT and PET imaging

DOEpatents

Mease, R.C.; Kolsky, K.L.; Mausner, L.F.; Srivastava, S.C.

1997-06-03

Cyclohexyl chelating agents useful in forming antibody-metal conjugates which are used for diagnostic and therapeutic purposes are synthesized. New compounds and processes of forming these compounds are disclosed including 4-haloacetamido-trans-1,2-diaminocyclohexyl polyaminocarboxylate and 4-isothiocyanato-trans-1,2-diamino cyclohexane-N,N,N{prime},N{prime}-tetra acetic acid.

Solution mining dawsonite from hydrocarbon containing formations with a chelating agent

DOEpatents

Vinegar, Harold J [Bellaire, TX

2009-07-07

A method for treating an oil shale formation comprising dawsonite includes providing heat from one or more heaters to the formation to heat the formation. Hydrocarbon fluids are produced from the formation. At least some dawsonite in the formation is decomposed with the provided heat. A chelating agent is provided to the formation to dissolve at least some dawsonite decomposition products. The dissolved dawsonite decomposition products are produced from the formation.

Chelating agents.

PubMed

Bergan, T; Klaveness, J; Aasen, A J

2001-01-01

The antibacterial activity of metal ions, metal chelates, and molecules with chelating ability for polyvalent cations have been evaluated. The chelator N, N'-ethylenebis[2-(2-hydroxyphenyl)-glycine] (EHPG) exerted moderate-to-good activity against isolates of pathogenic bacteria and fungi. Other chelating agents such as ethylenediamine-tetraacetic acid (EDTA) and diethylene-triamine-pentaacetic acid (DTPA) revealed weak-to-moderate activity. Metal chelation of ligands reduced the activity of EDTA and DTPA. Copyright 2001 S. Karger AG, Basel

In situ removal of contamination from soil

DOEpatents

Lindgren, Eric R.; Brady, Patrick V.

1997-01-01

A process of remediation of cationic heavy metal contamination from soil utilizes gas phase manipulation to inhibit biodegradation of a chelating agent that is used in an electrokinesis process to remove the contamination, and further gas phase manipulation to stimulate biodegradation of the chelating agent after the contamination has been removed. The process ensures that the chelating agent is not attacked by bioorganisms in the soil prior to removal of the contamination, and that the chelating agent does not remain as a new contaminant after the process is completed.

In situ removal of contamination from soil

DOEpatents

Lindgren, E.R.; Brady, P.V.

1997-10-14

A process of remediation of cationic heavy metal contamination from soil utilizes gas phase manipulation to inhibit biodegradation of a chelating agent that is used in an electrokinesis process to remove the contamination. The process also uses further gas phase manipulation to stimulate biodegradation of the chelating agent after the contamination has been removed. The process ensures that the chelating agent is not attacked by bioorganisms in the soil prior to removal of the contamination, and that the chelating agent does not remain as a new contaminant after the process is completed. 5 figs.

3-hydroxy-2(1H)-pyridinone chelating agents

DOEpatents

Raymond, K.; Xu, J.

1999-04-06

Disclosed is a series of improved chelating agents and the chelates formed from these agents, which are highly effective upon both injection and oral administration. Several of the most effective are of low toxicity. These chelating agents incorporate within their structure 3-hydroxy-2-pyridinone (3,2-HOPO) moieties with a substituted carbamoyl group ortho to the hydroxy group of the hydroxypyridinone ring. The electron-withdrawing carbamoyl group increases the acidity, as well as the chemical stability towards oxidation and reduction, of the hydroxypyridinones. In the metal complexes of the chelating agents, the amide protons form very strong hydrogen bonds with the adjacent HOPO oxygen donor, making these complexes very stable at physiological conditions. The terminal N-substituents provide a certain degree of lipophilicity to the 3,2-HOPO, increasing oral activity. 2 figs.

3-hydroxy-2(1H)-pyridinone chelating agents

DOEpatents

Raymond, Kenneth; Xu, Jide

1999-01-01

Disclosed is a series of improved chelating agents and the chelates formed from these agents, which are highly effective upon both injection and oral administration. Several of the most effective are of low toxicity. These chelating agents incorporate within their structure 3-hydroxy-2-pyridinone (3,2-HOPO) moieties with a substituted carbamoyl group ortho to the hydroxy group of the hydroxypyridinone ring. The electron-withdrawing carbamoyl group increases the acidity, as well as the chemical stability towards oxidation and reduction, of the hydroxypyridinones. In the metal complexes of the chelating agents, the amide protons form very strong hydrogen bonds with the adjacent HOPO oxygen donor, making these complexes very stable at physiological conditions. The terminal N-substituents provide a certain degree of lipophilicity to the 3,2-HOPO, increasing oral activity.

Bifunctional chelating agent for the design and development of site specific radiopharmaceuticals and biomolecule conjugation strategy

DOEpatents

Katti, Kattesh V.; Prabhu, Kandikere R.; Gali, Hariprasad; Pillarsetty, Nagavara Kishore; Volkert, Wynn A.

2003-10-21

There is provided a method of labeling a biomolecule with a transition metal or radiometal in a site specific manner to produce a diagnostic or therapeutic pharmaceutical compound by synthesizing a P.sub.2 N.sub.2 -bifunctional chelating agent intermediate, complexing the intermediate with a radio metal or a transition metal, and covalently linking the resulting metal-complexed bifunctional chelating agent with a biomolecule in a site specific manner. Also provided is a method of synthesizing the --PR.sub.2 containing biomolecules by synthesizing a P.sub.2 N.sub.2 -bifunctional chelating agent intermediate, complexing the intermediate with a radiometal or a transition metal, and covalently linking the resulting radio metal-complexed bifunctional chelating agent with a biomolecule in a site specific manner. There is provided a therapeutic or diagnostic agent comprising a --PR.sub.2 containing biomolecule.

Patents – Melvin Calvin

Science.gov Websites

plutonium from uranium and fission products in an aqueous acidic solution by use of a chelating agent. The concentration is adjusted to about 1 N bar. The aqueous solution is then contacted with a water-immiscible organic solvent solution and the chelating agent. The chelating agents covered by this invention comprise

Mercury removal in utility wet scrubber using a chelating agent

DOEpatents

Amrhein, Gerald T.

2001-01-01

A method for capturing and reducing the mercury content of an industrial flue gas such as that produced in the combustion of a fossil fuel or solid waste adds a chelating agent, such as ethylenediaminetetraacetic acid (EDTA) or other similar compounds like HEDTA, DTPA and/or NTA, to the flue gas being scrubbed in a wet scrubber used in the industrial process. The chelating agent prevents the reduction of oxidized mercury to elemental mercury, thereby increasing the mercury removal efficiency of the wet scrubber. Exemplary tests on inlet and outlet mercury concentration in an industrial flue gas were performed without and with EDTA addition. Without EDTA, mercury removal totaled 42%. With EDTA, mercury removal increased to 71%. The invention may be readily adapted to known wet scrubber systems and it specifically provides for the removal of unwanted mercury both by supplying S.sup.2- ions to convert Hg.sup.2+ ions into mercuric sulfide (HgS) and by supplying a chelating agent to sequester other ions, including but not limited to Fe.sup.2+ ions, which could otherwise induce the unwanted reduction of Hg.sup.2+ to the form, Hg.sup.0.

Extracting metals directly from metal oxides

DOEpatents

Wai, Chien M.; Smart, Neil G.; Phelps, Cindy

1997-01-01

A method of extracting metals directly from metal oxides by exposing the oxide to a supercritical fluid solvent containing a chelating agent is described. Preferably, the metal is an actinide or a lanthanide. More preferably, the metal is uranium, thorium or plutonium. The chelating agent forms chelates that are soluble in the supercritical fluid, thereby allowing direct removal of the metal from the metal oxide. In preferred embodiments, the extraction solvent is supercritical carbon dioxide and the chelating agent is selected from the group consisting of .beta.-diketones, halogenated .beta.-diketones, phosphinic acids, halogenated phosphinic acids, carboxylic acids, halogenated carboxylic acids, and mixtures thereof. In especially preferred embodiments, at least one of the chelating agents is fluorinated. The method provides an environmentally benign process for removing metals from metal oxides without using acids or biologically harmful solvents. The chelate and supercritical fluid can be regenerated, and the metal recovered, to provide an economic, efficient process.

Extracting metals directly from metal oxides

DOEpatents

Wai, C.M.; Smart, N.G.; Phelps, C.

1997-02-25

A method of extracting metals directly from metal oxides by exposing the oxide to a supercritical fluid solvent containing a chelating agent is described. Preferably, the metal is an actinide or a lanthanide. More preferably, the metal is uranium, thorium or plutonium. The chelating agent forms chelates that are soluble in the supercritical fluid, thereby allowing direct removal of the metal from the metal oxide. In preferred embodiments, the extraction solvent is supercritical carbon dioxide and the chelating agent is selected from the group consisting of {beta}-diketones, halogenated {beta}-diketones, phosphinic acids, halogenated phosphinic acids, carboxylic acids, halogenated carboxylic acids, and mixtures thereof. In especially preferred embodiments, at least one of the chelating agents is fluorinated. The method provides an environmentally benign process for removing metals from metal oxides without using acids or biologically harmful solvents. The chelate and supercritical fluid can be regenerated, and the metal recovered, to provide an economic, efficient process. 4 figs.

Chelation in Metal Intoxication

PubMed Central

Flora, Swaran J.S.; Pachauri, Vidhu

2010-01-01

Chelation therapy is the preferred medical treatment for reducing the toxic effects of metals. Chelating agents are capable of binding to toxic metal ions to form complex structures which are easily excreted from the body removing them from intracellular or extracellular spaces. 2,3-Dimercaprol has long been the mainstay of chelation therapy for lead or arsenic poisoning, however its serious side effects have led researchers to develop less toxic analogues. Hydrophilic chelators like meso-2,3-dimercaptosuccinic acid effectively promote renal metal excretion, but their ability to access intracellular metals is weak. Newer strategies to address these drawbacks like combination therapy (use of structurally different chelating agents) or co-administration of antioxidants have been reported recently. In this review we provide an update of the existing chelating agents and the various strategies available for the treatment of heavy metals and metalloid intoxications. PMID:20717537

Supercritical fluid extraction

DOEpatents

Wai, Chien M.; Laintz, Kenneth

1994-01-01

A method of extracting metalloid and metal species from a solid or liquid material by exposing the material to a supercritical fluid solvent containing a chelating agent. The chelating agent forms chelates that are soluble in the supercritical fluid to allow removal of the species from the material. In preferred embodiments, the extraction solvent is supercritical carbon dioxide and the chelating agent is a fluorinated or lipophilic crown ether or fluorinated dithiocarbamate. The method provides an environmentally benign process for removing contaminants from industrial waste without using acids or biologically harmful solvents. The chelate and supercritical fluid can be regenerated, and the contaminant species recovered, to provide an economic, efficient process.

21 CFR 176.150 - Chelating agents used in the manufacture of paper and paperboard.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Chelating agents used in the manufacture of paper... Chelating agents used in the manufacture of paper and paperboard. The substances named in paragraph (a) of this section may be safely used in the manufacture of paper and paperboard, in accordance with the...

Rates of nickel(II) capture from complexes with NTA, EDDA, and related tetradentate chelating agents by the hexadentate chelating agents EDTA and CDTA: Evidence of a "semijunctive" ligand exchange pathway

NASA Astrophysics Data System (ADS)

Boland, Nathan E.; Stone, Alan T.

2017-09-01

Many siderophores and metallophores produced by soil organisms, as well as anthropogenic chelating agent soil amendments, rely upon amine and carboxylate Lewis base groups for metal ion binding. UV-visible spectra of metal ion-chelating agent complexes are often similar and, as a consequence, whole-sample absorbance measurements are an unreliable means of monitoring the progress of exchange reactions. In the present work, we employ capillary electrophoresis to physically separate Ni(II)-tetradentate chelating agent complexes (NiL) from Ni(II)-hexadentate chelating agent complexes (NiY) prior to UV detection, such that progress of the reaction NiL + Y → NiY + L can be conveniently monitored. Rates of ligand exchange for Ni(II) are lower than for other +II transition metal ions. Ni(II) speciation in environmental media is often under kinetic rather than equilibrium control. Nitrilotriacetic acid (NTA), with three carboxylate groups all tethered to a central amine Lewis base group, ethylenediamine-N,N‧-diacetic acid (EDDA), with carboxylate-amine-amine-carboxylate groups arranged linearly, plus four structurally related compounds, are used as tetradentate chelating agents. Ethylenediaminetetraacetic acid (EDTA) and the structurally more rigid analog trans-cyclohexaneethylenediaminetetraacetic acid (CDTA) are used as hexadentate chelating agents. Effects of pH and reactant concentration are explored. Ni(II) capture by EDTA was consistently more than an order of magnitude faster than capture by CDTA, and too fast to quantify using our capillary electrophoresis-based technique. Using NiNTA as a reactant, Ni(II) capture by CDTA is independent of CDTA concentration and greatly enhanced by a proton-catalyzed pathway at low pH. Using NiEDDA as reactant, Ni(II) capture by CDTA is first order with respect to CDTA concentration, and the contribution from the proton-catalyzed pathway diminished by CDTA protonation. While the convention is to assign either a disjunctive pathway or adjunctive pathway to multidentate ligand exchange reactions, our results indicate that a third "semijunctive" pathway is necessary to account for slow reactions progressing through Lsbnd Nisbnd Y ternary complexes. Ligand exchange pathways with NTA-type chelating agents are assigned a disjunctive pathway, while pathways with EDDA-type chelating agents are assigned a semijunctive pathway. Based upon operative mechanism(s), magnitudes of exchange rates and effects of ambient geochemical conditions can be predicted.

Luminescent lanthanide chelates and methods of use

DOEpatents

Selvin, Paul R.; Hearst, John

1997-01-01

The invention provides lanthanide chelates capable of intense luminescence. The celates comprise a lanthanide chelator covalently joined to a coumarin-like or quinolone-like sensitizer. Exemplary sensitzers include 2- or 4-quinolones, 2- or 4-coumarins, or derivatives thereof e.g. carbostyril 124 (7-amino-4-methyl-2-quinolone), coumarin 120 (7-amino-4-methyl-2-coumarin), coumarin 124 (7-amino-4-(trifluoromethyl)-2-coumarin), aminomethyltrimethylpsoralen, etc. The chelates form high affinity complexes with lanthanides, such as terbium or europium, through chelator groups, such as DTPA. The chelates may be coupled to a wide variety of compounds to create specific labels, probes, diagnostic and/or therapeutic reagents, etc. The chelates find particular use in resonance energy transfer between chelate-lanthanide complexes and another luminescent agent, often a fluorescent non-metal based resonance energy acceptor. The methods provide useful information about the structure, conformation, relative location and/or interactions of macromolecules.

[Decorporation agents for internal radioactive contamination].

PubMed

Ohmachi, Yasushi

2015-01-01

When radionuclides are accidentally ingested or inhaled, blood circulation or tissue/organ deposition of the radionuclides causes systemic or local radiation effects. In such cases, decorporation therapy is used to reduce the health risks due to their intake. Decorporation therapy includes reduction and/or inhibition of absorption from the gastrointestinal tract, isotopic dilution, and the use of diuretics, adsorbents, and chelating agents. For example, penicillamine is recommended as a chelating agent for copper contamination, and diethylene triamine pentaacetic acid is approved for the treatment of internal contamination with plutonium. During chelation therapy, the removal effect of the drugs should be monitored using a whole-body counter and/or bioassay. Some authorities, such as the National Council on Radiation Protection and Measurements and International Atomic Energy Agency, have reported recommended decorporation agents for each radionuclide. However, few drugs are approved by the US Food and Drug Administration, and many are off-label-use agents. Because many decontamination agents are drugs that have been available for a long time and have limited efficacy, the development of new, higher-efficacy drugs has been carried out mainly in the USA and France. In this article, in addition to an outline of decorporation agents for internal radioactive contamination, an outline of our research on decorporation agents for actinide (uranium and plutonium) contamination and for radio-cesium contamination is also presented.

Preclinical Comparative Study of (68)Ga-Labeled DOTA, NOTA, and HBED-CC Chelated Radiotracers for Targeting PSMA.

PubMed

Ray Banerjee, Sangeeta; Chen, Zhengping; Pullambhatla, Mrudula; Lisok, Ala; Chen, Jian; Mease, Ronnie C; Pomper, Martin G

2016-06-15

(68)Ga-labeled, low-molecular-weight imaging agents that target the prostate-specific membrane antigen (PSMA) are increasingly used clinically to detect prostate and other cancers with positron emission tomography (PET). The goal of this study was to compare the pharmacokinetics of three PSMA-targeted radiotracers: (68)Ga-1, using DOTA-monoamide as the chelating agent; (68)Ga-2, containing the macrocyclic chelating agent p-SCN-Bn-NOTA; and (68)Ga-DKFZ-PSMA-11, currently in clinical trials, which uses the acyclic chelating agent, HBED-CC. The PSMA-targeting scaffold for all three agents utilized a similar Glu-urea-Lys-linker construct. Each radiotracer enabled visualization of PSMA+ PC3 PIP tumor, kidney, and urinary bladder as early as 15 min post-injection using small animal PET/computed tomography (PET/CT). (68)Ga-2 demonstrated the fastest rate of clearance from all tissues in this series and displayed higher uptake in PSMA+ PC3 PIP tumor compared to (68)Ga-1 at 1 h post-injection. There was no significant difference in PSMA+ PC3 PIP tumor uptake for the three agents at 2 and 3 h post-injection. (68)Ga-DKFZ-PSMA-11 demonstrated the highest uptake and retention in normal tissues, including kidney, blood, spleen, and salivary glands and PSMA-negative PC3 flu tumors up to 3 h post-injection. In this preclinical evaluation (68)Ga-2 had the most advantageous characteristics for PSMA-targeted PET imaging.

Evaluation of a new tablet formulation of deferasirox to reduce chronic iron overload after long-term blood transfusions

PubMed Central

Chalmers, Anna W; Shammo, Jamile M

2016-01-01

Transfusion-dependent anemia is a common feature in a wide array of hematological disorders, including thalassemia, sickle cell disease, aplastic anemia, myelofibrosis, and myelo-dysplastic syndromes. In the absence of a physiological mechanism to excrete excess iron, chronic transfusions ultimately cause iron overload. Without correction, iron overload can lead to end-organ damage, resulting in cardiac, hepatic, and endocrine dysfunction/failure. Iron chelating agents are utilized to reduce iron overload, as they form a complex with iron, leading to its clearance. Iron chelation has been proven to decrease organ dysfunction and improve survival in certain transfusion-dependent anemias, such as β-thalassemia. Several chelating agents have been approved by the United States Food and Drug Administration for the treatment of iron overload, including deferoxamine, deferiprone, and deferasirox. A variety of factors have to be considered when choosing an iron chelator, including dosing schedule, route of administration, tolerability, and side effect profile. Deferasirox is an orally administered iron chelator with proven efficacy and safety in multiple hematological disorders. There are two formulations of deferasirox, a tablet for suspension, and a new tablet form. This paper is intended to provide an overview of iron overload, with a focus on deferasirox, and its recently approved formulation Jadenu® for the reduction of transfusional iron overload in hematological disorders. PMID:26929633

Evaluation of a new tablet formulation of deferasirox to reduce chronic iron overload after long-term blood transfusions.

PubMed

Chalmers, Anna W; Shammo, Jamile M

2016-01-01

Transfusion-dependent anemia is a common feature in a wide array of hematological disorders, including thalassemia, sickle cell disease, aplastic anemia, myelofibrosis, and myelo-dysplastic syndromes. In the absence of a physiological mechanism to excrete excess iron, chronic transfusions ultimately cause iron overload. Without correction, iron overload can lead to end-organ damage, resulting in cardiac, hepatic, and endocrine dysfunction/failure. Iron chelating agents are utilized to reduce iron overload, as they form a complex with iron, leading to its clearance. Iron chelation has been proven to decrease organ dysfunction and improve survival in certain transfusion-dependent anemias, such as β-thalassemia. Several chelating agents have been approved by the United States Food and Drug Administration for the treatment of iron overload, including deferoxamine, deferiprone, and deferasirox. A variety of factors have to be considered when choosing an iron chelator, including dosing schedule, route of administration, tolerability, and side effect profile. Deferasirox is an orally administered iron chelator with proven efficacy and safety in multiple hematological disorders. There are two formulations of deferasirox, a tablet for suspension, and a new tablet form. This paper is intended to provide an overview of iron overload, with a focus on deferasirox, and its recently approved formulation Jadenu(®) for the reduction of transfusional iron overload in hematological disorders.

Anti-EpCAM scFv gadolinium chelate: a novel targeted MRI contrast agent for imaging of colorectal cancer.

PubMed

Khantasup, Kannika; Saiviroonporn, Pairash; Jarussophon, Suwatchai; Chantima, Warangkana; Dharakul, Tararaj

2018-05-08

The development of targeted contrast agents for magnetic resonance imaging (MRI) facilitates enhanced cancer imaging and more accurate diagnosis. In the present study, a novel contrast agent was developed by conjugating anti-EpCAM humanized scFv with gadolinium chelate to achieve target specificity. The material design strategy involved site-specific conjugation of the chelating agent to scFv. The scFv monomer was linked to maleimide-DTPA via unpaired cysteine at the scFv C-terminus, followed by chelation with gadolinium (Gd). Successful scFv-DTPA conjugation was achieved at 1:10 molar ratio of scFv to maleimide-DTPA at pH 6.5. The developed anti-EpCAM-Gd-DTPA MRI contrast agent was evaluated for cell targeting ability, in vitro serum stability, cell cytotoxicity, relaxivity, and MR contrast enhancement. A high level of targeting efficacy of anti-EpCAM-Gd-DTPA to an EpCAM-overexpressing HT29 colorectal cell was demonstrated by confocal microscopy. Good stability of the contrast agent was obtained and no cytotoxicity was observed in HT29 cells after 48 h incubation with 25-100 µM of Gd. Favorable imaging was obtained using anti-EpCAM-Gd-DTPA, including 1.8-fold enhanced relaxivity compared with Gd-DTPA, and MR contrast enhancement observed after binding to HT29. The potential benefit of this contrast agent for in vivo MR imaging of colorectal cancer, as well as other EpCAM positive cancers, is suggested and warrants further investigation.

Inhibitory activity of chelating agent against bacteria associated with poultry processing

USDA-ARS?s Scientific Manuscript database

Ethylenediaminetetraacetic acid (EDTA) and ethylenediamine-N, N’-disuccinic acid (EDDS) are chelating agents that can bind minerals that produce water hardness. By sequestering minerals in hard water, chelators reduce water hardness and increase the ability of cleansers to remove dirt and debris dur...

Thumbnail Sketches: EDTA-Type Chelating Agents in Everyday Consumer Products: Some Medicinal and Personal Care Products.

ERIC Educational Resources Information Center

Hart, J. Roger

1984-01-01

Discusses various ethylenediaminetetraacetate (EDTA)-type chelating agents found in ophthalmic products, personal care products, and disinfectants. Also discusses the properties and action of these EDTA agents. (JN)

EFFECT OF CHELATING AGENTS ON UPTAKE OF Ca$sup 45$ AND Sr$sup 85$ BY DEFATTED BONE IN VITRO

DOE Office of Scientific and Technical Information (OSTI.GOV)

Samachson, J.; Lederer, H.

The presence of chelating agents in buffered solutions affected the relative uptake of Ca/sup 45/ and Sr/sup 85/ by defatted bone powder. Strong chelating agents, like ethylenediaminetetraacetic acid and cyclohexanediaminetetraacetic acid, decreased the ratio of Ca/sup 45//Sr/sup 85/ uptake considerably in presence of Ca, Ca plus Sr, or Sr carrier. Citrate and adenosinetriphosphate had similar but weaker effects. No effect was shown by glucose, lactate, gluconate, bicarbonate, bicarbonate plus phosphate, glutamate, aspartate, borate, glycerophosphate, lysine or glutathione. Those compeunds which showed no effect had stability constants for Ca of less than 3. Strong chelating agents also decreased the relative amountmore » of Sr/sup 85/ removed from defatted bone powder by exchange. Results indicate that natural chelating agents may be partly responsible for the low Ca/sup 45//Sr/sup 85/ uptake ratio by bone from serum compared with uptake from synthetic inorganic solutions and emphasize the difficulty of removing be partly responsible for the low Ca/sup 45//Sr/sup 85/ uptske ratio by bone from serum compared with uptake from synthetic inorganic solutions and emphasize the difficulty of removing Sr/sup 35/ from bone with chelating agents now available. (auth)« less

Extraction of metals using supercritical fluid and chelate forming legand

DOEpatents

Wai, Chien M.; Laintz, Kenneth E.

1998-01-01

A method of extracting metalloid and metal species from a solid or liquid material by exposing the material to a supercritical fluid solvent containing a chelating agent is described. The chelating agent forms chelates that are soluble in the supercritical fluid to allow removal of the species from the material. In preferred embodiments, the extraction solvent is supercritical carbon dioxide and the chelating agent is a fluorinated .beta.-diketone. In especially preferred embodiments the extraction solvent is supercritical carbon dioxide, and the chelating agent comprises a fluorinated .beta.-diketone and a trialkyl phosphate, or a fluorinated .beta.-diketone and a trialkylphosphine oxide. Although a trialkyl phosphate can extract lanthanides and actinides from acidic solutions, a binary mixture comprising a fluorinated .beta.-diketone and a trialkyl phosphate or a trialkylphosphine oxide tends to enhance the extraction efficiencies for actinides and lanthanides. The method provides an environmentally benign process for removing contaminants from industrial waste without using acids or biologically harmful solvents. The method is particularly useful for extracting actinides and lanthanides from acidic solutions. The chelate and supercritical fluid can be regenerated, and the contaminant species recovered, to provide an economic, efficient process.

Extraction of metals using supercritical fluid and chelate forming ligand

DOEpatents

Wai, C.M.; Laintz, K.E.

1998-03-24

A method of extracting metalloid and metal species from a solid or liquid material by exposing the material to a supercritical fluid solvent containing a chelating agent is described. The chelating agent forms chelates that are soluble in the supercritical fluid to allow removal of the species from the material. In preferred embodiments, the extraction solvent is supercritical carbon dioxide and the chelating agent is a fluorinated {beta}-diketone. In especially preferred embodiments the extraction solvent is supercritical carbon dioxide, and the chelating agent comprises a fluorinated {beta}-diketone and a trialkyl phosphate, or a fluorinated {beta}-diketone and a trialkylphosphine oxide. Although a trialkyl phosphate can extract lanthanides and actinides from acidic solutions, a binary mixture comprising a fluorinated {beta}-diketone and a trialkyl phosphate or a trialkylphosphine oxide tends to enhance the extraction efficiencies for actinides and lanthanides. The method provides an environmentally benign process for removing contaminants from industrial waste without using acids or biologically harmful solvents. The method is particularly useful for extracting actinides and lanthanides from acidic solutions. The chelate and supercritical fluid can be regenerated, and the contaminant species recovered, to provide an economic, efficient process. 7 figs.

Hydroxypyridonate and hydroxypyrimidinone chelating agents

DOEpatents

Raymond, Kenneth N.; Doble, Daniel M.; Sunderland, Christopher J.; Thompson, Marlon

2005-01-25

The present invention provides hydroxypyridinone and hydroxypyrimidone chelating agents. Also provides are Gd(III) complexes of these agents, which are useful as contrast enhancing agents for magnetic resonance imaging. The invention also provides methods of preparing the compounds of the invention, as well as methods of using the compounds in magnetic resonance imaging applications.

Cell-permeable Ln(III) chelate-functionalized InP quantum dots as multimodal imaging agents.

PubMed

Stasiuk, Graeme J; Tamang, Sudarsan; Imbert, Daniel; Poillot, Cathy; Giardiello, Marco; Tisseyre, Céline; Barbier, Emmanuel L; Fries, Pascal Henry; de Waard, Michel; Reiss, Peter; Mazzanti, Marinella

2011-10-25

Quantum dots (QDs) are ideal scaffolds for the development of multimodal imaging agents, but their application in clinical diagnostics is limited by the toxicity of classical CdSe QDs. A new bimodal MRI/optical nanosized contrast agent with high gadolinium payload has been prepared through direct covalent attachment of up to 80 Gd(III) chelates on fluorescent nontoxic InP/ZnS QDs. It shows a high relaxivity of 900 mM(-1) s(-1) (13 mM(-1 )s(-1) per Gd ion) at 35 MHz (0.81 T) and 298 K, while the bright luminescence of the QDs is preserved. Eu(III) and Tb(III) chelates were also successfully grafted to the InP/ZnS QDs. The absence of energy transfer between the QD and lanthanide emitting centers results in a multicolor system. Using this convenient direct grafting strategy additional targeting ligands can be included on the QD. Here a cell-penetrating peptide has been co-grafted in a one-pot reaction to afford a cell-permeable multimodal multimeric MRI contrast agent that reports cellular localization by fluorescence and provides high relaxivity and increased tissue retention with respect to commercial contrast agents.

Method of treating tumors

DOEpatents

DeNardo, Sally J.; Burke, Patricia A.; DeNardo, Gerald L.; Goodman, Simon; Matzku, legal representative, Kerstin; Matzku, Siegfried

2006-04-18

A method of treating tumors, such as prostate tumors, breast tumors, non-Hodgkin's lymphoma, and the like, includes the sequential steps of administering to the patient at least one dose of an antiangiogenic cyclo-arginine-glycine-aspartic acid-containing pentapeptide (cRGD pentapeptide); administering to the patient an anti-tumor effective amount of a radioimmunotherapeutic agent (RIT); and then administering to the patient at least one additional dose of cRGD pentapeptide. The cRGD pentapeptide is preferably cyclo-(Arg-Gly-Asp-D-Phe-[N-Me]-Val), and the RIT is preferably a radionuclide-labeled chelating agent-ligand complex in which chelating agent is chemically bonded to a tumor-targeting molecule, such as a monoclonal antibody.

Fluid extraction

DOEpatents

Wai, Chien M.; Laintz, Kenneth E.

1999-01-01

A method of extracting metalloid and metal species from a solid or liquid material by exposing the material to a supercritical fluid solvent containing a chelating agent is described. The chelating agent forms chelates that are soluble in the supercritical fluid to allow removal of the species from the material. In preferred embodiments, the extraction solvent is supercritical carbon dioxide and the chelating agent is a fluorinated .beta.-diketone. In especially preferred embodiments the extraction solvent is supercritical carbon dioxide, and the chelating agent comprises a fluorinated .beta.-diketone and a trialkyl phosphate, or a fluorinated .beta.-diketone and a trialkylphosphine oxide. Although a trialkyl phosphate can extract lanthanides and actinides from acidic solutions, a binary mixture comprising a fluorinated .beta.-diketone and a trialkyl phosphate or a trialkylphosphine oxide tends to enhance the extraction efficiencies for actinides and lanthanides. The method provides an environmentally benign process for removing contaminants from industrial waste without using acids or biologically harmful solvents. The method is particularly useful for extracting actinides and lanthanides from acidic solutions. The chelate and supercritical fluid can be regenerated, and the contaminant species recovered, to provide an economic, efficient process.

Function of the iron-binding chelator produced by Coriolus versicolor in lignin biodegradation.

PubMed

Wang, Lu; Yan, WenChao; Chen, JiaChuan; Huang, Feng; Gao, PeiJi

2008-03-01

An ultrafiltered low-molecular-weight preparation of chelating compounds was isolated from a wood-containing culture of the white-rot basidiomycete Coriolus versicolor. This preparation could chelate Fe3+ and reduce Fe3+ to Fe2+, demonstrating that the substance may serve as a ferric chelator, oxygen-reducing agent, and redox-cycling molecule, which would include functioning as the electron transport carrier in Fenton reaction. Lignin was treated with the iron-binding chelator and the changes in structure were investigated by 1H-NMR, 13C-NMR, difference spectrum caused by ionization under alkaline conditions and nitrobenzene oxidation. The results indicated that the iron-binding chelator could destroy the beta-O-4 bonds in etherified lignin units and insert phenolic hydroxyl groups. The low-molecular-weight chelator secreted by C. versicolor resulted in new phenolic substructures in the lignin polymer, making it susceptible to attack by laccase or manganese peroxidase. Thus, the synergic action of the iron-binding chelator and the lignocellulolytic enzymes made the substrate more accessible to degradation.

Novel chelating agents for iron, manganese, zinc, and copper mixed fertilisation in high pH soil-less cultures.

PubMed

López-Rayo, Sandra; Nadal, Paloma; Lucena, Juan J

2016-03-15

Studies about simultaneous fertilisation with several micronutrients have increased in recent years, as Fe, Mn and Zn deficiencies may appear in the same culture conditions. In fertigation, the replacement of sulfates by synthetic chelates is essential in areas with high pH irrigation water and substrates. Ethylenediamine-N-(2-hydroxyphenylacetic acid)-N'-(4-hydroxyphenylacetic acid) (o,p-EDDHA) and ethylenediamine disuccinic acid (EDDS) are novel chelating agents whose efficacy in simultaneous fertilisation of Zn, Mn and Cu is unknown. This work evaluates the effectiveness of both ligands compared to traditional ligands (EDTA, HEEDTA and DTPA) applied as micronutrient chelate mixtures to soybean and navy bean plants grown in soil-less cultures at high pH by analysing the SPAD and micronutrient nutritional status, including the Composition Nutritional Diagnosis (CND) analysis tool. The application of micronutrients using o,p-EDDHA was more effective in providing Mn and Zn than traditional ligands or sulfates. The application using EDDS increased the Zn nutrition. The results are well correlated with the chemical stability of the formulations. The combined application of Mn and Zn as o,p-EDDHA chelates can represent a more effective source than traditional chelates in micronutrient fertiliser mixtures in soil-less cultures at a high pH. © 2015 Society of Chemical Industry.

Interaction of chelating agents with cadmium in mice and rats.

PubMed Central

Eybl, V; Sýkora, J; Koutenský, J; Caisová, D; Schwartz, A; Mertl, F

1984-01-01

The influence of several chelating agents (CaDTPA, ZnDTPA, CaEDTA, ZnEDTA, DMSA, D-penicillamine and DMPS, DMP and DDC) on the acute toxicity of CdCl2 and on the whole body retention and tissue distribution of cadmium after the IV application of 115mCdCl2 was compared in mice. The chelating agents were applied immediately after the application of cadmium. CaDTPA, ZnDTPA and DMSA appeared to be the most effective antidotes. However, DMSA increased the amount of cadmium retained in kidneys. The treatment of cadmium-poisoned mice with the combination of DMSA (IP) and ZnDTPA (SC) (all the compounds were injected in equimolar dose) decreased the toxicity of cadmium more than treatment with one chelating agents (given in a 2:1 dose). However, by studying the effect of these chelating agents and their combination of the retention and distribution of Cd in mice, it was demonstrated that the combined application of the antidotes showed little or no improvement over the results obtained with the most effective of the individual components. In the urine of rats injected with CdCl2 and treated with the chelating agents (CaDTPA, ZnDTPA, DMSA), the presence of cadmium complexes was demonstrated. The formation of mixed ligand chelates in vivo was not proved. Experiments in mice given a single injection of 115mCd-labeled Cd complexes of DMPS, DMSA and DTPA showed a high retention of cadmium in the organisms after the IV application of CdDMPS and CdDMSA complexes. PMID:6734561

SEPARATION PROCESS FOR TRANSURANIC ELEMENT AND COMPOUNDS THEREOF

DOEpatents

Calvin, M.

1958-10-14

S> A process is presented for the separation of pluto nium from uranium and fission products in an aqueous acidic solution by use of a chelating agent. The plutonium is maintained in the tetravalent state and the uranium in the hexavalent state, and the acidic concentration is adjusted to about 1 N bar. The aqueous solution is then contacted with a water-immiscible organic solvent solution and the chelating agent. The chelating agents covered by this invention comprise a group of compounds characterized as fluorinated beta-diketones.

Extraction of metals and/or metalloids from acidic media using supercritical fluids and salts

DOEpatents

Wai, Chien M.; Smart, Neil G.; Lin, Yuehe

1998-01-01

A method of extracting metalloid and metal species from a solid or liquid material by exposing the material to a fluid solvent, particularly supercritical carbon dioxide, containing a chelating agent is described. The chelating agent forms chelates that are soluble in the fluid to allow removal of the species from the material. In preferred embodiments, the extraction solvent is supercritical carbon dioxide and the chelating agent comprises a trialkyl phosphate, a triaryl phosphate, a trialkylphosphine oxide, a triarylphosphine oxide, or mixtures thereof. The method provides an environmentally benign process for removing contaminants from industrial waste. The method is particularly useful for extracting actinides from acidic solutions, and the process can be aided by the addition of nitrate salts. The chelate and supercritical fluid can be regenerated, and the contaminant species recovered, to provide an economic, efficient process.

Gadolinium Endohedral Metallofullerene-Based MRI Contrast Agents

NASA Astrophysics Data System (ADS)

Bolskar, Robert D.

With the ability to encapsulate and carry the highly paramagnetic Gd3+ ion, gadolinium endohedral metallofullerenes or "gadofullerenes" are being explored as alternatives to the chelate complexes that are currently used for contrast-enhanced magnetic resonance imaging (MRI). Reviewed here are the various water-soluble derivatives of the gadofullerenes Gd@C82, Gd@C60, and Gd3N@C80 that have been investigated as MRI contrast agents. The water proton r1 relaxivities of gadofullerenes can be more than an order of magnitude higher than those of clinically used chelate agents. Gadofullerene relaxivity mechanisms have been studied, and multiple factors are found to contribute to their high relaxivities. In vitro and in vivoT1-weighted MRI tests of gadofullerene derivatives have shown their utility as bright image-enhancing agents. The gadofullerene MRI contrast agents are a promising new and unique style of gadolinium carrier for advanced imaging applications, including cellular and molecular imaging.

Boiler scale prevention employing an organic chelant

DOEpatents

Wallace, Steven L.; Griffin, Jr., Freddie; Tvedt, Jr., Thorwald J.

1984-01-01

An improved method of treating boiler water which employs an oxygen scavenging compound and a compound to control pH together with a chelating agent, wherein the chelating agent is hydroxyethylethylenediaminetriacetic acid.

Assessment of iron chelates efficiency for photo-Fenton at neutral pH.

PubMed

De Luca, Antonella; Dantas, Renato F; Esplugas, Santiago

2014-09-15

In this study, homogeneous photo-Fenton like at neutral pH was applied to remove sulfamethoxazole from water. The process was performed using different chelating agents in order to solubilize iron in a neutral water solution. The chelating agents tested were: ethylenediaminetetraacetic acid (EDTA); nitrilotriacetic acid (NTA); oxalic acid (OA) and tartaric acid (TA). The iron leaching was monitored over reaction time to evaluate the chelates stability and their resistance to HO· and UV-A radiation. Chelates of EDTA and NTA presented more stability than OA and TA, which also confirmed their higher efficiency. Total Organic Carbon (TOC) analyses were also performed to evaluate the contribution in terms of solution contamination related to the use of chelating agents. The better properties of biodegradability in respect of EDTA combined with better efficiency in terms of microcontaminant removal and the smallest TOC contribution indicate that NTA could represent a useful option to perform photo-Fenton processes at neutral pH. Copyright © 2014 Elsevier Ltd. All rights reserved.

Chelate assisted phytoextraction of heavy metals from soil. Effect, mechanism, toxicity, and fate of chelating agents.

PubMed

Evangelou, Michael W H; Ebel, Mathias; Schaeffer, Andreas

2007-06-01

The low-cost, plant-based phytoextraction technique has often been described as a promising technique to remediate heavy metal contaminated agricultural land. The application of chelating agents has shown positive effects in increasing the solubility of heavy metals in soil and therefore in enhancing phytoextraction. This paper gives an overview of the chelating agents applied in recent studies. Various synthetic aminopolycarboxylic acids, such as ethylene diamine tetraacetic acid, and natural ones such as, ethylene diamine disuccinate and nitrilotriacetic acid, are described. Additionally, results of the application of natural low molecular weight organic acids, such as citric and tartaric acid are given. The effectiveness of these different chelating agents varies according to the plant and the heavy metals used. Furthermore, a focus is laid on the chelating agents fate after application and on its toxicity to plants and soil microorganisms, as well as it degradation. The rate of degradation is of great importance for the future of chelate assisted phytoextraction as it has a direct impact on the leaching probability. An effective prevention of leaching will be crucial for the acceptance and the economic breakthrough of enhanced phytoextraction, but a satisfactory solution to this key issue has so far not been found. Possibly further experiments in the field of enhanced phytoextraction will be able to solve this major problem, but over decades various greenhouse experiments and recently field experiments have resulted in different observations. Therefore, it is questionable if further research in this direction will lead to a promising solution. Phytoextraction has possibly reached a turning point in which it should distance itself from chelate assisted phytoextraction and focus on alternative options.

Antimicrobial action of chelating agents: repercussions on the microorganism development, virulence and pathogenesis.

PubMed

Santos, A L S; Sodre, C L; Valle, R S; Silva, B A; Abi-Chacra, E A; Silva, L V; Souza-Goncalves, A L; Sangenito, L S; Goncalves, D S; Souza, L O P; Palmeira, V F; d'Avila-Levy, C M; Kneipp, L F; Kellett, A; McCann, M; Branquinha, M H

2012-01-01

Infections caused by resistant microorganisms often fail to respond to conventional therapy, resulting in prolonged illness, increased treatment costs and greater risk of death. Consequently, the development of novel antimicrobial drugs is becoming more demanding every day since the existing drugs either have too many side-effects or they tend to lose effectiveness due to the selection of resistant strains. In view of these facts, a number of new strategies to obstruct vital biological processes of a microbial cell have emerged; one of these is focused on the use of metal-chelating agents, which are able to selectively disturb the essential metal metabolism of the microorganism by interfering with metal acquisition and bioavailability for crucial reactions. The chelation activity is able to inhibit the biological role of metal-dependent proteins (e.g., metalloproteases and transcription factors), disturbing the microbial cell homeostasis and culminating in the blockage of microbial nutrition, growth and development, cellular differentiation, adhesion to biotic (e.g., extracellular matrix components, cell and/or tissue) and abiotic (e.g., plastic, silicone and acrylic) structures as well as controlling the in vivo infection progression. Interestingly, chelating agents also potentiate the activity of classical antimicrobial compounds. The differences between the microorganism and host in terms of the behavior displayed in the presence of chelating agents could provide exploitable targets for the development of an effective chemotherapy for these diseases. Consequently, metal chelators represent a novel group of antimicrobial agents with potential therapeutic applications. This review will focus on the anti-fungal and anti-protozoan action of the most common chelating agents, deciphering and discussing their mode of action.

Effects of Application of NTA and EDTA on Accumulation of Soil Heavy Metals in Chrysanthemum

NASA Astrophysics Data System (ADS)

Bai, Weiyang

2018-02-01

In order to find out the effect of non-bio chelating agent EDTA and bio-chelating agent NTA on soil heavy metal pollution, the effects of different ratio of chelating agent NTA and EDTA on soil heavy metals (Pb, Cu and Cd ), the effects of chelating on content of chlorophyll and vitamin C and the degree of soil nutrient loss were evaluated. The results showed: that the contents of Pb and Cd were the highest in the roots of Chrysanthemum in the treatment (EDTA / NTA = 2: 1). The treatment (EDTA / NTA = 1: 1) was the best chelating agent ratio for the synergistic effect, which can significantly promoted the Chrysanthemum on heavy metal Cu uptake and transport to aboveground. Chrysanthemum were inhibited by all chelating agents treatments, while the content of chlorophyll and vitamin C of the Chrysanthemum physiological indexes were reduced. In the treatment (EDTA = 1), chlorophyll SPAD, vitamin C content reached a minimum of 36 and 38mg · 100g-1, respectively. The nutrient element TN in the leachate were gradually decreased with the time, and the tenth day was significantly lower than the leaching rate of the first day (p <0.05) in the treatments (NTA = 1, EDTA / NTA = 1: 2). The nutrient element TN was decreased most, reaching 51.6%, and the activation effect was decreased significantly in the fifteenth day in treatment (NTA = 1), Treatment(EDTA / NTA = 1: 1)> treatment (EDTA = 1) >treatment (EDTA / NTA = 2: 1) >treatment (EDTA / NTA = 1: 2)> treatment (NTA = 1). Treatment (EDTA / NTA = 2: 1) was recommended for the chelating agent ratio with the better physiological parameters, the more heavy metal extraction and the less nitrogen and phosphorus loss

Ironing out the role of the cyclin-dependent kinase inhibitor, p21 in cancer: Novel iron chelating agents to target p21 expression and activity.

PubMed

Moussa, Rayan S; Park, Kyung Chan; Kovacevic, Zaklina; Richardson, Des R

2018-03-20

Iron (Fe) has become an important target for the development of anti-cancer therapeutics with a number of Fe chelators entering human clinical trials for advanced and resistant cancer. An important aspect of the activity of these compounds is their multiple molecular targets, including those that play roles in arresting the cell cycle, such as the cyclin-dependent kinase inhibitor, p21. At present, the exact mechanism by which Fe chelators regulate p21 expression remains unclear. However, recent studies indicate the ability of chelators to up-regulate p21 at the mRNA level was dependent on the chelator and cell-type investigated. Analysis of the p21 promoter identified that the Sp1-3-binding site played a significant role in the activation of p21 transcription by Fe chelators. Furthermore, there was increased Sp1/ER-α and Sp1/c-Jun complex formation in melanoma cells, suggesting these complexes were involved in p21 promoter activation. Elucidating the mechanisms involved in the regulation of p21 expression in response to Fe chelator treatment in neoplastic cells will further clarify how these agents achieve their anti-tumor activity. It will also enhance our understanding of the complex roles p21 may play in neoplastic cells and lead to the development of more effective and specific anti-cancer therapies. Copyright © 2018 Elsevier Inc. All rights reserved.

Extraction of metals and/or metalloids from acidic media using supercritical fluids and salts

DOEpatents

Wai, C.M.; Smart, N.G.; Lin, Y.

1998-06-23

A method is described for extracting metalloid and metal species from a solid or liquid material by exposing the material to a fluid solvent, particularly supercritical carbon dioxide, containing a chelating agent. The chelating agent forms chelates that are soluble in the fluid to allow removal of the species from the material. In preferred embodiments, the extraction solvent is supercritical carbon dioxide and the chelating agent comprises a trialkyl phosphate, a triaryl phosphate, a trialkylphosphine oxide, a triarylphosphine oxide, or mixtures thereof. The method provides an environmentally benign process for removing contaminants from industrial waste. The method is particularly useful for extracting actinides from acidic solutions, and the process can be aided by the addition of nitrate salts. The chelate and supercritical fluid can be regenerated, and the contaminant species recovered, to provide an economic, efficient process. 7 figs.

SEPARATION PROCESS FOR TRANSURANIC ELEMENT AND COMPOUNDS THEREOF

DOEpatents

Magnusson, L.B.

1958-04-01

A process is described for the separation of neptunium, from aqueous solutions of neptunium, plutonium, uraniunn, and fission prcducts. This separation from an acidic aqueous solution of a tetravalent neptuniunn can be made by contacting the solution with a certain type of chelating,; agent, preferably dissolved in an organic solvent, to form a neptunium chelate compound. When the organic solvent is present, the neptunium chelate compound is extracted; otherwise, it precipitates from the aqueous solution and is separated by any suitable means. The chelating agent is a fluorinated BETA -diketone. such as trifluoroacetyl acetone.

Antimicrobial Properties of Copper Nanoparticles and Amino Acid Chelated Copper Nanoparticles Produced by Using a Soya Extract.

PubMed

DeAlba-Montero, I; Guajardo-Pacheco, Jesús; Morales-Sánchez, Elpidio; Araujo-Martínez, Rene; Loredo-Becerra, G M; Martínez-Castañón, Gabriel-Alejandro; Ruiz, Facundo; Compeán Jasso, M E

2017-01-01

This paper reports a comparison of the antibacterial properties of copper-amino acids chelates and copper nanoparticles against Escherichia coli , Staphylococcus aureus , and Enterococcus faecalis . These copper-amino acids chelates were synthesized by using a soybean aqueous extract and copper nanoparticles were produced using as a starting material the copper-amino acids chelates species. The antibacterial activity of the samples was evaluated by using the standard microdilution method (CLSI M100-S25 January 2015). In the antibacterial activity assays copper ions and copper-EDTA chelates were included as references, so that copper-amino acids chelates can be particularly suitable for acting as an antibacterial agent, so they are excellent candidates for specific applications. Additionally, to confirm the antimicrobial mechanism on bacterial cells, MTT assay (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) was carried out. A significant enhanced antimicrobial activity and a specific strain were found for copper chelates over E. faecalis . Its results would eventually lead to better utilization of copper-amino acids chelate for specific application where copper nanoparticles can be not used.

Antimicrobial Properties of Copper Nanoparticles and Amino Acid Chelated Copper Nanoparticles Produced by Using a Soya Extract

PubMed Central

DeAlba-Montero, I.; Morales-Sánchez, Elpidio; Araujo-Martínez, Rene

2017-01-01

This paper reports a comparison of the antibacterial properties of copper-amino acids chelates and copper nanoparticles against Escherichia coli, Staphylococcus aureus, and Enterococcus faecalis. These copper-amino acids chelates were synthesized by using a soybean aqueous extract and copper nanoparticles were produced using as a starting material the copper-amino acids chelates species. The antibacterial activity of the samples was evaluated by using the standard microdilution method (CLSI M100-S25 January 2015). In the antibacterial activity assays copper ions and copper-EDTA chelates were included as references, so that copper-amino acids chelates can be particularly suitable for acting as an antibacterial agent, so they are excellent candidates for specific applications. Additionally, to confirm the antimicrobial mechanism on bacterial cells, MTT assay (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) was carried out. A significant enhanced antimicrobial activity and a specific strain were found for copper chelates over E. faecalis. Its results would eventually lead to better utilization of copper-amino acids chelate for specific application where copper nanoparticles can be not used. PMID:28286459

Intrinsic dependence of the magnetic properties of CoFe2O4 nanoparticles prepared via chemical methods with addition of chelating agents

NASA Astrophysics Data System (ADS)

Mendonça, E. C.; Tenório, Mayara A.; Mecena, S. G.; Zucolotto, B.; Silva, L. S.; Jesus, C. B. R.; Meneses, C. T.; Duque, J. G. S.

2015-12-01

In this work, the effect of addition of different chelating agents on the magnetic properties of cobalt ferrite nanoparticles produced by the combining of both co-precipitation and hydrothermal methods is reported. The Rietveld analyses of X-ray diffraction patterns reveal that our samples are single phase (space group: Fd-3m) with small average sizes. The weight losses observed in the thermogravimetric measurements together with the M×H curves show that the organic contamination coming from chelating agent decomposition can give rise to misinterpretation of the magnetization measurements. Besides, analyses of the zero-field-cooled (ZFC) and field-cooled (FC) magnetization measurements and the M×H curves measured at room temperature allows us to state that both the average blocking temperature and particles size distribution are sensitive to the kind of chelating agent.

Effect of the tether on the Mg(II), Ca(II), Cu(II) and Fe(III) stability constants and pM values of chelating agents related to EDDHA.

PubMed

Sierra, Miguel A; Gómez-Gallego, Mar; Alcázar, Roberto; Lucena, Juan J; Yunta, Felipe; García-Marco, Sonia

2004-11-07

The effect of the length and the structure of the tether on the chelating ability of EDDHA-like chelates have not been established. In this work, PDDHA (propylenediamine-N,N'-bis(o-hydroxyphenyl)acetic acid), BDDHA (butylenediamine-N,N'-bis(o-hydroxyphenyl)acetic acid) and XDDHA (p-xylylenediamine-N,N'-bis(o-hydroxyphenyl)acetic acid) have been obtained and their chemical behaviour has been studied and compared with that of EDDHA following our methodology. The purity of the chelating agents, and their protonation, Ca(II), Mg(II), Fe(III) and Cu(II) stability constants and pM values have been determined. The stability constants and pM values indicate that EDDHA forms the most stable chelates followed by PDDHA. However, the differences among the pFe values are small when a nutrient solution is used, and in these conditions the XDDHA/Fe(III) chelate is the most stable. The results obtained in this work indicate that all the chelating agents studied can be used as iron chlorosis correctors and they can be applied to soil/plant systems.

Strategies for the preparation of bifunctional gadolinium(III) chelators

PubMed Central

Frullano, Luca; Caravan, Peter

2012-01-01

The development of gadolinium chelators that can be easily and readily linked to various substrates is of primary importance for the development high relaxation efficiency and/or targeted magnetic resonance imaging (MRI) contrast agents. Over the last 25 years a large number of bifunctional chelators have been prepared. For the most part, these compounds are based on ligands that are already used in clinically approved contrast agents. More recently, new bifunctional chelators have been reported based on complexes that show a more potent relaxation effect, faster complexation kinetics and in some cases simpler synthetic procedures. This review provides an overview of the synthetic strategies used for the preparation of bifunctional chelators for MRI applications. PMID:22375102

Evaluation of on-line chelant addition to PWR steam generators. Steam generator cleaning project

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tvedt, T.J.; Wallace, S.L.; Griffin, F. Jr.

1983-09-01

The investigation of chelating agents for continuous water treatment of secondary loops of PWR steam generators were conducted in two general areas: the study of the chemistry of chelating agents and the study of materials compatability with chelating agents. The thermostability of both EDTA and HEDTA metal chelates in All Volatile Treatment (AVT) water chemistry were shown to be greater than or equal to the thermostability of EDTA metal chelates in phosphate-sulfite water chemistry. HEDTA metal chelates were shown to have a much greater stability than EDTA metal chelates. Using samples taken from the EDTA metal chelate thermostability study andmore » from the Commonwealth Research Corporation (CRC) model steam generators (MSG), EDTA decomposition products were determined. Active metal surfaces were shown to become passivated when exposed to EDTA and HEDTA concentrations as high as 0.1% w/w in AVT. Trace amounts of iron in the water were found to increase the rate of passivation. Material balance and visual inspection data from CRC model steam generators showed that metal was transported through and cleaned from the MSG's. The Inconel 600 tubes of the salt water fouled model steam generators experienced pitting corrosion. Results of this study demonstrates the feasibility of EDTA as an on-line water treatment additive to maintain nuclear steam generators in a clean condition.« less

Enhancement effects of chelating agents on the degradation of tetrachloroethene in Fe(III) catalyzed percarbonate system

PubMed Central

Miao, Zhouwei; Gu, Xiaogang; Lu, Shuguang; Brusseau, Mark L.; Zhang, Xiang; Fu, Xiaori; Danish, Muhammad; Qiu, Zhaofu; Sui, Qian

2015-01-01

The performance of Fe(III)-based catalyzed sodium percarbonate (SPC) for stimulating the oxidation of tetrachloroethene (PCE) for groundwater remediation applications was investigated. The chelating agents citric acid monohydrate (CIT), oxalic acid (OA), and Glutamic acid (Glu) significantly enhanced the degradation of PCE. Conversely, ethylenediaminetetraacetic acid (EDTA) had a negative impact on PCE degradation, which may due to its strong Fe chelation and HO• scavenging abilities. However, excessive SPC or chelating agent will retard PCE degradation. In addition, investigations using free radical probe compounds and radical scavengers revealed that PCE was primarily degraded by HO• radical oxidation in both the chelated and non-chelated systems, while O2•− also participated in the non-chelated system and the OA and Glu modified systems. According to the electron paramagnetic resonance (EPR) studies, the presence of HO• in the Fe(III)/SPC system was maintained much longer than that in the Fe(II)/SPC system. The results indicated that the addition of CIT, OA or Glu indeed enhanced the generation of HO• in the first 10 min and promoted degradation efficiency by increasing the amount of Fe(III) and maintaining the concentration of HO• radicals in solution. In conclusion, chelated Fe(III)-based catalyzed SPC oxidation is a promising method for the remediation of PCE-contaminated groundwater. PMID:26549979

Catalytic superoxide scavenging by metal complexes of the calcium chelator EGTA and contrast agent EHPG.

PubMed

Fisher, Anna E O; Hague, Theresa A; Clarke, Charlotte L; Naughton, Declan P

2004-10-08

Metal ion chelators widely used in experimental protocols and clinical diagnosis are generally assumed to be inert. We previously reported that the ubiquitous chelator EDTA has high levels of superoxide suppressing activity. Here, we report that the common chelators calcium chelator EGTA and contrast agent EHPG have significant activities in suppressing superoxide levels depending on the nature of metal ion chelated. The most active species is Mn(II)-EGTA which exhibited an IC50 value of 0.19 microM for superoxide destruction. In addition, IC50 values for Mn(II)-EHPG and 2Cu(II)-EGTA were 0.69 and 0.60 microM, respectively. In conclusion, Mn(II) and Cu(II) complexes of the common chelators EGTA and EHPG exhibit considerable superoxide scavenging activities. Caution should be employed in their use in biological systems where superoxide has a key role and they may be useful for the development of catalytic anti-oxidants. Copyright 2004 Elsevier Inc.

Metal cation detection in positive ion mode electrospray ionization mass spectrometry using a tetracationic salt as a gas-phase ion-pairing agent: evaluation of the effect of chelating agents on detection sensitivity.

PubMed

Xu, Chengdong; Dodbiba, Edra; Padivitage, Nilusha L T; Breitbach, Zachary S; Armstrong, Daniel W

2012-12-30

The detection of metal cations continues to be essential in many scientific and industrial areas of interest. The most common electrospray ionization mass spectrometry (ESI-MS) approach involves chelating the metal ions and detecting the organometallic complex in the negative ion mode. However, it is well known that negative ion mode ESI-MS is generally less sensitive than the positive ion mode. To achieve greater sensitivity, it is necessary to examine the feasibility of detecting the chelated metal cations in positive ion mode ESI-MS. Since highly solvated native metal cations have relatively low ionization efficiency in ESI-MS, and can be difficult to detect in the positive ion mode, a tetracationic ion-pairing agent was added to form a complex with the negatively charged metal chelate. The use of the ion-pairing agent leads to the generation of an overall positively charged complex, which can be detected at higher m/z values in the positive ion mode by electrospray ionization linear quadrupole ion trap mass spectrometry. Thirteen chelating agents with diverse structures were evaluated in this study. The nature of the chelating agent played as important a role as was previously determined for cationic pairing agents. The detection limits of six metal cations reached sub-picogram levels and significant improvements were observed when compared to negative ion mode detection where the metal-chelates were monitored without adding the ion-pairing reagent (IPR). Also, selective reaction monitoring (SRM) analyses were performed on the ternary complexes, which improved detection limits by one to three orders of magnitude. With this method it was possible to analyze the metal cations in the positive ion mode ESI-MS with the advantage of speed, sensitivity and selectivity. The optimum solution pH for this type of analysis is 5-7. Tandem mass spectrometry (MS/MS) further increases the sensitivity. Speciation is straightforward making this a broadly useful approach for the analysis of metal ions. Copyright © 2012 John Wiley & Sons, Ltd.

[Bifunctional chelates of Rh-105, Au-199, and other metallic radionuclides as potential radiotherapeutic agents

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

1991-12-31

Progress during this period is reported under the following headings: Diethylenetriamine based and related bifunctional chelating agents and their complexation with Rh-105, Au-198, Pd-109, cu-67, In-111, and Co-57; studies of Pd-109, Rh-105 and Tc-99m with bifunctional chelates based on phenylenediamine; establishment of an appropriate protein assay method for conjugated proteins; studies of new bifunctional Bi, Tri and tetradentate amine oxime ligands with Rh-105; IgG and antibody B72.3 conjugation studies by HPLC Techniques with bifunctional metal chelates; and progress on ligand systems for Au(III).

(Bifunctional chelates of Rh-105, Au-199, and other metallic radionuclides as potential radiotherapeutic agents)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

1991-01-01

Progress during this period is reported under the following headings: Diethylenetriamine based and related bifunctional chelating agents and their complexation with Rh-105, Au-198, Pd-109, cu-67, In-111, and Co-57; studies of Pd-109, Rh-105 and Tc-99m with bifunctional chelates based on phenylenediamine; establishment of an appropriate protein assay method for conjugated proteins; studies of new bifunctional Bi, Tri and tetradentate amine oxime ligands with Rh-105; IgG and antibody B72.3 conjugation studies by HPLC Techniques with bifunctional metal chelates; and progress on ligand systems for Au(III).

Synthesis and evaluation of nanoglobular macrocyclic Mn(II) chelate conjugates as non-gadolinium(III) MRI contrast agents.

PubMed

Tan, Mingqian; Ye, Zhen; Jeong, Eun-Kee; Wu, Xueming; Parker, Dennis L; Lu, Zheng-Rong

2011-05-18

Because of the recent observation of the toxic side effects of Gd(III) based MRI contrast agents in patients with impaired renal function, there is strong interest on developing alternative contrast agents for MRI. In this study, macrocyclic Mn(II) chelates were conjugated to nanoglobular carriers, lysine dendrimers with a silsesquioxane core, to synthesize non-Gd(III) based MRI contrast agents. A generation 3 nanoglobular conjugate of Mn(II)-1,4,7-triaazacyclononane-1,4,7-triacetate-GA amide (G3-NOTA-Mn) was also synthesized and evaluated. The per ion T(1) and T(2) relaxivities of G2, G3, G4 nanoglobular Mn(II)-DOTA monoamide conjugates decreased with increasing generation of the carriers. The T(1) relaxivities of G2, G3, and G4 nanoglobular Mn(II)-DOTA conjugates were 3.3, 2.8, and 2.4 mM(-1) s(-1) per Mn(II) chelate at 3 T, respectively. The T(1) relaxivity of G3-NOTA-Mn was 3.80 mM(-1) s(-1) per Mn(II) chelate at 3 T. The nanoglobular macrocyclic Mn(II) chelate conjugates showed good in vivo stability and were readily excreted via renal filtration. The conjugates resulted in much less nonspecific liver enhancement than MnCl(2) and were effective for contrast-enhanced tumor imaging in nude mice bearing MDA-MB-231 breast tumor xenografts at a dose of 0.03 mmol Mn/kg. The nanoglobular macrocyclic Mn(II) chelate conjugates are promising nongadolinium based MRI contrast agents.

Rational Design, Development, and Stability Assessment of a Macrocyclic Four-Hydroxamate-Bearing Bifunctional Chelating Agent for 89 Zr.

PubMed

Seibold, Uwe; Wängler, Björn; Wängler, Carmen

2017-09-21

Zirconium-89 is a positron-emitting radionuclide of high interest for medical imaging applications with positron emission tomography (PET). For the introduction of this radiometal into biologically active targeting vectors, the chelating agent desferrioxamine B (DFO) is commonly applied. However, DFO is known to form 89 Zr complexes of limited in vivo stability. Herein we describe the rational design and chemical development of a new macrocyclic four-hydroxamate-bearing chelating agent-1,10,19,28-tetrahydroxy-1,5,10,14,19,23,28,32-octaazacyclohexatriacontan-2,6,11,15,20,24,29,33-octaone (CTH36)-for the stable complexation of Zr 4+ . For this purpose, we first performed computational studies to determine the optimal chelator geometry before we developed different synthesis pathways toward the target structures. The best results were obtained using an efficient solution-phase-based synthesis strategy toward the target chelating agent. To enable efficient and chemoselective conjugation to biomolecules, a tetrazine-modified variant of CTH36 was also developed. The excellent conjugation characteristics of the so-functionalized chelator were demonstrated on the example of the model peptide TCO-c(RGDfK). We determined the optimal 89 Zr radiolabeling parameters for CTH36 as well as its bioconjugate, and found that 89 Zr radiolabeling proceeds efficiently under very mild reaction conditions. Finally, we performed comparative complex stability tests for 89 Zr-CHT36-c(RGDfK) and 89 Zr-DFO-c(RGDfK), showing improved complex stability for the newly developed chelator CTH36. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Iron Reverses Impermeable Chelator Inhibition of DNA Synthesis in CCl39 Cells

NASA Astrophysics Data System (ADS)

Alcain, Francisco J.; Low, Hans; Crane, Frederick L.

1994-08-01

Treatment of Chinese hamster lung fibro-blasts (CCl 39 cells) with the impermeable iron(II) chelator bathophenanthroline disulfonate (BPS) inhibits DNA synthesis when cell growth is initiated with growth factors including epidermal growth factor plus insulin, thrombin, or ceruloplasmin, but not with 10% fetal calf serum. The BPS treatment inhibits transplasma membrane electron transport. The treatment leads to release of iron from the cells as determined by BPS iron(II) complex formation over 90 min. Growth factor stimulation of DNA synthesis and electron transport are restored by addition of di- or trivalent iron to the cells in the form of ferric ammonium citrate, ferrous ammonium sulfate, or diferric transferrin. The effect with BPS differs from the inhibition of growth by hydroxyurea, which acts on the ribonucleotide reductase, or diethylenetriaminepentaacetic acid, which is another impermeable chelating agent, in that these agents inhibit growth in 10% fetal calf serum. The BPS effect is consistent with removal of iron from a site on the cell surface that controls DNA synthesis.

Synthesis and evaluation of a class of 1,4,7-triazacyclononane derivatives as iron depletion antitumor agents.

PubMed

Wang, Sheng; Gai, Yongkang; Zhang, Shasha; Ke, Lei; Ma, Xiang; Xiang, Guangya

2018-01-15

Iron depletion has been confirmed as an efficient strategy for cancer treatment. In the current study, a series of 1,4,7-triazacyclononane derivatives HE-NO2A, HP-NO2A and NE2P2A, as well as the bifunctional chelators p-NO 2 -PhPr-NE3TA and p-NH 2 -PhPr-NE3TA were synthesized and evaluated as iron-depleting agents for the potential anti-cancer therapy against human hepatocellular carcinoma. The cytotoxicity of these chelators was measured using hepatocellular cancer cells and compared with the clinically available iron depletion agent DFO and the universal metal chelator DTPA. All these 1,4,7-triazacyclononane-based chelators exhibited much stronger antiproliferative activity than DFO and DTPA. Among them, chelators with phenylpropyl side chains, represented by p-NO 2 -PhPr-NE3TA and p-NH 2 -PhPr-NE3TA, displayed the highest antiproliferative activity against HepG2 cells. Hence, these compounds are attractive candidates for the advanced study as iron depletion agents for the potential anti-cancer therapy, and could be further in conjugation with a targeting moiety for the future development in targeted iron depletion therapy. Copyright © 2017 Elsevier Ltd. All rights reserved.

Thumbnail Sketches: EDTA-Type Chelating Agents in Everyday Consumer Products: Some Food, Cleaning, and Photographic Applications.

ERIC Educational Resources Information Center

Hart, J. Roger

1985-01-01

Discusses the role of chelating agents in (1) mayonnaise and salad dressings; (2) canned legumes; (3) plant foods; (4) liquid dishwashing detergents; (5) toilet soaps; (6) floor wax removers; (7) hard surface cleaners; (8) carpet cleaning; (9) bathtub and tile cleaners; and (10) photography. (JN)

21 CFR 176.150 - Chelating agents used in the manufacture of paper and paperboard.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Chelating agents used in the manufacture of paper and paperboard. 176.150 Section 176.150 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) INDIRECT FOOD ADDITIVES: PAPER AND PAPERBOARD COMPONENTS Substances...

21 CFR 176.150 - Chelating agents used in the manufacture of paper and paperboard.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Chelating agents used in the manufacture of paper and paperboard. 176.150 Section 176.150 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION (CONTINUED) INDIRECT FOOD ADDITIVES...

21 CFR 176.150 - Chelating agents used in the manufacture of paper and paperboard.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Chelating agents used in the manufacture of paper and paperboard. 176.150 Section 176.150 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION (CONTINUED) INDIRECT FOOD ADDITIVES...

21 CFR 176.150 - Chelating agents used in the manufacture of paper and paperboard.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Chelating agents used in the manufacture of paper and paperboard. 176.150 Section 176.150 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION (CONTINUED) INDIRECT FOOD ADDITIVES...

Regeneration of Three-Way Automobile Catalysts using Biodegradable Metal Chelating Agent – S, S-Ethylenediamine Disuccinic Acid (S, S-EDDS)

EPA Science Inventory

Regeneration of the activity of three-way catalytic converters (TWCs) was tested for the first time using a biodegradable metal chelating agent (S, S. Ethylenediamine disuccinic acid (S, S-EDDS). The efficiency of this novel environmentally friendly solvent in removing various c...

Supercritical Fluid Extraction of Metal Chelate: A Review.

PubMed

Ding, Xin; Liu, Qinli; Hou, Xiongpo; Fang, Tao

2017-03-04

Supercritical fluid extraction (SFE), as a new green extraction technology, has been used in extracting various metal species. The solubilities of chelating agents and corresponding metal chelates are the key factors which influence the efficiency of SFE. Other main properties of them such as stability and selectivity are also reviewed. The extraction mechanisms of mainly used chelating agents are explained by typical examples in this paper. This is the important aspect of SFE of metal ions. Moreover, the extraction efficiencies of metal species also depend on other factors such as temperature, pressure, extraction time and matrix effect. The two main complexation methods namely in-situ and on-line chelating SFE are described in detail. As an efficient chelating agent, tributyl phosphate-nitric acid (TBP-HNO 3 ) complex attracts much attention. The SFE of metal ions, lanthanides and actinides as well as organometallic compounds are also summarized. With the proper selection of ligands, high efficient extraction of metal species can be obtained. As an efficient sample analysis method, supercritical fluid chromatography (SFC) is introduced in this paper. Recently, the extraction method combining ionic liquids (ILs) with supercritical fluid has been becoming a novel technology for treating metal ions. The kinetics related to SFE of metal species is discussed with some specific examples.

Effect of the ultrasound-Fenton oxidation process with the addition of a chelating agent on the removal of petroleum-based contaminants from soil.

PubMed

Li, Ying; Li, Fangmin; Li, Fanxiu; Yuan, Fuqian; Wei, Pingfang

2015-12-01

The effects of ultrasonic irradiation, the chelating agent modified Fenton reaction, and a combination of ultrasound and the Fenton method in removing petroleum contaminants from a soil were studied. The results showed that the contaminant removal rate of the Fenton treatment combined with an oxalic acid chelating agent was 55.6% higher than that without a chelating agent. The average removal rate of the contaminants using the ultrasound-Fenton treatment was 59.0% higher than that without ultrasonic treatment. A combination of ultrasound and an Fe(2+)/Fe(3+)-oxalate complex-modified Fenton reagent resulted in significantly higher removal rates of n-alkanes (C(n)H(2n+2), n < 28), isoprenoid hydrocarbons, aromatic hydrocarbons, and saturated polycyclic terpenes compared with the ultrasound treatment alone or the Fenton method. The Fenton reaction and the ultrasound-Fenton treatment can unselectively remove multiple components of residual hydrocarbons and a number of benzene rings in polycyclic aromatic hydrocarbons. The chemistry of the heterocyclic compounds and the position and number of substituents can affect the degradation process.

Synergy and antagonism between iron chelators and antifungal drugs in Cryptococcus.

PubMed

Lai, Yu-Wen; Campbell, Leona T; Wilkins, Marc R; Pang, Chi Nam Ignatius; Chen, Sharon; Carter, Dee A

2016-10-01

Fungal infections remain very difficult to treat, and developing new antifungal drugs is difficult and expensive. Recent approaches therefore seek to augment existing antifungals with synergistic agents that can lower the therapeutic dose, increase efficacy and prevent resistance from developing. Iron limitation can inhibit microbial growth, and iron chelators have been employed to treat fungal infections. In this study, chequerboard testing was used to explore combinations of iron chelators with antifungal agents against pathogenic Cryptococcus spp. with the aim of determining how disruption to iron homeostasis affects antifungal susceptibility. The iron chelators ethylenediaminetetraacetic acid (EDTA), deferoxamine (DFO), deferiprone (DFP), deferasirox (DSX), ciclopirox olamine and lactoferrin (LF) were paired with the antifungal agents amphotericin B (AmB), fluconazole, itraconazole, voriconazole and caspofungin. All chelators except for DFO increased the efficacy of AmB, and significant synergy was seen between AmB and LF for all Cryptococcus strains. Addition of exogenous iron rescued cells from the antifungal effect of LF alone but could not prevent inhibition by AmB + LF, indicating that synergy was not due primarily to iron chelation but to other properties of LF that were potentiated in the presence of AmB. Significant synergy was not seen consistently for other antifungal-chelator combinations, and EDTA, DSX and DFP antagonised the activity of azole drugs in strains of Cryptococcus neoformans var. grubii. This study highlights the range of interactions that can be induced by chelators and indicates that most antifungal drugs are not enhanced by iron limitation in Cryptococcus. Copyright © 2016 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

[Enhanced phytoextraction of heavy metal contaminated soil by chelating agents and auxin indole-3-acetic acid].

PubMed

Zhou, Jian-min; Dang, Zhi; Chen, Neng-chang; Xu, Sheng-guang; Xie, Zhi-yi

2007-09-01

The environmental risk of chelating agents such as EDTA application to the heavy metals polluted soils and the stress on plant roots due to the abrupt increase metals concentration limit the wide commercial use of chelate-induced phytoextraction. Chelating agent ethylenediaminetetraacetic acid (EDTA) and nitrilotriacetic acid (NTA) and auxin indole-3-acetic acid (IAA) were used for enhancing heavy metals uptake from soils by Zea mays L. (corn) in pot experiments. The metals content in plant tissues was quantified using an inductively coupled plasma mass spectrometer (ICP-MS). The results showed that the combination of IAA and EDTA increased the biomass by about 40.0% and the contents of Cu, Zn, Cd and Pb in corn shoots by 27.0%, 26.8%, 27.5% and 32.8% respectively, as compared to those in EDTA treatment. While NTA&IAA treatment increased the biomass by about 29.9% and the contents of Cu, Zn, Cd and Pb in corn shoots by 31.8%, 27.6%, 17.0% and 26.9% respectively, as compared to those in NTA treatment. These results indicated that corn growth was promoted, and the biomass and the accumulation of heavy metals in plant shoots were increased significantly with the addition of IAA, which probably helps to change the cell membrane properties and the biomass distribution, resulting in the alleviation of the phytotoxicity of metals and the chelating agents.

Iron-chelating agents never suppress Fenton reaction but participate in quenching spin-trapped radicals.

PubMed

Li, Linxiang; Abe, Yoshihiro; Kanagawa, Kiyotada; Shoji, Tomoko; Mashino, Tadahiko; Mochizuki, Masataka; Tanaka, Miho; Miyata, Naoki

2007-09-19

Hydroxyl radical formation by Fenton reaction in the presence of an iron-chelating agent such as EDTA was traced by two different assay methods; an electron spin resonance (ESR) spin-trapping method with 5,5-dimethyl-1-pyrroline N-oxide (DMPO), and high Performance liquid chromatography (HPLC)-fluorescence detection with terephthalic acid (TPA), a fluorescent probe for hydroxyl radicals. From the ESR spin-trapping measurement, it was observed that EDTA seemed to suppress hydroxyl radical formation with the increase of its concentration. On the other hand, hydroxyl radical formation by Fenton reaction was not affected by EDTA monitored by HPLC assay. Similar inconsistent effects of other iron-chelating agents such as nitrylotriacetic acid (NTA), diethylenetriamine penta acetic acid (DTPA), oxalate and citrate were also observed. On the addition of EDTA solution to the reaction mixture 10 min after the Fenton reaction started, when hydroxyl radical formation should have almost ceased but the ESR signal of DMPO-OH radicals could be detected, it was observed that the DMPO-OH* signal disappeared rapidly. With the simultaneous addition of Fe(II) solution and EDTA after the Fenton reaction ceased, the DMPO-OH* signal disappeared more rapidly. The results indicated that these chelating agents should enhance the quenching of [DMPO-OH]* radicals by Fe(II), but they did not suppress Fenton reaction by forming chelates with iron ions.

Antimicrobial Polymer

DOEpatents

McDonald, William F.; Wright, Stacy C.; Taylor, Andrew C.

2004-09-28

A polymeric composition having antimicrobial properties and a process for rendering the surface of a substrate antimicrobial are disclosed. The polymeric composition comprises a crosslinked chemical combination of (i) a polymer having amino group-containing side chains along a backbone forming the polymer, (ii) an antimicrobial agent selected from metals, metal alloys, metal salts, metal complexes and mixtures thereof, and (iii) a crosslinking agent containing functional groups capable of reacting with the amino groups. In one example embodiment, the polymer is a polyamide formed from a maleic anhydride or maleic acid ester monomer and alkylamines thereby producing a polyamide having amino substituted alkyl chains on one side of the polyamide backbone; the crosslinking agent is a phosphine having the general formula (A).sub.3 P wherein A is hydroxyalkyl; and the metallic antimicrobial agent is selected from chelated silver ions, silver metal, chelated copper ions, copper metal, chelated zinc ions, zinc metal and mixtures thereof.

Monitoring the effects of chelating agents and electrical fields on active forms of Pb and Zn in contaminated soil.

PubMed

Tahmasbian, Iman; Safari Sinegani, Ali Akbar

2013-11-01

The application of electrical fields and chelating agents is an innovative hybrid technology used for the decontamination of soil polluted by heavy metals. The effects of four center-oriented electrical fields and chelating agents on active fractions of lead and zinc were investigated in this pot experiment. Ethylenediaminetetraacetic acid (EDTA) as a synthetic chelator and cow manure extract (CME) and poultry manure extract (PME) as natural chelators were applied to the pots (2 g kg(-1)) 30 days after the first irrigation. Two weeks later, four center-oriented electrical fields were applied in each pot (in three levels of 0, 10, and 30 V) for 1 h each day for 14 days. The soil near the cathode and anodes was collected and analyzed as cathodic and anodic soil, respectively. Results indicated that the soluble-exchangeable fraction of lead and zinc were decreased in the cathodic soil, while the carbonate-bound fractions were increased. In the anodic soil, however, the opposite result was observed. EDTA enhanced the soluble-exchangeable form of the metals in both anodic and cathodic soils. Furthermore, the amounts of carbonate-bound heavy metals were increased by the application of CME in both soils. The organic-bound fraction of the metals was increased by the application of natural chelators, while electrical fields had no significant impacts on this fraction.

Synthesis and chemical characterization of the novel agronomically relevant pentadentate chelate 2-(2-((2-hydroxybenzyl)amino)ethylamino)-2-(2-hydroxyphenyl)acetic acid (DCHA).

PubMed

López-Rayo, Sandra; Hernández, Diana; Lucena, Juan J; Escudero, Rosa; Gómez-Gallego, Mar; Sierra, Miguel A

2010-07-14

Iron chelates analogous to o,o-EDDHA/Fe(3+) are the fertilizers chosen to treat iron chlorosis in plants growing on calcareous soil. The isomer o,p-EDDHA/Fe(3+) presents less stability but faster assimilation by the plant than o,o-EDDHA/Fe(3+), because only five coordinating groups are able to complex Fe(3+). The new chelating agent 2-(2-((2-hydroxybenzyl)amino)ethylamino)-2-(2-hydroxyphenyl)acetic acid (DCHA) has been synthesized to obtain an iron fertilizer with intermediate stability between o,o-EDDHA/Fe(3+) and o,p-EDDHA/Fe(3+) and with fast assimilation. Its synthesis has been done starting from phenol, N-acetylethylendiamine, glyoxylic acid, and NaOH in a three-step sequence. The purity of the DCHA chelating agent, its protonation, and Ca(2+), Mg(2+), Fe(3+), and Cu(2+) stability constants, together with its ability to maintain iron in solution in different agronomic conditions, have been determined. The results indicate that the chelate DCHA/Fe(3+) has intermediate stability between those of o,o-EDDHA/Fe(3+) and o,p-EDDHA/Fe(3+) complexes and that it is capable of maintaining the Fe(3+) in agronomic conditions. This new chelating agent may be effective in correcting iron chlorosis in plants.

Synthesis of 4-substituted-trans-1, 2-diaminocyclohexyl polyaminocarboxylate metal chelating agents for the preparation of stable radiometal antibody immunoconjugates for therapy and spect and pet imaging

DOEpatents

Mease, Ronnie C.; Mausner, Leonard F.; Srivastava, Suresh C.

1994-01-01

Cyclo agents useful in forming antibody-metal conjugates useful for diagnostic and therapeutic purposes. New compounds and processes of forming these compounds are disclosed including 4-haloacetamido-trans-1,2-diaminocyclohexyl polyaminocarboxylate and 4-isothiocyanato-trans-1,2-diamino cyclohexane-N,N,N',N'-tetra acetic acid.

Iron-chelating agent, deferasirox, inhibits neutrophil activation and extracellular trap formation.

PubMed

Kono, Mari; Saigo, Katsuyasu; Yamamoto, Shiori; Shirai, Kohei; Iwamoto, Shuta; Uematsu, Tomoko; Takahashi, Takayuki; Imoto, Shion; Hashimoto, Makoto; Minami, Yosuke; Wada, Atsushi; Takenokuchi, Mariko; Kawano, Seiji

2016-10-01

Iron-chelating agents, which are frequently prescribed to transfusion-dependent patients, have various useful biological effects in addition to chelation. Reactive oxygen species (ROS) produced by neutrophils can cause pulmonary endothelial cell damage, which can lead to acute lung injury (ALI). We previously reported that deferasirox (DFS), an iron-chelating agent, inhibits phorbol myristate acetate (PMA) or formyl-methionyl-leucyl-phenylalanine (fMLP)-induced ROS production in neutrophils, in vitro. Here, we investigate whether DFS inhibits vacuolization in neutrophils and neutrophil extracellular trap (NET) formation. Human neutrophils were incubated with DFS and stimulated with PMA or fMLP. Human neutrophils were separated from heparinized peripheral blood using density gradient centrifugation, and subsequently incubated with DFS. After 10 minutes, neutrophils were stimulated by PMA or fMLP. Vacuole formation was observed by electron microscopy. For observing NET formations using microscopes, immunohistological analyses using citrullinated histone H3 and myeloperoxidase antibodies, and SYTOX Green (an impermeable DNA detection dye) staining, were conducted. NET formation was measured as the quantity of double-stranded DNA (dsDNA), using the AccuBlue Broad Range dsDNA Quantitation Kit. DFS (50 μmol/L) inhibited vacuole formation in the cytoplasm and NET formation. Additionally, 5-100 μmol/L concentration of DFS inhibited the release of dsDNA in a dose-independent manner. We demonstrate that DFS inhibits not only ROS production but also vacuolization and NET formation in neutrophils. These results suggest the possibility of protective effects of DFS against NET-related adverse effects, including ALI and thrombosis. © 2016 John Wiley & Sons Australia, Ltd.

Hydroxypyridinone Derivatives: A Fascinating Class of Chelators with Therapeutic Applications - An Update.

PubMed

Chaves, Sílvia; Piemontese, Luca; Hiremathad, Asha; Santos, Maria A

2018-01-01

Hydroxypyridinones (HPs) are a family of N-heterocyclic metal chelators, which have been an attractive target in the development of a variety of new pharmaceutical drugs, due to their high metal chelating efficacy/specificity and easy derivatization to tune the desired biological properties. In fact, along the last decades, hydroxypyridinone derivatives, but mostly 3-hydroxy-4-pyridinone (3,4-HP), have been intensively used in drug design, following either a multitarget approach, in which one chelating unity is extrafunctionalized (hybridized) to enable the interaction with other important specific biological sites, or a polydenticity approach, in which more than one chelating moiety is conveniently attached to one scaffold, to increase the metal chelating efficacy. This review represents an update of the most recent publications (2014-2016) in mono-HP hybrids, namely as potential anti-Alzheimer's drugs, inhibitors of metalloenzymes and anti-microbials, and also polychelating compounds (poly- HP), in view of potential application, such as anti-microbial/biostatic agents, luminescent biosensors or diagnostic agents. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Use of Iron Chelating Agents in Transfusion Dependent Thalassaemia Major Patients.

PubMed

Santra, S; Bhattacharya, A; Mukhopadhyay, T; Agrawal, D; Kumar, S; Das, P; Chakrabarty, P

2015-10-01

This cross-sectional study was done to find and investigate the utilization pattern of iron chelating agents among 73 transfusion-dependent thalassaemia major patients with continuous enrolment for at least 1 year in a day care treatment centre run by The Thalassaemia Society of India, Kolkata from November 2014 to January 2015. Transfusion dependent thalassaemia major patients above the age of 2 years managed by various haematologists and Thalassaemia specialists were studied. The administration of iron chelators namely Desferrioxamine (DFO), Deferiprone (DFP) and Deferasirox (DFX) were evaluated. Forty seven (64%) of the thalassaemics had serum ferritin level below 2500 ng/dl, of whom 20(27%) patients have ferritin level below 1000ng/dl. A number of 55(75%) of 73 patients who were treated with a single chelating agent consisted 50 patients only on DFX. Exact 8(67%) patients were on DFO+DFP and 4(33%) are treated with DFX+DFP. The mean age was 19 and mean serum ferritin level was 2280 ng/dl among the thalassaemia major patients. DFX was used 68% of patients as monotherapy and 5% patients in combination therapy with DFP. DFX in the dose of 30-40 mg/kg/day was prescribed in 52% of patients. Mean dose of 15 mg/kg/day of DFX was been administered in combination with DFP (75 mg/kg/day) in 5% patients. DFO+DFP were preferred by 8 patients, out of which 6 were aged above 25. Cost of monotherapy is twice that of combination therapy. These data demonstrates the ferritin status and present scenario of utilization of chelating agents among thalassaemia major patients on repeated transfusions. The dosing of new drug, Deferasirox and the cost analysis of various chelating regimen has also been dealt. Individualization rather than rationalization of chelation therapy should be focussed upon in managing iron overload in thalassaemia.

[Remediation of Cu-Pb-contaminated loess soil by leaching with chelating agent and biosurfactant].

PubMed

Liu, Xia; Wang, Jian-Tao; Zhang, Meng; Wang, Li; Yang, Ya-Ti

2013-04-01

Because of its strong chelation, solubilization characteristics, the chelating agents and biosurfactant are widely used in remediation of heavy metals and organic contaminated soils. Ethylenediamine tetraacetic acid (EDTA), citric acid (CIT) and dirhamnolipid (RL2) were selected as the eluent. Batch experiments and column experiments were conducted to investigate the leaching effect of the three kinds of eluent, as well as the mixture of biosurfactant and chelating agent for Cu, Pb contaminated loess soil. The results showed that the leaching efficiencies of different eluent on Cu, Pb contaminated loess soil followed the sequence of EDTA > CIT > RL2. At an eluent concentration of 0.02 mol x L(-1), the Cu leaching efficiency was 62.74% (EDTA), 52.28% (CIT) and 15.35% (RL2), respectively; the Pb leaching efficiency was 96.10% (EDTA), 23.08% (CIT) and 14.42% (RL2), respectively. When the concentration of RL2 was 100 CMC, it had synergistic effects on the other two kinds of chelating agent in Cu leaching, and when the concentration of RL2 was 200 CMC, it had antagonism effects. The effect of RL2 on EDTA in Pb leaching was similar to that in Cu leaching. Pb leaching by CIT was inhibited in the presence of RL2. EDTA and CIT could effectively remove Cu and Pb in exchangeable states, adsorption states, carbonate salts and organic bound forms; RL2 could effectively remove Cu and Pb in exchangeable and adsorbed states.

Y-90-DOTA-hLL2: An Agent for Radioimmunotherapy of Non-Hodgkin's Lymphoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Griffiths, Gary L.; Govindan, Serengulam V.; Sharkey, Robert M.

2003-01-01

The goal of this work was to determine an optimal radioimmunotherapy agent for non-Hodgkin's lymphoma. We established the stability profile of yttrium-90-labeled humanized LL2 (hLL2) monoclonal antibody prepared with different chelating agents, and from these data estimated the improvement using the most stable yttrium-90 chelate-hLL2 complex. Methods: The complementary-determining region- (cdr)-grafted (humanized) anti-CD22 mAb, hLL2 (epratuzumab), was conjugated to derivatives of DTPA and 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid (DOTA). The conjugates were labeled with Y-90 and tested against a 10,000-fold molar excess of free DTPA and against human serum. The conjugates were also labeled with Y-88 and compared for biodistribution in normal andmore » lymphoma xenograft-bearing athymic mice. In vivo data were analyzed for uptake of yttrium in bone and washed bone when either the DOTA or the Mx-DTPA chelates were used, and dosimetry calculations were made for each. Results: Y-90-DOTA -mAb were stable to either DTPA or serum challenge. DTPA complexes of hLL2 lost 3-4% of Y-90 (days 1-4) and 10-15% thereafter. In vivo, stability differences showed lower Y-90 uptake in bone using DOTA. Absorbed doses per 37 MBq (1 mCi) Y-90-mAb were 3555 and 5405 cGy for bone, and 2664 and 4524 cGy for washed-bone for 90Y-DOTA-hLL2 and 90Y-MxDTPA-hLL2, respectively, amounting to 52% and 69.8% increases in absorbed radiation doses for bone and washed-bone when switching from a DOTA to a Mx-DTPA chelate. Conclusion: Y-90-hLL2 prepared with the DOTA chelate represents a preferred agent for RAIT of non-Hodgkin's lymphoma, with an in vivo model demonstrating a large reduction in bone-deposited yttrium, as compared to yttrium-90-hLL2 agents prepared with open-chain DTPA-type chelating agents. Dosimetry suggests that this will result in a substantial toxicological advantage for a DOTA-based hLL2 conjugate.« less

New tris(dopamine) derivative as an iron chelator. Synthesis, solution thermodynamic stability, and antioxidant research.

PubMed

Zhang, Qingchun; Jin, Bo; Shi, Zhaotao; Wang, Xiaofang; Lei, Shan; Tang, Xingyan; Liang, Hua; Liu, Qiangqiang; Gong, Mei; Peng, Rufang

2017-06-01

A new tris(dopamine) derivative, containing three dopamine chelate moieties which were attached to a trimesic acid molecular scaffold, has been prepared and fully characterized by NMR, FTIR and HRMS. The solution thermodynamic stability of the chelator with Fe(III), Mg(II), Zn(II) and Fe(II) ions was investigated. Results demonstrated that the chelator exhibited effective binding ability and improved selectivity to Fe(III) ion. The chelator possessed affinity similar to that of diethylenetriaminepentaacetic acid chelator for Fe(III) ion. The high affinity could be attributed to the favorable geometric arrangement between the chelator and Fe(III) ion coordination preference. The chelator also exhibited high antioxidant activity and nontoxicity to neuron-like rat pheochromocytoma cells. Hence, the chelator could be used as chelating agent for iron overload situations without depleting essential metal ions, such as Mg(II) and Zn(II) ions. Copyright © 2017. Published by Elsevier Inc.

Glyphosate, a chelating agent-relevant for ecological risk assessment?

PubMed

Mertens, Martha; Höss, Sebastian; Neumann, Günter; Afzal, Joshua; Reichenbecher, Wolfram

2018-02-01

Glyphosate-based herbicides (GBHs), consisting of glyphosate and formulants, are the most frequently applied herbicides worldwide. The declared active ingredient glyphosate does not only inhibit the EPSPS but is also a chelating agent that binds macro- and micronutrients, essential for many plant processes and pathogen resistance. GBH treatment may thus impede uptake and availability of macro- and micronutrients in plants. The present study investigated whether this characteristic of glyphosate could contribute to adverse effects of GBH application in the environment and to human health. According to the results, it has not been fully elucidated whether the chelating activity of glyphosate contributes to the toxic effects on plants and potentially on plant-microorganism interactions, e.g., nitrogen fixation of leguminous plants. It is also still open whether the chelating property of glyphosate is involved in the toxic effects on organisms other than plants, described in many papers. By changing the availability of essential as well as toxic metals that are bound to soil particles, the herbicide might also impact soil life, although the occurrence of natural chelators with considerably higher chelating potentials makes an additional impact of glyphosate for most metals less likely. Further research should elucidate the role of glyphosate (and GBH) as a chelator, in particular, as this is a non-specific property potentially affecting many organisms and processes. In the process of reevaluation of glyphosate its chelating activity has hardly been discussed.

Biodegradation of PuEDTA and Impacts on Pu Mobility

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xun, Luying; Bolton, Jr., Harvey

Ethylenediaminetetraacetate (EDTA) and nitrilotriacetate (NTA) are synthetic chelating agents, which can form strong water-soluble complexes with radionuclides and metals and has been used to decontaminate and process nuclear materials. Synthetic chelating agents were co-disposed with radionuclides (e.g., 60Co, Pu) and heavy metals enhancing their transport in the subsurface. An understanding of EDTA biodegradation is essential to help mitigate enhanced radionuclide transport by EDTA. The objective of this research is to develop fundamental data on factors that govern the biodegradation of radionuclide-EDTA. These factors include the dominant EDTA aqueous species, the biodegradation of various metal-EDTA complexes, the uptake of various metal-EDTAmore » complexes into the cell, the distribution and mobility of the radionuclide during and after EDTA biodegradation, and the enzymology and genetics of EDTA biodegradation.« less

Role of different chelating agent in synthesis of copper doped tin oxide (Cu-SnO2) nanoparticles

NASA Astrophysics Data System (ADS)

Saravanakumar, B.; Anusiya, A.; Rani, B. Jansi; Ravi, G.; Yuvakkumar, R.

2018-05-01

An attempt was made to synthesis the copper doped tin oxide (Cu-SnO2) nanoparticles by adopting different chelating agents (NaOH, KOH and C2H2O4) by Sol-gel process. The synthesized products were characterized by XRD, Photoluminescence (PL), Infra- Red (FTIR) and SEM analysis. The XRD confirms the formation of Cu-SnO2 shows the maximum peak at 33.8° with lattice plane (101). The PL peak at 361 and 382 nm due to the recombination of electron in conduction band to valence band infers the optical properties. The IR spectra correspond to the peak at 551 and 620 cm-1 attributed to the characteristics peak for Cu-SnO2 nanoparticles. The SEM images for all three Cu-SnO2 nanoparticles formed by three chelating agent (NaOH, KOH and C2H2O4) facilitates the formation mechanism and the chelating agent Oxalic acid results in formation of nano flowers with diverse layers orientated in random direction. Further SEM studies reveal that, the Cu-SnO2 nanoparticles formed by oxalic acid could posses high surface area with large number layered structured enables the better electrochemical properties and its applications.

Nanogels from Metal-Chelating Crosslinkers as Versatile Platforms Applied to Copper-64 PET Imaging of Tumors and Metastases

DOE PAGES

Lux, Jacques; White, Alexander G.; Chan, Minnie; ...

2015-01-01

Metals are essential in medicine for both therapy and diagnosis. We recently created the first metal-chelating nanogel imaging agent, which employed versatile, reproducible chemistry that maximizes chelation stability. Here we demonstrate that our metal chelating crosslinked nanogel technology is a powerful platform by incorporating 64Cu to obtain PET radiotracers. Polyacrylamide-based nanogels were crosslinked with three different polydentate ligands (DTPA, DOTA, NOTA). NOTA-based nanogels stably retained 64Cu in mouse serum and accumulated in tumors in vivo as detected by PET/CT imaging. Measurement of radioactivity in major organs ex vivo confirmed this pattern, revealing a high accumulation (12.3% ID/g and 16.6% ID/g)more » in tumors at 24 and 48 h following administration, with lower accumulation in the liver (8.5% ID/g at 24 h) and spleen (5.5% ID/g). Nanogels accumulated even more efficiently in metastases (29.9% and 30.4% ID/g at 24 and 48 h). These metal-chelating nanogels hold great promise for future application as bimodal PET/MRI agents; chelation of β-emitting radionuclides could enable radiation therapy.« less

Impact of educational programme regarding chelation therapy on the quality of life for B-thalassemia major children.

PubMed

Abu Samra, Omayma; Auda, Wafaa; Kamhawy, Heba; Al-Tonbary, Youssef

2015-06-01

Objectives Thalassemia is the most common genetic disorder in Egypt, with an estimated carrier rate of 9-10%. It is a genetic blood disorder which can be fatal if proper chelation is not received. The introduction of chelating agents capable of removing excessive iron from the body has dramatically increased life expectancy and improved the overall quality of life. The aim of this study was to assess the impact of educational programmes regarding chelation therapy on the quality of life of thalassemic children. Methods The study was carried out at the Mansoura University Children's Hospital in the period between March 2010 and May 2011. It included 173 B-thalassemia children (84 boys and 89 girls) with age ranging between 8-18 years. The researcher used a predesigned interviewing questionnaire to collect data regarding children's knowledge about thalassemia and its management, especially regarding chelation therapy. The paediatric quality-of-life inventory tool (Peds QL 4.0 generic core) was also used to assess the studied children's quality of life. Results There was a significant statistical difference of the studied children's knowledge regarding chelation therapy and their quality of life. Conclusion There was a positive effect of the educational programme in improving children's knowledge score and their quality of life. Application of educational programmes for thalassemic children and their nurses regarding chelation therapy and its importance in preventing thalassemia complications is established.

Synthesis of 4-substituted-trans-1, 2-diaminocyclohexyl polyaminocarboxylate metal chelating agents for the preparation of stable radiometal antibody immunoconjugates for therapy and SPECT and PET imaging

DOEpatents

Mease, R.C.; Mausner, L.F.; Srivastava, S.C.

1994-03-08

Cyclo agents are described which are useful in forming antibody-metal conjugates which are used for diagnostic and therapeutic purposes. New compounds and processes of forming these compounds are disclosed including 4-haloacetamido-trans-1,2diaminocyclohexyl polyaminocarboxylate and 4-isothiocyanato-trans-1,2diamino cyclohexane-N,N,N',N'-tetra acetic acid. No Drawings

The Copper Sulfide Coating on Polyacrylonitrile with Chelating Agents by an Electroless Deposition Method and its EMI Shielding Effectiveness

DOE Office of Scientific and Technical Information (OSTI.GOV)

Roan, M.-L.; Chen, Y.-H.; Huang, C.-Y.

2008-08-28

In this study, a variety of concentrations of chelating agents were added to obtain the anchoring effect and chelating effect in the electroless plating bath. The mechanism of the Cu{sub x(x=1,2)}S growth and the electromagnetic interference shielding effectiveness (EMI SE) of the composite were studied. It was found that the vinyl acetate residued in PAN substrate would be purged due to the swelling effect by chelating agents solution. And then, the anchoring effect occurred due to the hydrogen bonding between the pits of PAN substrate and the chelating agent. Consequently, the copper sulfide layer deposited by the electroless plating reactionmore » with EDTA and TEA. The swelling degree (S{sub d}) was proposed and evaluated from the FT-IR spectra. The relationship between swelling degree of the PAN films and EDTA (C) is expressed as: S{sub d} = 0.13+0.90xe and (-15.15C). And TEA series is expressed as: S{sub d} = 0.07+1.00xe and (-15.15C). On the other hand, the FESEM micrograph showed that the average thickness of copper sulfide increased from 76 nm to 383 nm when the concentration of EDTA increased from 0.00M to 0.20M. Consequently, the EMI SE of the composites increased from 10{approx}12 dB to 25{approx}27 dB. The GIA-XRD analyze indicated that the deposited layer consisted of CuS and Cu{sub 2}S.« less

Influence of ionic complexation on release rate profiles from multiple water-in-oil-in-water (W/O/W) emulsions.

PubMed

Bonnet, Marie; Cansell, Maud; Placin, Frédéric; David-Briand, Elisabeth; Anton, Marc; Leal-Calderon, Fernando

2010-07-14

Water-in-oil-in-water (W/O/W) double emulsions were prepared, and the kinetics of release of magnesium ions from the internal to the external water phase was followed. Different chelating agents (phosvitin and gluconate) were used to bind magnesium within the prospect of improving the ion retention in the internal aqueous droplets. Magnesium release was monitored for 1 month of storage, for each formulation, with and without chelation, at two storage temperatures (4 and 25 degrees C). Leakage occurred without film rupturing (coalescence) and was mainly due to entropically driven diffusion/permeation phenomena. The experimental results revealed a clear correlation between the effectiveness of chelating agents to delay the delivery and their binding capacity characterized by the equilibrium affinity constant. The kinetic data (percent released versus time curves) were interpreted within the framework of a kinetic model based on diffusion and taking into account magnesium chelation.

Chiral DOTA chelators as an improved platform for biomedical imaging and therapy applications.

PubMed

Dai, Lixiong; Jones, Chloe M; Chan, Wesley Ting Kwok; Pham, Tiffany A; Ling, Xiaoxi; Gale, Eric M; Rotile, Nicholas J; Tai, William Chi-Shing; Anderson, Carolyn J; Caravan, Peter; Law, Ga-Lai

2018-02-27

Despite established clinical utilisation, there is an increasing need for safer, more inert gadolinium-based contrast agents, and for chelators that react rapidly with radiometals. Here we report the syntheses of a series of chiral DOTA chelators and their corresponding metal complexes and reveal properties that transcend the parent DOTA compound. We incorporated symmetrical chiral substituents around the tetraaza ring, imparting enhanced rigidity to the DOTA cavity, enabling control over the range of stereoisomers of the lanthanide complexes. The Gd chiral DOTA complexes are shown to be orders of magnitude more inert to Gd release than [GdDOTA] - . These compounds also exhibit very-fast water exchange rates in an optimal range for high field imaging. Radiolabeling studies with (Cu-64/Lu-177) also demonstrate faster labelling properties. These chiral DOTA chelators are alternative general platforms for the development of stable, high relaxivity contrast agents, and for radiometal complexes used for imaging and/or therapy.

Tin-117m-labeled stannic (Sn.sup.4+) chelates

DOEpatents

Srivastava, Suresh C.; Meinken, George E.; Richards, Powell

1985-01-01

The radiopharmaceutical reagents of this invention and the class of Tin-117m radiopharmaceuticals are therapeutic and diagnostic agents that incorporate gamma-emitting nuclides that localize in bone after intravenous injection in mammals (mice, rats, dogs, and rabbits). Images reflecting bone structure or function can then be obtained by a scintillation camera that detects the distribution of ionizing radiation emitted by the radioactive agent. Tin-117m-labeled chelates of stannic tin localize almost exclusively in cortical bone. Upon intravenous injection of the reagent, the preferred chelates are phosphonate compounds, preferable, PYP, MDP, EHDP, and DTPA. This class of reagents is therapeutically and diagnostically useful in skeletal scintigraphy and for the radiotherapy of bone tumors and other disorders.

Overcoming platinum drug resistance with copper-lowering agents.

PubMed

Chen, Helen H W; Kuo, Macus Tien

2013-10-01

Platinum (Pt)-based antitumor agents have been the mainstay of cancer chemotherapy for the last three decades. While multiple mechanisms are responsible for treatment failure, deficiency in drug transport is an important contributor. The human high-affinity copper (Cu) transporter-1 (hCtr1) can also transport Pt-based drugs including cisplatin (cDDP) and carboplatin. Reduced hCtr1 expression frequently occurs in cDDP-resistant cell lines and in cancer in patients who failed chemotherapy with these drugs. We previously demonstrated that Cu chelation induces the expression of transcription factor Sp1 which binds the promoters of Sp1 and hCtr1, thereby, up-regulating their expression, whereas Cu overload shuts down hCtr1 and Sp1 expression by dissociating Sp1 from their promoter promoters. Thus, mammalian Cu homeostasis is transcriptionally regulated within a loop consisting of Sp1, hCtr1, and Cu in a three-way mutually regulated manner. These findings suggest that it is feasible to module cDDP transport capacity through intervention of mammalian Cu homeostasis. Indeed, we found that cDDP resistance can be overcome by Cu-lowering agents through enhanced hCtr1 expression by up-regulation of Sp1 in cultured cells. This discovery provided a mechanistic basis for the ongoing clinical study using Cu chelator to overcome cDDP resistance in ovarian cancer chemotherapy. Preliminary study using copper chelator (trientine) for enhancing the treatment efficacy of carboplatin in 5 ovarian cancer patients showed encouraging results. This short review describes the perspectives of using Cu-lowering agents in overcoming Pt resistance in cancer chemotherapy.

Searching for new aluminium chelating agents: a family of hydroxypyrone ligands.

PubMed

Toso, Leonardo; Crisponi, Guido; Nurchi, Valeria M; Crespo-Alonso, Miriam; Lachowicz, Joanna I; Mansoori, Delara; Arca, Massimiliano; Santos, M Amélia; Marques, Sérgio M; Gano, Lurdes; Niclós-Gutíerrez, Juan; González-Pérez, Josefa M; Domínguez-Martín, Alicia; Choquesillo-Lazarte, Duane; Szewczuk, Zbigniew

2014-01-01

Attention is devoted to the role of chelating agents in the treatment of aluminium related diseases. In fact, in spite of the efforts that have drastically reduced the occurrence of aluminium dialysis diseases, they so far constitute a cause of great medical concern. The use of chelating agents for iron and aluminium in different clinical applications has found increasing attention in the last thirty years. With the aim of designing new chelators, we synthesized a series of kojic acid derivatives containing two kojic units joined by different linkers. A huge advantage of these molecules is that they are cheap and easy to produce. Previous works on complex formation equilibria of a first group of these ligands with iron and aluminium highlighted extremely good pMe values and gave evidence of the ability to scavenge iron from inside cells. On these bases a second set of bis-kojic ligands, whose linkers between the kojic chelating moieties are differentiated both in terms of type and size, has been designed, synthesized and characterized. The aluminium(III) complex formation equilibria studied by potentiometry, electrospray ionization mass spectroscopy (ESI-MS), quantum-mechanical calculations and (1)H NMR spectroscopy are here described and discussed, and the structural characterization of one of these new ligands is presented. The in vivo studies show that these new bis-kojic derivatives induce faster clearance from main organs as compared with the monomeric analog. © 2013.

Molecular engineering of lanthanide ion chelating phospholipids generating assemblies with a switched magnetic susceptibility.

PubMed

Isabettini, Stéphane; Massabni, Sarah; Hodzic, Arnel; Durovic, Dzana; Kohlbrecher, Joachim; Ishikawa, Takashi; Fischer, Peter; Windhab, Erich J; Walde, Peter; Kuster, Simon

2017-08-09

Lanthanide ion (Ln 3+ ) chelating amphiphiles are powerful molecules for tailoring the magnetic response of polymolecular assemblies. Mixtures of 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) and 1,2-dimyristoyl-sn-glycero-3-phospho-ethanolamine-diethylene triaminepentaacetate (DMPE-DTPA) complexed to Ln 3+ deliver highly magnetically responsive bicelles. Their magnetic properties are readily tuned by changing the bicellar size or the magnetic susceptibility Δχ of the bilayer lipids. The former technique is intrinsically bound to the region of the phase diagram guarantying the formation of bicelles. Methods aiming towards manipulating the Δχ of the bilayer are comparatively more robust, flexible and lacking. Herein, we synthesized a new Ln 3+ chelating phospholipid using glutamic acid as a backbone: DMPE-Glu-DTPA. The chelate polyhedron was specifically engineered to alter the Δχ, whilst remaining geometrically similar to DMPE-DTPA. Planar asymmetric assemblies hundreds of nanometers in size were achieved presenting unprecedented magnetic alignments. The DMPE-Glu-DTPA/Ln 3+ complex switched the Δχ, achieving perpendicular alignment of assemblies containing Dy 3+ and parallel alignment of those containing Tm 3+ . Moreover, samples with chelated Yb 3+ were more alignable than the Tm 3+ chelating counterparts. Such a possibility has never been demonstrated for planar Ln 3+ chelating polymolecular assemblies. The physico-chemical properties of these novel assemblies were further studied by monitoring the alignment behavior at different temperatures and by including 16 mol% of cholesterol (Chol-OH) in the phospholipid bilayer. The DMPE-Glu-DTPA/Ln 3+ complex and the resulting assemblies are promising candidates for applications in numerous fields including pharmaceutical technologies, structural characterization of membrane biomolecules by NMR spectroscopy, as contrasting agents for magnetic resonance imaging, and for the development of smart optical gels.

Demetalation of Fe, Mn, and Cu chelates and complexes: application to the NMR analysis of micronutrient fertilizers.

PubMed

López-Rayo, Sandra; Lucena, Juan J; Laghi, Luca; Cremonini, Mauro A

2011-12-28

The application of nuclear magnetic resonance (NMR) for the quality control of fertilizers based on Fe(3+), Mn(2+), and Cu(2+) chelates and complexes is precluded by the strong paramagnetism of metals. Recently, a method based on the use of ferrocyanide has been described to remove iron from commercial iron chelates based on the o,o-EDDHA [ethylenediamine-N,N'bis(2-hydroxyphenylacetic)acid] chelating agent for their analysis and quantification by NMR. The present work extended that procedure to other paramagnetic ions, manganese and copper, and other chelating, EDTA (ethylenediaminetetraacetic acid), IDHA [N-(1,2-dicarboxyethyl)-d,l-aspartic acid], and complexing agents, gluconate and heptagluconate. Results showed that the removal of the paramagnetic ions was complete, allowing us to obtain (1)H NMR spectra characterized by narrow peaks. The quantification of the ligands by NMR and high-performance liquid chromatography showed that their complete recovery was granted. The NMR analysis enabled detection and quantification of unknown impurities without the need of pure compounds as internal standards.

Synthesis and spectroscopic investigations of hydroxyapatite using a green chelating agent as template

NASA Astrophysics Data System (ADS)

Gopi, D.; Bhuvaneshwari, N.; Indira, J.; Kavitha, L.

2013-03-01

Hydroxyapatite [Ca10(PO4)6(OH)2, HAP] particles have been successfully synthesized by a cost-effective, eco-friendly green template method using natural and commercially available sucrose as a chelating agent. The sucrose used in this method has been extracted from various sources, three from natural and one from commercially available sources are exploited in our study to achieve a controlled crystallinity, particle size as well as uniform morphology. Spectral characterizations involving Fourier transform infrared spectroscopy (FT-IR) for the functional group analysis of sucrose and HAP; carbon-13 nuclear magnetic resonance spectroscopy (13C NMR) for the identification of the carbon atoms in sucrose and in HAP; liquid chromatography/mass spectrometry (LC-MS) for the determination of the hydrolyzed products of sucrose; and X-ray diffraction (XRD) techniques for the phase identification of the HAP particles were performed. The morphology of the HAP particles were assessed thoroughly using a scanning electron microscope (SEM) equipped with energy dispersive X-ray analysis (EDAX). The experimental results indicate that the obtained HAP using the natural sucrose as a chelating agent is of phase pure, with a well defined morphology having discrete particles without any agglomeration than the HAP from commercially available sucrose. Further, the reduced particle size can be achieved from the stem sugarcane extract as the source of the chelating agent.

Synthesis and spectroscopic investigations of hydroxyapatite using a green chelating agent as template.

PubMed

Gopi, D; Bhuvaneshwari, N; Indira, J; Kavitha, L

2013-03-01

Hydroxyapatite [Ca(10)(PO(4))(6)(OH)(2), HAP] particles have been successfully synthesized by a cost-effective, eco-friendly green template method using natural and commercially available sucrose as a chelating agent. The sucrose used in this method has been extracted from various sources, three from natural and one from commercially available sources are exploited in our study to achieve a controlled crystallinity, particle size as well as uniform morphology. Spectral characterizations involving Fourier transform infrared spectroscopy (FT-IR) for the functional group analysis of sucrose and HAP; carbon-13 nuclear magnetic resonance spectroscopy ((13)C NMR) for the identification of the carbon atoms in sucrose and in HAP; liquid chromatography/mass spectrometry (LC-MS) for the determination of the hydrolyzed products of sucrose; and X-ray diffraction (XRD) techniques for the phase identification of the HAP particles were performed. The morphology of the HAP particles were assessed thoroughly using a scanning electron microscope (SEM) equipped with energy dispersive X-ray analysis (EDAX). The experimental results indicate that the obtained HAP using the natural sucrose as a chelating agent is of phase pure, with a well defined morphology having discrete particles without any agglomeration than the HAP from commercially available sucrose. Further, the reduced particle size can be achieved from the stem sugarcane extract as the source of the chelating agent. Copyright © 2012 Elsevier B.V. All rights reserved.

Novel treatment options for transfusional iron overload in patients with myelodysplastic syndromes.

PubMed

Goldberg, Stuart L

2007-12-01

Red blood cell transfusion dependency is common in myelodysplastic syndromes and is associated with inferior survival. The use of parenteral deferoxamine therapy for transfusional iron overload has been sparse, in part due to cumbersome administration schedules. Deferasirox is an oral iron-chelating agent with favorable pharmacokinetics, including a long half-life allowing continuous 24-hour chelation with once-daily dosing. Deferasirox produces dose-dependent reductions in liver iron content and reduces cardiac iron levels. In-vitro studies with deferasirox suggest improved cardiomyocyte contractility potentially important in reducing excess cardiac mortality noted in transfusion-dependent MDS. Deferasirox has a manageable safety profile with favorable patient satisfaction reports.

Clioquinol-zinc chelate: a candidate causative agent of subacute myelo-optic neuropathy.

PubMed Central

Arbiser, J. L.; Kraeft, S. K.; van Leeuwen, R.; Hurwitz, S. J.; Selig, M.; Dickersin, G. R.; Flint, A.; Byers, H. R.; Chen, L. B.

1998-01-01

BACKGROUND: 5-chloro-7-iodo-8-hydroxyquinoline (clioquinol) was used clinically three decades ago as an oral antiparasitic agent and to increase intestinal absorption of zinc in patients with acrodermatitis enteropathica, a genetic disorder of zinc absorption. Use of clioquinol was epidemiologically linked to subacute myelo-optic neuropathy (SMON), characterized by peripheral neuropathy and blindness, which affected 10,000 patients in Japan. Discontinuation of oral clioquinol use led to elimination of SMON, however, the mechanism of how clioquinol induces neurotoxicity is unclear. MATERIALS AND METHODS: We tested the effect of clioquinol-metal chelates on neural crest-derived melanoma cells. The effect of clioquinol chelates on cells was further studied by electron microscopy and by a mitochondrial potential-sensitive fluorescent dye. RESULTS: Of the ions tested, only clioquinol-zinc chelate demonstrated cytotoxicity. The cytotoxicity of clioquinol-zinc chelate was extremely rapid, suggesting that its primary effect was on the mitochondria. Electron microscopic analysis demonstrated that clioquinol-zinc chelate caused mitochondrial damage. This finding was further confirmed by the observation that clioquinol-zinc chelate caused a decrease in mitochondrial membrane potential. CONCLUSIONS: We demonstrate that clioquinol, in the presence of zinc, is converted to a potent mitochondrial toxin. The phenomenon of clioquinol mediated toxicity appears to be specific to zinc and is not seen with other metals tested. Since clioquinol has been shown to cause increased systemic absorption of zinc in humans, it is likely that clioquinol-zinc chelate was present in appreciable levels in patients with SMON and may be the ultimate causative toxin of SMON. Images Fig. 2 Fig. 3 PMID:9848083

Enhancing Potentially Plant-Available Lead Concentrations in Contaminated Residential Soils Using a Biodegradable Chelating Agent

NASA Astrophysics Data System (ADS)

Andra, S.; Datta, R.; Sarkar, D.; Saminathan, S.

2007-12-01

Chelation of heavy metals is an important factor in enhancing metal solubility and, hence, metal availability to plants to promote phytoremediation. In the present study, we compared the effects of application of a biodegradable chelating agent, namely, ethylenediaminedisuccinic acid (EDDS) on enhancing plant available form of lead (Pb) in Pb-based paint contaminated residential soils compared to that of a more commonly used, but non-biodegradable chelate, i.e., ethylenediaminetetraacetic acid (EDTA). Development of a successful phytoremediation model for metals such as Pb depends on a thorough understanding of the physical and chemical properties of the soil, along with the optimization of a chelate treatment to mobilize Pb from `unavailable' pools to potentially plant available fraction. In this context, we set out to perform batch incubation experiments to investigate the effectiveness of the two aforementioned chelates in enhancing plant available Pb at four different concentrations (0, 5, 10 and 15 mM/kg soil) and three treatment durations (0, 10 and 30 days). We selected 12 contaminated residential soils from two major metropolitan areas (San Antonio, TX and Baltimore, MD) with varying soil physico-chemical properties - the soils from San Antonio were primarily alkaline and those from Baltimore were typically acidic. Total soil Pb concentrations ranged between 256 mg/kg and 4,182 mg/kg. Our results show that both chelates increased the solubility of Pb, otherwise occluded in the complex soil matrix. For both EDTA and EDDS, the exchangeable concentrations of soil Pb also increased with increase in chelate concentration and incubation time. The most effective treatment was 15 mM chelate kg-1 soil incubated for 30 days, which caused many fold increase in potentially plant available Pb (a combination of the soluble and exchangeable fractions) relative to the unamended controls. Step wise multiple linear regression analysis using chelate-extractable Pb and soil properties showed that plant available Pb fraction could be assessed from the two inter-related soil parameters: soil organic matter and soil pH. Although EDTA was more effective in Pb solubilization than EDDS, the rapid kinetics of the Pb-EDTA complexation process and the prolonged persistence of EDTA in soils pose a potential groundwater contamination problem via metal leaching. In contrast to EDTA, EDDS addition caused relatively slow release of Pb from the soil matrix. The biodegradable nature (and short half life) of EDDS in soils makes it a promising chelating agent for use as soil amendment to enhance Pb solubilization and hence, potential plant uptake.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Peigong; Fan, Caimei, E-mail: fancm@163.com; Wang, Yawen

Graphical abstract: The cubic phase BaTiO{sub 3} nanoparticles can be obtained at 600 °C and changed into tetragonal phase at 900 °C by a dual chelating sol–gel method, and the photocatalytic activities of the photocatalysts calcined at different temperatures were investigated by the removal of humic acid (HA) from water under UV light irradiation. Highlights: ► The humic acid in water was firstly degradated by BaTiO{sub 3} photocatalyst. ► The cubic BaTiO{sub 3} was obtained and changed into tetragonal phase at lower temperature. ► The chelating agents had an important influence on the phase formation of BaTiO{sub 3}. ► Themore » tetragonal phase BaTiO{sub 3} calcined at 900 °C exhibited higher photocatalytic activity under UV irradiation. -- Abstract: In this paper, a dual chelating sol–gel method was used to synthesize BaTiO{sub 3} nanoparticles by using acetylacetone and citric acid as chelating agents. The samples calcined at different temperatures were analyzed by thermogravimetric and differential thermal analysis (TG-DTA), X-ray diffraction (XRD), X-ray photoelectron spectra (XPS), scanning electron microscope (SEM) and UV–vis diffuse reflectance spectra (UV–vis). The results indicated that cubic phase BaTiO{sub 3} nanoparticles about 19.6 nm can be obtained at 600 °C and changed into tetragonal phase at 900 °C about 97.1 nm. All the BaTiO{sub 3} nanoparticles showed effective photocatalytic activities on the removal of humic acid (HA) under UV light irradiation. A comparison of single (acetylacetone or citric acid) and dual chelating (acetylacetone and citric acid) synthetic processes was also studied and the results demonstrated that the dual chelating agents indeed reduced phase transformation temperature from cubic to tetragonal BaTiO{sub 3}.« less

Synthetic Ni3S2/Ni hybrid architectures as potential contrast agents in MRI

NASA Astrophysics Data System (ADS)

Ma, J.; Chen, K.

2016-04-01

Traditional magnetic resonance imaging (MRI) contrast agents mainly include superparamagnetic (SPM) iron oxide nanoparticle as T 2 contrast agent for liver and paramagnetic Gd (III)-chelate as T 1 contrast agent for all organs. In this work, weak ferromagnetic kale-like and SPM cabbage-like Ni3S2@Ni hybrid architectures were synthesized and evaluated as potential T 1 MRI contrast agents. Their relatively small r 2/r 1 ratios of 2.59 and 2.38, and high r 1 values of 11.27 and 4.89 mmol-1 L s-1 (for the kale-like and cabbage-like Ni3S2@Ni, respectively) will shed some light on the development of new-type MRI contrast agents.

Hypersensitivity reaction with deferasirox

PubMed Central

Sharma, Atul; Arora, Ekta; Singh, Harmanjit

2015-01-01

Thalassemias comprise a group of hereditary blood disorders. Thalassemia major presents with anemia within the first 2 years of life requiring frequent blood transfusions for sustaining life. Regular blood transfusions lead to iron overload-related complications. Prognosis of thalassemia has improved because of the availability of iron-chelating agents. Oral iron chelators are the mainstay of chelation therapy. Deferasirox is a new-generation oral iron chelator for once daily usage. We herein describe a patient of beta thalassemia major who developed an allergic manifestation in the form of erythematous pruritic skin rashes to the oral iron chelator deferasirox. This is a rare adverse reaction reported with deferasirox that led to a therapeutic dilemma in this particular case. PMID:25969661

Quantitative Determination of NTA and Other Chelating Agents in Detergents by Potentiometric Titration with Copper Ion Selective Electrode.

PubMed

Ito, Sana; Morita, Masaki

2016-01-01

Quantitative analysis of nitrilotriacetate (NTA) in detergents by titration with Cu 2+ solution using a copper ion selective electrode was achieved. This method tolerates a wide range of pH and ingredients in detergents. In addition to NTA, other chelating agents, having relatively lower stability constants toward Cu 2+ , were also qualified with sufficient accuracy by this analytical method for model detergent formulations. The titration process was automated by automatic titrating systems available commercially.

Imaging of Ep-CAM Positive Metastatic Cancer in the Lymph System

DTIC Science & Technology

2011-01-01

bind Ep-CAM positive breast cancer cells in pH up to 8.3, which will be important for the chelating agent DOTA . The DOTA -NHS-ester is best conjugated...must be conjugated with the fluorophore (IRDye 800CW) and a chelating agent ( DOTA ), which sequesters the radio-metal completing the dual-label...done simultaneously, anti-Ep-CAM (9601) was conjugated with 5-fold excess IRDye, 5- fold excess DOTA or 500-fold excess DOTA overnight. After size

DEGRADATION OF NITRILOTRIS (METHYLENEPHOSPHONIC ACID) AND RELATED (AMINO) PHOSPHONATE CHELATING AGENTS IN THE PRESENCE OF MANGANESE AND MOLECULAR OXYGEN. (R826376)

EPA Science Inventory

Phosphonates are used in an increasing variety of industrial and household
applications including cooling waters systems, oil production, textile industry,
and detergents. Phosphonates are not biodegraded during wastewater treatment but
instead are removed by adsor...

Effect Of Inorganic, Synthetic And Naturally Occurring Chelating Agents On Fe(II) Mediated Advanced Oxidation Of Chlorophenols

EPA Science Inventory

This study examines the feasibility and application of Advanced Oxidation Technologies (AOTs) for the treatment of chlorophenols that are included in US EPA priority pollutant list. A novel class of sulfate/hydroxyl radical-based homogeneous AOTs (Fe(II)/PS, Fe(II)/PMS, Fe(II)/H...

CONTROL OF CHELATOR-BASED UPSETS IN SURFACE FINISHING SHOP WASTE WATER TREATMENT SYSTEMS

EPA Science Inventory

Actual surface finishing shop examples are used to illustrate the use of process chemistry understanding and analyses to identify immediate, interim and permanent response options for industrial waste water treatment plant (IWTP) upset problems caused by chelating agents. There i...

Effects of iron(III)chelates on the solubility of heavy metals in calcareous soils.

PubMed

Ylivainio, Kari

2010-10-01

In this study I evaluated the effects of complexing agents on the solubility of heavy metals in an incubation experiment up to 56 days when complexing agents were applied as Fe-chelates (Fe-EDDS(S,S), Fe-EDDS(mix), Fe-EDTA and Fe-EDDHA) on calcareous soils at a level sufficient to correct Fe chlorosis (0.1 mmol kg(-1)). Of these ligands, EDDHA was the most efficient in keeping Fe in water-soluble form, and EDDS increased the solubility of Cu and Zn most, and only EDTA increased the solubility of Cd and Pb. EDTA increased the solubility of Ni steadily during the incubation period, equalling about 5-8% of the added EDTA concentration. [S,S]-EDDS was biodegraded within 56 days, whereas EDDS(mix) was less biodegradable. Ni-chelates were the most recalcitrant against biodegradation. The study shows that even a moderate input of chelates to soil increases the solubility of toxic heavy metals and their risk of leaching. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

Synthesis of SrFe12O19 magnetic nanoparticles by EDTA complex method

NASA Astrophysics Data System (ADS)

Wang, Shifa; Li, Danming; Xiao, Yuhua; Dang, Wenqiang; Feng, Jie

2017-10-01

A modified polyacrylamide gel route was used to prepare SrFe12O19 magnetic nanoparticles; ethylenediaminetetraacetic acid (EDTA) was used as a carboxyl chelating agent. The phase purity, morphology and magnetic properties of as-prepared samples were analyzed via X-ray diffraction (XRD), Raman spectroscopy, scanning electron microscopy (SEM), transmission electron microscopy (TEM) and vibrating sample magnetometery (VSM). XRD analysis indicates that high-purity SrFe12O19 magnetic nanoparticles can be synthesized at 700°C in air. The characteristic peaks of as-prepared sample at 210, 283, 321, 340, 381, 411, 432, 475, 532, 618, 686, and 726 cm-1 were observed in Raman spectra. SEM and TEM show that the synthesized SrFe12O19 magnetic nanoparticles are uniform with the mean particle size of 60 nm. VSM measurement shows that the maximum magnetic energy product (BH)max of sample prepared using EDTA as a chelating agent is higher than that of sample prepared using citric acid as a chelating agent.

Actinide and lanthanide separation process (ALSEP)

DOEpatents

Guelis, Artem V.

2013-01-15

The process of the invention is the separation of minor actinides from lanthanides in a fluid mixture comprising, fission products, lanthanides, minor actinides, rare earth elements, nitric acid and water by addition of an organic chelating aid to the fluid; extracting the fluid with a solvent comprising a first extractant, a second extractant and an organic diluent to form an organic extractant stream and an aqueous raffinate. Scrubbing the organic stream with a dicarboxylic acid and a chelating agent to form a scrubber discharge. The scrubber discharge is stripped with a simple buffering agent and a second chelating agent in the pH range of 2.5 to 6.1 to produce actinide and lanthanide streams and spent organic diluents. The first extractant is selected from bis(2-ethylhexyl)hydrogen phosphate (HDEHP) and mono(2-ethylhexyl)2-ethylhexyl phosphonate (HEH(EHP)) and the second extractant is selected from N,N,N,N-tetra-2-ethylhexyl diglycol amide (TEHDGA) and N,N,N',N'-tetraoctyl-3-oxapentanediamide (TODGA).

Optimizing therapy for iron overload in the myelodysplastic syndromes: recent developments.

PubMed

Leitch, Heather A

2011-01-22

The myelodysplastic syndromes (MDS) are characterized by cytopenias and risk of progression to acute myeloid leukaemia (AML). Most MDS patients eventually require transfusion of red blood cells for anaemia, placing them at risk of transfusional iron overload. In β-thalassaemia major, transfusional iron overload leads to organ dysfunction and death; however, with iron chelation therapy, organ function is improved, and survival improved to near normal and correlated with the degree of compliance with chelation. In lower-risk MDS, several nonrandomized studies suggest an adverse effect of iron overload on survival and that lowering iron with chelation may minimize this impact. Emerging data indicate that chelation may improve organ function, particularly hepatic function, and a minority of patients may have improvement in cell counts and decreased transfusion requirements. While guidelines for MDS generally recommend chelation in selected lower-risk patients, data from nonrandomized trials suggest iron overload may impact adversely on the outcome of higher-risk MDS and stem cell transplantation (SCT). This effect may be due to increased transplant-related mortality, infection and AML progression, and preliminary data suggest that lowering iron may be beneficial in this patient group. Other areas of active and future investigation include optimizing the monitoring of iron overload using imaging such as T2* MRI and measures of labile iron and oxidative stress; correlating new methods of measuring iron to clinical outcomes; clarifying the contribution of different cellular and extracellular iron pools to iron toxicity; optimizing chelation by using agents that access the appropriate iron pools to minimize the relevant clinical consequences in individual patients; and incorporating measures of quality of life and co-morbidities into clinical trials of chelation in MDS. It should be noted that chelation is costly and potentially toxic, and in MDS should be initiated after weighing potential risks and benefits for each patient until more definitive data are available. In this review, data on the impact of iron overload in MDS and SCT are discussed; for example, several noncontrolled studies show inferior survival in patients with iron overload in these clinical settings, including an increase in transplant-related mortality and infection risk. Possible mechanisms of iron toxicity include oxidative stress, which can damage cellular components, and the documented impact of lowering iron on organ function with measures such as iron chelation therapy includes an improvement in elevated liver transaminases. Lowering iron also appears to improve survival in both lower-risk MDS and SCT in nonrandomized studies. Selected aspects of iron metabolism, transport, storage and distribution that may be amenable to future intervention and improved removal of iron from important cellular sites are discussed, as are attempts to quantify quality of life and the importance of co-morbidities in measures to treat MDS, including chelation therapy.

Investigation of a potential macromolecular MRI contrast agent prepared from PPI (G = 2, polypropyleneimine, generation 2) dendrimer bifunctional chelates

NASA Astrophysics Data System (ADS)

Wang, Jianxin Steven

The long-term objective is to develop magnetic resonance (MR) contrast agents that actively and passively target tumors for diagnosis and therapy. Many diagnostic imaging techniques for cancer lack specificity. A dendrimer based magnetic resonance imaging contrast agent has been developed with large proton relaxation enhancements and high molecular relaxivities. A new type of linear dendrimer based MRI contrast agent that is built from the polypropyleneimine and polyamidoamine dendrimers in which free amines have been conjugated to the chelate DTPA, which further formed the complex with Gadolinium (Gd) was studied. The specific research goals were to test the hypothesis that a linear chelate with macromolecular agents can be used in vitro and in vivo. This work successfully examined the adequacy and viability of the application for this agent in vitro and in vivo. A small animal whole body counter was designed and constructed to allow us to monitor biodistribution and kinetic mechanisms using a radioisotope labeled complex. The procedures of metal labeling, separation and purification have been established from this work. A biodistribution study has been performed using radioisotope induced organ/tissue counting and gamma camera imaging. The ratio of percentage of injected dose per gram organ/tissue for kidney and liver is 3.71 from whole body counter and 3.77 from the gamma camera. The results suggested that retention of Gd (III) is too high and a more kinetically stable chelate should be developed. The pharmacokinetic was evaluated in the whole animal model with the whole body clearance, and a kinetics model was developed. The pharmacokinetic results showed a bi-exponential decay in the animal model with two component excretion constants 1.43e(-5) and 0.0038511, which give half-lives of 3 hours and 33.6 days, respectively. Magnetic resonance imaging of this complex resulted in a 52% contrast enhancement in the rat kidney following the agents' administration in vivo.

Tin-117m-labeled stannic (Sn/sup 4 +/) chelate of diethylenetriamine pentaacetic acid (DTPA) for application in diagnosis and therapy

DOEpatents

Srivastava, S.C.; Meinken, G.E.; Richards, P.

1983-08-25

The radiopharmaceutical reagents of this invention and the class of Tin-117m radiopharmaceuticals are therapeutic and diagnostic agents that incorporate gamma-emitting nuclides that localize in bone after intravenous injection in mammals (mice, rats, dogs, and rabbits). Images reflecting bone structure or function can then be obtained by a scintillation camera that detects the distribution of ionizing radiation emitted by the radioactive agent. Tin-117m-labeled chelates of stannic tin localize almost exclusively in cortical bone. Upon intravenous injection of the reagent, the preferred chelates are phosphonate compounds, preferable, PYP, MDP, EHDP, and DTPA. This class of reagents is therapeutically and diagnostically useful in skeletal scintigraphy and for the radiotherapy of bone tumors and other disorders.

Chelator free gallium-68 radiolabelling of silica coated iron oxide nanorods via surface interactions

NASA Astrophysics Data System (ADS)

Burke, Benjamin P.; Baghdadi, Neazar; Kownacka, Alicja E.; Nigam, Shubhanchi; Clemente, Gonçalo S.; Al-Yassiry, Mustafa M.; Domarkas, Juozas; Lorch, Mark; Pickles, Martin; Gibbs, Peter; Tripier, Raphaël; Cawthorne, Christopher; Archibald, Stephen J.

2015-09-01

The commercial availability of combined magnetic resonance imaging (MRI)/positron emission tomography (PET) scanners for clinical use has increased demand for easily prepared agents which offer signal or contrast in both modalities. Herein we describe a new class of silica coated iron-oxide nanorods (NRs) coated with polyethylene glycol (PEG) and/or a tetraazamacrocyclic chelator (DO3A). Studies of the coated NRs validate their composition and confirm their properties as in vivo T2 MRI contrast agents. Radiolabelling studies with the positron emitting radioisotope gallium-68 (t1/2 = 68 min) demonstrate that, in the presence of the silica coating, the macrocyclic chelator was not required for preparation of highly stable radiometal-NR constructs. In vivo PET-CT and MR imaging studies show the expected high liver uptake of gallium-68 radiolabelled nanorods with no significant release of gallium-68 metal ions, validating our innovation to provide a novel simple method for labelling of iron oxide NRs with a radiometal in the absence of a chelating unit that can be used for high sensitivity liver imaging.The commercial availability of combined magnetic resonance imaging (MRI)/positron emission tomography (PET) scanners for clinical use has increased demand for easily prepared agents which offer signal or contrast in both modalities. Herein we describe a new class of silica coated iron-oxide nanorods (NRs) coated with polyethylene glycol (PEG) and/or a tetraazamacrocyclic chelator (DO3A). Studies of the coated NRs validate their composition and confirm their properties as in vivo T2 MRI contrast agents. Radiolabelling studies with the positron emitting radioisotope gallium-68 (t1/2 = 68 min) demonstrate that, in the presence of the silica coating, the macrocyclic chelator was not required for preparation of highly stable radiometal-NR constructs. In vivo PET-CT and MR imaging studies show the expected high liver uptake of gallium-68 radiolabelled nanorods with no significant release of gallium-68 metal ions, validating our innovation to provide a novel simple method for labelling of iron oxide NRs with a radiometal in the absence of a chelating unit that can be used for high sensitivity liver imaging. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr02753e

Enhanced in vitro activity of tigecycline in the presence of chelating agents.

PubMed

Deitchman, Amelia N; Singh, Ravi Shankar Prasad; Rand, Kenneth H; Derendorf, Hartmut

2018-05-01

The lack of availability of novel antibiotic agents and the rise of resistance to existing therapies has led clinicians to utilise combination therapy to adequately treat bacterial infections. Here we examined how chelators may impact the in vitro activity of tigecycline (TIG) against Pseudomonas aeruginosa, Escherichia coli and Klebsiella pneumoniae. Minimum inhibitory concentrations (MICs) were determined by broth dilution with and without various combinations of chelators (EDTA and other tetracyclines) and metal ions (i.e. calcium, magnesium). Trimethoprim (TMP) was used as a non-chelating control. Addition of metal ions led to increases in MICs, whilst addition of EDTA led to decreases in MICs. The chelating effects of EDTA were reversed by addition of magnesium and most profoundly calcium. Similar effects of EDTA and calcium were observed for tetracycline (TET) and TMP. When other tetracyclines (TET, oxytetracycline (OXY) and chlortetracycline (CHL)) were used as chelators at concentrations below their MICs, TIG MICs decreased for P. aeruginosa but not for E. coli. Some decreases in TIG MICs were observed for K. pneumoniae when TET and CHL were added. A dose-dependent decrease in TIG MIC was observed for TET and was reversed by the addition of calcium. The presence of effects of EDTA and calcium on TMP MICs indicates that mechanisms outside of TIG chelation likely play a role in enhanced activity. Full characterisation of an unexpected interaction such as TIG-TET with different microorganisms could provide valuable insights into the underlying mechanisms and design of physiologically viable chelators as candidates for future combinations regimens. Copyright © 2018 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

ParaCEST Agents Encapsulated in Reverse Nano-Assembled Capsules (RACs): How Slow Molecular Tumbling Can Quench CEST Contrast.

PubMed

Farashishiko, Annah; Slack, Jacqueline R; Botta, Mauro; Woods, Mark

2018-01-01

Although paraCEST is a method with immense scope for generating image contrast in MRI, it suffers from the serious drawback of high detection limits. For a typical discrete paraCEST agent the detection limit is roughly an order of magnitude higher than that of a clinically used relaxation agent. One solution to this problem may be the incorporation of a large payload of paraCEST agents into a single macromolecular agent. Here we report a new synthetic method for accomplishing this goal: incorporating a large payload of the paraCEST agent DyDOTAM 3+ into a Reverse Assembled nano-Capsule. An aggregate can be generated between this chelate and polyacrylic acid (PAA) after the addition of ethylene diamine. Subsequent addition of polyallylamine hydrochloride (PAH) followed by silica nanoparticles generated a robust encapsulating shell and afforded capsule with a mean hydrodynamic diameter of 650 ± 250 nm. Unfortunately this encapsulation did not have the effect of amplifying the CEST effect per agent, but quenched the CEST altogether. The quenching effect of encapsulation could be attributed to the effect of slowing molecular tumbling, which is inevitable when the chelate is incorporated into a nano-scale material. This increases the transverse relaxation rate of chelate protons and a theoretical examination using Solomon Bloembergen Morgan theory and the Bloch equations shows that the increase in the transverse relaxation rate constant for the amide protons, in even modestly sized nano-materials, is sufficient to significantly quench CEST.

ParaCEST Agents Encapsulated in Reverse Nano-Assembled Capsules (RACs): How Slow Molecular Tumbling Can Quench CEST Contrast

PubMed Central

Farashishiko, Annah; Slack, Jacqueline R.; Botta, Mauro; Woods, Mark

2018-01-01

Although paraCEST is a method with immense scope for generating image contrast in MRI, it suffers from the serious drawback of high detection limits. For a typical discrete paraCEST agent the detection limit is roughly an order of magnitude higher than that of a clinically used relaxation agent. One solution to this problem may be the incorporation of a large payload of paraCEST agents into a single macromolecular agent. Here we report a new synthetic method for accomplishing this goal: incorporating a large payload of the paraCEST agent DyDOTAM3+ into a Reverse Assembled nano-Capsule. An aggregate can be generated between this chelate and polyacrylic acid (PAA) after the addition of ethylene diamine. Subsequent addition of polyallylamine hydrochloride (PAH) followed by silica nanoparticles generated a robust encapsulating shell and afforded capsule with a mean hydrodynamic diameter of 650 ± 250 nm. Unfortunately this encapsulation did not have the effect of amplifying the CEST effect per agent, but quenched the CEST altogether. The quenching effect of encapsulation could be attributed to the effect of slowing molecular tumbling, which is inevitable when the chelate is incorporated into a nano-scale material. This increases the transverse relaxation rate of chelate protons and a theoretical examination using Solomon Bloembergen Morgan theory and the Bloch equations shows that the increase in the transverse relaxation rate constant for the amide protons, in even modestly sized nano-materials, is sufficient to significantly quench CEST. PMID:29682499

78 FR 77471 - Prospective Grant of Exclusive License for: Convection Enhanced Delivery of a Therapeutic Agent...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-23

...-toxic macromolecular MRI contrast agents such as chelated Gd(III). These macromolecular imaging agents... Exclusive License for: Convection Enhanced Delivery of a Therapeutic Agent With a Surrogate Tracer for... Enhanced Delivery of Therapeutic Agents'', U.S. Provisional Patent Application 60/413,673 (filed September...

Physical and Chemical Characterization of Therapeutic Iron Containing Materials: A Study of Several Superparamagnetic Drug Formulations with the β-FeOOH or Ferrihydrite Structure

NASA Astrophysics Data System (ADS)

Funk, Felix; Long, Gary J.; Hautot, Dimitri; Büchi, Ruth; Christl, Iso; Weidler, Peter G.

2001-03-01

The effectiveness of therapeutically used iron compounds is related to their physical and chemical properties. Four different iron compounds used in oral, intravenous, and intramuscular therapy have been examined by X-ray powder diffraction, iron-57 Mössbauer spectroscopy, transmission electron microscopy, BET surface area measurement, potentiometric titration and studied through dissolution kinetics determinations using acid, reducing and chelating agents. All compounds are nanosized with particle diameters, as determined by X-ray diffraction, ranging from 1 to 4.1 nm. The superparamagnetic blocking temperatures, as determined by Mössbauer spectroscopy, indicate that the relative diameters of the aggregates range from 2.5 to 4.1 nm. Three of the iron compounds have an akaganeite-like structure, whereas one has a ferrihydrite-like structure. As powders the particles form large and dense aggregates which have a very low surface area on the order of 1 m2 g-1. There is evidence, however, that in a colloidal solution the surface area is increased by two to three orders of magnitude, presumably as a result of the break up of the aggregates. Iron release kinetics by acid, chelating and reducing agents reflect the high surface area, the size and crystallinity of the particles, and the presence of the protective carbohydrate layer coating the iron compound. Within a physiologically relevant time period, the iron release produced by acid or large chelating ligands is small. In contrast, iron is rapidly mobilized by small organic chelating agents, such as oxalate, or by chelate-forming reductants, such as thioglycolate.

Maximizing T2-exchange in Dy3+DOTA-(amide)X chelates: Fine-tuning the water molecule exchange rate for enhanced T2 contrast in MRI

PubMed Central

Soesbe, Todd C.; Ratnakar, S. James; Milne, Mark; Zhang, Shanrong; Do, Quyen N.; Kovacs, Zoltan; Sherry, A. Dean

2014-01-01

Purpose The water molecule exchange rates in a series of DyDOTA-(amide)X chelates were fine-tuned to maximize the effects of T2-exchange line broadening and improve T2 contrast. Methods Four DyDOTA-(amide)X chelates having a variable number of glycinate side-arms were prepared and characterized as T2-exchange agents. The non-exchanging DyTETA chelate was also used to measure the bulk water T2 reduction due solely to T2*. The total transverse relaxivity (r2tot) at 22, 37, and 52 °C for each chelate was measured in vitro at 9.4 T (400 MHz) by fitting plots of total T2−1 versus concentration. The water molecule exchange rates for each complex were measured by fitting 17O line-width versus temperature data taken at 9.4 T (54.3 MHz). Results The measured transverse relaxivities due to water molecule exchange (r2ex) and bound water lifetimes (τM) were in excellent agreement with Swift-Connick theory, with DyDOTA-(gly)3 giving the largest r2ex = 11.8 s−1 mM−1 at 37 °C. Conclusion By fine-tuning the water molecule exchange rate at 37 °C, the transverse relaxivity has been increased by 2 to 30 times compared to previously studied Dy3+-based chelates. Polymerization or dendrimerization of the optimal chelate could yield a highly sensitive, molecule-sized T2 contrast agent for improved molecular imaging applications. PMID:24390729

Quantitative property-property relationship (QPPR) approach in predicting flotation efficiency of chelating agents as mineral collectors.

PubMed

Natarajan, R; Nirdosh, I; Venuvanalingam, P; Ramalingam, M

2002-07-01

The QPPR approach has been used to model cupferrons as mineral collectors. Separation efficiencies (Es) of these chelating agents have been correlated with property parameters namely, log P, log Koc, substituent-constant sigma, Mullikan and ESP derived charges using multiple regression analysis. Es of substituted-cupferrons in the flotation of a uranium ore could be predicted within experimental error either by log P or log Koc and an electronic parameter. However, when a halo, methoxy or phenyl substituent was in para to the chelating group, experimental Es was greater than the predicted values. Inclusion of a Boolean type indicative parameter improved significantly the predictability power. This approach has been extended to 2-aminothiophenols that were used to float a zinc ore and the correlations were found to be reasonably good.

Iron-[S,S']-EDDS (FeEDDS) Chelate as an Iron Source for Horticultural Crop Production: Marigold Growth and Nutrition, Spectral Properties, and Photodegradation

USDA-ARS?s Scientific Manuscript database

Aminopolycarboxylic acid (APCA) complexones, commonly referred to as ligands or chelating agents, like ethylenediaminetetraacetic acid (EDTA) and diethylenetriaminepentaacetic acid (DTPA) are commonly used in soluble fertilizers to supply copper (Cu), iron (Fe), manganese (Mn), and/or zinc (Zn) to p...

Bifunctional Coupling Agents for Radiolabeling of Biomolecules and Target-Specific Delivery of Metallic Radionuclides

PubMed Central

Liu, Shuang

2008-01-01

Receptor-based radiopharmaceuticals are of great current interest in early molecular imaging and radiotherapy of cancers, and provide a unique tool for target-specific delivery of radionuclides to the diseased tissues. In general, a target-specific radiopharmaceutical can be divided into four parts: targeting biomolecule (BM), pharmacokinetic modifying (PKM) linker, bifunctional coupling or chelating agent (BFC), and radionuclide. The targeting biomolecule serves as a “carrier” for specific delivery of the radionuclide. PKM linkers are used to modify radiotracer excretion kinetics. BFC is needed for radiolabeling of biomolecules with a metallic radionuclide. Different radiometals have significant difference in their coordination chemistry, and require BFCs with different donor atoms and chelator frameworks. Since the radiometal chelate can have a significant impact on physical and biological properties of the target-specific radiopharmaceutical, its excretion kinetics can be altered by modifying the coordination environment with various chelators or coligand, if needed. This review will focus on the design of BFCs and their coordination chemistry with technetium, copper, gallium, indium, yttrium and lanthanide radiometals. PMID:18538888

Studies of the Interaction of Influenza Virus RNA Polymerase PAN with Endonuclease Inhibitors.

PubMed

Dong, Li-Hua; Cao, Xiao-Rong

2018-06-01

Influenza virus is a major causative agent of respiratory viral infections, and RNA polymerase catalyzes its replication and transcription activities in infected cell nuclei. Since it is highly conserved in all virus strains, RNA polymerase becomes a key target of anti-influenza virus agents. Although experimental studies have revealed the good inhibitory activity of endonuclease inhibitors to RNA polymerase, the mechanism is still unclear. In this study, the docking and molecular dynamics simulations have been performed to explore the interaction of three kinds of endonuclease inhibitors with the subunit (PA N ) of RNA polymerase. Our calculations indicate that all these endonuclease inhibitors can bind to the binding pocket of PA N , in which the electronegative oxygen atoms of the inhibitors form a chelated structure with the two Mn 2+ cations of the active center. The most important interaction between these inhibitors and PA N is electrostatic interaction. The electron density of the chelate oxygen atoms determines the magnitude of the electrostatic energy, and the chelated structure and orientation of inhibitors depend largely on the distance between the chelate oxygen atoms.

Headgroup interactions and ion flotation efficiency in mixtures of a chelating surfactant, different foaming agents, and divalent metal ions.

PubMed

Svanedal, Ida; Boija, Susanne; Norgren, Magnus; Edlund, Håkan

2014-06-10

The correlation between interaction parameters and ion flotation efficiency in mixtures of chelating surfactant metal complexes and different foaming agents was investigated. We have recently shown that chelating surfactant 2-dodecyldiethylenetriaminepentaacetic acid (4-C12-DTPA) forms strong coordination complexes with divalent metal ions, and this can be utilized in ion flotation. Interaction parameters for mixed micelles and mixed monolayer formation for Mg(2+) and Ni(2+) complexes with the chelating surfactant 4-C12-DTPA and different foaming agents were calculated by Rubingh's regular solution theory. Parameters for the calculations were extracted from surface tension measurements and NMR diffusometry. The effects of metal ion coordination on the interactions between 4-C12-DTPA and the foaming agents could be linked to a previously established difference in coordination chemistry between the examined metal ions. As can be expected from mixtures of amphoteric surfactants, the interactions were strongly pH-dependent. Strong correlation was found between interaction parameter β(σ) for mixed monolayer formation and the phase-transfer efficiency of Ni(2+) complexes with 4-C12-DTPA during flotation in a customized flotation cell. In a mixture of Cu(2+) and Zn(2+), the significant difference in conditional stability constants (log K) between the metal complexes was utilized to selectively recover the metal complex with the highest log K (Cu(2+)) by ion flotation. Flotation experiments in an excess concentration of metal ions confirmed the coordination of more than one metal ion to the headgroup of 4-C12-DTPA.

Comparison of various iron chelators and prochelators as protective agents against cardiomyocyte oxidative injury.

PubMed

Jansová, Hana; Macháček, Miloslav; Wang, Qin; Hašková, Pavlína; Jirkovská, Anna; Potůčková, Eliška; Kielar, Filip; Franz, Katherine J; Simůnek, Tomáš

2014-09-01

Oxidative stress is a common denominator of numerous cardiovascular disorders. Free cellular iron catalyzes the formation of highly toxic hydroxyl radicals, and iron chelation may thus be an effective therapeutic approach. However, using classical iron chelators in diseases without iron overload poses risks that necessitate more advanced approaches, such as prochelators that are activated to chelate iron only under disease-specific oxidative stress conditions. In this study, three cell-membrane-permeable iron chelators (clinically used deferasirox and experimental SIH and HAPI) and five boronate-masked prochelator analogs were evaluated for their ability to protect cardiac cells against oxidative injury induced by hydrogen peroxide. Whereas the deferasirox-derived agents TIP and TRA-IMM displayed negligible protection and even considerable toxicity, the aroylhydrazone prochelators BHAPI and BSIH-PD provided significant cytoprotection and displayed lower toxicity after prolonged cellular exposure compared to their parent chelators HAPI and SIH, respectively. Overall, the most favorable properties in terms of protective efficiency and low inherent cytotoxicity were observed with the aroylhydrazone prochelator BSIH. BSIH efficiently protected both H9c2 rat cardiomyoblast-derived cells and isolated primary rat cardiomyocytes against hydrogen peroxide-induced mitochondrial and lysosomal dysregulation and cell death. At the same time, BSIH was nontoxic at concentrations up to its solubility limit (600 μM) and in 72-h incubation. Hence, BSIH merits further investigation for prevention and/or treatment of cardiovascular disorders associated with a known (or presumed) component of oxidative stress. Copyright © 2014 Elsevier Inc. All rights reserved.

A new approach to isolating siderophore-producing actinobacteria.

PubMed

Nakouti, I; Sihanonth, P; Hobbs, G

2012-07-01

This study was conducted to investigate the application of 2,2'-dipyridyl as a new approach to isolating siderophore-producing actinobacteria. Isolation of actinobacteria from soil was conducted by a soil dilution plate technique using starch-casein agar. Iron starvation was fostered by the incorporation of the iron chelator 2,2'-dipyridyl in the isolation medium. Pretreatment of the samples at an elevated temperature (40°C) ensured that the majority of nonsporulating bacteria were excluded. The survivors of this treatment were largely actinobacteria. Of the viable cultures grown in the presence of 2,2'-dipyridyl, more than 78-88% (average of three separate studies) were reported to produce siderophore-like compounds compared to 13-18% (average of three separate studies) when grown on the basic media in the absence of the chelating agent. The most prolific producers as assessed by the chrome azurol sulphate (CAS) assay were further characterized and found to belong to the genus Streptomyces. Selective pressure using 2,2'-dipyridyl as an iron-chelating agent in starch-casein media increased the isolation of siderophore-producing actinobacteria compared to the unamended medium. The study described represents a new approach to the isolation of siderophore-producing actinobacteria using a novel procedure that places a selection on cell population based upon the incorporation of a chelating agent in the medium. © 2012 The Authors. Letters in Applied Microbiology © 2012 The Society for Applied Microbiology.

ParaCEST agents encapsulated in Reverse nano-Assembled Capsules (RACs): How slow molecular tumbling can quench CEST

NASA Astrophysics Data System (ADS)

Farashishiko, Annah; Slack, Jacqueline R.; Botta, Mauro; Woods, Mark

2018-04-01

Although paraCEST is a method with immense scope for generating image contrast in MRI, it suffers from the series the serious drawback of high detection limits. For a typical discrete paraCEST agent the detection limit is roughly an order of magnitude higher than that of a clinically used relaxation agent. One solution to this problem may be the incorporation of a large payload of paraCEST agents into a single macromolecular agent. Here we report a new synthetic method for accomplishing this goal: incorporating a large payload of the paraCEST agent DyDOTAM3+ into a Reverse Assembled nano-Capsule. An aggregate can be generated between this chelate and polyacrylic acid after the addition of ethylene diamine. Subsequent addition of polyallylamine hydrochloride followed by silica nanoparticles generated a robust encapsulating shell and afforded capsule with a mean hydrodynamic diameter of 650 ± 250 nm. Unfortunately this encapsulation did not have the effect of amplifying the CEST effect per agent, but quenched the CEST altogether. A significant proportion of the quenching effect of encapsulation could be attributed to the effect of slowing molecular tumbling, which is inevitable when the chelate is incorporated into a nano-scale material. This increases the transverse relaxation rate of chelate protons and a theoretical examination using Solomon Bloembergen Morgan theory and the Bloch equations shows that the increase in the transverse relaxation rate constant for the amide protons, in even modestly sized nano-materials, is sufficient to significantly quench CEST.

Structural, chemical and biological aspects of antioxidants for strategies against metal and metalloid exposure

PubMed Central

2009-01-01

Oxidative stress contributes to the pathophysiology of exposure to heavy metals/metalloid. Beneficial renal effects of some medications, such as chelation therapy depend at least partially on the ability to alleviate oxidative stress. The administration of various natural or synthetic antioxidants has been shown to be of benefit in the prevention and attenuation of metal induced biochemical alterations. These include vitamins, N-acetylcysteine, α-lipoic acid, melatonin, dietary flavonoids and many others. Human studies are limited in this regard. Under certain conditions, surprisingly, the antioxidant supplements may exhibit pro-oxidant properties and even worsen metal induced toxic damage. To date, the evidence is insufficient to recommend antioxidant supplements in subject with exposure to metals. Prospective, controlled clinical trials on safety and effectiveness of different therapeutic antioxidant strategies either individually or in combination with chelating agent are indispensable. The present review focuses on structural, chemical and biological aspects of antioxidants particularly related to their chelating properties. PMID:20716905

Determination of cadmium in seawater by chelate vapor generation atomic fluorescence spectrometry

NASA Astrophysics Data System (ADS)

Sun, Rui; Ma, Guopeng; Duan, Xuchuan; Sun, Jinsheng

2018-03-01

A method for the determination of cadmium in seawater by chelate vapor generation (Che-VG) atomic fluorescence spectrometry is described. Several commercially available chelating agents, including ammonium pyrrolidine dithiocarbamate (APDC), sodium dimethyl dithiocarbamate (DMDTC), ammonium dibutyl dithiophosphate (DBDTP) and sodium O,O-diethyl dithiophosphate (DEDTP), are compared with sodium diethyldithiocarbamate (DDTC) for the Che-VG of cadmium, and results showed that DDTC and DEDTP had very good cadmium signal intensity. The effect of the conditions of Che-VG with DDTC on the intensity of cadmium signal was investigated. Under the optimal conditions, 85 ± 3% Che-VG efficiency is obtained for cadmium. The detection limit (3σ) obtained in the optimal conditions was 0.19 ng ml- 1. The relative standard deviation (RSD, %) for ten replicate determinations at 2 ng ml- 1 Cd was 3.42%. The proposed method was successfully applied to the ultratrace determination of cadmium in seawater samples by the standard addition method.

The stability of DOTA-chelated radiopharmaceuticals within 225Ac decay pathway studied with density functional theory.

NASA Astrophysics Data System (ADS)

Karolak, Aleksandra; Khabibullin, Artem; Budzevich, Mikalai; Martinez, M.; Doliganski, Michael; McLaughlin, Mark; Woods, Lilia; Morse, David

Ligand structures encapsulating metal ions play a central role as contrast agents in Magnetic Resonance Imaging (MRI) or as agents delivering toxic cargo directly to tumor cells in targeted cancer therapy. The structural stability and interaction with solutions of such complexes are the key elements in understanding the foundation of delivery process. We present a comparative study for the 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) chelated to radioactive isotopes of 225Ac, 221Fr, 217At, 213Bi and a control 68Gd. Using density functional theory methods we investigate the structural stability of complexes for cancer therapy including binding energies, charge transfer, electron densities. The van der Waals interactions are included in the simulations to take into account weak dispersion forces present in such structures. Our results reveal that Ac-DOTA, Bi-DOTA and Gd-DOTA are the most stable complexes in the group. We also show that the water environment is a key ingredient for the structural coordination of the DOTA structures. Support from the US Department of Energy under Grant No. DE-FG02-06ER46297 is acknowledged.

NMR structural studies of the supramolecular adducts between a liver cytosolic bile acid binding protein and gadolinium(III)-chelates bearing bile acids residues: molecular determinants of the binding of a hepatospecific magnetic resonance imaging contrast agent.

PubMed

Assfalg, Michael; Gianolio, Eliana; Zanzoni, Serena; Tomaselli, Simona; Russo, Vito Lo; Cabella, Claudia; Ragona, Laura; Aime, Silvio; Molinari, Henriette

2007-11-01

The binding affinities of a selected series of Gd(III) chelates bearing bile acid residues, potential hepatospecific MRI contrast agents, to a liver cytosolic bile acid transporter, have been determined through relaxivity measurements. The Ln(III) complexes of compound 1 were selected for further NMR structural analysis aimed at assessing the molecular determinants of binding. A number of NMR experiments have been carried out on the bile acid-like adduct, using both diamagnetic Y(III) and paramagnetic Gd(III) complexes, bound to a liver bile acid binding protein. The identified protein "hot spots" defined a single binding site located at the protein portal region. The presented findings will serve in a medicinal chemistry approach for the design of hepatocytes-selective gadolinium chelates for liver malignancies detection.

Developing Targeted Hybrid Imaging Probes by Chelator Scaffolding

PubMed Central

2017-01-01

Positron emission tomography (PET) as well as optical imaging (OI) with peptide receptor targeting probes have proven their value for oncological applications but also show restrictions depending on the clinical field of interest. Therefore, the combination of both methods, particularly in a single molecule, could improve versatility in clinical routine. This proof of principle study aims to show that a chelator, Fusarinine C (FSC), can be utilized as scaffold for novel dimeric dual-modality imaging agents. Two targeting vectors (a minigastrin analogue (MG11) targeting cholecystokinin-2 receptor overexpression (CCK2R) or integrin αVβ3 targeting cyclic pentapeptides (RGD)) and a near-infrared fluorophore (Sulfo-Cyanine7) were conjugated to FSC. The probes were efficiently labeled with gallium-68 and in vitro experiments including determination of logD, stability, protein binding, cell binding, internalization, and biodistribution studies as well as in vivo micro-PET/CT and optical imaging in U-87MG αVβ3- and A431-CCK2R expressing tumor xenografted mice were carried out. Novel bioconjugates showed high receptor affinity and highly specific targeting properties at both receptors. Ex vivo biodistribution and micro-PET/CT imaging studies revealed specific tumor uptake accompanied by slow blood clearance and retention in nontargeted tissues (spleen, liver, and kidneys) leading to visualization of tumors at early (30 to 120 min p.i.). Excellent contrast in corresponding optical imaging studies was achieved especially at delayed time points (24 to 72 h p.i.). Our findings show the proof of principle of chelator scaffolding for hybrid imaging agents and demonstrate FSC being a suitable bifunctional chelator for this approach. Improvements to fine-tune pharmacokinetics are needed to translate this into a clinical setting. PMID:28462989

Comparison of the antibacterial activity of chelating agents using the agar diffusion method

USDA-ARS?s Scientific Manuscript database

The agar diffusion assay was used to examine antibacterial activity of 2 metal chelators. Concentrations of 0 to 40 mM of ethylenediaminetetraacetic acid (EDTA) and ethylenediamine-N,N’-disuccinic acid (EDDS) were prepared in 1.0 M potassium hydroxide (KOH). The pH of the solutions was adjusted to 1...

Rationale for the Successful Management of EDTA Chelation Therapy in Human Burden by Toxic Metals

PubMed Central

2016-01-01

Exposure to environmental and occupational toxicants is responsible for adverse effects on human health. Chelation therapy is the only procedure able to remove toxic metals from human organs and tissue, aiming to treat damage related to acute and/or chronic intoxication. The present review focuses on the most recent evidence of the successful use of the chelating agent ethylenediaminetetraacetic acid (EDTA). Assessment of toxic-metal presence in humans, as well as the rationale of EDTA therapy in cardiovascular and neurodegenerative diseases, is reported. PMID:27896275

Gd-DTPA L-cystine bisamide copolymers as novel biodegradable macromolecular contrast agents for MR blood pool imaging.

PubMed

Kaneshiro, Todd L; Ke, Tianyi; Jeong, Eun-Kee; Parker, Dennis L; Lu, Zheng-Rong

2006-06-01

The purpose of this study was to synthesize biodegradable Gd-DTPA L-cystine bisamide copolymers (GCAC) as safe and effective, macromolecular contrast agents for magnetic resonance imaging (MRI) and to evaluate their biodegradability and efficacy in MR blood pool imaging in an animal model. Three new biodegradable GCAC with different substituents at the cystine bisamide [R = H (GCAC), CH2CH2CH3 (Gd-DTPA L-cystine bispropyl amide copolymers, GCPC), and CH(CH3)2 (Gd-DTPA cystine bisisopropyl copolymers, GCIC)] were prepared by the condensation copolymerization of diethylenetriamine pentaacetic acid (DTPA) dianhydride with cystine bisamide or bisalkyl amides, followed by complexation with gadolinium triacetate. The degradability of the agents was studied in vitro by incubation in 15 microM cysteine and in vivo with Sprague-Dawley rats. The kinetics of in vivo contrast enhancement was investigated in Sprague-Dawley rats on a Siemens Trio 3 T scanner. The apparent molecular weight of the polydisulfide Gd(III) chelates ranged from 22 to 25 kDa. The longitudinal (T1) relaxivities of GCAC, GCPC, and GCIC were 4.37, 5.28, and 5.56 mM(-1) s(-1) at 3 T, respectively. The polymeric ligands and polymeric Gd(III) chelates readily degraded into smaller molecules in incubation with 15 microM cysteine via disulfide-thiol exchange reactions. The in vitro degradation rates of both the polymeric ligands and macromolecular Gd(III) chelates decreased as the steric effect around the disulfide bonds increased. The agents readily degraded in vivo, and the catabolic degradation products were detected in rat urine samples collected after intravenous injection. The agents showed strong contrast enhancement in the blood pool, major organs, and tissues at a dose of 0.1 mmol Gd/kg. The difference of their in vitro degradability did not significantly alter the kinetics of in vivo contrast enhancement of the agents. These novel GCAC are promising contrast agents for cardiovascular and tumor MRI, which are later cleaved into low molecular weight Gd(III) chelates and rapidly cleared from the body.

Chelation in root canal therapy reconsidered.

PubMed

Zehnder, Matthias; Schmidlin, Patrick; Sener, Beatrice; Waltimo, Tuomas

2005-11-01

The aim of this study was to assess interactions of EDTA and citric acid (CA) with sodium hypochlorite (NaOCl), the indispensable endodontic irrigant. Other chelators were simultaneously evaluated as possible alternatives: sodium triphosphate (STP), amino tris methylenephosphonic acid (ATMA), and 1- hydroxyethylidene-1, 1-bisphosphonate (HEBP). Available chlorine was titrated in chelator-NaOCl solutions. All chelators other than HEBP and STP caused an almost complete, immediate loss of available chlorine in solution. Atomic absorbtion spectrometry and SEM evaluation of root canal walls of instrumented teeth indicated that NaOCl had no negative effect on calcium-complexing ability of chelators. STP was too weak a complexing agent to warrant further studies. Finally, CA-, EDTA-, and HEBP-NaOCl mixtures were evaluated for their antimicrobial capacity. Again, EDTA and CA negatively interfered with NaOCl, while HEBP did not.

The Effect of Different Tea Varieties on Iron Chelation

NASA Astrophysics Data System (ADS)

Truong, S. K.; Karim, R.

2016-12-01

The chief objectives of this experiment are to distinguish which type of tea of four variants, pomegranate blackberry green, green, lemon chamomile (herbal), and earl grey (black), are capable of chelating the most iron (III) chloride (FeCl3) through titration. We hypothesized that if each tea variety chelates differing amounts of iron chloride, and if we conduct an experiment in which four different teas are mixed in the same amount of water, iron chloride, and iron chloride indicator EDTA, then the pomegranate blackberry green tea will bind to the most iron due to its large amount of fruit antioxidants. To summarize our methodology, we prepared three solutions of each tea, dissolved with 1 gram of FeCl3 to test three trials per tea variety. The chelation process took place overnight as teas cooled. Six drops of iron chloride indicator added to each solution began the titration. The necessary amount of 0.1M EDTA (ethylenediaminetetraacetic acid) drops required for each solution to turn to a universal amber color from its original dark tone indicates how many free iron molecules were left unbound by the tea solution. After careful analysis of the data, we discovered that blackberry pomegranate green tea possessed the best chelating abilities with 97.48% of FeCl3 adsorbed. Green tea followed with 96.67%. Herbal tea chelated 94.24% of the iron while earl grey absorbed the least amount at 93.43%. From our conclusion, we drew that since blackberry pomegranate green tea contained the highest amount of polyphenols and antioxidants as well as epigallocatechin gallate (EGCG) found in green teas, it was able to chelate the most amount of iron. The substances mentioned in blackberry pomegranate green tea possess the ability to form strong bonds with multiple heavy metals, such as iron (III) chloride atoms. Overall, each variety of tea contains different organic substances. Each of these substances possesses a unique chelating ability, determining how well the type of tea can bond to iron. Among the teas being tested in this experiment, blackberry pomegranate green tea absorbed the most iron, thus acting as the superior chelating agent. Our experiment opens up new opportunities for investigations in chelation therapy and heavy metal poisoning through the knowledge of biological chelating agents.

Development of an iron chelating polyethylene film for active packaging applications.

PubMed

Tian, Fang; Decker, Eric A; Goddard, Julie M

2012-02-29

Metal-promoted oxidation reactions are a major cause of food quality deterioration. Active packaging offers novel approaches to controlling such oxidation for the purpose of extending shelf life. Herein, we report modification of the surface of polyethylene (PE) films to possess metal chelating activity. Metal chelating carboxylic acids were introduced to the film surface using cross-linking agents [polyethylenimine (PEI) or ethylenediamine (ED)] to increase the number of available carboxylic acids. ATR-FTIR, contact angle, dye assay, and iron chelating assay were used to characterize changes in surface chemistry after each functionalization step. The chelator poly(acrylic acid) (PAA) was attached to the surface at a density of 9.12 ± 0.71 nmol carboxyl groups/cm², and exhibited an iron chelating activity. The results indicate that PAA-modified PE films might have a higher affinity to Fe³⁺ than Fe²⁺ with the optimum binding pH at 5.0. Such inexpensive active packaging materials are promising in food industry for the preservation of liquid and semiliquid food products and have application in heavy metal chelation therapy for biomedical materials as well.

Comparison of the effects of deferasirox, deferoxamine, and combination of deferasirox and deferoxamine on an aplastic anemia mouse model complicated with iron overload.

PubMed

Wu, Dijiong; Wen, Xiaowen; Liu, Wenbin; Hu, Huijin; Ye, Baodong; Zhou, Yuhong

2018-01-01

Iron overload is commonly observed during the course of aplastic anemia (AA), which is believed to aggravate hematopoiesis, cause multiple organ dysfunction, lead to disease progression, and impair quality of life. Deferasirox (DFX) and deferoxamine (DFO) are among the most common iron chelation agents available in the clinical setting. The aim of this study was to investigate if the combination therapy with DFX and DFO is superior in hematopoietic recovery and iron chelation. Briefly, we developed a composite mouse model with AA and iron overload that was consequently treated with DFX, DFO, or with a combination of both agents. The changes in peripheral hemogram, marrow apoptosis, and its related protein expressions were compared during the process of iron chelation, while the iron depositions in liver and bone marrow and its regulator were also detected. The obtained results showed that compared to DFX, DFO has a better effect in protecting the bone marrow from apoptosis-induced failure. The combination of DFO and DFX accelerated the chelation of iron, while their efficiency on further hemogram improvement appeared limited. To sum up, our data suggest that single treatment with DFO may be a better choice for improving the hematopoiesis during the gradual chelation treatment irrespective of the convenience of oral DFX, while the combination treatment should be considered for urgent reduction of the iron burden.

Synthesis, characterization and in vitro anticancer evaluations of two novel derivatives of deferasirox iron chelator.

PubMed

Salehi, Samie; Saljooghi, Amir Sh; Shiri, Ali

2016-06-15

Iron (Fe) chelation therapy was initially designed to alleviate the toxic effects of excess Fe evident in Fe-overload diseases. However, the novel toxicological properties of some Fe chelator-metal complexes have shifted significant attention to their application in cancer chemotherapy. The present study investigates the new role of deferasirox as an anticancer agent due to its ability to chelate with iron. Because of aminoacids antioxidant effect, deferasirox and its two novel amino acid derivatives have been synthesized through the treatment of deferasirox with DCC as well as glycine or phenylalanine methyl ester. All new compounds have been characterized by elemental analysis, FT-IR NMR and mass spectrometry. Therefore, the cytotoxicity of these compounds was screened for antitumor activity against some cell lines using cisplatin as a comparative standard by MTT assay and Flow cytometry. The impact of iron in the intracellular generation of reactive oxygen species was assessed on HT29 and MDA-MB-231 cells. The potential of the synthesized iron chelators for their efficacy to protect cells against model oxidative injury induced was compared. The reactive oxygen species intracellular fluorescence intensity were measured and the result showed that the reactive oxygen species intensity after iron incubation increased while after chelators incubation the reactive oxygen species intensity were decreased significantly. Besides, the effect of the synthesized compounds on mouse fibroblast cell line (L929) was simultaneously evaluated as control. The pharmacological results showed that deferasirox and its two novel aminoacid derivatives were potent anticancer agents. Copyright © 2016 Elsevier B.V. All rights reserved.

Iron chelation therapy in transfusion-dependent thalassemia patients: current strategies and future directions

PubMed Central

Saliba, Antoine N; Harb, Afif R; Taher, Ali T

2015-01-01

Transfusional iron overload is a major target in the care of patients with transfusion-dependent thalassemia (TDT) and other refractory anemias. Iron accumulates in the liver, heart, and endocrine organs leading to a wide array of complications. In this review, we summarize the characteristics of the approved iron chelators, deferoxamine, deferiprone, and deferasirox, and the evidence behind the use of each, as monotherapy or as part of combination therapy. We also review the different guidelines on iron chelation in TDT. This review also discusses future prospects and directions in the treatment of transfusional iron overload in TDT whether through innovation in chelation or other therapies, such as novel agents that improve transfusion dependence. PMID:26124688

Iron uptake in Mycelia sterilia EP-76.

PubMed Central

Adjimani, J P; Emery, T

1987-01-01

The cyclic trihydroxamic acid, N,N',N''-triacetylfusarinine C, produced by Mycelia sterilia EP-76, was shown to be a ferric ionophore for this organism. The logarithm of the association constant k for the ferric triacetylfusarinine C chelate was determined to be 31.8. Other iron-chelating agents, such as rhodotorulic acid, citric acid, and the monomeric subunit of triacetylfusarinine C, N-acetylfusarinine, delivered iron to the cells by an indirect mechanism involving iron exchange into triacetylfusarinine C. In vitro ferric ion exchange was found to be rapid with triacetylfusarinine C. Gallium uptake rates comparable to those of iron were observed with the chelating agents that transport iron into the cell. Ferrichrome, but not ferrichrome A, was also capable of delivering iron and gallium to this organism, but not by an exchange mechanism. Unlike triacetylfusarinine C, the 14C-ligand of ferrichrome was retained by the cell. A midpoint potential of -690 mV with respect to the saturated silver chloride electrode was obtained for the ferric triacetylfusarinine C complex, indicating that an unfavorable reduction potential was not the reason for the use of a hydrolytic mechanism of intracellular iron release from the ferric triacetylfusarinine C chelate. PMID:3611025

Determination of Ultra-trace Rhodium in Water Samples by Graphite Furnace Atomic Absorption Spectrometry after Cloud Point Extraction Using 2-(5-Iodo-2-Pyridylazo)-5-Dimethylaminoaniline as a Chelating Agent.

PubMed

Han, Quan; Huo, Yanyan; Wu, Jiangyan; He, Yaping; Yang, Xiaohui; Yang, Longhu

2017-03-24

A highly sensitive method based on cloud point extraction (CPE) separation/preconcentration and graphite furnace atomic absorption spectrometry (GFAAS) detection has been developed for the determination of ultra-trace amounts of rhodium in water samples. A new reagent, 2-(5-iodo-2-pyridylazo)-5-dimethylaminoaniline (5-I-PADMA), was used as the chelating agent and the nonionic surfactant TritonX-114 was chosen as extractant. In a HAc-NaAc buffer solution at pH 5.5, Rh(III) reacts with 5-I-PADMA to form a stable chelate by heating in a boiling water bath for 10 min. Subsequently, the chelate is extracted into the surfactant phase and separated from bulk water. The factors affecting CPE were investigated. Under the optimized conditions, the calibration graph was linear in the range of 0.1-6.0 ng/mL, the detection limit was 0.023 ng/mL for rhodium and relative standard deviation was 3.67% ( c = 1.0 ng/mL, n = 11)．The method has been applied to the determination of trace rhodium in water samples with satisfactory results.

Fe(III)-EDDHA and -EDDHMA sorption on Ca-montmorillonite, ferrihydrite, and peat.

PubMed

Hernández-Apaolaza, L; Lucena, J J

2001-11-01

The effectiveness of Fe chelates as Fe sources and carriers in soil can be severely limited by the adsorption of Fe chelates or chelating agents in the solid phase. To study this phenomenon, well-characterized peat, Ca-montmorillonite, and ferrihydrite were used as model compounds, and the adsorption of Fe-EDDHA and Fe-EDDHMA chelates were studied. Sorption isotherms for the meso and racemic isomers of these chelates on the soil materials are described. The variability of sorption with pH in peat and ferrihydrite was also determined because both have variable surface charge at different pH values. In montmorillonite, at low concentrations, the retention of Fe from the Fe-EDDHMA chelate is greater than the one of the Fe-EDDHA chelate. As well as the concentration increased, the inverse situation occurs. The behavior of both meso and racemic isomers of chelates in contact with Ca-montmorillonite is similar. The Fe-meso-EDDHA isomer was highly adsorbed on ferrihydrite, but the racemic isomer is not significantly retained by this oxide. For Fe-EDDHMA isomers, the racemic isomer was more retained by the oxide, but a small sorption of the racemic isomer was also observed. Results suggest that Fe-EDDHA chelates were more retained in peat than Fe-EDDHMA chelates. The most retained isomer of Fe-EDDHA was the meso isomer. For Fe-EDDHMA, the adsorption was very low for both racemic and meso isomers.

The influence of EDDS and EDTA on the uptake of heavy metals of Cd and Cu from soil with tobacco Nicotiana tabacum.

PubMed

Evangelou, Michael W H; Bauer, Uwe; Ebel, Mathias; Schaeffer, Andreas

2007-06-01

Phytoextraction, the use of plants to extract contaminants from soils and groundwater, is a promising approach for cleaning up soils contaminated with heavy metals. In order to enhance phytoextraction the use of chelating agents has been proposed. This study aims to assess whether ethylene diamine disuccinate (EDDS), a biodegradable chelator, can be used for enhanced phytoextraction purposed, as an alternative to ethylene diamine tetraacetate (EDTA). EDDS revealed a higher toxicity to tobacco (Nicotiana tabacum) in comparison to EDTA, but no toxicity to microorganisms. The uptake of Cu was increased by the addition of EDTA and EDDS, while no increase was observed in the uptake of Cd. Both chelating agents showed a very low root to shoot translocation capability and the translocation factor was lower than the one of the control. Heavy metals where significantly more phytoavailable than in the control, even after harvesting, resulting in a high heavy metal leaching possibility, probably owing to a low biodegradation rate of EDDS. New seedlings which were transplanted into the EDDS treated pots 7d after the phytoextraction experiment, showed signs of necrosis and chlorosis, which resulted in a significantly lower biomass in comparison to the control. The seedlings on the EDTA treated pots showed no toxicity signs. Contrary to previous opinions the results of this study revealed the chelating agents EDTA and EDDS as unsuitable for enhanced phytoextraction using tobacco.

Effects of chelating agents on the mineral content of root canal dentin.

PubMed

Cobankara, Funda Kont; Erdogan, Hilal; Hamurcu, Mehmet

2011-12-01

The objective of this in vitro study was to assess the effect of several chelating agents on the mineral content of root dentin. Extracted human mandibular incisor roots were prepared and divided into groups according to the following irrigation protocols: 1) 17% ethylenediaminetetraacetic acid (EDTA); 2) 10% citric acid solution; 3) 18% etidronate; 4) 2.25% peracetic acid; 5) and deionized water (control). Dentin chips were obtained (Gates-Glidden nos. 3, 4, and 5). The levels of different minerals were analyzed with the use of inductively coupled plasma-atomic emission spectrometry (ICP-AES). 1) Peracetic acid significantly decreased P, K, Mg, Na, and S levels compared with the other groups (P < .05). 2) S decreased by different levels in all of the chelating solutions (P < .05), and the greatest decrease was observed in peracetic acid. 3) Ca levels significantly decreased in peracetic acid, citric acid, and EDTA (P < .05). 4) Mn levels significantly decreased in the citric acid and peracetic acid groups (P < .05). 5) Na and Zn levels significantly decreased in the peracetic acid, citric acid, and etidronate groups (P < .05). The chelation agents can create different effects on mineral contents of root dentin, so it is important to know what effects each solution will have on root dentin before their clinical use. In addition, according to the results of this in vitro study, it might be recommended that peracetic acid, in particular, should be used with caution. Copyright © 2011 Mosby, Inc. All rights reserved.

Fabrication and evaluation of tumor-targeted positive MRI contrast agent based on ultrasmall MnO nanoparticles.

PubMed

Huang, Haitao; Yue, Tao; Xu, Ke; Golzarian, Jafar; Yu, Jiahui; Huang, Jin

2015-07-01

Gd(III) chelate is currently used as positive magnetic resonance imaging (MRI) contrast agent in clinical diagnosis, but generally induces the risk of nephrogenic systemic fibrosis (NSF) due to the dissociated Gd(3+) from Gd(III) chelates. To develop a novel positive MRI contrast agent with low toxicity and high sensitivity, ultrasmall MnO nanoparticles were PEGylated via catechol-Mn chelation and conjugated with cRGD as active targeting function to tumor. Particularly, the MnO nanoparticles with a size of ca. 5nm were modified by α,β-poly(aspartic acid)-based graft polymer containing PEG and DOPA moieties and, meanwhile, conjugated with cRGD to produce the contrast agent with a size of ca. 100nm and a longitudinal relaxivity (r1) of 10.2mM(-1)S(-1). Such nanoscaled contrast agent integrated passive- and active-targeting function to tumor, and its efficient accumulation behavior in tumor was verified by in vivo distribution study. At the same time, the PEG moiety played a role of hydrophilic coating to improve the biocompatibility and stability under storing and physiological conditions, and especially might guarantee enough circulation time in blood. Moreover, in vivo MRI revealed a good and long-term effect of enhancing MRI signal for as-fabricated contrast agent while cell viability assay proved its acceptable cytotoxicity for MRI application. On the whole, the as-fabricated PEGylated and cRGD-functionalized contrast agent based on ultrasmall MnO nanoparticles showed a great potential to the T1-weighted MRI diagnosis of tumor. Crown Copyright © 2015. Published by Elsevier B.V. All rights reserved.

Gadolinium chelate coated gold nanoparticles as contrast agents for both X-ray computed tomography and magnetic resonance imaging.

PubMed

Alric, Christophe; Taleb, Jacqueline; Le Duc, Géraldine; Mandon, Céline; Billotey, Claire; Le Meur-Herland, Alice; Brochard, Thierry; Vocanson, Francis; Janier, Marc; Perriat, Pascal; Roux, Stéphane; Tillement, Olivier

2008-05-07

Functionalized gold nanoparticles were applied as contrast agents for both in vivo X-ray and magnetic resonance imaging. These particles were obtained by encapsulating gold cores within a multilayered organic shell which is composed of gadolinium chelates bound to each other through disulfide bonds. The contrast enhancement in MRI stems from the presence of gadolinium ions which are entrapped in the organic shell, whereas the gold core provides a strong X-ray absorption. This study revealed that these particles suited for dual modality imaging freely circulate in the blood vessels without undesirable accumulation in the lungs, spleen, and liver.

Ultrafine nanoporous palladium-aluminum film fabricated by citric acid-assisted hot-water-treatment of aluminum-palladium alloy film

DOE Office of Scientific and Technical Information (OSTI.GOV)

Harumoto, Takashi; Tamura, Yohei; Ishiguro, Takashi, E-mail: ishiguro@rs.noda.tus.ac.jp

Hot-water-treatment has been adapted to fabricate ultrafine nanoporous palladium-aluminum film from aluminum-palladium alloy film. Using citric acid as a chelating agent, a precipitation of boehmite (aluminum oxide hydroxide, AlOOH) on the nanoporous palladium-aluminum film was suppressed. According to cross-sectional scanning transmission electron microscopy observations, the ligament/pore sizes of the prepared nanoporous film were considerably small (on the order of 10 nm). Since this fabrication method only requires aluminum alloy film and hot-water with chelating agent, the ultrafine nanoporous film can be prepared simply and environmentally friendly.

Benzyl and Methyl Fatty Hydroxamic Acids Based on Palm Kernel Oil as Chelating Agent for Liquid-Liquid Iron(III) Extraction

PubMed Central

Haron, Md Jelas; Jahangirian, Hossein; Silong, Sidik; Yusof, Nor Azah; Kassim, Anuar; Rafiee-Moghaddam, Roshanak; Mahdavi, Behnam; Peyda, Mazyar; Abdollahi, Yadollah; Amin, Jamileh

2012-01-01

Liquid-liquid iron(III) extraction was investigated using benzyl fatty hydroxamic acids (BFHAs) and methyl fatty hydroxamic acids (MFHAs) as chelating agents through the formation of iron(III) methyl fatty hydroxamate (Fe-MFHs) or iron(III) benzyl fatty hydroxamate (Fe-BFHs) in the organic phase. The results obtained under optimized conditions, showed that the chelating agents in hexane extract iron(III) at pH 1.9 were realized effectively with a high percentage of extraction (97.2% and 98.1% for MFHAs and BFHAs, respectively). The presence of a large amount of Mg(II), Ni(II), Al(III), Mn(II) and Co(II) ions did affect the iron(III) extraction. Finally stripping studies for recovering iron(III) from organic phase (Fe-MFHs or Fe-BFHs dissolved in hexane) were carried out at various concentrations of HCl, HNO3 and H2SO4. The results showed that the desired acid for recovery of iron(III) was 5 M HCl and quantitative recovery of iron(III) was achieved from Fe(III)-MFHs and Fe(III)-BFHs solutions in hexane containing 5 mg/L of Fe(III). PMID:22408444

Improved paramagnetic chelate for molecular imaging with MRI

NASA Astrophysics Data System (ADS)

Winter, Patrick; Athey, Phillip; Kiefer, Garry; Gulyas, Gyongyi; Frank, Keith; Fuhrhop, Ralph; Robertson, David; Wickline, Samuel; Lanza, Gregory

2005-05-01

The relaxivity and transmetallation of two lipophilic paramagnetic chelates incorporated onto perfluorocarbon nanoparticles, i.e., gadolinium-methoxy-tetraazacyclododecane-tetraacetic acid phosphatidylethanolamine (Gd-MeO-DOTA-PE) and gadolinium-methoxy-tetraazacyclododecane-tetraacetic acid triglycine phosphatidylethanolamine (Gd-MeO-DOTA-triglycine-PE (Gd-MeO-DOTA-triglycine-PE)), were compared to a prototypic gadolinium-diethylene-triamine-pentaacetic acid bis-oleate (Gd-DTPA-BOA) paramagnetic formulation. Nanoparticles with MeO-DOTA-based chelates demonstrated higher relaxivity (40% higher for Gd-MeO-DOTA-PE and 55% higher for Gd-MeO-DOTA-triglycine-PE) and less transmetallation than the original Gd-DTPA-BOA-based agent.

Chelating agents related to ethylenediamine bis(2-hydroxyphenyl)acetic acid (EDDHA): synthesis, characterization, and equilibrium studies of the free ligands and their Mg2+, Ca2+, Cu2+, and Fe3+ chelates.

PubMed

Yunta, Felipe; García-Marco, Sonia; Lucena, Juan J; Gómez-Gallego, Mar; Alcázar, Roberto; Sierra, Miguel A

2003-08-25

Iron chelates such as ethylenediamine-N,N'-bis(2-hydroxyphenyl)acetic acid (EDDHA) and their analogues are the most efficient soil fertilizers to treat iron chlorosis in plants growing in calcareous soils. EDDHA, EDDH4MA (ethylenediamine-N,N'-bis(2-hydroxy-4-methylphenyl)acetic acid), and EDDCHA (ethylenediamine-N,N'-bis(2-hydroxy-5-carboxyphenyl)acetic acid) are allowed by the European directive, but also EDDHSA (ethylenediamine-N,N'-bis(2-hydroxy-5-sulfonylphenyl)acetic acid) and EDDH5MA (ethylenediamine-N,N'-bis(2-hydroxy-5-methylphenyl)acetic acid) are present in several commercial iron chelates. In this study, these chelating agents as well as p,p-EDDHA (ethylenediamine-N,N'-bis(4-hydroxyphenyl)acetic acid) and EDDMtxA (ethylenediamine-N,N'-bis(2-metoxyphenyl)acetic acid) have been obtained following a new synthetic pathway. Their chemical behavior has been studied to predict the effect of the substituents in the benzene ring on their efficacy as iron fertilizers for soils above pH 7. The purity of the chelating agents has been determined using a novel methodology through spectrophotometric titration at 480 nm with Fe(3+) as titrant to evaluate the inorganic impurities. The protonation constants were determined by both spectrophotometric and potentiometric methods, and Ca(2+) and Mg(2+) stability constants were determined from potentiometric titrations. To establish the Fe(3+) and Cu(2+) stability constants, a new spectrophotometric method has been developed, and the results were compared with those reported in the literature for EDDHA and EDDHMA and their meso- and rac-isomers. pM values have been also determined to provide a comparable basis to establish the relative chelating ability of these ligands. The purity obtained for the ligands is higher than 87% in all cases and is comparable with that obtained by (1)H NMR. No significant differences have been found among ligands when their protonation and stability constants were compared. As expected, no Fe(3+) complexation was observed for p,p-EDDHA and EDDMtxA. The presence of sulfonium groups in EDDHSA produces an increase in acidity that affects their protonation and stability constants, although the pFe values suggest that EDDHSA could be also effective to correct iron chlorosis in plants.

Synthesis and Properties of Chelating N-Heterocyclic Carbene Rhodium(I) Complexes: Synthetic Experiments in Current Organometallic Chemistry

ERIC Educational Resources Information Center

Mata, Jose A.; Poyatos, Macarena; Mas-Marza, Elena

2011-01-01

The preparation and characterization of two air-stable Rh(I) complexes bearing a chelating N-heterocyclic carbene (NHC) ligand is described. The synthesis involves the preparation of a Ag(I)-NHC complex and its use as carbene transfer agent to a Rh(I) precursor. The so obtained complex can be further reacted with carbon monoxide to give the…

Chelating capture and magnetic removal of non-magnetic heavy metal substances from soil

PubMed Central

Fan, Liren; Song, Jiqing; Bai, Wenbo; Wang, Shengping; Zeng, Ming; Li, Xiaoming; Zhou, Yang; Li, Haifeng; Lu, Haiwei

2016-01-01

A soil remediation method based on magnetic beneficiation is reported. A new magnetic solid chelator powder, FS@IDA (core-shell Fe3O4@SiO2 nanoparticles coated with iminodiacetic acid chelators), was used as a reactive magnetic carrier to selectively capture non-magnetic heavy metals in soil by chelation and removal by magnetic separation. FS@IDA was prepared via inorganic-organic and organic synthesis reactions that generated chelating groups on the surface of magnetic, multi-core, core-shell Fe3O4@SiO2 (FS) nanoparticles. These reactions used a silane coupling agent and sodium chloroacetate. The results show that FS@IDA could chelate the heavy metal component of Cd, Zn, Pb, Cu and Ni carbonates, lead sulfate and lead chloride in water-insoluble salt systems. The resulting FS@IDA-Cd and FS@IDA-Pb chelates could be magnetically separated, resulting in removal rates of approximately 84.9% and 72.2% for Cd and Pb, respectively. FS@IDA could not remove the residual heavy metals and those bound to organic matter in the soil. FS@IDA did not significantly alter the chemical composition of the soil, and it allowed for fast chelating capture, simple magnetic separation and facilitated heavy metal elution. FS@IDA could also be easily prepared and reprocessed. PMID:26878770

Chelating capture and magnetic removal of non-magnetic heavy metal substances from soil.

PubMed

Fan, Liren; Song, Jiqing; Bai, Wenbo; Wang, Shengping; Zeng, Ming; Li, Xiaoming; Zhou, Yang; Li, Haifeng; Lu, Haiwei

2016-02-16

A soil remediation method based on magnetic beneficiation is reported. A new magnetic solid chelator powder, FS@IDA (core-shell Fe3O4@SiO2 nanoparticles coated with iminodiacetic acid chelators), was used as a reactive magnetic carrier to selectively capture non-magnetic heavy metals in soil by chelation and removal by magnetic separation. FS@IDA was prepared via inorganic-organic and organic synthesis reactions that generated chelating groups on the surface of magnetic, multi-core, core-shell Fe3O4@SiO2 (FS) nanoparticles. These reactions used a silane coupling agent and sodium chloroacetate. The results show that FS@IDA could chelate the heavy metal component of Cd, Zn, Pb, Cu and Ni carbonates, lead sulfate and lead chloride in water-insoluble salt systems. The resulting FS@IDA-Cd and FS@IDA-Pb chelates could be magnetically separated, resulting in removal rates of approximately 84.9% and 72.2% for Cd and Pb, respectively. FS@IDA could not remove the residual heavy metals and those bound to organic matter in the soil. FS@IDA did not significantly alter the chemical composition of the soil, and it allowed for fast chelating capture, simple magnetic separation and facilitated heavy metal elution. FS@IDA could also be easily prepared and reprocessed.

Chelating capture and magnetic removal of non-magnetic heavy metal substances from soil

NASA Astrophysics Data System (ADS)

Fan, Liren; Song, Jiqing; Bai, Wenbo; Wang, Shengping; Zeng, Ming; Li, Xiaoming; Zhou, Yang; Li, Haifeng; Lu, Haiwei

2016-02-01

A soil remediation method based on magnetic beneficiation is reported. A new magnetic solid chelator powder, FS@IDA (core-shell Fe3O4@SiO2 nanoparticles coated with iminodiacetic acid chelators), was used as a reactive magnetic carrier to selectively capture non-magnetic heavy metals in soil by chelation and removal by magnetic separation. FS@IDA was prepared via inorganic-organic and organic synthesis reactions that generated chelating groups on the surface of magnetic, multi-core, core-shell Fe3O4@SiO2 (FS) nanoparticles. These reactions used a silane coupling agent and sodium chloroacetate. The results show that FS@IDA could chelate the heavy metal component of Cd, Zn, Pb, Cu and Ni carbonates, lead sulfate and lead chloride in water-insoluble salt systems. The resulting FS@IDA-Cd and FS@IDA-Pb chelates could be magnetically separated, resulting in removal rates of approximately 84.9% and 72.2% for Cd and Pb, respectively. FS@IDA could not remove the residual heavy metals and those bound to organic matter in the soil. FS@IDA did not significantly alter the chemical composition of the soil, and it allowed for fast chelating capture, simple magnetic separation and facilitated heavy metal elution. FS@IDA could also be easily prepared and reprocessed.

Synthesis of a novel 'smart' bifunctional chelating agent 1-(2-[beta,D-galactopyranosyloxy]ethyl)-7-(1-carboxy-3-[4-aminophenyl]propyl)-4,10-bis(carboxymethyl)-1,4,7,10-tetraazacyclododecane (Gal-PA-DO3A-NH2) and its Gd(III) complex.

PubMed

Wardle, Nick J; Herlihy, Amy H; So, Po-Wah; Bell, Jimmy D; Bligh, S W Annie

2007-07-15

A new synthetic pathway to 1-(2-[beta,D-galactopyranosyloxy]ethyl)-7-(1-carboxy-3-[4-aminophenyl]propyl)-4,10-bis(carboxymethyl)-1,4,7,10-tetraazacyclododecane (Gal-PA-DO3A-NH2) and 1-(2-[beta,D-galactopyranosyloxy]ethyl)-4,7,10-tris(carboxymethyl)-1, 4,7,10-tetraazacyclododecane (Gal-DO3A) chelating agents was developed involving full hydroxyl- and carboxyl-group protection in precursors to product. Two sequences of cyclen-N-functionalisation were subsequently investigated, one successfully, towards synthesis of the novel 'smart' bifunctional Gal-PA-DO3A-NH2 chelate. The longitudinal proton relaxivities of the neutral [Gd-(Gal-PA-DO3A-NH2)] and [Gd-(Gal-DO3A)] complexes were increased by 28% and 37% in the presence of beta-galactosidase, respectively.

Modeling the chelation of As(III) in lewisite by dithiols using density functional theory and solvent-assisted proton exchange.

PubMed

Harper, Lenora K; Bayse, Craig A

2015-12-01

Dithiols such as British anti-lewisite (BAL, rac-2,3-dimercaptopropanol) are an important class of antidotes for the blister agent lewisite (trans-2-chlorovinyldichloroarsine) and, more generally, are chelating agents for arsenic and other toxic metals. The reaction of the vicinal thiols of BAL with lewisite through the chelation of the As(III) center has been modeled using density functional theory (DFT) and solvent-assisted proton exchange (SAPE), a microsolvation method that uses a network of water molecules to mimic the role of bulk solvent in models of aqueous phase chemical reactions. The small activation barriers for the stepwise SN2-type nucleophilic attack of BAL on lewisite (0.7-4.9kcal/mol) are consistent with the favorable leaving group properties of the chloride and the affinity of As(III) for soft sulfur nucleophiles. Small, but insignificant, differences in activation barriers were found for the initial attack of the primary versus secondary thiol of BAL and the R vs S enantiomer. An examination of the relative stability of various dithiol-lewisite complexes shows that ethanedithiols like BAL form the most favorable chelation complexes because the angles formed in five-membered ring are most consistent with the hybridization of As(III). More obtuse S-As-S angles are required for larger chelate rings, but internal As⋯N or As⋯O interactions can enhance the stability of moderate-sized rings. The low barriers for lewisite detoxification by BAL and the greater stability of the chelation complexes of small dithiols are consistent with the rapid reversal of toxicity demonstrated in previously reported animal models. Copyright © 2015 Elsevier Inc. All rights reserved.

Electromarking solution

DOEpatents

Bullock, Jonathan S.; Harper, William L.; Peck, Charles G.

1976-06-22

This invention is directed to an aqueous halogen-free electromarking solution which possesses the capacity for marking a broad spectrum of metals and alloys selected from different classes. The aqueous solution comprises basically the nitrate salt of an amphoteric metal, a chelating agent, and a corrosion-inhibiting agent.

Luminescent Properties of Eu(III) Chelates on Metal Nanorods

PubMed Central

Zhang, Jian; Fu, Yi; Ray, Krishanu; Wang, Yuan; Lakowicz, Joseph. R.

2013-01-01

In this article, we report the change of optical properties for europium chelates on silver nanorods by near-field interactions. The silver rods were fabricated in a seed-growth method followed by depositing thin layers of silica on the surfaces. The europium chelates were physically absorbed in the silica layers on the silver rods. The silver rods were observed to exhibit two plasmon absorption bands from longitudinal and transverse directions, respectively, centered at 394 and 675 nm, close to absorption and emission bands from the Eu(III) chelates. As a result, the immobilized Eu(III) chelates on the silver rods should have strong interactions with the silver nanorods and lead to greatly improved optical properties. The Eu–Ag rod complexes were observed to have enhanced emission intensity up to 240-fold in comparison with the Eu(III) chelates in the metal-free silica templates. This enhancement is much larger than the value for the Eu(III) chelates on the gold rods or silver spheres indicating the presence of stronger interactions for the Eu(III) chelates with the silver rods. The interactions of Eu(III) chelates with the silver rods were also proven by extremely reduced lifetime. Moreover, the Eu–Ag rod complexes exhibited a polarized emission, which was also due to strong interactions of the Eu(III) chelates with the silver rods. All of these features may promise that the Eu(III)–Ag rod complexes have great potential for use as fluorescence imaging agents in biological assays. PMID:24363816

Biodegradable gadolinium-chelated cationic poly(urethane amide) copolymers for gene transfection and magnetic resonance imaging.

PubMed

Gao, Xiaolong; Wang, Gangmin; Shi, Ting; Shao, Zhihong; Zhao, Peng; Shi, Donglu; Ren, Jie; Lin, Chao; Wang, Peijun

2016-08-01

Theranostic nano-polyplexes containing gene and imaging agents hold a great promise for tumor diagnosis and therapy. In this work, we develop a group of new gadolinium (Gd)-chelated cationic poly(urethane amide)s for gene delivery and T1-weighted magnetic resonance (MR) imaging. Cationic poly(urethane amide)s (denoted as CPUAs) having multiple disulfide bonds, urethane and amide linkages were synthesized by stepwise polycondensation reaction between 1,4-bis(3-aminopropyl)piperazine and a mixture of di(4-nitrophenyl)-2, 2'-dithiodiethanocarbonate (DTDE-PNC) and diethylenetriaminepentaacetic acid (DTPA) dianhydride at varied molar ratios. Then, Gd-chelated CPUAs (denoted as GdCPUAs) were produced by chelating Gd(III) ions with DTPA residues of CPUAs. These GdCPUAs could condense gene into nanosized and positively-charged polyplexes in a physiological condition and, however, liberated gene in an intracellular reductive environment. In vitro transfection experiments revealed that the GdCPUA at a DTDE-PNC/DTPA residue molar ratio of 85/15 induced the highest transfection efficiency in different cancer cells. This efficiency was higher than that yielded with 25kDa branched polyethylenimine as a positive control. GdCPUAs and their polyplexes exhibited low cytotoxicity when an optimal transfection activity was detected. Moreover, GdCPUAs may serve as contrast agents for T1-weighted magnetic resonance imaging. The results of this work indicate that biodegradable Gd-chelated cationic poly(urethane amide) copolymers have high potential for tumor theranostics. Copyright © 2016 Elsevier B.V. All rights reserved.

Monooxorhenium(V) complexes with 222-N2S2 MAMA ligands for bifunctional chelator agents: Syntheses and preliminary in vivo evaluation

PubMed Central

Demoin, Dustin Wayne; Dame, Ashley N.; Minard, William D.; Gallazzi, Fabio; Seickman, Gary L.; Rold, Tammy L.; Bernskoetter, Nicole; Fassbender, Michael E.; Hoffman, Timothy J.; Deakyne, Carol A.; Jurisson, Silvia S.

2016-01-01

Introduction Targeted radiotherapy using the bifunctional chelate approach with 186/188Re(V) is challenging because of the susceptibility of monooxorhenium(V)-based complexes to oxidize in vivo at high dilution. A monoamine-monoamide dithiol (MAMA)-based bifunctional chelating agent was evaluated with both rhenium and technetium to determine its utility for in vivo applications. Methods A 222-MAMA chelator, 222-MAMA(N-6-Ahx-OEt) bifunctional chelator, and 222- MAMA(N-6-Ahx-BBN(7-14)NH2) were synthesized, complexed with rhenium, radiolabeled with 99mTc and 186Re (carrier added and no carrier added), and evaluated in initial biological distribution studies. Results An IC50 value of 2.0 ± 0.7 nM for natReO-222-MAMA(N-6-Ahx-BBN(7-14)NH2) compared to [125I]-Tyr4-BBN(NH2) was determined through competitive cell binding assays with PC-3 tumor cells. In vivo evaluation of the no-carrier added 99mTc-222-N2S2(N-6-Ahx-BBN(7-14)NH2) complex showed little gastric uptake and blockable pancreatic uptake in normal mice. Conclusions The 186ReO-222-N2S2(N-6-Ahx-BBN(7-14)NH2) complex showed stability in biological media, which indicates that the 222-N2S2 chelator is appropriate for chelating 186/188Re in radiopharmaceuticals involving peptides. Additionally, the in vitro cell studies showed that the ReO-222-N2S2(N-6-Ahx-BBN(7-14)NH2) complex (macroscopically) bound to PC3-tumor cell surface receptors with high affinity. The 99mTc analog was stable in vivo and exhibited pancreatic uptake in mice that was blockable, indicating BB2r targeting. PMID:27694058

Heavy metal displacement in chelate-irrigated soil during phytoremediation

NASA Astrophysics Data System (ADS)

Madrid, F.; Liphadzi, M. S.; Kirkham, M. B.

2003-03-01

Heavy metals in wastewater sewage sludge (biosolids), applied to land, contaminate soils. Phytoremediation, the use of plants to clean up toxic heavy metals, might remove them. Chelating agents are added to soil to solubilize the metals for enhanced phytoextraction. Yet no studies follow the displacement and leaching of heavy metals in soil with and without roots following solubilization with chelates. The objective of this work was to determine the mobility of heavy metals in biosolids applied to the surface of soil columns (76 cm long; 17 cm diam.) with or without plants (barley; Hordeum vulgare L.). Three weeks after barley was planted, all columns were irrigated with the disodium salt of the chelating agent, EDTA (ethylenediamine tetraacetic acid) (0.5 g/kg soil). Drainage water, soil, and plants were analyzed for heavy metals (Cd, Cu, Fe, Mn, Ni, Pb, Zn). Total concentrations of the heavy metals in all columns at the end of the experiment generally were lower in the top 30 cm of soil with EDTA than without EDTA. The chelate increased concentrations of heavy metals in shoots. With or without plants, the EDTA mobilized Cd, Fe, Mn, Ni, Pb, and Zn, which leached to drainage water. Drainage water from columns without EDTA had concentrations of these heavy metals below detection limits. Only Cu did not leach in the presence of EDTA. Even though roots retarded the movement of Cd, Fe, Mn, Ni, Pb, and Zn through the EDTA-treated soil from 1 d (Cd) to 5 d (Fe), the drainage water from columns with EDTA had concentrations of Cd, Fe, Mn, and Pb that exceeded drinking water standards by 1.3, 500, 620, and 8.6 times, respectively. Because the chelate rendered Cd, Fe, Mn, Ni, Pb, and Zn mobile, it is suggested that the theory for leaching of soluble salts, put forward by Nielsen and associates in 1965, could be applied to control movement of the heavy metals for maximum uptake during chelate-assisted phytoremediation.

1,10-phenanthroline inhibits the metallopeptidase secreted by Phialophora verrucosa and modulates its growth, morphology and differentiation.

PubMed

Granato, Marcela Queiroz; Massapust, Priscila de Araújo; Rozental, Sonia; Alviano, Celuta Sales; dos Santos, André Luis Souza; Kneipp, Lucimar Ferreira

2015-04-01

Phialophora verrucosa is one of the etiologic agents of chromoblastomycosis, a fungal infection that affects cutaneous and subcutaneous tissues. This disease is chronic, recurrent and difficult to treat. Several studies have shown that secreted peptidases by fungi are associated with important pathophysiological processes. Herein, we have identified and partially characterized the peptidase activity secreted by P. verrucosa conidial cells. Using human serum albumin as substrate, the best hydrolysis profile was detected at extreme acidic pH (3.0) and at 37 °C. The enzymatic activity was completely blocked by classical metallopeptidase inhibitors/chelating agents as 1,10-phenanthroline and EGTA. Zinc ions stimulated the metallo-type peptidase activity in a dose-dependent manner. Several proteinaceous substrates were cleaved, in different extension, by the P. verrucosa metallopeptidase activity, including immunoglobulin G, fibrinogen, collagen types I and IV, fibronectin, laminin and keratin; however, mucin and hemoglobin were not susceptible to proteolysis. As metallopeptidases participate in different cellular metabolic pathways in fungal cells, we also tested the influence of 1,10-phenanthroline and EGTA on P. verrucosa development. Contrarily to EGTA, 1,10-phenanthroline inhibited the fungal viability (MIC 0.8 µg/ml), showing fungistatic effect, and induced profound morphological alterations as visualized by transmission electron microscopy. In addition, 1,10-phenanthroline arrested the filamentation process in P. verrucosa. Our results corroborate the supposition that metallopeptidase inhibitors/chelating agents have potential to control crucial biological events in fungal agents of chromoblastomycosis.

Chelate-Assisted Heavy Metal Movement Through the Root Zone

NASA Astrophysics Data System (ADS)

Kirkham, M.; Madrid, F.; Liphadzi, M. S.

2001-12-01

Chelating agents are added to soil as a means to mobilize heavy metals for plant uptake during phytoremediation. Yet almost no studies follow the displacement of heavy metals through the vadose zone following solubilization with chelating agents. The objective of this work was to determine the movement of heavy metals through the soil profile and their absorption by barley (Hordeum vulgare L.) in a soil amended with biosolids and in the presence of a chelating agent (EDTA). Twelve columns 75 cm in height and 17 in diameter were packed with a Haynie very fine sandy loam (coarse-silty, mixed, calcareous, mesic Mollic Udifluvents) and watered with liquid biosolids applied at the surface at a rate of 120 kg N/ha. Three weeks after plants germinated, soil was irrigated with a solution of the disodium salt of EDTA added at a rate of 0.5 g/kg soil. Four treatments were imposed: columns with no plants and no EDTA; columns with no plants plus EDTA; columns with plants and no EDTA; and columns with plants and EDTA. Columns were watered intensively for 35 days until two pore volumes of water had been added, and the leachates were collected daily. With or without plants, columns with EDTA had lower total concentrations of Cu, Zn, Cd, Ni, and Pb in the surface 20 cm than columns without EDTA. Concentrations of the heavy metals in this layer were not afffected by the presence of roots. Iron in leachate was followed as an indicator metal for movement to groundwater. No iron appeared in the leachate without EDTA, either in the columns with plants or without plants. The peak concentration of iron in the leachate occurred three days earlier in the columns without plants and EDTA compared to the columns with plants and EDTA. The results indicated the importance of vegetation on retarding heavy metal leaching to groundwater during chelate-facilitated phytoremediation.

Low-Molecular-Weight Iron Chelates May Be an Alternative to Gadolinium-based Contrast Agents for T1-weighted Contrast-enhanced MR Imaging.

PubMed

Boehm-Sturm, Philipp; Haeckel, Akvile; Hauptmann, Ralf; Mueller, Susanne; Kuhl, Christiane K; Schellenberger, Eyk A

2018-02-01

Purpose To synthesize two low-molecular-weight iron chelates and compare their T1 contrast effects with those of a commercial gadolinium-based contrast agent for their applicability in dynamic contrast material-enhanced (DCE) magnetic resonance (MR) imaging. Materials and Methods The animal experiments were approved by the local ethics committee. Two previously described iron (Fe) chelates of pentetic acid (Fe-DTPA) and of trans-cyclohexane diamine tetraacetic acid (Fe-tCDTA) were synthesized with stability constants several orders of magnitude higher than those of gadolinium-based contrast agents. The T1 contrast effects of the two chelates were compared with those of gadopentetate dimeglumine in blood serum phantoms at 1.5 T, 3 T, and 7 T. For in vivo studies, a human breast cancer cell line (MDA-231) was implanted in five mice per group. The dynamic contrast effects of the chelates were compared by performing DCE MR imaging with intravenous application of Fe-DTPA or Fe-tCDTA on day 1 and DCE MR imaging in the same tumors with gadopentetate dimeglumine on day 2. Quantitative DCE maps were generated with software and were compared by means of a one-tailed Pearson correlation test. Results Relaxivities in serum (0.94 T at room temperature) of Fe-tCDTA (r1 = 2.2 mmol -1 · sec -1 , r2 = 2.5 mmol -1 · sec -1 ) and Fe-DTPA (r1 = 0.9 mmol -1 · sec -1 , r2 = 0.9 mmol -1 · sec -1 ) were approximately twofold and fivefold lower, respectively, compared with those of gadopentetate dimeglumine (r1 = 4.1 mmol -1 · sec -1 , r2 = 4.8 mmol -1 · sec -1 ). Used at moderately higher concentrations, however, iron chelates generated similar contrast effects at T1-weighted MR imaging in vitro in serum, in vivo in blood, and for DCE MR imaging of breast cancer xenografts. The volume transfer constant values for Fe-DTPA and Fe-tCDTA in the same tumors correlated well with those observed for gadopentetate dimeglumine (Fe-tCDTA Pearson R, 0.99; P = .0003; Fe-DTPA Pearson R, 0.97; P = .003). Conclusion Iron-based contrast agents are promising as alternatives for contrast enhancement at T1-weighted MR imaging and have the potential to contribute to the safety of MR imaging. © RSNA, 2017 Online supplemental material is available for this article.

Antibacterial and antibiofilm effects of iron chelators against Prevotella intermedia.

PubMed

Moon, Ji-Hoi; Kim, Cheul; Lee, Hee-Su; Kim, Sung-Woon; Lee, Jin-Yong

2013-09-01

Prevotella intermedia, a major periodontopathogen, has been shown to be resistant to many antibiotics. In the present study, we examined the effect of the FDA-approved iron chelators deferoxamine (DFO) and deferasirox (DFRA) against planktonic and biofilm cells of P. intermedia in order to evaluate the possibility of using these iron chelators as alternative control agents against P. intermedia. DFRA showed strong antimicrobial activity (MIC and MBC values of 0.16 mg ml(-1)) against planktonic P. intermedia. At subMICs, DFRA partially inhibited the bacterial growth and considerably prolonged the bacterial doubling time. DFO was unable to completely inhibit the bacterial growth in the concentration range tested and was not bactericidal. Crystal violet binding assay for the assessment of biofilm formation by P. intermedia showed that DFRA significantly decreased the biofilm-forming activity as well as the biofilm formation, while DFO was less effective. DFRA was chosen for further study. In the ATP-bioluminescent assay, which reflects viable cell counts, subMICs of DFRA significantly decreased the bioactivity of biofilms in a concentration-dependent manner. Under the scanning electron microscope, P. intermedia cells in DFRA-treated biofilm were significantly elongated compared to those in untreated biofilm. Further experiments are necessary to show that iron chelators may be used as a therapeutic agent for periodontal disease.

INCREASE IN THE CHEMOTHERAPEUTIC COEFFICIENT OF MECHLORETHAMINE BY THE ACTION OF THE RADIOPROTECTIVE AGENT SODIUM DIETHYLDITHIOCARBAMATE (in Italian)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cima, L; Pozza, F

1963-01-01

In mice of the SMZ strain the protective effect of various kinds of radioprotectant agents against the toxicity of the alkylating agent mechiorethamine (HN2) was investigated. HN2 was injected subcutaneously in doses of 6 mg/kg, corresponding to the LD/sub 99/6/. The most effective protective agent tested was the chelating agent Na diethyldithiocarbamate (DEDTC), which when injected intraperitoneally in doses of 335 mg/kg raised the 4-day survival rate to 90% from a control value of 20%. Other chelating agents were less effective, showing the specific action of the dithiocarbamate anion: tetraethylthiuram disulfide (disulfiram), 2-guanidinothiazolidone, and diethylamine. Moderately effective against the toxicitymore » of HN2 were (in decreasing order): reserpine, chlorpromazine, propylene glycol, malononitrile, glutathione, cysteamine, oxytocin, and Na ethylenediaminetatraacetate. Tryptamine was ineffective and cysteine augmented the toxicity of HN2. DEDTC did not modify the carcinostatic effect of HN2 against Ehrlich ascites tumor and thus, by markedly reducing the toxicity of HN2, enhances the therapeutic index of HN2 3 fold. The protective effect of DEDTC and the other radioprotectant agents against HN2 suggest that alkylating agents and ionizing radiation have analogous effects on tissue constituents. (H.H.D.)« less

Management of transfusional iron overload – differential properties and efficacy of iron chelating agents

PubMed Central

Kwiatkowski, Janet L

2011-01-01

Regular red cell transfusion therapy ameliorates disease-related morbidity and can be lifesaving in patients with various hematological disorders. Transfusion therapy, however, causes progressive iron loading, which, if untreated, results in endocrinopathies, cardiac arrhythmias and congestive heart failure, hepatic fibrosis, and premature death. Iron chelation therapy is used to prevent iron loading, remove excess accumulated iron, detoxify iron, and reverse some of the iron-related complications. Three chelators have undergone extensive testing to date: deferoxamine, deferasirox, and deferiprone (although the latter drug is not currently licensed for use in North America where it is available only through compassionate use programs and research protocols). These chelators differ in their modes of administration, pharmacokinetics, efficacy with regard to organ-specific iron removal, and adverse-effect profiles. These differential properties influence acceptability, tolerability and adherence to therapy, and, ultimately, the effectiveness of treatment. Chelation therapy, therefore, must be individualized, taking into account patient preferences, toxicities, ongoing transfusional iron intake, and the degree of cardiac and hepatic iron loading. PMID:22287873

Management of transfusional iron overload - differential properties and efficacy of iron chelating agents.

PubMed

Kwiatkowski, Janet L

2011-01-01

Regular red cell transfusion therapy ameliorates disease-related morbidity and can be lifesaving in patients with various hematological disorders. Transfusion therapy, however, causes progressive iron loading, which, if untreated, results in endocrinopathies, cardiac arrhythmias and congestive heart failure, hepatic fibrosis, and premature death. Iron chelation therapy is used to prevent iron loading, remove excess accumulated iron, detoxify iron, and reverse some of the iron-related complications. Three chelators have undergone extensive testing to date: deferoxamine, deferasirox, and deferiprone (although the latter drug is not currently licensed for use in North America where it is available only through compassionate use programs and research protocols). These chelators differ in their modes of administration, pharmacokinetics, efficacy with regard to organ-specific iron removal, and adverse-effect profiles. These differential properties influence acceptability, tolerability and adherence to therapy, and, ultimately, the effectiveness of treatment. Chelation therapy, therefore, must be individualized, taking into account patient preferences, toxicities, ongoing transfusional iron intake, and the degree of cardiac and hepatic iron loading.

Chemistry of carcinogenic metals.

PubMed Central

Martell, A E

1981-01-01

The periodic distribution of known and suspected carcinogenic metal ions is described, and the chemical behavior of various types of metal ions is explained in terms of the general theory of hard and soft acids and bases. The chelate effect is elucidated, and the relatively high stability of metal chelates in very dilute solutions is discussed. The concepts employed for the chelate effect are extended to explain the high stabilities of macrocyclic and cryptate complexes. Procedures for the use of equilibrium data to determine the speciation of metal ions and complexes under varying solution conditions are described. Methods for assessing the interferences by hydrogen ion, competing metal ions, hydrolysis, and precipitation are explained, and are applied to systems containing iron(III) chelates of fourteen chelating agents designed for effective binding of the ferric ion. The donor groups available for the building up of multidentate ligands are presented, and the ways in which they may be combined to achieve high affinity and selectivity for certain types of metal ions are explained. PMID:6791915

Thermodynamic stability and kinetic inertness of a Gd-DTPA bisamide complex grafted onto gold nanoparticles.

PubMed

Mogilireddy, Vijetha; Déchamps-Olivier, Isabelle; Alric, Christophe; Laurent, Gautier; Laurent, Sophie; Vander Elst, Luce; Muller, Robert; Bazzi, Rana; Roux, Stéphane; Tillement, Olivier; Chuburu, Françoise

2015-01-01

Gold nanoparticles coated by gadolinium (III) chelates (Au@DTDTPA) where DTDTPA is a dithiolated bisamide derivative of diethylenetriamine-N,N,N',N'',N''-pentaacetic acid (DTPA), constituted contrast agents for both X-ray computed tomography and magnetic resonance imaging. In an MRI context, highly stable Gd(3+) complexes are needed for in vivo applications. Thus, knowledge of the thermodynamic stability and kinetic inertness of these chelates, when grafted onto gold nanoparticles, is crucial since bisamide DTPA chelates are usually less suited for Gd(3+) coordination than DTPA. Therefore, these parameters were evaluated by means of potentiometric titrations and relaxivity measurements. The results showed that, when the chelates were grafted onto the nanoparticle, not only their thermodynamic stability but also their kinetic inertness were improved. These positive effects were correlated to the chelate packing at the nanoparticle surface that stabilized the corresponding Gd(3+) complexes and greatly enhanced their kinetic inertness. Copyright © 2014 John Wiley & Sons, Ltd.

Performance of Nonmigratory Iron Chelating Active Packaging Materials in Viscous Model Food Systems.

PubMed

Roman, Maxine J; Decker, Eric A; Goddard, Julie M

2015-09-01

Many packaged food products undergo quality deterioration due to iron promoted oxidative reactions. Recently, we have developed a nonmigratory iron chelating active packaging material that represents a novel approach to inhibit oxidation of foods while addressing consumer demands for "cleanˮ labels. A challenge to the field of nonmigratory active packaging is ensuring that surface-immobilized active agents retain activity in a true food system despite diffusional limitations. Yet, the relationship between food viscosity and nonmigratory active packaging activity retention has never been characterized. The objective of this study was to investigate the influence of food viscosity on iron chelation by a nonmigratory iron chelating active packaging material. Methyl cellulose was added to aqueous buffered iron solutions to yield model systems with viscosities ranging from ∼1 to ∼10(5)  mPa·s, representing viscosities ranging from beverage to mayonnaise. Iron chelation was quantified by material-bound iron content using colorimetry and inductively coupled plasma-optical emission spectrometry (ICP-OES).  Maximum iron chelation was reached in solutions up to viscosity ∼10(2)  mPa·s. In more viscous solutions (up to ∼10(4)  mPa·s), there was a significant decrease in iron chelating capacity (P < 0.05). However, materials still retained at least 76% iron chelating capacity. Additionally, the influence of different food hydrocolloids on the performance of nonmigratory iron chelating active packaging was characterized. Methyl cellulose and carrageenan did not compete with the material for specific iron chelation (P > 0.05). Materials retained 32% to 45% chelating capacity when in contact with competitively chelating hydrocolloids guar gum, locust bean gum, and xanthan gum. This work demonstrates the potential application of nonmigratory iron chelating active packaging in liquid and semi-liquid foods to allow for the removal of synthetic chelators, while maintaining food quality. © 2015 Institute of Food Technologists®

Comparative leaching of six toxic metals from raw and chemically stabilized MSWI fly ash using citric acid.

PubMed

Wang, Huawei; Fan, Xinxiu; Wang, Ya-Nan; Li, Weihua; Sun, Yingjie; Zhan, Meili; Wu, Guizhi

2018-02-15

The leaching behavior of six typical toxic metals (Pb, Zn, Cr, Cd, Cu and Ni) from raw and chemically stabilized (phosphate and chelating agent) municipal solid waste incineration (MSWI) fly ash were investigated using citric acid. Leaching tests indicated that phosphate stabilization can effectively decrease the leaching of Zn, Cd and Cr; whereas chelating agent stabilization shows a strong ability to lower the release of Pb, Cd and Cu, but instead increases the solubility of Zn and Cr at low pH conditions. Sequential extraction results suggested that the leaching of Pb, Zn and Cd in both the stabilized MSWI fly ash samples led to the decrease in Fe/Mn oxide fraction and the increase in exchangeable and carbonate fractions. The leaching of Cr was due to the decrease in exchangeable, carbonate and Fe/Mn oxide fractions in phosphate-stabilized and chelating agent-stabilized MSWI fly ash. The leaching of Cu in both stabilized MSWI fly ash was greatly ascribed to the decrease in Fe/Mn oxide and oxidisable fractions. Moreover, predicted curves by geochemical model indicated that both stabilized MSWI fly ash have the risk of releasing toxic metals under strong acid environment. Copyright © 2017 Elsevier Ltd. All rights reserved.

A gadolinium(III) complex of a carboxylic-phosphorus acid derivative of diethylenetriamine covalently bound to inulin, a potential macromolecular MRI contrast agent.

PubMed

Lebdusková, Petra; Kotek, Jan; Hermann, Petr; Vander Elst, Luce; Muller, Robert N; Lukes, Ivan; Peters, Joop A

2004-01-01

A novel conjugate of a polysaccharide and a Gd(III) chelate with potential as contrast agent for magnetic resonance imaging (MRI) was synthesized. The structure of the chelate was derived from H5DTPA by replacing the central pendant arm by a phosphinic acid functional group, which was covalently bound to the polysaccharide inulin. On the average, each monosaccharide unit of the inulin was attached to approximately one (0.9) chelate moiety. The average molecular weight is 23110 and the average number of Gd3+ ions per molecule is 24. The ligand binds the Gd3+ ion in an octadentate fashion via three nitrogen atoms, four carboxylate oxygen atoms, and one P-O oxygen atom, and its first coordination sphere is completed by a water molecule. This compound shows promising properties for application as a contrast agent for MRI thanks to a favorable residence lifetime of this water molecule (170 ns at 298 K), a relatively long rotational correlation time (866 ps at 298 K), and the presence of two water molecules in the second coordination sphere of the Gd3+ ion. Furthermore, its stability toward transmetalation with Zn(II) is as high as that of the clinically used [Gd(DTPA)(H2O)]2-.

Carbon Monoxide-Reacting Pigment from Desulfotomaculum nigrificans and Its Possible Relevance to Sulfite Reduction

PubMed Central

Trudinger, P. A.

1970-01-01

The separation of an autoxidizable brown pigment, P582, from Desulfotomaculum nigrificans is described. It reacted with Na2S2O4 and was characterized by absorption maxima in the oxidized state at 392, 582, and 700 nm. In the presence of Na2S2O4, P582 formed complexes with CO and, under alkaline conditions, pyridine. There was no reaction with cyanide. The molecular weight of P582 was approximately 145,000, and the purest preparations contained Fe, Zn, and acid-labile sulfide but not Cu, Mo, or Mn. Preparations of P582 catalyzed the reduced methyl viologen (MVH)-linked reduction of sulfite, hydroxylamine, and nitrite but not of sulfate, thiosulfate, or nitrate. Reduced pyridine nucleotides did not substitute for MVH. A major product of the MVH-sulfite reaction was sulfide. CO partially inhibited the enzymatic activities. Sulfite, hydroxylamine, and nitrite and CO caused changes in the spectrum of Na2S2O4-reduced P582. Fe2+-chelating reagents reacted with part of the Fe of P582 and caused partial losses of labile sulfide and enzymatic activity. The spectral and CO-reacting properties of P582 were, however, unaffected by chelating agents. The reaction between P582 and chelating agents was stimulated by reducing agents. PMID:5473884

Synergetic effect of chelating agent and nonionic surfactant for benzotriazole removal on post Cu-CMP cleaning

NASA Astrophysics Data System (ADS)

Yanlei, Li; Yuling, Liu; Chenwei, Wang; Yue, Li

2016-08-01

The cleaning of copper interconnects after chemical mechanical planarization (CMP) process is a critical step in integrated circuits (ICs) fabrication. Benzotriazole (BTA), which is used as corrosion inhibitor in the copper CMP slurry, is the primary source for the formation of organic contaminants. The presence of BTA can degrade the electrical properties and reliability of ICs which needs to be removed by using an effective cleaning solution. In this paper, an alkaline cleaning solution was proposed. The alkaline cleaning solution studied in this work consists of a chelating agent and a nonionic surfactant. The removal of BTA was characterized by contact angle measurements and potentiodynamic polarization studies. The cleaning properties of the proposed cleaning solution on a 300 mm copper patterned wafer were also quantified, total defect counts after cleaning was studied, scanning electron microscopy (SEM) review was used to identify types of BTA to confirm the ability of cleaning solution for BTA removal. All the results reveal that the chelating agent can effectively remove the BTA residual, nonionic surfactant can further improve the performance. Project supported by the Natural Science Foundation of Hebei Province, China (No. F2015202267) and the Scientific Innovation Grant for Excellent Young Scientists of Hebei University of Technology (No. 2015007).

Color stabilization of porcine hemoglobin during spray-drying and powder storage by combining chelating and reducing agents.

PubMed

Salvador, P; Toldrà, M; Parés, D; Carretero, C; Saguer, E

2009-10-01

This work focuses on the effects of adding a chelating agent - such as nicotinic acid (NA, 2% w/v) or nicotinamide (Nam, 2.5% w/v) - along with glucose as a reducing agent (G, 10% w/v) to fresh porcine hemoglobin in order to stabilize its red color during spray-drying and powder storage at room temperature. Correlations between the CIELAB color parameters and the relative percentages of the different hemoglobin derivatives (liganded and deliganded ferrohemoglobin, and methemoglobin) were analyzed. The results indicate that, although little effects could be observed for any of the combined treatments on fresh hemoglobin, they were effective against pigment autoxidation during dehydration and subsequent storage. From the results, it can also be concluded that glucose was the main contributor to the color stabilization of the hemoglobin powder, probably due to its high water retention capacity.

Situ formation of apatite for sequestering radionuclides and heavy metals

DOEpatents

Moore, Robert C.

2003-07-15

Methods for in situ formation in soil of a permeable reactive barrier or zone comprising a phosphate precipitate, such as apatite or hydroxyapatite, which is capable of selectively trapping and removing radionuclides and heavy metal contaminants from the soil, while allowing water or other compounds to pass through. A preparation of a phosphate reagent and a chelated calcium reagent is mixed aboveground and injected into the soil. Subsequently, the chelated calcium reagent biodegrades and slowly releases free calcium. The free calcium reacts with the phosphate reagent to form a phosphate precipitate. Under the proper chemical conditions, apatite or hydroxyapatite can form. Radionuclide and heavy metal contaminants, including lead, strontium, lanthanides, and uranium are then selectively sequestered by sorbing them onto the phosphate precipitate. A reducing agent can be added for reduction and selective sequestration of technetium or selenium contaminants.

Drawbacks of Dialysis Procedures for Removal of EDTA

PubMed Central

Mónico, Andreia; Martínez-Senra, Eva; Cañada, F. Javier; Zorrilla, Silvia

2017-01-01

Ethylenediaminetetraacetic acid (EDTA) is a chelating agent commonly used in protein purification, both to eliminate contaminating divalent cations and to inhibit protease activity. For a number of subsequent applications EDTA needs to be exhaustively removed. Most purification methods rely in extensive dialysis and/or gel filtration in order to exchange or remove protein buffer components, including metal chelators. We report here that dialysis protocols, even as extensive as those typically employed for protein refolding, may not effectively remove EDTA, which is reduced only by approximately two-fold and it also persists after spin-column gel filtration, as determined by NMR and by colorimetric methods. Remarkably, the most efficient removal was achieved by ultrafiltration, after which EDTA became virtually undetectable. These results highlight a potentially widespread source of experimental variability affecting free divalent cation concentrations in protein applications. PMID:28099451

Topical efficacy of dimercapto-chelating agents against lewisite-induced skin lesions in SKH-1 hairless mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mouret, Stéphane, E-mail: stephane.mouret@irba.fr; Wartelle, Julien; Emorine, Sandy

2013-10-15

Lewisite is a potent chemical warfare arsenical vesicant that can cause severe skin lesions. Today, lewisite exposure remains possible during demilitarization of old ammunitions and as a result of deliberate use. Although its cutaneous toxicity is not fully elucidated, a specific antidote exists, the British anti-lewisite (BAL, dimercaprol) but it is not without untoward effects. Analogs of BAL, less toxic, have been developed such as meso-2,3-dimercaptosuccinic acid (DMSA) and have been employed for the treatment of heavy metal poisoning. However, efficacy of DMSA against lewisite-induced skin lesions remains to be determined in comparison with BAL. We have thus evaluated inmore » this study the therapeutic efficacy of BAL and DMSA in two administration modes against skin lesions induced by lewisite vapor on SKH-1 hairless mice. Our data demonstrate a strong protective efficacy of topical application of dimercapto-chelating agents in contrast to a subcutaneous administration 1 h after lewisite exposure, with attenuation of wound size, necrosis and impairment of skin barrier function. The histological evaluation also confirms the efficacy of topical application by showing that treatments were effective in reversing lewisite-induced neutrophil infiltration. This protective effect was associated with an epidermal hyperplasia. However, for all the parameters studied, BAL was more effective than DMSA in reducing lewisite-induced skin injury. Together, these findings support the use of a topical form of dimercaprol-chelating agent against lewisite-induced skin lesion within the first hour after exposure to increase the therapeutic management and that BAL, despite its side-effects, should not be abandoned. - Highlights: • Topically applied dimercapto-chelating agents reduce lewisite-induced skin damage. • One topical application of BAL or DMSA is sufficient to reverse lewisite effects. • Topical BAL is more effective than DMSA to counteract lewisite-induced skin damage.« less

Self-assembly of PEGylated tetra-phenylalanine derivatives: structural insights from solution and solid state studies

PubMed Central

Diaferia, Carlo; Mercurio, Flavia Anna; Giannini, Cinzia; Sibillano, Teresa; Morelli, Giancarlo; Leone, Marilisa; Accardo, Antonella

2016-01-01

Water soluble fibers of PEGylated tetra-phenylalanine (F4), chemically modified at the N-terminus with the DOTA chelating agent, have been proposed as innovative contrast agent (CA) in Magnetic Resonance Imaging (MRI) upon complexation of the gadolinium ion. An in-depth structural characterization of PEGylated F4-fibers, in presence (DOTA-L6-F4) and in absence of DOTA (L6-F4), is reported in solution and at the solid state, by a multiplicity of techniques including CD, FTIR, NMR, DLS, WAXS and SAXS. This study aims to better understand how the aggregation process influences the performance of nanostructures as MRI CAs. Critical aggregation concentrations for L6-F4 (43 μM) and DOTA-L6-F4 (75 μM) indicate that self-aggregation process occurs in the same concentration range, independently of the presence of the CA. The driving force for the aggregation is the π-stacking between the side chains of the aromatic framework. CD, FTIR and WAXS measurements indicate an antiparallel β-sheet organization of the monomers in the resulting fibers. Moreover, WAXS and FTIR experiments point out that in solution the nanomaterials retain the same morphology and monomer organizations of the solid state, although the addition of the DOTA chelating agent affects the size and the degree of order of the fibers. PMID:27220817

The bovine immune response to Brucella abortus. II. Elimination of some sporadic serological reactions by chelation of divalent cations.

PubMed Central

Nielsen, K; Samagh, B S; Speckmann, G; Stemshorn, B

1979-01-01

The standard agglutination tests for detecting antibody to Brucella abortus were modified by addition of chelating agents (EDTA and EGTA) to the antigens. Approximately 80% of "singleton" agglutination test reactions, negative on the diagnostic complement fixation test, obtained with cattle sera were eliminated while no decrease in titer was apparent when sera from B. abortus infected or vaccinated cattle were tested. PMID:121242

Flue gas desulfurization/denitrification using metal-chelate additives

DOEpatents

Harkness, John B. L.; Doctor, Richard D.; Wingender, Ronald J.

1986-01-01

A method of simultaneously removing SO.sub.2 and NO from oxygen-containing flue gases resulting from the combustion of carbonaceous material by contacting the flue gas with an aqueous scrubber solution containing an aqueous sulfur dioxide sorbent and an active metal chelating agent which promotes a reaction between dissolved SO.sub.2 and dissolved NO to form hydroxylamine N-sulfonates. The hydroxylamine sulfonates are then separated from the scrubber solution which is recycled.

Molecular Innovations Towards Theranostics of Aggressive Prostate Cancer

DTIC Science & Technology

2013-09-01

14. ABSTRACT: In this project, we propose to develop a new drug delivery vehicle based on dendrimer nanotechnology for personalized medicine. This new...PI’s lab will make dendrimers bearing functional handles to conjugate with chelating agents provided by the Initiating PI’s lab for PET imaging and...has designed and synthesized the proposed bifunctional chelator scaffold system, CB-TE2A(tBu)2-N3 for the further construction of dendrimer -based

Gadolinium-Based Contrast Agents for MR Cancer Imaging

PubMed Central

Zhou, Zhuxian; Lu, Zheng-Rong

2013-01-01

Magnetic resonance imaging (MRI) is a clinical imaging modality effective for anatomical and functional imaging of diseased soft tissues, including solid tumors. MRI contrast agents have been routinely used for detecting tumor at an early stage. Gadolinium based contrast agents are the most commonly used contrast agents in clinical MRI. There have been significant efforts to design and develop novel Gd(III) contrast agents with high relaxivity, low toxicity and specific tumor binding. The relaxivity of the Gd(III) contrast agents can be increased by proper chemical modification. The toxicity of Gd(III) contrast agents can be reduced by increasing the agents’ thermodynamic and kinetic stability, as well as optimizing their pharmacokinetic properties. The increasing knowledge in the field of cancer genomics and biology provides an opportunity for designing tumor-specific contrast agents. Various new Gd(III) chelates have been designed and evaluated in animal models for more effective cancer MRI. This review outlines the design and development, physicochemical properties, and in vivo properties of several classes of Gd(III)-based MR contrast agents for tumor imaging. PMID:23047730

Iron chelation therapy of transfusion-dependent β-thalassemia during pregnancy in the era of novel drugs: is deferasirox toxic?

PubMed

Diamantidis, Michael D; Neokleous, Nikolaos; Agapidou, Aleka; Vetsiou, Evaggelia; Manafas, Achilles; Fotiou, Paraskevi; Vlachaki, Efthymia

2016-05-01

The life expectancy of thalassemic patients has increased, and now approaches that of healthy individuals, thanks to improved treatment regimens. However, pregnancy in women with β-Thalassemia Μajor remains a challenging condition. Recent advances in managing this haemoglobinopathy offer the potential for safe pregnancies with favorable outcome. However, clinical data regarding the use of chelation therapy during pregnancy are limited, and it is unclear whether these agents impose any risk to the developing fetus. Successful pregnancies following unintentional treatment with deferoxamine or deferasirox have rarely been reported. Generally, chelators are not recommended during pregnancy. Regarding the new oral chelators, data on fetotoxicity are lacking. In the present study, we describe the evolution and successful outcome of nine pregnancies in six Greek thalassemic women who received deferasirox inadvertently during early pregnancy, and review the literature regarding fetal anomalies due to chelators. Use of chelation before embarking upon a non-programmed pregnancy remains a difficult and unresolved question. In our study, chelation treatment during pregnancy did not prevent the delivery of healthy children. Nonetheless, the use of deferasirox is contraindicated in pregnant women, based on the product label. Deferasirox should only be used during pregnancy if the potential benefit outweighs the potential fetal risk.

Bioinspired Interfacial Chelating-like Reinforcement Strategy toward Mechanically Enhanced Lamellar Materials.

PubMed

Chen, Ke; Zhang, Shuhao; Li, Anran; Tang, Xuke; Li, Lidong; Guo, Lin

2018-05-22

Many biological organisms usually derived from the ordered assembly of heterogeneous, hierarchical inorganic/organic constituents exhibit outstanding mechanical integration, but have proven to be difficult to produce the combination of excellent mechanical properties, such as strength, toughness, and light weight, by merely mimicking their component and structural characteristics. Herein, inspired by biologically strong chelating interactions of phytic acid (PA) or IP6 in many biomaterials, we present a biologically interfacial chelating-like reinforcement (BICR) strategy for fabrication of a highly dense ordered "brick-and-mortar" microstructure by incorporating tiny amounts of a natural chelating agent ( e. g., PA) into the interface or the interlamination of a material ( e. g., graphene oxide (GO)), which shows joint improvement in hardness (∼41.0%), strength (∼124.1%), maximum Young's modulus (∼134.7%), and toughness (∼118.5%) in the natural environment. Besides, for different composite matrix systems and artificial chelating agents, the BICR strategy has been proven successful for greatly enhancing their mechanical properties, which is superior to many previous reinforcing approaches. This point can be mainly attributed to the stronger noncovalent cross-linking interactions such as dense hydrogen bonds between the richer phosphate (hydroxyl) groups on its cyclohexanehexol ring and active sites of GO, giving rise to the larger energy dissipation at its hybrid interfaces. It is also simple and environmentally friendly for further scale-up fabrication and can be readily extended to other material systems, which opens an advanced reinforcement route to construct structural materials with high mechanical performance in an efficient way for practical applications.

Remediation of lead-contaminated soils

DOE Office of Scientific and Technical Information (OSTI.GOV)

Peters, R.W.; Shem, L.

1992-01-01

Excavation and transport of soil contaminated with heavy metals has generally been the standard remediation technique for treatment of heavy-metal-contaminated soils. This approach is not a permanent solution; moreover, off-site shipment and disposal of contaminated soil involves high expense, liability, and appropriate regulatory approval. Recently, a number of other techniques have been investigated for treating such contaminated sites, including flotation, solidification/stabilization, vitrification, and chemical extraction. This paper reports the results of a laboratory investigation determining the efficiency of using chelating agents to extract lead from contaminated soils. Lead concentrations in the soils ranged from 500 to 10,000 mg/kg. Ethylenediaminetetraacetic acidmore » (EDTA) and nitrilotriacetic acid (NTA) were examined for their potential extractive capabilities. Concentrations of the chelating agents ranged from 0.01 to 0.10 M. The pH of the suspensions in which the extractions were performed ranged from 4 to 12. Results showed that the removal of lead using NTA and water was ph-dependent, whereas the removal of lead using EDTA was ph-insensitive. Maximum removals of lead were 68.7%,19.1%, and 7.3% using EDTA, NTA, and water, respectively (as compared with initial lead concentrations).« less

Remediation of lead-contaminated soils

DOE Office of Scientific and Technical Information (OSTI.GOV)

Peters, R.W.; Shem, L.

1992-09-01

Excavation and transport of soil contaminated with heavy metals has generally been the standard remediation technique for treatment of heavy-metal-contaminated soils. This approach is not a permanent solution; moreover, off-site shipment and disposal of contaminated soil involves high expense, liability, and appropriate regulatory approval. Recently, a number of other techniques have been investigated for treating such contaminated sites, including flotation, solidification/stabilization, vitrification, and chemical extraction. This paper reports the results of a laboratory investigation determining the efficiency of using chelating agents to extract lead from contaminated soils. Lead concentrations in the soils ranged from 500 to 10,000 mg/kg. Ethylenediaminetetraacetic acidmore » (EDTA) and nitrilotriacetic acid (NTA) were examined for their potential extractive capabilities. Concentrations of the chelating agents ranged from 0.01 to 0.10 M. The pH of the suspensions in which the extractions were performed ranged from 4 to 12. Results showed that the removal of lead using NTA and water was ph-dependent, whereas the removal of lead using EDTA was ph-insensitive. Maximum removals of lead were 68.7%,19.1%, and 7.3% using EDTA, NTA, and water, respectively (as compared with initial lead concentrations).« less

Polyphenolic content and antioxidant activity of some wild Saudi Arabian Asteraceae plants.

PubMed

Shahat, Abdelaaty A; Ibrahim, Abeer Y; Elsaid, Mansour S

2014-07-01

To study the antioxidant properties of crude extract of different Asteraceae plants. The antioxidant properties of six extracts were evaluated using different antioxidant tests, including free radical scavenging, reducing power, metal chelation, superoxide anion radical scavenging, total antioxidant capacity and inhibition of lipid peroxidation activities. Picris cyanocarpa (P. cyanocarpa) and Anthemis deserti (A. deserti) had powerful antioxidant properties as radical scavenger, reducing agent and superoxide anion radical scavenger while Achillia fragrantissima (A. fragrantissima) and Artemissia monosperma (A. monosperma) were the most efficient as ion chelator (100% at 100, 200 and 400 μg/mL) A. fragrantissima and Rhantarium appoposum (R. appoposum) showed 100% inhibition on peroxidation of linoleic acid emulsion at 200 and 400 μg/mL, while butylatedhydroxy toluene and ascorbic acid showed 100 and 95% inhibition percentage at 400 μg/mL, respectively. Those various antioxidant activities were compared to standard antioxidants such as butylated hydroxyl toluene and ascorbic acid. In most tests P. cyanocarpa and A. deserti had powerful antioxidant properties as radical scavenger, reducing agent and superoxide anion radical scavenger. Copyright © 2014 Hainan Medical College. Published by Elsevier B.V. All rights reserved.

Chemical Properties of Caffeic and Ferulic Acids in Biological System: Implications in Cancer Therapy. A Review.

PubMed

Damasceno, Sarah S; Dantas, Bruna B; Ribeiro-Filho, Jaime; Antônio M Araújo, Demetrius; Galberto M da Costa, José

2017-01-01

The antioxidant properties of caffeic and ferulic acids in biological systems have been extensively demonstrated. As antioxidants, these compounds prevent the production of reactive oxygen species (ROS), which cause cell lesions that are associated with the development of several diseases, including cancer. Recent findings suggest that the chemoprotective action of these phenolic acids occurs through the following mechanisms: regulation of gene expression, chelation and / or reduction of transition metals, formation of covalent adducts and direct toxicity. The biological efficacy of these promising chemoprotective agents is strongly related with their chemical structure. Therefore, in this study, we discuss the structural characteristics of ferulic and caffeic acids that are responsible for their biological activities, as well as the mechanisms of action involved with the anti-cancer activity. Several reports indicated that the antioxidant effect of these phenylpropanoids results from reactions with free radicals with formation of stable products in the cells. The chelating effect of these compounds was also reported as an important protective mechanism against oxidative. Finally, the lipophilicity of these agents facilitates their entry into the cells, and thus, contributes to the anticancer activity. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Ion-pairing HPLC methods to determine EDTA and DTPA in small molecule and biological pharmaceutical formulations.

PubMed

Wang, George; Tomasella, Frank P

2016-06-01

Ion-pairing high-performance liquid chromatography-ultraviolet (HPLC-UV) methods were developed to determine two commonly used chelating agents, ethylenediaminetetraacetic acid (EDTA) in Abilify® (a small molecule drug with aripiprazole as the active pharmaceutical ingredient) oral solution and diethylenetriaminepentaacetic acid (DTPA) in Yervoy® (a monoclonal antibody drug with ipilimumab as the active pharmaceutical ingredient) intravenous formulation. Since the analytes, EDTA and DTPA, do not contain chromophores, transition metal ions (Cu 2+ , Fe 3+ ) which generate highly stable metallocomplexes with the chelating agents were added into the sample preparation to enhance UV detection. The use of metallocomplexes with ion-pairing chromatography provides the ability to achieve the desired sensitivity and selectivity in the development of the method. Specifically, the sample preparation involving metallocomplex formation allowed sensitive UV detection. Copper was utilized for the determination of EDTA and iron was utilized for the determination of DTPA. In the case of EDTA, a gradient mobile phase separated the components of the formulation from the analyte. In the method for DTPA, the active drug substance, ipilimumab, was eluted in the void. In addition, the optimization of the concentration of the ion-pairing reagent was discussed as a means of enhancing the retention of the aminopolycarboxylic acids (APCAs) including EDTA and DTPA and the specificity of the method. The analytical method development was designed based on the chromatographic properties of the analytes, the nature of the sample matrix and the intended purpose of the method. Validation data were presented for the two methods. Finally, both methods were successfully utilized in determining the fate of the chelates.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Walker, E.M. Jr.; Gale, G.R.

Cisplatin, an agent widely used in the chemotherapy of a variety of human malignancies, is often dose-limited owing to its nephrotoxicity. Some of the approaches under consideration, regarding the reduction of cisplatin nephrotoxicity, include the use of hydration and osmotic diuresis, pharmacological diuretics, chelating agents or agents which otherwise react with cisplatin or reverse cisplatin-induced deoxyribonucleic acid cross-links, and antioxidants to destroy free radicals, especially superoxide radicals, produced by cisplatin. The effects of each of these and other interventions on cisplatin-induced nephrotoxicity are delineated, along with their proposed mechanisms and effects on therapeutic efficacy. The current status of development ofmore » organoplatinum analogs yielding congeners with less nephrotoxicity and greater efficacy is discussed briefly. Finally, a possible role of endogenous and/or exogenous prostaglandins in protecting against or reversing heavy metal nephrotoxicity is suggested.« less

Improving the efficiency of phytoremediation using electrically charged plant and chelating agents.

PubMed

Tahmasbian, Iman; Safari Sinegani, Ali Akbar

2016-02-01

The low efficiency of phytoremediation is a considerable problem that limits the application of this environmentally friendly method on heavy metal-polluted soils. The combination of chelate-assisted phytoextraction and electrokinetic remediation could offer new opportunities to improve the effectiveness of phytoextraction. The current experiment aims to investigate the effects of electrical fields and chelating agents on phytoremediation efficiency. In a pot experiment using mine soil, poultry manure extract (PME), cow manure extract (CME), and ethylenediaminetetraacetic acid (EDTA) were applied to soil as chelating agents (2 g kg(-1)) at the beginning of the flowering stage. A week later, Helianthus annuus (sunflower) was negatively charged by inserting a stainless steel needle with 10 and 30 V DC electricity in the lowest part of the stems for 1 h each day for a 14-day period. At the end of the experiment, the shoot and root dry weight, lead (Pb) concentration in plant organs, translocation factor (TF), metal uptake index (UI), and soil available Pb (diethylene triamine pentaacetic acid (DTPA) extractable) were detected. Results indicated that the application of electrical fields had no significant impact on the shoot and root dry weights, while Pb concentration and UI increased in the 10-V EDTA treatment by 500 % compared to control. There was no significant difference between UI in 30- and 10-V EDTA treatments. Soil available Pb significantly increased in the 30-V treated soil. A positive correlation was observed between the available Pb in soil near the root and Pb concentration in shoot, its TF, and UI. In conclusion, a negatively charged plant along with the application of EDTA significantly increased the phytoremediation efficiency.

Photo-Fenton treatment of saccharin in a solar pilot compound parabolic collector: Use of olive mill wastewater as iron chelating agent, preliminary results.

PubMed

Davididou, K; Chatzisymeon, E; Perez-Estrada, L; Oller, I; Malato, S

2018-03-14

The aim of this work was to investigate the treatment of the artificial sweetener saccharin (SAC) in a solar compound parabolic collector pilot plant by means of the photo-Fenton process at pH 2.8. Olive mill wastewater (OMW) was used as iron chelating agent to avoid acidification of water at pH 2.8. For comparative purposes, Ethylenediamine-N, N-disuccinic acid (EDDS), a well-studied iron chelator, was also employed at circumneutral pH. Degradation products formed along treatment were identified by LC-QTOF-MS analysis. Their degradation was associated with toxicity removal, evaluated by monitoring changes in the bioluminescence of Vibrio fischeri bacteria. Results showed that conventional photo-Fenton at pH 2.8 could easily degrade SAC and its intermediates yielding k, apparent reaction rate constant, in the range of 0.64-0.82 L kJ -1 , as well as, eliminate effluent's chronic toxicity. Both OMW and EDDS formed iron-complexes able to catalyse H 2 O 2 decomposition and generate HO. OMW yielded lower SAC oxidation rates (k = 0.05-0.1 L kJ -1 ) than EDDS (k = 2.21-7.88 L kJ -1 ) possibly due to its higher TOC contribution. However, the degradation rates were improved (k = 0.13 L kJ -1 ) by increasing OMW dilution in the reactant mixture. All in all, encouraging results were obtained by using OMW as iron chelating agent, thus rendering this approach promising towards the increase of process sustainability. Copyright © 2018 Elsevier B.V. All rights reserved.

Description of 3,180 courses of chelation with dimercaptosuccinic acid in children ≤ 5 y with severe lead poisoning in Zamfara, Northern Nigeria: a retrospective analysis of programme data.

PubMed

Thurtle, Natalie; Greig, Jane; Cooney, Lauren; Amitai, Yona; Ariti, Cono; Brown, Mary Jean; Kosnett, Michael J; Moussally, Krystel; Sani-Gwarzo, Nasir; Akpan, Henry; Shanks, Leslie; Dargan, Paul I

2014-10-01

In 2010, Médecins Sans Frontières (MSF) discovered extensive lead poisoning impacting several thousand children in rural northern Nigeria. An estimated 400 fatalities had occurred over 3 mo. The US Centers for Disease Control and Prevention (CDC) confirmed widespread contamination from lead-rich ore being processed for gold, and environmental management was begun. MSF commenced a medical management programme that included treatment with the oral chelating agent 2,3-dimercaptosuccinic acid (DMSA, succimer). Here we describe and evaluate the changes in venous blood lead level (VBLL) associated with DMSA treatment in the largest cohort of children ≤ 5 y of age with severe paediatric lead intoxication reported to date to our knowledge. In a retrospective analysis of programme data, we describe change in VBLL after DMSA treatment courses in a cohort of 1,156 children ≤ 5 y of age who underwent between one and 15 courses of chelation treatment. Courses of DMSA of 19 or 28 d duration administered to children with VBLL ≥ 45 µg/dl were included. Impact of DMSA was calculated as end-course VBLL as a percentage of pre-course VBLL (ECP). Mixed model regression with nested random effects was used to evaluate the relative associations of covariates with ECP. Of 3,180 treatment courses administered, 36% and 6% of courses commenced with VBLL ≥ 80 µg/dl and ≥ 120 µg/dl, respectively. Overall mean ECP was 74.5% (95% CI 69.7%-79.7%); among 159 inpatient courses, ECP was 47.7% (95% CI 39.7%-57.3%). ECP after 19-d courses (n = 2,262) was lower in older children, first-ever courses, courses with a longer interval since a previous course, courses with more directly observed doses, and courses with higher pre-course VBLLs. Low haemoglobin was associated with higher ECP. Twenty children aged ≤ 5 y who commenced chelation died during the period studied, with lead poisoning a primary factor in six deaths. Monitoring of alanine transaminase (ALT), creatinine, and full blood count revealed moderate ALT elevation in <2.5% of courses. No clinically severe adverse drug effects were observed, and no laboratory findings required discontinuation of treatment. Limitations include that this was a retrospective analysis of clinical data, and unmeasured variables related to environmental exposures could not be accounted for. Oral DMSA was a pharmacodynamically effective chelating agent for the treatment of severe childhood lead poisoning in a resource-limited setting. Re-exposure to lead, despite efforts to remediate the environment, and non-adherence may have influenced the impact of outpatient treatment. Please see later in the article for the Editors' Summary.

Reduction of mercury from mackerel fillet using combined solution of cysteine, EDTA, and sodium chloride.

PubMed

Hajeb, P; Jinap, S

2012-06-13

An acidic solution containing mercury chelating agents to eliminate mercury in raw fish (mackerel) fillet was developed. The solution contained hydrochloric acid, sodium hydroxide, cysteine, EDTA, and NaCl. The optimum conditions for mercury reduction were achieved using response surface methodology (RSM) at cysteine concentration of 1.25%, EDTA of 275 mg/L, NaCl of 0.5%, pH of 3.75, and exposure time of 18 min. The optimized conditions produced a solution which can remove up to 91% mercury from raw fish fillet. Cysteine and EDTA were identified as potential chelating agents with the greatest potential for use. The solution can be employed in fish industries to reduce mercury in highly contaminated fish.

In vitro and in vivo evaluation of potential aluminum chelators.

PubMed

Graff, L; Muller, G; Burnel, D

1995-10-01

The potential for aluminium (Al) chelation by different compounds was determined using 2 in vitro techniques. The formation of stable complexes with Al in an aqueous solution was evaluated using pulse polarography. This technique allowed the influence of temperature and calcium (Ca) to be studied for each compound. Certain compounds (EDDHA, HAES, citric acid and HBED) showed great chelation in the absence of Ca2+ at a temperature of 37 +/- 1 C. An ultrafiltration technique combined with Al determination by atomic emission spectroscopy allowed the efficiency of different substances to complex Al that were previously bound to serum proteins to be estimated. The kinetics of chelation and minimum efficient concentration have been determined for all products studied. EDDHA had chelation potential similar to DFO. The real efficacies of the compounds were studied in vivo to compare the effectiveness of repeated administrations of the best chelating agents (EDDHA, DFO, HAES and tartaric acid) on the distribution and excretion of Al after repeated i.p. administrations to rats. Intraperitoneal EDDHA significantly increased urinary metal (Al, Ca, Cu, Fe and Zn) excretion. These excretions may be correlated to a renal toxic potential property.

Analysis of Supercritical-Extracted Chelated Metal Ions From Mixed Organic-Inorganic Samples

NASA Technical Reports Server (NTRS)

Sinha, Mahadeva P. (Inventor)

1996-01-01

Organic and inorganic contaminants of an environmental sample are analyzed by the same GC-MS instrument by adding an oxidizing agent to the sample to oxidize metal or metal compounds to form metal ions. The metal ions are converted to chelate complexes and the chelate complexes are extracted into a supercritical fluid such as CO2. The metal chelate extract after flowing through a restrictor tube is directly injected into the ionization chamber of a mass spectrometer, preferably containing a refractory metal filament such as rhenium to fragment the complex to release metal ions which are detected. This provides a fast, economical method for the analysis of metal contaminants in a sample and can be automated. An organic extract of the sample in conventional or supercritical fluid solvents can be detected in the same mass spectrometer, preferably after separation in a supercritical fluid chromatograph.

MA-NOTMP: A Triazacyclononane Trimethylphosphinate Based Bifunctional Chelator for Gallium Radiolabelling of Biomolecules.

PubMed

Poty, Sophie; Désogère, Pauline; Šimeček, Jakub; Bernhard, Claire; Goncalves, Victor; Goze, Christine; Boschetti, Frédéric; Notni, Johannes; Wester, Hans J; Denat, Franck

2015-09-01

In the past few years, gallium-68 has demonstrated significant potential as a radioisotope for positron emission tomography (PET), and the optimization of chelators for gallium coordination is a major goal in the development of radiopharmaceuticals. Methylaminotriazacyclononane trimethylphosphinate (MA-NOTMP), a new C-functionalized triazacyclononane derivative with phosphinate pendant arms, presents excellent coordination properties for (68) Ga (low ligand concentration, labelling at low pH even at room temperature). A "ready-to-be-grafted" bifunctional chelating agent (p-NCS-Bz-MA-NOTMP) was prepared to allow (68) Ga labelling of sensitive biological vectors. Conjugation to a bombesin(7-14) derivative was performed, and preliminary in vitro experiments demonstrated the potential of MA-NOTMP in the development of radiopharmaceuticals. This new chelator is therefore of major interest for labelling sensitive biomolecules, and further in vivo experiments will soon be performed. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Facile deferration of commercial fertilizers containing iron chelates for their NMR analysis.

PubMed

Laghi, Luca; Alcañiz, Sara; Cerdán, Mar; Gomez-Gallego, Mar; Sierra, Miguel Angel; Placucci, Giuseppe; Cremonini, Mauro Andrea

2009-06-24

Ethylenediamine-N,N'-bis(o-hydroxyphenylacetic) acid (o,o-EDDHA) is widely used in commercial formulations as a Fe(3+) chelating agent to remedy iron shortage in calcareous and alkaline soils. Commercially available o,o-EDDHA-Fe(3+) formulations contain a mixture of EDDHA regioisomers (o,p-EDDHA and p,p-EDDHA), together with other, still uncharacterized, products. NMR spectroscopy can be applied to their study as long as iron is accurately removed prior to the observation. This paper shows that it is possible to obtain a deferrated solution of the organic ligands present in commercial fertilizers containing the EDDHA-Fe(3+) chelate by treating the chelate with ferrocyanide, thus forming Prussian Blue that can be easily removed by centrifugation. This iron removal process does not cause significant losses of the o,o-EDDHA ligand or its minor structural isomers.

A new contrast media for functional MR urography: Gd-MAG3.

PubMed

Algin, Oktay

2011-07-01

Tc-99m-MAG3 (tubular agent) provides high imaging quality and extraction efficiency; and has become one of the most widely used agent for scintigraphic examinations of urinary system pathologies and renal transplants. Recently, it was reported that functional magnetic resonance urography (FMRU) can be sufficient in detection of urinary tract obstruction, renal artery stenosis, calculation of kidney functions and evaluation of renal transplants. However the pharmacokinetics of magnetic resonance (MR) contrast-media used in FMRU and Tc-99m-MAG3 differs from each other. This may cause discordant results between the FMRU and most of the scintigraphic studies. To our knowledge, there is no contrast-media which is specific for FMRU. A kidney specific contrast material can be developed for FMRU studies as well. MAG3 is a good candidate for this chelation. In conclusion, MR imaging (MRI) will be the most useful and important technique for morphologic-functional evaluation of urinary system. FMRU examinations performed with MAG3 chelated gadolinium can be sufficient for the complete evaluation of urinary tract even in patients with impaired renal functions ("all in one MRI"). MRI has some important advantages including no risk for radiation exposure, high temporal and spatial resolution, no need for nephrotoxic contrast agent; besides being a fast and feasible technique. Gadolinium-containing contrast agents may cause a life-threatening adverse reaction known as nephrogenic systemic fibrosis in patients with severe renal impairment, but Gd-MAG3 may reduce the risk of nephrogenic systemic fibrosis due to its higher extraction capacity and other features. Copyright © 2011 Elsevier Ltd. All rights reserved.

Flue gas desulfurization/denitrification using metal-chelate additives

DOEpatents

Harkness, J.B.L.; Doctor, R.D.; Wingender, R.J.

1985-08-05

A method of simultaneously removing SO/sub 2/ and NO from oxygen-containing flue gases resulting from the combustion of carbonaceous material by contacting the flue gas with an aqueous scrubber solution containing an aqueous sulfur dioxide sorbent and an active metal chelating agent which promotes a reaction between dissolved SO/sub 2/ and dissolved NO to form hydroxylamine N-sulfonates. The hydroxylamine sulfonates are then separated from the scrubber solution which is recycled. 3 figs.

Speciation in Metal Toxicity and Metal-Based Therapeutics

PubMed Central

Templeton, Douglas M.

2015-01-01

Metallic elements, ions and compounds produce varying degrees of toxicity in organisms with which they come into contact. Metal speciation is critical to understanding these adverse effects; the adjectives “heavy” and “toxic” are not helpful in describing the biological properties of individual elements, but detailed chemical structures are. As a broad generalization, the metallic form of an element is inert, and the ionic salts are the species that show more significant bioavailability. Yet the salts and other chelates of a metal ion can give rise to quite different toxicities, as exemplified by a range of carcinogenic potential for various nickel species. Another important distinction comes when a metallic element is organified, increasing its lipophilicity and hence its ability to penetrate the blood brain barrier, as is seen, for example, with organic mercury and tin species. Some metallic elements, such as gold and platinum, are themselves useful therapeutic agents in some forms, while other species of the same element can be toxic, thus focusing attention on species interconversions in evaluating metal-based drugs. The therapeutic use of metal-chelating agents introduces new species of the target metal in vivo, and this can affect not only its desired detoxification, but also introduce a potential for further mechanisms of toxicity. Examples of therapeutic iron chelator species are discussed in this context, as well as the more recent aspects of development of chelation therapy for uranium exposure. PMID:29056656

Effective sulfur and energy recovery from hydrogen sulfide through incorporating an air-cathode fuel cell into chelated-iron process.

PubMed

Sun, Min; Song, Wei; Zhai, Lin-Feng; Cui, Yu-Zhi

2013-12-15

The chelated-iron process is among the most promising techniques for the hydrogen sulfide (H2S) removal due to its double advantage of waste minimization and resource recovery. However, this technology has encountered the problem of chelate degradation which made it difficult to ensure reliable and economical operation. This work aims to develop a novel fuel-cell-assisted chelated-iron process which employs an air-cathode fuel cell for the catalyst regeneration. By using such a process, sulfur and electricity were effectively recovered from H2S and the problem of chelate degradation was well controlled. Experiment on a synthetic sulfide solution showed the fuel-cell-assisted chelated-iron process could maintain high sulfur recovery efficiencies generally above 90.0%. The EDTA was preferable to NTA as the chelating agent for electricity generation, given the Coulombic efficiencies (CEs) of 17.8 ± 0.5% to 75.1 ± 0.5% for the EDTA-chelated process versus 9.6 ± 0.8% to 51.1 ± 2.7% for the NTA-chelated process in the pH range of 4.0-10.0. The Fe (III)/S(2-) ratio exhibited notable influence on the electricity generation, with the CEs improved by more than 25% as the Fe (III)/S(2-) molar ratio increased from 2.5:1 to 3.5:1. Application of this novel process in treating a H2S-containing biogas stream achieved 99% of H2S removal efficiency, 78% of sulfur recovery efficiency, and 78.6% of energy recovery efficiency, suggesting the fuel-cell-assisted chelated-iron process was effective to remove the H2S from gas streams with favorable sulfur and energy recovery efficiencies. Copyright © 2013 Elsevier B.V. All rights reserved.

Kinetic behavior of Fe(o,o-EDDHA)-humic substance mixtures in several soil components and in calcareous soils.

PubMed

Cerdán, Mar; Alcañiz, Sara; Juárez, Margarita; Jordá, Juana D; Bermúdez, Dolores

2007-10-31

Ferric ethylenediamine- N, N'-bis-(o-hydroxyphenylacetic)acid chelate (Fe(o, o-EDDHA)) is one of the most effective Fe fertilizers in calcareous soils. However, humic substances are occasionally combined with iron chelates in drip irrigation systems in order to lower costs. The reactivity of iron chelate-humic substance mixtures in several soil components and in calcareous soils was investigated through interaction tests, and their behavior was compared to the application of iron chelates and humic substances separately. Two commercial humic substances and two Fe(o, o-EDDHA) chelates (one synthesized in the laboratory and one commercial) were used to prepare iron chelate-humic substance mixtures at 50% (w/w). Various soil components (calcium carbonate, gibbsite, amorphous iron oxide, hematite, tenorite, zincite, amorphous Mn oxide, and peat) and three calcareous soils were shaken for 15 days with the mixtures and with iron chelate and humic substance solutions. The kinetic behavior of Fe(o, o-EDDHA) and Fe non-(o,o-EDDHA) (Fe bonded to (o,p-EDDHA) and other polycondensated ligands) and of the different nutrients solubilized after the interaction assay was determined. The results showed that the mixtures did not significantly reduce the retention of Fe(o, o-EDDHA) and Fe non-(o,o-EDDHA) in the soil components and the calcareous soils compared to the iron chelate solutions, but they did produce changes in the retention rate. Moreover, the competition between humic substances and synthetic chelating agents for complexing metal cations limited the effectiveness of the mixtures to mobilize nutrients from the substrates. The presence of Fe(o, p-EDDHA) and other byproducts in the commercial iron chelate had an important effect on the evolution of Fe(o, o-EDDHA) and the nutrient solubilization process.

ChelomEx: Isotope-assisted discovery of metal chelates in complex media using high-resolution LC-MS.

PubMed

Baars, Oliver; Morel, François M M; Perlman, David H

2014-11-18

Chelating agents can control the speciation and reactivity of trace metals in biological, environmental, and laboratory-derived media. A large number of trace metals (including Fe, Cu, Zn, Hg, and others) show characteristic isotopic fingerprints that can be exploited for the discovery of known and unknown organic metal complexes and related chelating ligands in very complex sample matrices using high-resolution liquid chromatography mass spectrometry (LC-MS). However, there is currently no free open-source software available for this purpose. We present a novel software tool, ChelomEx, which identifies isotope pattern-matched chromatographic features associated with metal complexes along with free ligands and other related adducts in high-resolution LC-MS data. High sensitivity and exclusion of false positives are achieved by evaluation of the chromatographic coherence of the isotope pattern within chromatographic features, which we demonstrate through the analysis of bacterial culture media. A built-in graphical user interface and compound library aid in identification and efficient evaluation of results. ChelomEx is implemented in MatLab. The source code, binaries for MS Windows and MAC OS X as well as test LC-MS data are available for download at SourceForge ( http://sourceforge.net/projects/chelomex ).

Determining lead, cadmium and mercury in cosmetics using sweeping via dynamic chelation by capillary electrophoresis.

PubMed

Chen, Kuan-Ling; Jiang, Shiuh-Jen; Chen, Yen-Ling

2017-03-01

International limits have been established for metal impurities in cosmetics to prevent overexposure to heavy metal ions. Sweeping via dynamic chelation was developed using capillary electrophoresis to analyze lead (Pb), cadmium (Cd) and mercury (Hg) impurities in cosmetics. The sweeping via dynamic chelation mechanism involves a large volume of metal ions being swept by a small quantity of chelating agents that were electrokinetically injected into the capillary to chelate metal ions and increase the detection sensitivity. The optimized conditions were as follows: Firstly, the capillary was rinsed by a 0.6 mM TTAB solution to reverse the EOF. The sample solution, which was diluted using 25 mM ammonium acetate (pH 6.0), was injected into the capillary using a pressure of 3.5 psi for 99.9 s. Then, EDTA was injected at -25 kV for 1 min from the EDTA buffer (25 mM ammonium acetate containing 0.6 mM TTAB and 5 mM EDTA), and the metal ions were swept and stacked simultaneously. Finally, the separation was performed at -20 kV using a separation buffer (100 mM ammonium acetate (pH 6.0)). A small quantity of chelating agents introduced into the capillary could yield 33-, 50- and 100-fold detection improvements for Pb, Cd and Hg, respectively, more sensitive than conventional capillary zone electrophoresis. Correlation coefficients greater than 0.998 indicated that this method exhibited good linearity. The relative standard deviation and relative error were less than 8.7%, indicating high precision and accuracy. The recovery value of the homemade lotion, which was employed to simulate the real sample matrix, was 93-104%, which indicated that the sample matrix does not affect the quantitative results. Finally, commercial cosmetics were employed to demonstrate the feasibility of the method to determine Pb, Cd and Hg without complicated sample pretreatment. Graphical Abstract The procedure of analyzing metal ions in cosmetics by sweeping via dynamic chelation.

Comparison of MRI properties between derivatized DTPA and DOTA gadolinium-dendrimer conjugates.

PubMed

Nwe, K; Bernardo, M; Regino, C A S; Williams, M; Brechbiel, M W

2010-08-15

In this report we directly compare the in vivo and in vitro MRI properties of gadolinium-dendrimer conjugates of derivatized acyclic diethylenetriamine-N,N',N',N'',N''-pentaacetic acid (1B4M-DTPA) and macrocyclic 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid (C-DOTA). The metal-ligand chelates were pre-formed in alcohol prior to conjugation to the generation 4 PAMAM dendrimer (G4D), and the dendrimer-based agents were purified by Sephadex(R) G-25 column. The analysis and SE-HPLC data indicated chelate to dendrimer ratios of 30:1 and 28:1, respectively. Molar relaxivity measured at pH 7.4, 22 degrees C, and 3T are comparable (29.5 vs 26.9 mM(-1)s(-1)), and both conjugates are equally viable as MRI contrast agents based on the images obtained. The macrocyclic agent however exhibits a faster rate of clearance in vivo (t(1/2)=16 vs 29 min). Our conclusion is that the macrocyclic-based agent is the more suitable agent for in vivo use for these reasons combined with kinetic inertness associated with the Gd(III) DOTA complex stability properties. Published by Elsevier Ltd.

Comparison of MRI properties between derivatized DTPA and DOTA gadolinium-dendrimer conjugates

PubMed Central

Nwe, K.; Bernardo, M; Regino, C. A. S.; Williams, M; Brechbiel, M. W.

2010-01-01

In this report we directly compare the in vivo and in vitro MRI properties of gadolinium-dendrimer conjugates of derivatized acyclic diethylenetriamine-N,N’,N’,N’’, N’’-pentaacetic acid (1B4M-DTPA) and macrocyclic 1,4,7,10-tetraazacyclododecane-N,N’,N’’,N’’’-tetraacetic acid (C-DOTA). The metal-ligand chelates were pre-formed in alcohol prior to conjugation to the generation 4 PAMAM dendrimer (G4D), and the dendrimer-based agents were purified by Sephadex® G-25 column. The analysis and SE-HPLC data indicated chelate to dendrimer ratios of 30:1 and 28:1 respectively. Molar relaxivity measured at pH 7.4, 22°C, and 3T are comparable (29.5 vs. 26.9 mM−1s−1), and both conjugates are equally viable as MRI contrast agents based on the images obtained. The macrocyclic agent however exhibits a faster rate of clearance in vivo (t1/2 = 16 vs. 29 min.). Our conclusion is that the macrocyclic-based agent is the more suitable agent for in vivo use for these reasons combined with kinetic inertness associated with the Gd(III) DOTA complex stability properties. PMID:20663676

Evaluating the potential of chelation therapy to prevent and treat gadolinium deposition from MRI contrast agents

DOE PAGES

Rees, Julian A.; Deblonde, Gauthier J. -P.; An, Dahlia D.; ...

2018-03-13

Several MRI contrast agent clinical formulations are now known to leave deposits of the heavy metal gadolinium in the brain, bones, and other organs of patients. This persistent biological accumulation of gadolinium has been recently recognized as a deleterious outcome in patients administered Gd-based contrast agents (GBCAs) for MRI, prompting the European Medicines Agency to recommend discontinuing the use of over half of the GBCAs currently approved for clinical applications. Here, to address this problem, we find that the orally-available metal decorporation agent 3,4,3-LI(1,2-HOPO) demonstrates superior efficacy at chelating and removing Gd from the body compared to diethylenetriaminepentaacetic acid, amore » ligand commonly used in the United States in the GBCA Gadopentetate (Magnevist). Using the radiotracer 153Gd to obtain precise biodistribution data, the results herein, supported by speciation simulations, suggest that the prophylactic or post-hoc therapeutic use of 3,4,3-LI(1,2-HOPO) may provide a means to mitigate Gd retention in patients requiring contrast-enhanced MRI.« less

Evaluating the potential of chelation therapy to prevent and treat gadolinium deposition from MRI contrast agents

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rees, Julian A.; Deblonde, Gauthier J. -P.; An, Dahlia D.

Several MRI contrast agent clinical formulations are now known to leave deposits of the heavy metal gadolinium in the brain, bones, and other organs of patients. This persistent biological accumulation of gadolinium has been recently recognized as a deleterious outcome in patients administered Gd-based contrast agents (GBCAs) for MRI, prompting the European Medicines Agency to recommend discontinuing the use of over half of the GBCAs currently approved for clinical applications. Here, to address this problem, we find that the orally-available metal decorporation agent 3,4,3-LI(1,2-HOPO) demonstrates superior efficacy at chelating and removing Gd from the body compared to diethylenetriaminepentaacetic acid, amore » ligand commonly used in the United States in the GBCA Gadopentetate (Magnevist). Using the radiotracer 153Gd to obtain precise biodistribution data, the results herein, supported by speciation simulations, suggest that the prophylactic or post-hoc therapeutic use of 3,4,3-LI(1,2-HOPO) may provide a means to mitigate Gd retention in patients requiring contrast-enhanced MRI.« less

Characterization of the effect of serum and chelating agents on Staphylococcus aureus biofilm formation; chelating agents augment biofilm formation through clumping factor B

NASA Astrophysics Data System (ADS)

Abraham, Nabil Mathew

Staphylococcus aureus is the causative agent of a diverse array of acute and chronic infections, and some these infections, including infective endocarditis, joint infections, and medical device-associated bloodstream infections, depend upon its capacity to form tenacious biofilms on surfaces. Inserted medical devices such as intravenous catheters, pacemakers, and artificial heart valves save lives, but unfortunately, they can also serve as a substrate on which S. aureus can form a biofilm, attributing S. aureus as a leading cause of medical device-related infections. The major aim of this work was take compounds to which S. aureus would be exposed during infection and to investigate their effects on its capacity to form a biofilm. More specifically, the project investigated the effects of serum, and thereafter of catheter lock solutions on biofilm formation by S. aureus. Pre-coating polystyrene with serum is frequently used as a method to augment biofilm formation. The effect of pre-coating with serum is due to the deposition of extracellular matrix components onto the polystyrene, which are then recognized by MSCRAMMs. We therefore hypothesized that the major component of blood, serum, would induce biofilm formation. Surprisingly, serum actually inhibited biofilm formation. The inhibitory activity was due to a small molecular weight, heat-stable, non-proteinaceous component/s of serum. Serum-mediated inhibition of biofilm formation may represent a previously uncharacterized aspect of host innate immunity that targets the expression of a key bacterial virulence factor: the ability to establish a resistant biofilm. Metal ion chelators like sodium citrate are frequently chosen to lock intravenous catheters because they are regarded as potent inhibitors of bacterial biofilm formation and viability. We found that, while chelating compounds abolished biofilm formation in most strains of S. aureus, they actually augmented the phenotype in a subset of strains. We investigated the molecular basis of this phenomenon. Deletion and complementation analysis and thereafter antibody based inhibition assays confirmed a functional role for the surface adhesin clumping factor B as the causative determinant associated with the increased biofilm phenotype. Finally, we investigated the regulation of clumping factor B-mediated biofilm formation and the basis for the strain dependence. Regulation was determined to occur via two novel post-translational networks- one affecting ClfB activity, mediated by Ca2+ binding to the EF-Hand domain, and the other affecting protein stability, mediated by the enzymatic activity of the metalloprotease-aureolysin. Polymorphisms within the aureolysin gene sequence, between strains, was identified as the basis for some strains forming robust biofilms within chelated media versus other than do not exhibit this phenotype.

Acyclic chelate with ideal properties for (68)Ga PET imaging agent elaboration.

PubMed

Boros, Eszter; Ferreira, Cara L; Cawthray, Jacqueline F; Price, Eric W; Patrick, Brian O; Wester, Dennis W; Adam, Michael J; Orvig, Chris

2010-11-10

We have investigated novel bifunctional chelate alternatives to the aminocarboxylate macrocycles NOTA (N(3)O(3)) or DOTA (N(4)O(4)) for application of radioisotopes of Ga to diagnostic nuclear medicine and have found that the linear N(4)O(2) chelate H(2)dedpa coordinates (67)Ga quantitatively to form [(67)Ga(dedpa)](+) after 10 min at RT. Concentration-dependent coordination to H(2)dedpa of either (68)Ga or (67)Ga showed quantitative conversion to the desired products with ligand concentrations as low as 10(-7) M. With (68)Ga, specific activities as high as 9.8 mCi nmol(-1) were obtained without purification. In a 2 h competition experiment against human apo-transferrin, [(67)Ga(dedpa)](+) showed no decomposition. Two bifunctional versions of H(2)dedpa are also described, and these both coordinate to (67)Ga at RT within 10 min. Complete syntheses, characterizations, labeling studies, and biodistribution profiles of the (67)Ga complexes are presented for the new platform chelates. The stability of these platform chelates is higher than that of DOTA.

Optical property measurements of a novel type of upconverting reporter

NASA Astrophysics Data System (ADS)

Xiao, Xudong; Herring, Michael E.; Haushalter, Jeanne; Lee, Seonkyung; Kalogerakis, Kostas S.; Faris, Gregory W.

2003-07-01

We have recently developed a new type of reporter (upconverting chelate) for biomedical diagnostics. For this reporter, the light is absorbed and emitted by a lanthanide ion, rather than an organic molecule, as is the case for a typical fluorescent dye. These materials do not photobleach and have no autofluorescent background. We focus in this paper on neodymium ions complexed with the familiar chelating agents, EDTA, DPA, DTPA and DOTA. We have performed experimental measurements with one- and two-color laser light excitation for different chelate compounds. The samples are excited using two Nd:YAG-pumped dye laser systems that provide laser light near 587 nm and 800 nm. For one-color excitation, the emitted light depends quadratically on the incident laser power, as expected. Three strongly emitting lines are observed, located near 360 nm, 387 nm, and 417 nm. We observed more efficient upconversion in EDTA although the DPA chelates show comparable ground state absorbance. We have studied the influence of temporal delay between the two laser pulses and obtained the decay lifetime of the first intermediate state in the various chelated compounds.

[Contribution of blue-green pigments to hemolytic activity of Pseudomonas aeruginosa cultural fluid].

PubMed

Pyzh, A É; Nikandrov, V N

2011-01-01

To assess the contribution of blue-green pigments of Pseudomonas aeruginosa to hemolytic activity of its cultural fluid. MATERIALS AND METHODS. Eight hospital strains and reference strain ATCC 15442 were used. Growth dynamics of strains as well as features of accumulation of hemolytic and phospholipase activity were studied. Purified samples of pyoverdin and pyocyanin were extracted by gel-chromatography and chloroform extraction methods. Hemolytic and lecitinase activities of the samples as well as effect of active oxygen scavengers and chelating agents on these activities were studied. Dynamics of accumulation of hemolytic activity significantly differed from that of phospholipase activity when strains were grown in liquid medium. Chromatographic separation of the pigments from cultural fluid supernatants sharply reduced its hemolytic activity. Purified samples of pyoverdin and pyocyanin were capable to lyse erythrocytes and chicken egg lecitin. These characteristics of the pigments were inhibited by nitroblue tetrazolium and sensitive to chelating agents. Conclusion. Pyoverdin and pyocyanin of pathogenic strains of P. aeruginosa are capable to lyse erythrocytes and suspension of purified chicken egg lecitin, they contribute to total hemolytic activity of pathogenic strains of Pseudomonas, which is not determined only by phospholipase C produced by microorganism. Lytic activity of the pigments is blocked by nitroblue tetrazolium and susceptible to some chelating agents. Apparently, this activity is mediated by superoxide radical and determined by presence of metals with transient valence in pigments' molecules.

Effect of Chelating Agents on the Stability of Nano-TiO2 Sol Particles for Sol-Gel Coating.

PubMed

Maeng, Wan Young; Yoo, Mi

2015-11-01

Agglomeration of sol particles in a titanium alkoxide (tetrabutyl orthotitanate (TBOT), > 97%) solution during the hydrolysis and condensation steps makes the sol solution difficult to use for synthesizing homogeneous sol-gel coating. Here, we have investigated the effect of stabilizing agents (acetic acid and ethyl acetoacetate (EAcAc)) on the agglomeration of Ti alkoxide particles during hydrolysis and condensation in order to determine the optimized conditions for controlling the precipitation of TiO2 particles. The study was conducted at R(AC) ([acetic acid]/[TBOT]) = 0.1-5 and R(EAcAc)([EAcAc]/[TBOT]) = 0.05-0.65. We also studied the effects of a basic catalyst ethanolamine (ETA), water, and HCl on sol stability. The chelating ligands in the precursor sol were analyzed with FT-IR. The coating properties were examined by focused ion beam. The stabilizing agents (acetic acid and EAcAc) significantly influenced the agglomeration and precipitation of TBOT precursor particles during hydrolysis. As R(AC) and R(EAcAc) increased, the agglomeration remarkably decreased. The stability of the sol with acetic acid and EAcAc arises from the coordination of the chelating ligand to TBOT that hinders hydrolysis and condensation. A uniform fine coating (thickness: 30 nm) on stainless steel was obtained by using an optimized sol with R(AC) = 0.5 and R(EAcAc) = 0.65.

Modified carbohydrate-chitosan compounds, methods of making the same and methods of using the same

DOEpatents

Venditti, Richard A; Pawlak, Joel J; Salam, Abdus; El-Tahlawy, Khaled Fathy

2015-03-10

Compositions of matter are provided that include chitosan and a modified carbohydrate. The modified carbohydrate includes a carbohydrate component and a cross linking agent. The modified carbohydrate has increased carboxyl content as compared to an unmodified counterpart carbohydrate. A carboxyl group of the modified carbohydrate is covalently bonded with an amino group of chitosan. The compositions of matter provided herein may include cross linked starch citrate-chitosan and cross linked hemicellulose citrate-chitosan, including foams thereof. These compositions yield excellent absorbency and metal chelation properties. Methods of making cross linked modified carbohydrate-chitosan compounds are also provided.

Safety and pharmacokinetics of the oral iron chelator SP-420 in β-thalassemia.

PubMed

Taher, Ali T; Saliba, Antoine N; Kuo, Kevin H; Giardina, Patricia J; Cohen, Alan R; Neufeld, Ellis J; Aydinok, Yesim; Kwiatkowski, Janet L; Jeglinski, Brenda I; Pietropaolo, Keith; Berk, Gregory; Viprakasit, Vip

2017-12-01

Our phase I, open-label, multi-center, dose-escalation study evaluated the pharmacokinetics (PK) of SP-420, a tridentate oral iron chelating agent of the desferrithiocin class, in patients with transfusion dependent β-thalassemia. SP-420 was administered as a single dose of 1.5 (n = 3), 3 (n = 3), 6 (n = 3), 12 (n = 3), and 24 (n = 6) mg/kg or as a twice-daily dose of 9 mg/kg (n = 6) over 14-28 days. There was a near dose-linear increase in the mean plasma SP-420 concentrations and in the mean values for C max and AUC 0-τ over the dose range evaluated. The median t max ranged from 0.5 to 2.25 h and was not dose dependent. The study was prematurely terminated by the sponsor due to renal adverse events (AE) including proteinuria, increase in serum creatinine, and one case of Fanconi syndrome. Other adverse effects included hypersensitivity reactions and gastrointestinal disturbances. Based on current dose administration, the renal AE observed outweighed the possible benefits from chelation therapy. However, additional studies assessing efficacy and safety of lower doses or less frequent dosing of SP-420 over longer durations with close monitoring would be necessary to better explain the findings of our study and characterize the safety of the study drug. © 2017 Wiley Periodicals, Inc.

40 CFR 710.4 - Scope of the inventory.

Code of Federal Regulations, 2011 CFR

2011-07-01

... modifier, pH neutralizer, sequesterant, coagulant, flocculant, fire retardant, lubricant, chelating agent... upon use of curable plastic or rubber molding compounds, inks, drying oils, metal finishing compounds...

Differential targeting of the cyclin-dependent kinase inhibitor, p21CIP1/WAF1, by chelators with anti-proliferative activity in a range of tumor cell-types

PubMed Central

Moussa, Rayan S.; Kovacevic, Zaklina; Richardson, Des R.

2015-01-01

Chelators such as 2-hydroxy-1-napthylaldehyde isonicotinoyl hydrazone (311) and di-2-pyridylketone-4,4-dimethyl-3-thiosemicarbazone (Dp44mT) target tumor cell iron pools and inhibit proliferation. These agents also modulate multiple targets, one of which is the cyclin-dependent kinase inhibitor, p21. Hence, this investigation examined the mechanism of action of these compounds in targeting p21. All the chelators up-regulated p21 mRNA in the five tumor cell-types assessed. In contrast, examining their effect on total p21 protein levels, these agents induced either: (1) down-regulation in MCF-7 cells; (2) up-regulation in SK-MEL-28 and CFPAC-1 cells; or (3) had no effect in LNCaP and SK-N-MC cells. The nuclear localization of p21 was also differentially affected by the ligands depending upon the cell-type, with it being decreased in MCF-7 cells, but increased in SK-MEL-28 and CFPAC-1 cells. Further studies assessing the mechanisms responsible for these effects demonstrated that p21 expression was not correlated with p53 status, suggesting a p53-independent mechanism. Considering this, we examined proteins that modulate p21 independently of p53, namely NDRG1, MDM2 and ΔNp63. These studies demonstrated that a dominant negative MDM2 isoform (p75MDM2) closely resembled p21 expression in response to chelation in three cell lines. These data suggest MDM2 may be involved in the regulation of p21 by chelators. PMID:26335183

Iron chelation as a possible mechanism for aspirin-induced malondialdehyde production by mouse liver microsomes and mitochondria.

PubMed Central

Schwarz, K B; Arey, B J; Tolman, K; Mahanty, S

1988-01-01

To investigate the possibility that lipid peroxidation is the mechanism responsible for aspirin-induced liver damage, pure neutralized acetylsalicylic acid (ASA), 0.6-90.9 mM, was added to calcium-aggregated mouse liver microsomes followed by incubation in NADPH buffer at 37 degrees C for 60 min and subsequent measurement of malondialdehyde (MDA). MDA production at ASA concentrations from 1.2 to 4.6 mM was greater than control (P less than 0.004). Peak MDA values were observed with 4.6 mM ASA, 39.58 +/- 6.73 nmol MDA/mg protein vs. 16.16 +/- 2.85 (P less than 0.004). Higher concentrations of ASA were inhibitory compared with the value at 4.6 mM (P less than 0.001). Aspirin had similar effects on MDA production by mouse liver mitochondria. MDA production with either ASA or buffer was completely suppressed by the potent iron-chelating agents desferrioxamine and alpha,alpha' dipyridyl when these were added to the microsomal preparations. Since MDA production in this system is known to be affected by iron-chelating agents (enhanced at low concentration, inhibited at higher concentration), the iron-chelating properties of ASA were investigated. Conductivity titration curves of Fe(OH)3 added to water or ASA suggested that the ASA was complexing with iron. The presence of an iron-ASA complex was established by high pressure liquid chromatographic analysis of the solution from this study. We conclude that aspirin enhances MDA production by hepatic microsomes and mitochondria via an aspirin-iron chelate and that this represents at least one mechanism by which aspirin may produce liver damage. PMID:3335633

Chemical evaluation of HBED/Fe(3+) and the novel HJB/Fe(3+) chelates as fertilizers to alleviate iron chlorosis.

PubMed

López-Rayo, Sandra; Hernández, Diana; Lucena, Juan J

2009-09-23

Iron chelates such as ethylenediamine-N,N'-bis(2-hydroxyphenylacetic) acid (o,o-EDDHA) and their analogues are the most efficient soil fertilizers to treat iron chlorosis in plants growing in calcareous soil. A new chelating agent, HJB (N,N'-bis(2-hydroxy-5-methylphenyl)ethylendiamine-N,N'-diacetic acid) may be an alternative to o,o-EDDHA since its synthesis yields a purer product, but its chemical behavior and efficiency as chlorosis corrector should be evaluated. In this research, a known analogous HBED (N,N'-bis(2-hydroxyphenyl)ethylendiamine-N,N'-diacetic acid) has also been considered. First, an ion-pair high performance liquid chromatography (HPLC) method has been tested for the HJB/Fe(3+) and HBED/Fe(3+) determination. The ability of HJB and HBED to maintain Fe in solution has been compared with respect to o,o-EDDHA. Theoretical modelization for HBED and HJB in agronomic conditions has been done after the determination of the protonation and Ca(II), Mg(II), Fe(III), and Cu(II) stability constants for HJB. Also, batch interaction experiments with soils and soil materials have been conducted. According to our results, HJB/Fe(3+) and HBED/Fe(3+) present high stability, even when competing cations (Cu(2+), Ca(2+)) are present, and have low reactivity with soils and soil components. The chelating agent HJB dissolves a higher amount of Fe than o,o-EDDHA, and it seems as effective as o,o-EDDHA in keeping Fe in solution. These results indicate that these chelates may be very efficient products to correct Fe chlorosis, and additional plant experiments should demonstrate plants' ability to assimilate Fe from HJB/Fe(3+) and HBED/Fe(3+).

ISOTOPE FRACTIONATION PROCESS

DOEpatents

Clewett, G.H.; Lee, DeW.A.

1958-05-20

A new method is described for isotopic enrichment of uranium. It has been found that when an aqueous acidic solution of ionic tetravalent uraniunn is contacted with chelate complexed tetravalent uranium, the U/sup 238/ preferentially concentrates in the complexed phase while U/sup 235/ concentrates in the ionic phase. The effect is enhanced when the chelate compound is water insoluble and is dissolved in a water-immiscible organic solvent. Cupferron is one of a number of sultable complexing agents, and chloroform is a suitable organic solvent.

Ethylenediaminetetraacetic acid in endodontics

PubMed Central

Mohammadi, Zahed; Shalavi, Sousan; Jafarzadeh, Hamid

2013-01-01

Ethylenediaminetetraacetic acid (EDTA) is a chelating agent can bind to metals via four carboxylate and two amine groups. It is a polyamino carboxylic acid and a colorless, water-soluble solid, which is widely used to dissolve lime scale. It is produced as several salts, notably disodium EDTA and calcium disodium EDTA. EDTA reacts with the calcium ions in dentine and forms soluble calcium chelates. A review of the literature and a discussion of the different indications and considerations for its usage are presented. PMID:24966721

Chelators influenced synthesis of chitosan-carboxymethyl cellulose microparticles for controlled drug delivery

NASA Astrophysics Data System (ADS)

Samrot, Antony V.; Akanksha; Jahnavi, Tatipamula; Padmanaban, S.; Philip, Sheryl-Ann; Burman, Ujjala; Rabel, Arul Maximus

2016-11-01

In this study, polyphenolic curcumin is entrapped within microcomposites made of biopolymers chitosan (CS) and carboxymethyl cellulose (CMC) formulated by ionic gelation method. Here, different concentrations of two chelating agents, barium chloride and sodium tripolyphosphate, are used to make microcomposites. Thus, the synthesized microparticles were characterized by FTIR, and their surface morphology was studied by SEM. Drug encapsulation efficiency and the drug release kinetics of CS-CMC composites are also studied. The produced microcomposites were used to study antibacterial activity in vitro.

Chelation in metal intoxication. VIII. Removal of chromium from organs of potassium chromate administered rats.

PubMed

Behari, J R; Tandon, S K

1980-03-01

Some polyaminocarboxylic acids were examined for their ability to mobilize chromium from certain vital organs, their subcellular fractions, and blood cells of potassium chromate administered rats. Hexamethylene 1,6-diamino tetraacetic acid (TDTA), triethylene tetramine hexaacetic acid (TTHA), and ethylene diamine di (O-hydroxylphenyl acetic acid) (EDDHA) may be useful in preventing or reducing chromate toxicity. No definite relationship could be observed between the structure of the chelating agents and their chromium-removing capacity.

40 CFR 720.30 - Chemicals not subject to notification requirements.

Code of Federal Regulations, 2011 CFR

2011-07-01

... modifier, pH neutralizer, sequesterant, coagulant, flocculant, fire retardant, lubricant, chelating agent... plastic or rubber molding compounds, inks, drying oils, metal finishing compounds, adhesives, or paints...

Solution thermodynamic stability of complexes formed with the octadentate hydroxypyridinonate ligand 3,4,3-LI(1,2-HOPO): A critical feature for efficient chelation of lanthanide(IV) and actinide(IV) ions

PubMed Central

Deblonde, Gauthier J-P.; Sturzbecher-Hoehne, Manuel; Abergel, Rebecca J.

2013-01-01

The solution thermodynamics of water soluble complexes formed between Ce(III), Ce(IV), Th(IV) and the octadentate chelating agent 3,4,3-LI(1,2-HOPO) were investigated. Several techniques including spectrofluorimetric and automated spectrophotometric titrations were used to overcome the slow spontaneous oxidation of Ce(III) complexes yielding to stability constants of log β110 = 17.4 ± 0.5, log β11-1 = 8.3 ± 0.4 and log β111 = 21.2 ± 0.4 for [Ce(III)(3,4,3-LI(1,2-HOPO))]−, [Ce(III)(3,4,3-LI(1,2-HOPO)(OH)]2− and [Ce(III)(3,4,3-LI(1,2-HOPO)H], respectively. Using the spectral properties of the hydroxypyridinonate chelator in ligand competition titrations against nitrilotriacetic acid, the stability constant log β110 = 41.5 ± 0.5 was determined for [Ce(IV)(3,4,3-LI(1,2-HOPO))]. Finally, the extraordinarily stable complex [Ce(IV)(3,4,3-LI(1,2-HOPO))] was used in Th(IV) competition titrations, resulting in a stability constant of log β110 = 40.1 ± 0.5 for [Th(IV)3,4,3-LI(1,2-HOPO))]. These experimental values are in excellent agreement with previous estimates, they are discussed with respect to the ionic radius and oxidation state of each cationic metal and allow predictions on the stability of other actinide complexes including [U(IV)(3,4,3-LI(1,2-HOPO))], [Np(IV)(3,4,3-LI(1,2-HOPO))] and [Pu(IV)(3,4,3-LI(1,2-HOPO))]. Comparisons with the standard ligand diethylenetriamine pentaacetic acid (DTPA) provide a thermodynamic basis for the observed significantly higher efficacy of 3,4,3-LI(1,2-HOPO) as an in vivo actinide decorporation agent. PMID:23855806

The use of dihexyldithiocarbamate in reverse-phase HPLC of metal chelates

NASA Astrophysics Data System (ADS)

Fatimah, S. S.; Bahti, H. H.; Hastiawan, I.; Permanasari, A.

2018-05-01

Dialkyldithiocarbamates have long been used as chelating agents in reverse-phase HPLC of transition metals. In the previous study, an alkyl homolog of this type of ligand, namely dihexyldithiocarbamate (DHDTC), was synthesized and characterized. The use of this particular ligand in the revese-phase HPLC of some selected transition metal ions is now reported for the first time. The mobile phase comprising of the flow rate and of the detection, in the separation of the metal chelates of Cd (II), Fe (III), Cu (II), and Co (III), were investigated on a C-18 column. The results showed that dihexylditiocarbamate could be used for separating Cd (II), Fe(III), Cu(II), and Co(III). Therefore, it could be used in simultaneous analysis.

Graphene Oxide and Gadolinium-Chelate Functionalized Poly(lactic acid) Nanocapsules Encapsulating Perfluorooctylbromide for Ultrasound/Magnetic Resonance Bimodal Imaging Guided Photothermal Ablation of Cancer.

PubMed

Li, Zhenglin; Ke, Hengte; Wang, Jinrui; Miao, Zhaohua; Yue, Xiuli

2016-03-01

This paper successfully fabricated a novel multifunctional theranostic agent (PFOB@PLA/GO/Gd-DTPA NCs) by loading perfluorooctylbromide (PFOB) into poly(lactic acid) (PLA) nanocapsules (NCs) followed by surface functionalization with graphene oxide (GO) and gadolinium-chelate (Gd-DTPA). It was found that the resulting nanoagent could serve as a contrast agent simultaneously to enhance ultrasound (US) and magnetic resonance imaging (MRI). Benefiting from the strong absorption in the near infrared (NIR) region, the nanocapsules could efficiently kill cancer cells under NIR laser irradiation. Thus, such a single theranostic agent with the combination of realtime US imaging and high-resolution MR imaging could achieve great therapeutic effectiveness without systemic damage to the body. In addition, the cytotoxicity assay on HUVEC cells revealed a good biocompatibility of PFOB@PLA/GO/Gd-DTPA NCs, showing that the versatile nanocapsule system may hold great potential as an effective nanoplatform for contrast enhanced imaging guided photothermal therapy.

Presidential Green Chemistry Challenge: 2001 Greener Synthetic Pathways Award

EPA Pesticide Factsheets

Presidential Green Chemistry Challenge 2001 award winners, Bayer Corporation and Bayer AG, developed a waste-free manufacturing process for sodium iminodisuccinate (Baypure CX), a biodegradable, nontoxic chelating agent.

EDTA chelation effects on urinary losses of cadmium, calcium, chromium, cobalt, copper, lead, magnesium, and zinc.

PubMed

Waters, R S; Bryden, N A; Patterson, K Y; Veillon, C; Anderson, R A

2001-12-01

The efficacy of a chelating agent in binding a given metal in a biological system depends on the binding constants of the chelator for the particular metals in the system, the concentration of the metals, and the presence and concentrations of other ligands competing for the metals in question. In this study, we make a comparison of the in vitro binding constants for the chelator, ethylenediaminetetraacetic acid, with the quantitative urinary excretion of the metals measured before and after EDTA infusion in 16 patients. There were significant increases in lead, zinc, cadmium, and calcium, and these increases roughly corresponded to the expected relative increases predicted by the EDTA-metal-binding constants as measured in vitro. There were no significant increases in urinary cobalt, chromium, or copper as a result of EDTA infusion. The actual increase in cobalt could be entirely attributed to the cobalt content of the cyanocobalamin that was added to the infusion. Although copper did increase in the post-EDTA specimens, the increase was not statistically significant. In the case of magnesium, there was a net retention of approximately 85% following chelation. These data demonstrate that EDTA chelation therapy results in significantly increased urinary losses of lead, zinc, cadmium, and calcium following EDTA chelation therapy. There were no significant changes in cobalt, chromium, or copper and a retention of magnesium. These effects are likely to have significant effects on nutrient concentrations and interactions and partially explain the clinical improvements seen in patients undergoing EDTA chelation therapy.

Lectin conjugates as biospecific contrast agents for MRI. Coupling of Lycopersicon esculentum agglutinin to linear water-soluble DTPA-loaded oligomers.

PubMed

Pashkunova-Martic, Irena; Kremser, Christian; Galanski, Markus; Schluga, Petra; Arion, Vladimir; Debbage, Paul; Jaschke, Werner; Keppler, Bernhard

2011-06-01

Magnetic resonance imaging (MRI) requires synthesis of contrast media bearing targeting groups and numerous gadolinium chelating groups generating high relaxivity. This paper explores the results of linking the gadolinium chelates to the targeting group, a protein molecule, via various types of linkers. Polycondensates of diethylenetriaminepentaacetic acid (DTPA) with either diols or diamines were synthesised and coupled to the targeting group, a lectin (Lycopersicon esculentum agglutinin, tomato lectin) which binds with high affinity to specific oligosaccharide configurations in the endothelial glycocalyx. The polycondensates bear up to four carboxylic groups per constitutive unit. Gd-chelate bonds are created through dative interactions with the unshared pair of electrons on each oxygen and nitrogen atom on DTPA. This is mandatory for complexation of Gd(III) and avoidance of the severe toxicity of free gadolinium ions. The polymer-DTPA compounds were characterised by (1)H NMR and mass spectrometry. The final lectin-DTPA-polycondensate conjugates were purified by fast protein liquid chromatography (FPLC). The capacity for specific binding was assessed, and the MRI properties were examined in order to evaluate the use of these oligomers as components of selective perfusional contrast agents.

Is DTPA a good competing chelating agent for Th(IV) in human serum and suitable in targeted alpha therapy?

PubMed

Le Du, Alicia; Sabatié-Gogova, Andrea; Morgenstern, Alfred; Montavon, Gilles

2012-04-01

The interaction between thorium and human serum components was studied using difference ultraviolet spectroscopy (DUS), ultrafiltration and high-pressure-anion exchange chromatography (HPAEC) with external inductively conducted plasma mass spectrometry (ICP-MS) analysis. Experimental data are compared with modelling results based on the law of mass action. Human serum transferrin (HSTF) interacts strongly with Th(IV), forming a ternary complex including two synergistic carbonate anions. This complex governs Th(IV) speciation under blood serum conditions. Considering the generally used Langmuir-type model, values of 10(33.5) and 10(32.5) were obtained for strong and weak sites, respectively. We showed that trace amounts of diethylene triamine pentaacetic acid (DTPA) cannot complex Th(IV) in the blood serum at equilibrium. Unexpectedly this effect is not related to the competition with HSTF but is due to the strong competition with major divalent metal ions for DTPA. However, Th-DTPA complex was shown to be stable for a few hours when it is formed before addition in the biological medium; this is related to the high kinetic stability of the complex. This makes DTPA a potential chelating agent for synthesis of (226)Th-labelled biomolecules for application in targeted alpha therapy. Copyright © 2011 Elsevier Inc. All rights reserved.

Chelation of Thallium (III) in Rats Using Combined Deferasirox and Deferiprone Therapy.

PubMed

Salehi, Samie; Saljooghi, Amir Sh; Badiee, Somayeh; Moqadam, Mojtaba Mashmool

2017-10-01

Thallium and its compounds are a class of highly toxic chemicals that cause wide-ranging symptoms such as gastrointestinal disturbances; polyneuritis; encephalopathy; tachycardia; skin eruptions; hepatic, renal, cardiac, and neurological toxicities; and have mutagenic and genotoxic effects. The present research aimed to evaluate the efficacy of the chelating agents deferasirox (DFX) and deferiprone (L1) in reducing serum and tissue thallium levels after the administration of thallium (III), according to two different dosing regimens, to several groups of Wistar rats for 60 days. It was hypothesized that the two chelators might be more efficient as a combined therapy than as monotherapies in removing thallium (III) from the rats' organs. The chelators were administered orally as either single or combined therapies for a period of 14 days. Serum and tissue thallium (III) and iron concentrations were determined by flame atomic absorption spectroscopy. Serum and tissue thallium (III) levels were significantly reduced by combined therapy with DFX and L1. Additionally, iron concentrations returned to normal levels and symptoms of toxicity decreased.

Combinational chelation therapy abrogates lead-induced neurodegeneration in rats.

PubMed

Pachauri, Vidhu; Saxena, Geetu; Mehta, Ashish; Mishra, Deepshikha; Flora, Swaran J S

2009-10-15

Lead, a ubiquitous and potent neurotoxicant causes oxidative stress which leads to numerous neurobehavioral and physiological alterations. The ability of lead to bind sulfhydryl groups or compete with calcium could be one of the reasons for its debilitating effects. In the present study, we addressed: i) if chelation therapy could circumvent the altered oxidative stress and prevent neuronal apoptosis in chronic lead-intoxicated rats, ii) whether chelation therapy could reverse biochemical and behavioral changes, and iii) if mono or combinational therapy with captopril (an antioxidant) and thiol chelating agents (DMSA/MiADMSA) is more effective than individual thiol chelator in lead-exposed rats. Results indicated that lead caused a significant increase in reactive oxygen species, nitric oxide, and intracellular free calcium levels along with altered behavioral abnormalities in locomotor activity, exploratory behavior, learning, and memory that were supported by changes in neurotransmitter levels. A fall in membrane potential, release of cytochrome c, and DNA damage indicated mitochondrial-dependent apoptosis. Most of these alterations showed significant recovery following combined therapy with captopril with MiADMSA and to a smaller extend with captopril+DMSA over monotherapy with these chelators. It could be concluded from our present results that co-administration of a potent antioxidant (like captopril) might be a better treatment protocol than monotherapy to counter lead-induced oxidative stress. The major highlight of the work is an interesting experimental evidence of the efficacy of combinational therapy using an antioxidant with a thiol chelator in reversing neurological dystrophy caused due to chronic lead exposure in rats.

Description of 3,180 Courses of Chelation with Dimercaptosuccinic Acid in Children ≤5 y with Severe Lead Poisoning in Zamfara, Northern Nigeria: A Retrospective Analysis of Programme Data

PubMed Central

Thurtle, Natalie; Greig, Jane; Cooney, Lauren; Amitai, Yona; Ariti, Cono; Brown, Mary Jean; Kosnett, Michael J.; Moussally, Krystel; Sani-Gwarzo, Nasir; Akpan, Henry; Shanks, Leslie; Dargan, Paul I.

2014-01-01

Background In 2010, Médecins Sans Frontières (MSF) discovered extensive lead poisoning impacting several thousand children in rural northern Nigeria. An estimated 400 fatalities had occurred over 3 mo. The US Centers for Disease Control and Prevention (CDC) confirmed widespread contamination from lead-rich ore being processed for gold, and environmental management was begun. MSF commenced a medical management programme that included treatment with the oral chelating agent 2,3-dimercaptosuccinic acid (DMSA, succimer). Here we describe and evaluate the changes in venous blood lead level (VBLL) associated with DMSA treatment in the largest cohort of children ≤5 y of age with severe paediatric lead intoxication reported to date to our knowledge. Methods and Findings In a retrospective analysis of programme data, we describe change in VBLL after DMSA treatment courses in a cohort of 1,156 children ≤5 y of age who underwent between one and 15 courses of chelation treatment. Courses of DMSA of 19 or 28 d duration administered to children with VBLL ≥ 45 µg/dl were included. Impact of DMSA was calculated as end-course VBLL as a percentage of pre-course VBLL (ECP). Mixed model regression with nested random effects was used to evaluate the relative associations of covariates with ECP. Of 3,180 treatment courses administered, 36% and 6% of courses commenced with VBLL ≥ 80 µg/dl and ≥ 120 µg/dl, respectively. Overall mean ECP was 74.5% (95% CI 69.7%–79.7%); among 159 inpatient courses, ECP was 47.7% (95% CI 39.7%–57.3%). ECP after 19-d courses (n = 2,262) was lower in older children, first-ever courses, courses with a longer interval since a previous course, courses with more directly observed doses, and courses with higher pre-course VBLLs. Low haemoglobin was associated with higher ECP. Twenty children aged ≤5 y who commenced chelation died during the period studied, with lead poisoning a primary factor in six deaths. Monitoring of alanine transaminase (ALT), creatinine, and full blood count revealed moderate ALT elevation in <2.5% of courses. No clinically severe adverse drug effects were observed, and no laboratory findings required discontinuation of treatment. Limitations include that this was a retrospective analysis of clinical data, and unmeasured variables related to environmental exposures could not be accounted for. Conclusions Oral DMSA was a pharmacodynamically effective chelating agent for the treatment of severe childhood lead poisoning in a resource-limited setting. Re-exposure to lead, despite efforts to remediate the environment, and non-adherence may have influenced the impact of outpatient treatment. Please see later in the article for the Editors' Summary PMID:25291378

Soluble organic substances extracted from compost as amendments for Fenton-like oxidation of contaminated sites.

PubMed

Zingaretti, Daniela; Lombardi, Francesco; Baciocchi, Renato

2018-04-01

The Fenton process is a well known treatment that proved to be effective for the remediation of sites contaminated by a wide range of organic pollutants. Its application to soil-water systems typically requires the addition of a stabilizer, in order to increase the H 2 O 2 lifetime and thus the radius of influence of the treatment, and a chelating agent, aimed to extract and maintain in solution the iron present in the soil. However, as the use of these compounds has been debated for their environmental impact, efforts have been placed to test new "greener" amendments. Namely, in line with the concept of circular economy introduced by the European Council, in this study we have tested the use of humic acids extracted from compost as amendment in a Fenton-like process. These substances are of potential interest as can form complexes with metal ions and act as sorbents for hydrophobic organic compounds. Fenton-like lab-scale tests with the extracted humic acids were performed on a soil-water system artificially contaminated by chlorophenol. The obtained results were compared with those achieved applying commercial humic acids or traditional amendments (i.e. KH 2 PO 4 or EDTA) used as reference. The humic acids extracted from compost allowed to achieve a H 2 O 2 lifetime close to the one obtained with traditional stabilizing agent; besides, humic acids proved also effective in removing chlorophenol, with performance close to the one achieved using a traditional chelating agent. These findings hence suggest that the use of the humic acids extracted from wastes in a Fenton-like process could allow to replace at the same time the H 2 O 2 stabilizer and the chelating agent. Copyright © 2017 Elsevier B.V. All rights reserved.

Imaging agents for in vivo magnetic resonance and scintigraphic imaging

DOEpatents

Engelstad, Barry L.; Raymond, Kenneth N.; Huberty, John P.; White, David L.

1991-01-01

Methods are provided for in vivo magnetic resonance imaging and/or scintigraphic imaging of a subject using chelated transition metal and lanthanide metal complexes. Novel ligands for these complexes are provided.

Transition metal-substituted cobalt ferrite nanoparticles for biomedical applications.

PubMed

Sanpo, Noppakun; Berndt, Christopher C; Wen, Cuie; Wang, James

2013-03-01

Transition metals of copper, zinc, chromium and nickel were substituted into cobalt ferrite nanoparticles via a sol-gel route using citric acid as a chelating agent. The microstructure and elemental composition were characterized using scanning electron microscopy combined with energy-dispersive X-ray spectroscopy. Phase analysis of transition metal-substituted cobalt ferrite nanoparticles was performed via X-ray diffraction. Surface wettability was measured using the water contact angle technique. The surface roughness of all nanoparticles was measured using profilometry. Moreover, thermogravimetric analysis and differential scanning calorimetry were performed to determine the temperature at which the decomposition and oxidation of the chelating agents took place. Results indicated that the substitution of transition metals influences strongly the microstructure, crystal structure and antibacterial property of the cobalt ferrite nanoparticles. Copyright © 2012 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Determining the EDTA Content in a Consumer Shower Cleaner. An Introductory Chemistry Laboratory Experiment

NASA Astrophysics Data System (ADS)

Weigand, Willis A.

2000-10-01

At Altoona College, Chemistry 11 is offered to students as a preparatory course for the University's Chemical Principles course, Chem 12. A relevant laboratory is a source of motivation for the students to learn the chemistry. One way of making the laboratory relevant is to analyze the chemical components of consumer products. Several new shower-cleaning products have been introduced, which advertise that cleaning the shower is no longer necessary. The cleaners work using a combination of surfactants, alcohols, and a chelating agent. The Web site of a popular shower cleaner lists EDTA (ethylenediamine tetraacetate ion) as the chelating agent. The classic EDTA/calcium complexometric titration can be used to determine the EDTA content of the cleaner. This article describes the experiment to determine the EDTA content in a shower-cleaning product.

Effects of method of detachment on electrophoretic mobility of mammalian cells grown in monolayer culture

NASA Technical Reports Server (NTRS)

Plank, L. D.; Kunze, M. E.; Todd, P. W.

1985-01-01

A variety of proteolytic and micolytic enzumes, mechanical procedures, and changes in the ionic environment, especially Ca chelation, are used for dispersal of monolayer grown cells. If either chelating agents or mechanical dispersion are used alone, the cell yield is often low and suspensions of single cells are difficult to obtain. Confluent monolayers treated with EDTA tend to be released from their surfaces in sheets, and clumps of cells remain even after further incubation in EDTA. Crude trypsin is the most popular dispersal agent and is known to contain a variety of contaminating enzymes which contribute to the dispersal of cells. A variety of cell injuries resulting from the activity of proteolytic enzymes are reported. It is shown that crystalline trypsin is least harmful to cell integrity as judged by trypan blue uptake.

Thiourea derivatives as chelating agents for bioconjugation of rhenium and technetium.

PubMed

Gomez, J D Castillo; Hagenbach, A; Gerling-Driessen, U I M; Koksch, B; Beindorff, N; Brenner, W; Abram, U

2017-10-31

Potential tetradentate thiocarbamoylbenzamidine derivatives H 4 L have been synthesized from the corresponding benzimidoyl chlorides and triglycine. They are suitable chelating agents for the oxidotechnetium(v) and oxidorhenium(v) cores and form stable, neutral [MO(HL)] complexes with an equatorial SN 3 coordination sphere and an additional, uncoordinated carboxylic group, which can be used for bioconjugation. Representatives of the rhenium and 99 Tc products have been isolated and analyzed with spectroscopic methods and X-ray diffraction. Bioconjugates of these complexes with angiotensin-II have been synthesized and structurally characterized. Analogous 99m Tc complexes have been produced and tested in vitro and in vivo. The experiments confirm a considerable stability for the [ 99m Tc(HL)] product as well as for its bioconjugate and recommend this class of compounds for further bioconjugation studies towards clinical applications.

Enzymes and chelating agent in cotton pretreatment.

PubMed

Csiszár, E; Losonczi, A; Szakács, G; Rusznák, I; Bezúr, L; Reicher, J

2001-08-23

Desized cotton fabric and cotton seed-coat fragments (impurities) have been treated with commercial cellulase (Celluclast 1.5 L), hemicellulase-pectinase (Viscozyme 120 L) and xylanase (Pulpzyme HC) enzymes. Seed-coat fragments hydrolyzed much faster than the cotton fabric itself. This relative difference in hydrolysis rates makes possible a direct enzymatic removal of seed-coat fragments from desized cotton fabric. Addition of chelating agents such as ethylenediamine-tetra-acetic acid (EDTA) markedly enhanced the directed enzyme action. Pretreatments carried out in acidic solution at pH 5 increased the lightness of seed-coat fragments, contrary to the samples treated in neutral medium at pH 7. Alkaline scouring resulted in darker seed-coat fragments except for the samples pretreated with Pulpzyme HC plus EDTA. This effect is similar to that observed in the biobleaching process in pulp and paper industry.

Determination of o,oEDDHA - a xenobiotic chelating agent used in Fe fertilizers - in plant tissues by liquid chromatography/electrospray mass spectrometry: overcoming matrix effects.

PubMed

Orera, Irene; Abadía, Anunciación; Abadía, Javier; Alvarez-Fernández, Ana

2009-06-01

The Fe(III)-chelate of ethylenediamine-N,N'-bis(o-hydroxyphenylacetic) acid (o,oEDDHA) is generally considered as the most efficient and widespread Fe fertilizer for fruit crops and intensive horticulture. The determination of the xenobiotic chelating agent o,oEDDHA inside the plant is a key issue in the study of this fertilizer. Both the low concentrations of o,oEDDHA expected and the complexity of plant matrices have been important drawbacks in the development of analytical methods for the determination of o,oEDDHA in plant tissues. The determination of o,oEDDHA in plant materials has been tackled in this study by liquid chromatography coupled to mass spectrometry using several plant species and tissues. Two types of internal standards have been tested: Iron stable isotope labeled compounds and a structural analogue compound, the Fe(III) chelate of ethylenediamine-N,N'-bis(2-hydroxy-4-methylphenylacetic) acid (o,oEDDHMA). Iron stable isotope labeled internal standards did not appear to be suitable because of the occurrence of isobaric endogenous compounds and/or isotope exchange reactions between plant native Fe pools and the Fe stable isotope of the internal standard. However, the structural analogue Fe(III)-o,oEDDHMA is an adequate internal standard for the determination of both isomers of o,oEDDHA (racemic and meso) in plant tissues. The method was highly sensitive, with limits of detection and quantification in the range of 3-49 and 11-162 pmol g(-1) fresh weight, respectively, and analyte recoveries were in the range of 74-116%. Using this methodology, both o,oEDDHA isomers were found in all tissues of sugar beet and tomato plants treated with 90 microM Fe(III)-o,oEDDHA for 24 h, including leaves, roots and xylem sap. This methodology constitutes a useful tool for studies on o,oEDDHA plant uptake, transport and allocation. Copyright (c) 2009 John Wiley & Sons, Ltd.

Modern Chemistry Techniques Applied to Metal Behavior and Chelation in Medical and Environmental Systems ? Final Report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sutton, M; Andresen, B; Burastero, S R

2005-02-03

This report details the research and findings generated over the course of a 3-year research project funded by Lawrence Livermore National Laboratory (LLNL) Laboratory Directed Research and Development (LDRD). Originally tasked with studying beryllium chemistry and chelation for the treatment of Chronic Beryllium Disease and environmental remediation of beryllium-contaminated environments, this work has yielded results in beryllium and uranium solubility and speciation associated with toxicology; specific and effective chelation agents for beryllium, capable of lowering beryllium tissue burden and increasing urinary excretion in mice, and dissolution of beryllium contamination at LLNL Site 300; {sup 9}Be NMR studies previously unstudied atmore » LLNL; secondary ionization mass spec (SIMS) imaging of beryllium in spleen and lung tissue; beryllium interactions with aerogel/GAC material for environmental cleanup. The results show that chelator development using modern chemical techniques such as chemical thermodynamic modeling, was successful in identifying and utilizing tried and tested beryllium chelators for use in medical and environmental scenarios. Additionally, a study of uranium speciation in simulated biological fluids identified uranium species present in urine, gastric juice, pancreatic fluid, airway surface fluid, simulated lung fluid, bile, saliva, plasma, interstitial fluid and intracellular fluid.« less

Post-transfusional iron overload in the haemoglobinopathies.

PubMed

Thuret, Isabelle

2013-03-01

In this report, we review the recent advances in evaluation and treatment of transfusional iron overload (IO). Results of the French thalassaemia registry are described. According to the disease, thalassaemia major or sickle cell anaemia, mechanisms and toxicity of iron overload, knowledge about IO long-term outcome and chelation treatment results, respective value of IO markers, differ. The recent tools evaluating organ specific IO and the diversification of iron chelator agents make possible to individualize chelation therapy in clinical practice. The severity of IO and the level of transfusional iron intake, the preferential localization of IO (heart/liver) as well as the tolerance and adherence profiles of the patient can now be taken into account. Introduction of cardiac magnetic resonance imaging for the quantification of myocardial iron and use of oral chelators have already been reported as decreasing the cardiac mortality rate related to IO in thalassaemia major patients. Long-term observation of patients under oral chelators will show if morbidity is also improving via a more continuous control of toxic iron and/or a better accessibility to cellular iron pools. Copyright © 2012 Académie des sciences. Published by Elsevier SAS. All rights reserved.

Alternative Chelator for 89Zr Radiopharmaceuticals: Radiolabeling and Evaluation of 3,4,3-(LI-1,2-HOPO)

PubMed Central

2015-01-01

Zirconium-89 is an effective radionuclide for antibody-based positron emission tomography (PET) imaging because its physical half-life (78.41 h) matches the biological half-life of IgG antibodies. Desferrioxamine (DFO) is currently the preferred chelator for 89Zr4+; however, accumulation of 89Zr in the bones of mice suggests that 89Zr4+ is released from DFO in vivo. An improved chelator for 89Zr4+ could eliminate the release of osteophilic 89Zr4+ and lead to a safer PET tracer with reduced background radiation dose. Herein, we present an octadentate chelator 3,4,3-(LI-1,2-HOPO) (or HOPO) as a potentially superior alternative to DFO. The HOPO ligand formed a 1:1 Zr-HOPO complex that was evaluated experimentally and theoretically. The stability of 89Zr-HOPO matched or surpassed that of 89Zr-DFO in every experiment. In healthy mice, 89Zr-HOPO cleared the body rapidly with no signs of demetalation. Ultimately, HOPO has the potential to replace DFO as the chelator of choice for 89Zr-based PET imaging agents. PMID:24814511

Copper Loading of Preformed Nanoparticles for PET-Imaging Applications.

PubMed

Lu, Hoang D; Wang, Leon Z; Wilson, Brian K; McManus, Simon A; Jumai'an, Jenny; Padakanti, Prashanth K; Alavi, Abass; Mach, Robert H; Prud'homme, Robert K

2018-01-31

Nanoparticles (NP) are promising contrast agents for positron emission tomography (PET) radionuclide imaging that can increase signal intensity by localizing clusters of PET radionuclides together. However, methods to load NPs with PET radionuclides suffer from harsh loading conditions or poor loading efficacies or result in NP surface modifications that alter targeting in vivo. We present the formation of water-dispersible, polyethylene glycol coated NPs that encapsulate phthalocyanines into NP cores at greater than 50 wt % loading, using the self-assembly technique Flash NanoPrecipitation. Particles from 70 to 160 nm are produced. Phthalocyanine NPs rapidly and spontaneously chelate metals under mild conditions and can act as sinks for PET radionuclides such as 64-Cu to produce PET-active NPs. NPs chelate copper(II) with characteristic rates of 1845 M -1 h -1 at pH 6 and 37 °C, which produced >90% radionuclide chelation within 1 h. NP physical properties, such as core composition, core fluidity, and size, can be tuned to modulate chelation kinetics. These NPs retain 64 Cu even in the presence of the strong chelator ethylene diamine tetraacetic acid. The development of these constructs for rapid and facile radionuclide labeling expands the applications of NP-based PET imaging.

Tripeptide GGH as the Inhibitor of Copper-Amyloid-β-Mediated Redox Reaction and Toxicity.

PubMed

Hu, Xiaoyu; Zhang, Qian; Wang, Wei; Yuan, Zhi; Zhu, Xushan; Chen, Bing; Chen, Xingyu

2016-09-21

The Aβ complexes of some redox-active species, such as Cu, cause oxidative stress and induce severe toxicity by generating reactive oxygen species (ROS). Thus, Cu chelation therapy should be considered as a valuable strategy for the treatment of Alzheimer's disease (AD). However, more attention should be paid to the specific chelating ability of these chelating agents. Herein, a tripeptide GGH was used to selectively chelate the Cu(2+) in Aβ-Cu complex in the presence of other metal ions (e.g., K(+), Ca(2+), Ni(2+), Mg(2+), and Zn(2+)) as shown by isothermal titration calorimetry results. GGH decreased the level of HO(•) radicals by preventing the formation of intermediate Cu(I) ion. Thus, the Cu species completely lost its catalytic activity at a superequimolar GGH/Cu(II) ratio (4:1) as observed by UV-visible spectroscopy, coumarin-3-carboxylic acid fluorescence, and BCA assay. Moreover, (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) (MTT) assay indicates that GGH increased PC-12 cell viability from 36% to 63%, and neurotoxicity partly triggered by ROS decreased. These results indicate potential development of peptide chelation therapy for AD treatment.

Integrin Targeted MR Imaging

PubMed Central

Tan, Mingqian; Lu, Zheng-Rong

2011-01-01

Magnetic resonance imaging (MRI) is a powerful medical diagnostic imaging modality for integrin targeted imaging, which uses the magnetic resonance of tissue water protons to display tissue anatomic structures with high spatial resolution. Contrast agents are often used in MRI to highlight specific regions of the body and make them easier to visualize. There are four main classes of MRI contrast agents based on their different contrast mechanisms, including T1, T2, chemical exchange saturation transfer (CEST) agents, and heteronuclear contrast agents. Integrins are an important family of heterodimeric transmembrane glycoproteins that function as mediators of cell-cell and cell-extracellular matrix interactions. The overexpressed integrins can be used as the molecular targets for designing suitable integrin targeted contrast agents for MR molecular imaging. Integrin targeted contrast agent includes a targeting agent specific to a target integrin, a paramagnetic agent and a linker connecting the targeting agent with the paramagnetic agent. Proper selection of targeting agents is critical for targeted MRI contrast agents to effectively bind to integrins for in vivo imaging. An ideal integrin targeted MR contrast agent should be non-toxic, provide strong contrast enhancement at the target sites and can be completely excreted from the body after MR imaging. An overview of integrin targeted MR contrast agents based on small molecular and macromolecular Gd(III) complexes, lipid nanoparticles and superparamagnetic nanoparticles is provided for MR molecular imaging. By using proper delivery systems for loading sufficient Gd(III) chelates or superparamagnetic nanoparticles, effective molecular imaging of integrins with MRI has been demonstrated in animal models. PMID:21547154

The National Shipbuilding Research Program. Trailer Mounted Water Recovery and Reuse System

DTIC Science & Technology

2000-11-30

surfactants, and stabilize oil emulsions. • Sequestering or chelating agents bind problematic ions such as calcium or iron, which tend to form deposits on...cleaned parts. • Wetting/emulsifying agents (surfactants) help remove oil from dirty parts and stabilize the removed oil, preventing it from redepositing...neutralized; • The metal-loading can overcome the sequestering agents ’ capacity to keep the metals in solution; and • Oil and grease, if held in the emulsified

Quantitative structure-property relationship (correlation analysis) of phosphonic acid-based chelates in design of MRI contrast agent.

PubMed

Tiwari, Anjani K; Ojha, Himanshu; Kaul, Ankur; Dutta, Anupama; Srivastava, Pooja; Shukla, Gauri; Srivastava, Rakesh; Mishra, Anil K

2009-07-01

Nuclear magnetic resonance imaging is a very useful tool in modern medical diagnostics, especially when gadolinium (III)-based contrast agents are administered to the patient with the aim of increasing the image contrast between normal and diseased tissues. With the use of soft modelling techniques such as quantitative structure-activity relationship/quantitative structure-property relationship after a suitable description of their molecular structure, we have studied a series of phosphonic acid for designing new MRI contrast agent. Quantitative structure-property relationship studies with multiple linear regression analysis were applied to find correlation between different calculated molecular descriptors of the phosphonic acid-based chelating agent and their stability constants. The final quantitative structure-property relationship mathematical models were found as--quantitative structure-property relationship Model for phosphonic acid series (Model 1)--log K(ML) = {5.00243(+/-0.7102)}- MR {0.0263(+/-0.540)}n = 12 l r l = 0.942 s = 0.183 F = 99.165 quantitative structure-property relationship Model for phosphonic acid series (Model 2)--log K(ML) = {5.06280(+/-0.3418)}- MR {0.0252(+/- .198)}n = 12 l r l = 0.956 s = 0.186 F = 99.256.

Clinical consequences of iron overload in patients with myelodysplastic syndromes: the case for iron chelation therapy.

PubMed

Shammo, Jamile M; Komrokji, Rami S

2018-06-14

Patients with myelodysplastic syndromes (MDS) are at increased risk of iron overload due to ineffective erythropoiesis and chronic transfusion therapy. The clinical consequences of iron overload include cardiac and/or hepatic failure, endocrinopathies, and infection risk. Areas covered: Iron chelation therapy (ICT) can help remove excess iron and ultimately reduce the clinical consequences of iron overload. The authors reviewed recent (last five years) English-language articles from PubMed on the topic of iron overload-related complications and the use of ICT (primarily deferasirox) to improve outcomes in patients with MDS. Expert Commentary: While a benefit of ICT has been more firmly established in other transfusion-dependent conditions such as thalassemia, its role in reducing iron overload in MDS remains controversial due to the lack of prospective controlled data demonstrating a survival benefit. Orally administered chelation agents (e.g., deferasirox), are now available, and observational and/or retrospective data support a survival benefit of using ICT in MDS. The placebo-controlled TELESTO trial (NCT00940602) is currently examining the use of deferasirox in MDS patients with iron overload, and is evaluating specifically whether use of ICT to alleviate iron overload can also reduce iron overload-related complications in MDS and improve survival.

Imaging agents for in vivo magnetic resonance and scintigraphic imaging

DOEpatents

Engelstad, B.L.; Raymond, K.N.; Huberty, J.P.; White, D.L.

1991-04-23

Methods are provided for in vivo magnetic resonance imaging and/or scintigraphic imaging of a subject using chelated transition metal and lanthanide metal complexes. Novel ligands for these complexes are provided. No Drawings

Corrosion Inhibitors for Aluminum.

ERIC Educational Resources Information Center

Muller, Bodo

1995-01-01

Describes a simple and reliable test method used to investigate the corrosion-inhibiting effects of various chelating agents on aluminum pigments in aqueous alkaline media. The experiments that are presented require no complicated or expensive electronic equipment. (DDR)

Inert Reassessment Document for Ethylenediaminetetracetric acid (EDTA)

EPA Pesticide Factsheets

EDTA is a chelating agent. Its ability to bind heavy metal ions can be used to sequester these trace metals. However, trace amounts of various metals are necessary for the proper functioning of the body.

Transglutaminase-mediated conjugation and nitride-technetium-99m labelling of a bis(thiosemicarbazone) bifunctional chelator.

PubMed

Salvarese, Nicola; Spolaore, Barbara; Marangoni, Selena; Pasin, Anna; Galenda, Alessandro; Tamburini, Sergio; Cicoria, Gianfranco; Refosco, Fiorenzo; Bolzati, Cristina

2018-06-01

An assessment study involving the use of the transglutaminase (TGase) conjugation method and the nitride-technetium-99m labelling on a bis(thiosemicarbazone) (BTS) bifunctional chelating agent is presented. The previously described chelator diacetyl-2-(N 4 -methyl-3-thiosemicarbazone)-3-(N 4 -amino-3-thiosemicarbazone), H 2 ATSM/A, has been functionalized with 6-aminohexanoic acid (ε-Ahx) to generate the bifunctional chelating agent diacetyl-2-(N 4 -methyl-3-thiosemicarbazone)-3-[N 4 -(amino)-(6-aminohexanoic acid)-3-thiosemicarbazone], H 2 ATSM/A-ε-Ahx (1), suitable for conjugation to glutamine (Gln) residues of bioactive molecules via TGase. The feasibility of the TGase reaction in the synthesis of a bioconjugate derivative was investigated using Substance P (SP) as model peptide. Compounds 1 and H 2 ATSM/A-ε-Ahx-SP (2) were labelled with nitride-technetium-99m, obtaining the complexes [ 99m Tc][Tc(N)(ATSM/A-ε-Ahx)] ( 99m Tc1) and [ 99m Tc][Tc(N)(ATSM/A-ε-Ahx-SP)] ( 99m Tc2). The chemical identity of 99m Tc1 and 99m Tc2 was confirmed by radio/UV-RP-HPLC combined with ESI-MS analysis on the respective carrier-added products 99g/99m Tc1 and 99g/99m Tc2. The stability of the radiolabelled complexes after incubation in various environments was investigated. All the results were compared with those obtained for the corresponding 64 Cu-analogues, 64 Cu1 and 64 Cu2. The TGase reaction allows the conjugation of 1 with the peptide, but it is not highly efficient due to instability of the chelator in the required conditions. The SP-conjugated complexes are unstable in mouse and human sera. However, indeed the BTS system can be exploited as nitride-technetium-99m chelator for highly efficient technetium labelling, thus making compound 1 worthy of further investigations for new targeted technetium and copper radiopharmaceuticals encompassing Single Photon Emission Computed Tomography and Positron Emission Tomography imaging. Copyright © 2018 Elsevier Inc. All rights reserved.

Surface impact on nanoparticle-based magnetic resonance imaging contrast agents

PubMed Central

Zhang, Weizhong; Liu, Lin; Chen, Hongmin; Hu, Kai; Delahunty, Ian; Gao, Shi; Xie, Jin

2018-01-01

Magnetic resonance imaging (MRI) is one of the most widely used diagnostic tools in the clinic. To improve imaging quality, MRI contrast agents, which can modulate local T1 and T2 relaxation times, are often injected prior to or during MRI scans. However, clinically used contrast agents, including Gd3+-based chelates and iron oxide nanoparticles (IONPs), afford mediocre contrast abilities. To address this issue, there has been extensive research on developing alternative MRI contrast agents with superior r1 and r2 relaxivities. These efforts are facilitated by the fast progress in nanotechnology, which allows for preparation of magnetic nanoparticles (NPs) with varied size, shape, crystallinity, and composition. Studies suggest that surface coatings can also largely affect T1 and T2 relaxations and can be tailored in favor of a high r1 or r2. However, the surface impact of NPs has been less emphasized. Herein, we review recent progress on developing NP-based T1 and T2 contrast agents, with a focus on the surface impact. PMID:29721097

A New Approach in the Preparation of Dendrimer-Based Bifunctional Diethylenetriaminepentaacetic Acid MR Contrast Agent Derivatives

PubMed Central

Nwe, Kido; Xu, Heng; Regino, Celeste Aida S.; Bernardo, Marcelino; Ileva, Lilia; Riffle, Lisa; Wong, Karen J.; Brechbiel, Martin W.

2009-01-01

In this paper we report a new method to prepare and characterize a contrast agent based on a fourth-generation (G4) polyamidoamine (PAMAM) dendrimer conjugated to the gadolinium complex of the bifunctional diethylenetriamine pentaacetic acid derivative (1B4M-DTPA). The method involves pre-forming the metal-ligand chelate in alcohol prior to conjugation to the dendrimer. The dendrimer-based agent was purified by a Sephadex® G-25 column and characterized by elemental analysis. The analysis and SEHPLC data gave a chelate to dendrimer ratio of 30:1 suggesting conjugation at approximately every other amine terminal on the dendrimer. Molar relaxivity of the agent measured at pH 7.4 displayed a higher value than that of the analogous G4 dendrimer based agent prepared by the post-metal incorporation method (r1 = 26.9 vs. 13.9 mM-1s-1 at 3T and 22°C). This is hypothesized to be due to the higher hydrophobicity of this conjugate, and the lack of available charged carboxylate groups from non-complexed free ligands that might coordinate to the metal and thus also reduce water exchange sites. Additionally, the distribution populations of compounds that result from the post-metal incorporation route are eliminated from the current product simplifying characterization as quality control issues pertaining to the production of such agents for clinical use as MR contrast agents. In vivo imaging in mice showed a reasonably fast clearance (t1/2 = 24 min) suggesting a viable agent for use in clinical application. PMID:19555072

A new approach in the preparation of dendrimer-based bifunctional diethylenetriaminepentaacetic acid MR contrast agent derivatives.

PubMed

Nwe, Kido; Xu, Heng; Regino, Celeste Aida S; Bernardo, Marcelino; Ileva, Lilia; Riffle, Lisa; Wong, Karen J; Brechbiel, Martin W

2009-07-01

In this paper, we report a new method to prepare and characterize a contrast agent based on a fourth-generation (G4) polyamidoamine (PAMAM) dendrimer conjugated to the gadolinium complex of the bifunctional diethylenetriamine pentaacetic acid derivative (1B4M-DTPA). The method involves preforming the metal-ligand chelate in alcohol prior to conjugation to the dendrimer. The dendrimer-based agent was purified by a Sephadex G-25 column and characterized by elemental analysis. The analysis and SE-HPLC data gave a chelate to dendrimer ratio of 30:1 suggesting conjugation at approximately every other amine terminal on the dendrimer. Molar relaxivity of the agent measured at pH 7.4 displayed a higher value than that of the analogous G4 dendrimer based agent prepared by the postmetal incorporation method (r(1) = 26.9 vs 13.9 mM(-1) s(-1) at 3 T and 22 degrees C). This is hypothesized to be due to the higher hydrophobicity of this conjugate and the lack of available charged carboxylate groups from noncomplexed free ligands that might coordinate to the metal and thus also reduce water exchange sites. Additionally, the distribution populations of compounds that result from the postmetal incorporation route are eliminated from the current product simplifying characterization as quality control issues pertaining to the production of such agents for clinical use as MR contrast agents. In vivo imaging in mice showed a reasonably fast clearance (t(1/2) = 24 min) suggesting a viable agent for use in clinical application.

Complementary and Alternative Therapies in ALS

PubMed Central

Bedlack, Richard S.; Joyce, Nanette; Carter, Gregory T.; Pagononi, Sabrina; Karam, Chafic

2015-01-01

Synopsis Given the severity of their illness and lack of effective disease modifying agents, it is not surprising that most patients with ALS consider trying complementary and alternative therapies. Some of the most commonly considered alternative therapies include special diets, nutritional supplements, cannabis, acupuncture, chelation and energy healing. This chapter reviews these in detail. We also describe 3 models by which physicians may frame discussions about alternative therapies: paternalism, autonomy and shared decision making. Finally, we review a program called ALSUntangled which using shared shared decision making to review alternative therapies for ALS. PMID:26515629

Fabrication of transparent ceramics using nanoparticles

DOEpatents

Cherepy, Nerine J; Tillotson, Thomas M; Kuntz, Joshua D; Payne, Stephen A

2012-09-18

A method of fabrication of a transparent ceramic using nanoparticles synthesized via organic acid complexation-combustion includes providing metal salts, dissolving said metal salts to produce an aqueous salt solution, adding an organic chelating agent to produce a complexed-metal sol, heating said complexed-metal sol to produce a gel, drying said gel to produce a powder, combusting said powder to produce nano-particles, calcining said nano-particles to produce oxide nano-particles, forming said oxide nano-particles into a green body, and sintering said green body to produce the transparent ceramic.

Structures and mechanisms of antitumor agents: xestoquinones uncouple cellular respiration and disrupt HIF signaling in human breast tumor cells.

PubMed

Du, Lin; Mahdi, Fakhri; Datta, Sandipan; Jekabsons, Mika B; Zhou, Yu-Dong; Nagle, Dale G

2012-09-28

The organic extract of a marine sponge, Petrosia alfiani, selectively inhibited iron chelator-induced hypoxia-inducible factor-1 (HIF-1) activation in a human breast tumor T47D cell-based reporter assay. Bioassay-guided fractionation yielded seven xestoquinones (1-7) including three new compounds: 14-hydroxymethylxestoquinone (1), 15-hydroxymethylxestoquinone (2), and 14,15-dihydroxestoquinone (3). Compounds 1-7 were evaluated for their effects on HIF-1 signaling, mitochondrial respiration, and tumor cell proliferation/viability. The known metabolites adociaquinones A (5) and B (6), which possess a 3,4-dihydro-2H-1,4-thiazine-1,1-dioxide moiety, potently and selectively inhibited iron chelator-induced HIF-1 activation in T47D cells, each with an IC(50) value of 0.2 μM. Mechanistic studies revealed that adociaquinones promote oxygen consumption without affecting mitochondrial membrane potential. Compound 1 both enhances respiration and decreases mitochondrial membrane potential, suggesting that it acts as a protonophore that uncouples mitochondrial respiration.

Efficacy of chelation therapy to remove aluminium intoxication.

PubMed

Fulgenzi, Alessandro; De Giuseppe, Rachele; Bamonti, Fabrizia; Vietti, Daniele; Ferrero, Maria Elena

2015-11-01

There is a distinct correlation between aluminium (Al) intoxication and neurodegenerative diseases (ND). We demonstrated how patients affected by ND showing Al intoxication benefit from short-term treatment with calcium disodium ethylene diamine tetraacetic acid (EDTA) (chelation therapy). Such therapy further improved through daily treatment with the antioxidant Cellfood. In the present study we examined the efficacy of long-term treatment, using both EDTA and Cellfood. Slow intravenous treatment with the chelating agent EDTA (2 g/10 mL diluted in 500 mL physiological saline administered in 2 h) (chelation test) removed Al, which was detected (using inductively coupled plasma mass spectrometry) in urine samples collected from patients over 12 h. Patients that revealed Al intoxication (expressed in μg per g creatinine) underwent EDTA chelation therapy once a week for ten weeks, then once every two weeks for a further six or twelve months. At the end of treatment (a total of 22 or 34 chelation therapies, respectively), associated with daily assumption of Cellfood, Al levels in the urine samples were analysed. In addition, the following blood parameters were determined: homocysteine, vitamin B12, and folate, as well as the oxidative status e.g. reactive oxygen species (ROS), total antioxidant capacity (TAC), oxidized LDL (oxLDL), and glutathione. Our results showed that Al intoxication reduced significantly following EDTA and Cellfood treatment, and clinical symptoms improved. After treatment, ROS, oxLDL, and homocysteine decreased significantly, whereas vitamin B12, folate and TAC improved significantly. In conclusion, our data show the efficacy of chelation therapy associated with Cellfood in subjects affected by Al intoxication who have developed ND.

Reversible loss of gravitropic sensitivity in maize roots after tip application of calcium chelators

NASA Technical Reports Server (NTRS)

Lee, J. S.; Mulkey, T. J.; Evans, M. L.

1983-01-01

The application of calcium chelating agents (EDTA or EGTA) to the tips of maize roots caused a loss of gravitropic sensitivity. When the chelator was replaced with calcium chloride, gravitropic sensitivity was restored. Asymmetric application of calcium chloride near the tip of a vertical root caused curvature toward the calcium source. When the calcium was applied to the upper surface of the tip of a root oriented horizontally, the root curved upward even though control roots exhibited strong downward curvature. Application of calcium chloride to the tips of decapped roots, which are known to be gravitropically insensitive, did not restore gravitropic sensitivity. However, asymmetric application of calcium chloride near the tips of decapped roots caused curvature toward the calcium source. Calcium may play a key role in linking gravity detection to gravitropic curvature in roots.

Removal of mercury from the environment: a quantum-chemical study with the normalized elimination of the small component method.

PubMed

Zou, Wenli; Filatov, Michael; Atwood, David; Cremer, Dieter

2013-03-04

1,3-Benzenediamidoethanethiolatemercury [BDT-Hg or BD(S)-Hg] and its derivatives are investigated utilizing the Dirac exact relativistic normalized elimination of the small component method in connection with B3LYP, CCSD(T), and polarizable continuum calculations. It is shown that the chelating energy of BDT-Hg can be significantly increased by replacing sulfur with selenium or tellurium, thus leading to BD(Se)-Hg or BD(Te)-Hg. In this particular case, the chalcogenophilicity of mercury increases from S to Te because increasing the E-Hg bond lengths leads to a reduction of ring strain. Various possibilities of increasing the metal (M) chelating strength in BDT-M complexes are investigated, and suggestions for new chelating agents based on the BDT-M template are made.

Cage-like bifunctional chelators, copper-64 radiopharmaceuticals and PET imaging using the same

DOEpatents

Conti, Peter S.; Cai, Hancheng; Li, Zibo; Liu, Shuanglong

2016-08-02

Disclosed is a class of versatile Sarcophagine based bifunctional chelators (BFCs) containing a hexa-aza cage for labeling with metals having either imaging, therapeutic or contrast applications radiolabeling and one or more linkers (A) and (B). The compounds have the general formula ##STR00001## where A is a functional group selected from group consisting of an amine, a carboxylic acid, an ester, a carbonyl, a thiol, an azide and an alkene, and B is a functional group selected from the group consisting of hydrogen, an amine, a carboxylic acid, and ester, a carbonyl, a thiol, an azide and an alkene. Also disclosed are conjugate of the BFC and a targeting moiety, which may be a peptide or antibody. Also disclosed are metal complexes of the BFC/targeting moiety conjugates that are useful as radiopharmaceuticals, imaging agents or contrast agents.

Profound Morphological Changes in the Erythrocytes and Fibrin Networks of Patients with Hemochromatosis or with Hyperferritinemia, and Their Normalization by Iron Chelators and Other Agents

PubMed Central

Pretorius, Etheresia; Bester, Janette; Vermeulen, Natasha; Lipinski, Boguslaw; Gericke, George S.; Kell, Douglas B.

2014-01-01

It is well-known that individuals with increased iron levels are more prone to thrombotic diseases, mainly due to the presence of unliganded iron, and thereby the increased production of hydroxyl radicals. It is also known that erythrocytes (RBCs) may play an important role during thrombotic events. Therefore the purpose of the current study was to assess whether RBCs had an altered morphology in individuals with hereditary hemochromatosis (HH), as well as some who displayed hyperferritinemia (HF). Using scanning electron microscopy, we also assessed means by which the RBC and fibrin morphology might be normalized. An important objective was to test the hypothesis that the altered RBC morphology was due to the presence of excess unliganded iron by removing it through chelation. Very striking differences were observed, in that the erythrocytes from HH and HF individuals were distorted and had a much greater axial ratio compared to that accompanying the discoid appearance seen in the normal samples. The response to thrombin, and the appearance of a platelet-rich plasma smear, were also markedly different. These differences could largely be reversed by the iron chelator desferal and to some degree by the iron chelator clioquinol, or by the free radical trapping agents salicylate or selenite (that may themselves also be iron chelators). These findings are consistent with the view that the aberrant morphology of the HH and HF erythrocytes is caused, at least in part, by unliganded (‘free’) iron, whether derived directly via raised ferritin levels or otherwise, and that lowering it or affecting the consequences of its action may be of therapeutic benefit. The findings also bear on the question of the extent to which accepting blood donations from HH individuals may be desirable or otherwise. PMID:24416376

Screening of chelating ligands to enhance mercury accumulation from historically mercury-contaminated soils for phytoextraction.

PubMed

Wang, Jianxu; Xia, Jicheng; Feng, Xinbin

2017-01-15

Screening of optimal chelating ligands which not only have high capacities to enhance plant uptake of mercury (Hg) from soil but also can decrease bioavailable Hg concentration in soil is necessary to establish a viable chemically-assisted phytoextraction. Therefore, Brassica juncea was exposed to historically Hg-contaminated soil (total Hg, 90 mg kg -1 ) to investigate the efficiency of seven chelating agents [ammonium thiosulphate, sodium thiosulphate, ammonium sulfate, ammonium chloride, sodium nitrate, ethylenediaminetetraacetic acid (EDTA), and sodium sulfite] at enhancing Hg phytoextraction; the leaching of bioavailable Hg caused by these chelating agents was also investigated. The Hg concentration in control (treated with double-distilled water) plant tissues was below 1 mg kg -1 . The remarkably higher Hg concentration was found in plants receiving ammonium thiosulphate and sodium sulfite treatments. The bioaccumulation factors and translocation factors of ammonium thiosulphate and sodium sulfite treatments were significantly higher than those of the other treatments. The more efficient uptake of Hg by plants upon treatment with ammonium thiosulphate and sodium sulfite compared to the other treatments might be explained by the formation of special Hg-thiosulphate complexes that could be preferentially taken up by the roots and transported in plant tissues. The application of sulfite significantly increased bioavailable Hg concentration in soil compared with that in initial soil and control soil, whereas ammonium thiosulphate significantly decreased bioavailable Hg concentration. The apparent decrease of bioavailable Hg in ammonium thiosulphate-treated soil compared with that in sodium sulfite-treated soil might be attributable to the unstable Hg-thiosulphate complexes formed between thiosulphate and Hg; they could react to produce less bioavailable Hg in the soil. The results of this study indicate that ammonium thiosulphate may be an optimal chelating ligand for phytoextraction due to its great potential to enhance Hg accumulation in plants while decreasing bioavailable Hg concentration in the soil. Copyright © 2016 Elsevier Ltd. All rights reserved.

Repurposing of Copper(II)-chelating Drugs for the Treatment of Neurodegenerative Diseases.

PubMed

Lanza, Valeria; Milardi, Danilo; Di Natale, Giuseppe; Pappalardo, Giuseppe

2018-02-12

There is mounting urgency to find new drugs for the treatment of neurodegenerative disorders. A large number of reviews have exhaustively described either the molecular or clinical aspects of neurodegenerative diseases such as Alzheimer's (AD) and Parkinson's (PD). Conversely, reports outlining how known drugs in use for other diseases can also be effective as therapeutic agents in neurodegenerative diseases are less reported. This review focuses on the current uses of some copper(II) chelating molecules as potential drug candidates in neurodegeneration. Starting from the well-known harmful relationships existing between the dyshomeostasis and mis-management of metals and AD onset, we surveyed the experimental work reported in the literature, which deals with the repositioning of metal-chelating drugs in the field of neurodegenerative diseases. The reviewed papers were retrieved from common literature and their selection was limited to those describing the biomolecular aspects associated with neuroprotection. In particular, we emphasized the copper(II) coordination abilities of the selected drugs. Copper, together with zinc and iron, are known to play a key role in regulating neuronal functions. Changes in copper homeostasis are crucial for several neurodegenerative disorders. The studies included in this review may provide an overview on the current strategies aimed at repurposing copper (II) chelating drugs for the treatment of neurodegenerative disorders. Starting from the exemplary case of clioquinol repurposing, we discuss the challenge and the opportunities that repurposing of other metal-chelating drugs may provide (e.g. PBT-2, metformin and cyclodipeptides) in the treatment of neurodegenerative disease. In order to improve the success rate of drug repositioning, comprehensive studies on the molecular mechanism and therapeutic efficacy are still required. The present review upholds that drug repurposing makes significant advantages over drug discovery since repositioned drugs had already passed the safety and toxicity tests. Promising drug candidates in neurodegenerative diseases may be represented by copper chelating classes of drugs, provided that sufficient details on their mechanism of action are available to encourage further investigations and clinical trials. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Superfund Record of Decision (EPA Region 4): Ciba-Geigy, Washington County, Mcintosh, AL. (Second remedial action), September 1991

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

1991-09-30

The 1,500-acre Ciba-Geigy site is an active chemical manufacturer in an industrial area in McIntosh, Washington County, Alabama. From 1952 to present, Ciba-Geigy, formerly Geigy Chemical Corporation, has produced various chemicals including DDT, laundry products, herbicides, insecticides, agricultural chelating agents, sequestering agents, plastic resins and additives, antioxidants, and specialty chemicals. In 1985, EPA issued a RCRA permit that included a corrective action plan requiring Ciba-Geigy to remove and treat ground water and surface water contamination at the site. In 1987, as part of the corrective action plan requirements, Ciba-Geigy installed an additional wastewater treatment system and ground water monitoring wells.more » The ROD addresses highly contaminated soil and sludge at 10 of the 11 former waste management areas as OU2. The primary contaminants of concern affecting the soil, sludge, and debris are VOCs including benzene and toluene; other organics including PCBs and pesticides (e.g., DDT); and metals including lead. The selected remedial action for the site is included.« less

Detecting microdamage in bone.

PubMed

Lee, T C; Mohsin, S; Taylor, D; Parkesh, R; Gunnlaugsson, T; O'Brien, F J; Giehl, M; Gowin, W

2003-08-01

Fatigue-induced microdamage in bone contributes to stress and fragility fractures and acts as a stimulus for bone remodelling. Detecting such microdamage is difficult as pre-existing microdamage sustained in vivo must be differentiated from artefactual damage incurred during specimen preparation. This was addressed by bulk staining specimens in alcohol-soluble basic fuchsin dye, but cutting and grinding them in an aqueous medium. Nonetheless, some artefactual cracks are partially stained and careful observation under transmitted light, or epifluorescence microscopy, is required. Fuchsin lodges in cracks, but is not site-specific. Cracks are discontinuities in the calcium-rich bone matrix and chelating agents, which bind calcium, can selectively label them. Oxytetracycline, alizarin complexone, calcein, calcein blue and xylenol orange all selectively bind microcracks and, as they fluoresce at different wavelengths and colours, can be used in sequence to label microcrack growth. New agents that only fluoresce when involved in a chelate are currently being developed--fluorescent photoinduced electron transfer (PET) sensors. Such agents enable microdamage to be quantified and crack growth to be measured and are useful histological tools in providing data for modelling the material behaviour of bone. However, a non-invasive method is needed to measure microdamage in patients. Micro-CT is being studied and initial work with iodine dyes linked to a chelating group has shown some promise. In the long term, it is hoped that repeated measurements can be made at critical sites and microdamage accumulation monitored. Quantification of microdamage, together with bone mass measurements, will help in predicting and preventing bone fracture failure in patients with osteoporosis.

Optimized ultrasound-assisted emulsification microextraction for simultaneous trace multielement determination of heavy metals in real water samples by ICP-OES.

PubMed

Sereshti, Hassan; Heravi, Yeganeh Entezari; Samadi, Soheila

2012-08-15

Ultrasonic-assisted emulsification microextraction (USAEME) combined with inductively coupled plasma-optical emission spectrometry (ICP-OES) was used for preconcentration and determination of aluminum, bismuth, cadmium, cobalt, copper, iron, gallium, indium, nickel, lead, thallium and zinc in real water samples. Ammonium pyrrolidine dithiocarbamate (APDC) and carbon tetrachloride (CCl(4)) were used as the chelating agent and extraction solvent, respectively. The effective parameters (factors) of the extraction process such as volume of extraction solvent, pH, sonication time, and concentration of chelating agent were optimized by a small central composite design (CCD). The optimum conditions were found to be 98 μL for extraction solvent, 1476 mg L(-1) for chelating agent, 3.8 for pH and 9 min for sonication time. Under the optimal conditions, the limits of detection (LODs) for Al, Bi, Cd, Co, Cu, Fe, Ga, In, Ni, Pb, Tl and Zn were 0.13, 0.48, 0.19, 0.28, 0.29, 0.27, 0.27, 0.38, 0.44, 0.47, 0.52 and 0.17 μg L(-1), respectively. The linear dynamic range (LDR) was 1-1000 μ gL(-1) with determination coefficients of 0.991-0.998. Relative standard deviations (RSDs, C=200 μg L(-1), n=6) were between 1.87%-5.65%. The proposed method was successfully applied to the extraction and determination of heavy metals in real water samples and the satisfactory relative recoveries (90.3%-105.5%) were obtained. Copyright © 2012 Elsevier B.V. All rights reserved.

Detecting microdamage in bone

PubMed Central

Lee, TC; Mohsin, S; Taylor, D; Parkesh, R; Gunnlaugsson, T; O'Brien, FJ; Giehl, M; Gowin, W

2003-01-01

Fatigue-induced microdamage in bone contributes to stress and fragility fractures and acts as a stimulus for bone remodelling. Detecting such microdamage is difficult as pre-existing microdamage sustained in vivo must be differentiated from artefactual damage incurred during specimen preparation. This was addressed by bulk staining specimens in alcohol-soluble basic fuchsin dye, but cutting and grinding them in an aqueous medium. Nonetheless, some artefactual cracks are partially stained and careful observation under transmitted light, or epifluorescence microscopy, is required. Fuchsin lodges in cracks, but is not site-specific. Cracks are discontinuities in the calcium-rich bone matrix and chelating agents, which bind calcium, can selectively label them. Oxytetracycline, alizarin complexone, calcein, calcein blue and xylenol orange all selectively bind microcracks and, as they fluoresce at different wavelengths and colours, can be used in sequence to label microcrack growth. New agents that only fluoresce when involved in a chelate are currently being developed – fluorescent photoinduced electron transfer (PET) sensors. Such agents enable microdamage to be quantified and crack growth to be measured and are useful histological tools in providing data for modelling the material behaviour of bone. However, a non-invasive method is needed to measure microdamage in patients. Micro-CT is being studied and initial work with iodine dyes linked to a chelating group has shown some promise. In the long term, it is hoped that repeated measurements can be made at critical sites and microdamage accumulation monitored. Quantification of microdamage, together with bone mass measurements, will help in predicting and preventing bone fracture failure in patients with osteoporosis. PMID:12924817

Conception of the first magnetic resonance imaging contrast agents: a brief history.

PubMed

de Haën, C

2001-08-01

About 20 years ago, a technological innovation process started that eventually led to the affirmation of magnetic resonance imaging (MRI) contrast agents, which are used today in about 25% of all MRI procedures, as medical diagnostic tools. The process began with exploration of various technical possibilities and the conception in the years 1981 to 1982 of two types of agents (soluble paramagnetic chelates and protection colloid-stabilized colloidal particle solutions of magnetite) that eventually found embodiments in commercially available products. The pioneering products that eventually reached the market were gadopentetate dimeglumine (Magnevist, Schering AG) and the ferumoxides (Endorem, Guerbet SA; or Ferridex , Berlex Laboratories Inc.). The history of the conception phase of the technology is reconstructed here, focusing on the social dynamics rather than on technological aspects. In the period 1981 to 1982, a number of independent inventors from industry and academia conceived of water-soluble paramagnetic chelates and protection colloid-stabilized colloidal solutions of small particles of magnetite, both of acceptable tolerability, as contrast agents for MRI. Priorities on patents conditioned the further course of events. The analyzed history helps in understanding the typical roles of different institutions in technological innovation. The foundation of MRI contrast agent technology in basic science clearly was laid in academia. During the conception of practical products, industry assumed a dominant role. Beginning with the radiological evaluation of candidate products, the collaboration between industry and academia became essential.

Humic Acids as Therapeutic Compounds in Lead Intoxication.

PubMed

Krempaská, Klára; Vaško, Ladislav; Vašková, Janka

2016-01-01

The toxicity of lead and its compounds is well known, causing anemia by inhibiting the synthesis of porphyrins. The neurotoxic effects, particularly in the young, alter the structure of cell membranes and DNA. Chronic exposure to lead has adverse effects on the body by disrupting the mechanisms of energy production and tissue damage, in particular in its links with thiol groups and competition for binding sites with zinc. This review is therefore a description of the mechanism of lead toxicity as well as of possible interventions for the detoxification of the body. Part of the clinical intervention is the provision of chelates that form insoluble complexes with lead and eliminate the load in tissues. Most of these chelating agents have a number of side effects. It is therefore not surprising that active compounds with distinctive antioxidant and chelating properties are being sought after. The possibility of administering lower amounts, and the corresponding decrease in side effects, would be important for clinical practice. Both prospective studies and our initial studies on humic acids have highlighted positive effects based on their antioxidant and chelating properties.

Labeling of monoclonal antibodies with a 67Ga-phenolic aminocarboxylic acid chelate. Part I. Chemistry and labeling technique.

PubMed

Schuhmacher, J; Matys, R; Hauser, H; Maier-Borst, W; Matzku, S

1986-01-01

As a chelating agent for labeling antibodies (Abs) with metallic radionuclides, a propionic acid substituted ethylenediamine N,N'-di-[(o-hydroxyphenyl) acetic acid] (P-EDDHA), which tightly complexes 67Ga, was synthesized. The 67Ga-P-EDDHA chelate was coupled in aqueous solution to IgG at a molar ratio of 1:1 via carbodiimide. The average coupling yield was 15%. A specific activity of 4 mCi/mg IgG could be obtained with commercially supplied 67Ga. In vitro stability was evaluated in human serum at 37 degrees C and showed a half-life of about 120 h for the release of 67Ga from the labeled Ab during the initial phase of incubation. This in vitro halflife is similar to that measured for 111In-DTPA labeled Abs. Because of the high stability of the 67Ga-P-EDDHA chelate, the in vivo formation of radioactive labeled transferrin by transchelation, as described for 111In-DTPA labeled Abs, should, however, be reduced by this labeling technique.

Functionalization of Cellulose Nanocrystals with PEG-Metal-Chelating Diblock Copolymers via Controlled Conjugation in Aqueous Medium

NASA Astrophysics Data System (ADS)

Guo, Melinda

The surface of cellulose nanocrystals (CNCs) was successfully functionalized with metal chelating diblock copolymers via HyNic-4FB conjugation. Two types of PEG-metal-chelating block polymers with hydrazinonicotinate acetone hydrazine (HyNic) end groups were synthesized: mPEG-PGlu(DTPA) 18-HyNic and mPEG-PGlu(DTPA)25-HyNic. These two polymers both had a methoxy PEG (M ˜ 2000 Da) block that differed in the mean degree of polymerization of the metal-chelating block. They were characterized by 1H NMR spectroscopy and gel-permeation chromatography (GPC). 4-Formylbenzamide (4FB) groups were introduced onto the surface of CNCs and quantified through their reaction with 2-hydrazinopyridine. The polymers were grafted onto the surface of CNCs via bis-aryl hydrazone bond formation, and the kinetics of this reaction was explored by UV/Vis spectroscopy. The CNCs were also labeled with rhodamine and Alexa FluorRTM 488 dyes. Students in our collaborator's group in Pharmacy are examining applications of these materials as radiotherapeutic agents for cancer treatment.

TLc-A, the leading nanochelating-based nanochelator, reduces iron overload in vitro and in vivo.

PubMed

Kalanaky, Somayeh; Hafizi, Maryam; Safari, Sepideh; Mousavizadeh, Kazem; Kabiri, Mahboubeh; Farsinejad, Alireza; Fakharzadeh, Saideh; Nazaran, Mohammad Hassan

2016-03-01

Iron chelation therapy is an effective approach to the treatment of iron overload conditions, in which iron builds up to toxic levels in the body and may cause organ damage. Treatments using deferoxamine, deferasirox and deferiprone have been introduced and despite their disadvantages, they remain the first-line therapeutics in iron chelation therapy. Our study aimed to compare the effectiveness of the iron chelation agent TLc-A, a nano chelator synthetized based on the novel nanochelating technology, with deferoxamine. We found that TLc-A reduced iron overload in Caco2 cell line more efficiently than deferoxamine. In rats with iron overload, very low concentrations of TLc-A lowered serum iron level after only three injections of the nanochelator, while deferoxamine was unable to reduce iron level after the same number of injections. Compared with deferoxamine, TLc-A significantly increased urinary iron excretion and reduced hepatic iron content. The toxicity study showed that the intraperitoneal median lethal dose for TLc-A was at least two times higher than that for deferoxamine. In conclusion, our in vitro and in vivo studies indicate that the novel nano chelator compound, TLc-A, offers superior performance in iron reduction than the commercially available and widely used deferoxamine.

[Guidelines for diagnosis and treatment of secondary iron overload in patients with congenital anemia].

PubMed

Cario, H; Grosse, R; Janssen, G; Jarisch, A; Meerpohl, J; Strauss, G

2010-11-01

In Germany and Central Europe, congenital disorders leading to secondary hemochromatosis are rare. The majority of these patients are treated in peripheral medical institutions. As a consequence, the experience of each institution in the treatment of secondary hemochromatosis in patients with congenital anemia is limited. Recent developments concerning new chelating agents, their combination for intensified chelation and new possibilities to diagnose and monitor iron overload have important consequences for the management of patients with secondary hemochromatosis and increase its complexity enormously. Therefore, the development of a guideline for rational and efficient diagnostics and treatment was necessary. The new guideline was developed within a formal consensus process and finally approved by a consensus conference with participants from both the pediatric and adult German hematology societies (GPOH and DGHO). Apart from general information and recommendations, the guideline contains 9 consensus statements on diagnostics (iron status, siderotic complications, chelator side-effects), the start of chelation, indications for intensified chelation, iron elimination in specific disorders, and iron elimination after stem cell transplantation. Here, these consensus statements are presented and discussed in detail. For the complete text of the guideline, please visit the AWMF homepage at http://www.leitlinien.net . © Georg Thieme Verlag KG Stuttgart · New York.

Bioconjugation of luminescent silicon quantum dots to gadolinium ions for bioimaging applications

NASA Astrophysics Data System (ADS)

Erogbogbo, Folarin; Chang, Ching-Wen; May, Jasmine L.; Liu, Liwei; Kumar, Rajiv; Law, Wing-Cheung; Ding, Hong; Yong, Ken Tye; Roy, Indrajit; Sheshadri, Mukund; Swihart, Mark T.; Prasad, Paras N.

2012-08-01

Luminescent imaging agents and MRI contrast agents are desirable components in the rational design of multifunctional nanoconstructs for biological imaging applications. Luminescent biocompatible silicon quantum dots (SiQDs) and gadolinium chelates can be applied for fluorescence microscopy and MRI, respectively. Here, we report the first synthesis of a nanocomplex incorporating SiQDs and gadolinium ions (Gd3+) for biological applications. The nanoconstruct is composed of a PEGylated micelle, with hydrophobic SiQDs in its core, covalently bound to DOTA-chelated Gd3+. Dynamic light scattering reveals a radius of 85 nm for these nanoconstructs, which is consistent with the electron microscopy results depicting radii ranging from 25 to 60 nm. Cellular uptake of the probes verified that they maintain their optical properties within the intracellular environment. The magnetic resonance relaxivity of the nanoconstruct was 2.4 mM-1 s-1 (in terms of Gd3+ concentration), calculated to be around 6000 mM-1 s-1 per nanoconstruct. These desirable optical and relaxivity properties of the newly developed probe open the door for use of SiQDs in future multimodal applications such as tumour imaging.Luminescent imaging agents and MRI contrast agents are desirable components in the rational design of multifunctional nanoconstructs for biological imaging applications. Luminescent biocompatible silicon quantum dots (SiQDs) and gadolinium chelates can be applied for fluorescence microscopy and MRI, respectively. Here, we report the first synthesis of a nanocomplex incorporating SiQDs and gadolinium ions (Gd3+) for biological applications. The nanoconstruct is composed of a PEGylated micelle, with hydrophobic SiQDs in its core, covalently bound to DOTA-chelated Gd3+. Dynamic light scattering reveals a radius of 85 nm for these nanoconstructs, which is consistent with the electron microscopy results depicting radii ranging from 25 to 60 nm. Cellular uptake of the probes verified that they maintain their optical properties within the intracellular environment. The magnetic resonance relaxivity of the nanoconstruct was 2.4 mM-1 s-1 (in terms of Gd3+ concentration), calculated to be around 6000 mM-1 s-1 per nanoconstruct. These desirable optical and relaxivity properties of the newly developed probe open the door for use of SiQDs in future multimodal applications such as tumour imaging. Electronic supplementary information (ESI) available: SEM images of MSiQD-Gd3+, DLS plot of MSiQD-NH2, images of Gd3+-functionalized Si QDs micelles in water, plot of percentages of Gd3+ leaked from original sample, and determination of free Gd3+ in solutions of Gd chelates. See DOI: 10.1039/c2nr31002c

The Urinary Antibiotic 5-Nitro-8-Hydroxyquinoline (Nitroxoline) Reduces the Formation and Induces the Dispersal of Pseudomonas aeruginosa Biofilms by Chelation of Iron and Zinc

PubMed Central

Klinger, M.; Hermann, B.; Sachse, S.; Nietzsche, S.; Makarewicz, O.; Keller, P. M.; Pfister, W.; Straube, E.

2012-01-01

Since cations have been reported as essential regulators of biofilm, we investigated the potential of the broad-spectrum antimicrobial and cation-chelator nitroxoline as an antibiofilm agent. Biofilm mass synthesis was reduced by up to 80% at sub-MIC nitroxoline concentrations in Pseudomonas aeruginosa, and structures formed were reticulate rather than compact. In preformed biofilms, viable cell counts were reduced by 4 logs at therapeutic concentrations. Complexation of iron and zinc was demonstrated to underlie nitroxoline's potent antibiofilm activity. PMID:22926564

Polycatecholamide chelating agents

DOEpatents

Weitl, Frederick L.; Raymond, Kenneth N.

1984-01-01

Novel polybenzamide compounds useful for in vitro or in vivo chelation are described. The compounds have the formula ##STR1## Polyamines are reacted with 2,3-dimethoxy benzoyl chloride unsubstituted or substituted with SO.sub.3 H, SO.sub.3 M, NO.sub.2, CO.sub.2 H or CO.sub.2 M as desired is reacted with a polyamine in an inert solvent then demethylated with BBr.sub.3 or BCl.sub.3 in an inert solvent. Where compounds symmetrically substituted on the terminal N's are desired, the polyamine is first reductively alkylated by reaction with an aldehyde or ketone and the resulting Schiff base is hydrogenated.

Oxidative degradation stability and hydrogen sulfide removal performance of dual-ligand iron chelate of Fe-EDTA/CA.

PubMed

Miao, Xinmei; Ma, Yiwen; Chen, Zezhi; Gong, Huijuan

2017-09-05

Catalytic oxidation desulfurization using chelated iron catalyst is an effective method to remove H 2 S from various gas streams including biogas. However, the ligand of ethylenediaminetetraacetic acid (EDTA), which is usually adopted to prepare chelated iron catalyst, is liable to be oxidative degraded, and leads to the loss of desulfurization performance. In order to improve the degradation stability of the iron chelate, a series of iron chelates composed of two ligands including citric acid (CA) and EDTA were prepared and the oxidative degradation stability as well as desulfurization performance of these chelated iron catalysts were studied. Results show that the iron chelate of Fe-CA is more stable than Fe-EDTA, while for the desulfurization performance, the situation is converse. For the dual-ligand iron chelates of Fe-EDTA/CA, with the increase of mol ratio of CA to EDTA in the iron chelate solution, the oxidative degradation stability increased while the desulfurization performance decreased. The results of this work showed that Fe-EDTA/CA with a mol ratio of CA:EDTA = 1:1 presents a relative high oxidative degradation stability and an acceptable desulfurization performance with over 90% of H 2 S removal efficiency.

Efficacy of the chelating agent CaEDTA in reversing lead-induced changes in behavior.

PubMed

Cory-Slechta, D A; Weiss, B

1989-01-01

The chelating agent CaEDTA has been reported to reverse the deficits in intellectual function and performance associated with Pb (lead) exposure in children. However, such studies have not included rigorous controls for the intervention procedures per se. The experiments reported here examined reversibility of performance changes in a rat model based on behavior sensitive to low-level Pb exposure. Rats were exposed to 50 ppm sodium or Pb acetate in drinking water from weaning. Performance maintained under a Fixed-Interval schedule of food reinforcement began at 55 days of age. Following the onset of the characteristic increase in short interresponse times (IRTs) associated with low-level Pb exposure after 35 experimental sessions, Pb treatment was terminated. Animals within both the control and Pb groups were then matched on the basis of performance indices and injected daily for 5 days with either saline, 75 mg/kg or 150 mg/kg CaEDTA. Subsequent changes in F1 performance were monitored for 35-60 sessions. No consistent effects of CaEDTA were detected in control animals. CaEDTA treatment failed to reverse the behavioral effects in Pb-exposed animals. If anything, it tended to further increase the proportion of short IRTs. These data suggest that better controlled clinical studies are warranted to evaluate the efficacy of CaEDTA in reversing Pb-induced behavioral effects before its application for these purposes becomes widespread.

Liver transplantation for Wilson disease.

PubMed

Catana, Andreea M; Medici, Valentina

2012-01-27

The aim of this paper is to review the current status of liver transplantation (LT) for Wilson disease (WD), focusing on indications and controversies, especially in patients with neuropsychiatric disease, and on identification of acute liver failure (ALF) cases related to WD. LT remains the treatment of choice for patients with ALF, as initial presentation of WD or when anti-copper agents are stopped, and for patients with chronic liver disease progressed to cirrhosis, unresponsive to chelating medications or not timely treated with copper chelating agents. The indication for LT in WD remains highly debated in patients with progressive neurological deterioration and failure to improve with appropriate medical treatment. In case of Wilsonian ALF, early identification is key as mortality is 100% without emergency LT. As many of the copper metabolism parameters are believed to be less reliable in ALF, simple biochemical tests have been proposed for diagnosis of acute WD with good sensitivity and specificity. LT corrects copper metabolism and complications resulting from WD with excellent 1 and 5 year survival. Living related liver transplantation represents an alternative to deceased donor LT with excellent long-term survival, without disease recurrence. Future options may include hepatocyte transplantation and gene therapy. Although both of these have shown promising results in animal models of WD, prospective human studies are much needed to demonstrate their long-term beneficial effects and their potential to replace the need for medical therapy and LT in patients with WD.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pachauri, Vidhu; Saxena, Geetu; Mehta, Ashish

Lead, a ubiquitous and potent neurotoxicant causes oxidative stress which leads to numerous neurobehavioral and physiological alterations. The ability of lead to bind sulfhydryl groups or compete with calcium could be one of the reasons for its debilitating effects. In the present study, we addressed: i) if chelation therapy could circumvent the altered oxidative stress and prevent neuronal apoptosis in chronic lead-intoxicated rats, ii) whether chelation therapy could reverse biochemical and behavioral changes, and iii) if mono or combinational therapy with captopril (an antioxidant) and thiol chelating agents (DMSA/MiADMSA) is more effective than individual thiol chelator in lead-exposed rats. Resultsmore » indicated that lead caused a significant increase in reactive oxygen species, nitric oxide, and intracellular free calcium levels along with altered behavioral abnormalities in locomotor activity, exploratory behavior, learning, and memory that were supported by changes in neurotransmitter levels. A fall in membrane potential, release of cytochrome c, and DNA damage indicated mitochondrial-dependent apoptosis. Most of these alterations showed significant recovery following combined therapy with captopril with MiADMSA and to a smaller extend with captopril + DMSA over monotherapy with these chelators. It could be concluded from our present results that co-administration of a potent antioxidant (like captopril) might be a better treatment protocol than monotherapy to counter lead-induced oxidative stress. The major highlight of the work is an interesting experimental evidence of the efficacy of combinational therapy using an antioxidant with a thiol chelator in reversing neurological dystrophy caused due to chronic lead exposure in rats.« less

Target binding improves relaxivity in aptamer-gadolinium conjugates.

PubMed

Bernard, Elyse D; Beking, Michael A; Rajamanickam, Karunanithi; Tsai, Eve C; Derosa, Maria C

2012-12-01

MRI contrast agents (CA) have been heavily used over the past several decades to enhance the diagnostic value of the obtained images. From a design perspective, two avenues to improve the efficacy of contrast agents are readily evident: optimization of magnetic properties of the CA, and optimization of the pharmacokinetics and distribution of the CA in the patient. Contrast agents consisting of DNA aptamer-gadolinium(III) conjugates provide a single system in which these factors can be addressed simultaneously. In this proof-of-concept study, the 15mer thrombin aptamer was conjugated to diethylenetriaminepentaacetic (DTPA) dianhydride to form a monoamide derivative of the linear open-chain chelate present in the commonly used contrast agent Magnevist(®). The stability of the conjugated DNA aptamer-DTPA-Gd(III) chelate in a transmetallation study using Zn(II) was found to be similar to that reported for DTPA-Gd(III). Relaxivity enhancements of 35 ± 4 and 20 ± 1 % were observed in the presence of thrombin compared to a control protein at fields of 9.4 and 1.5 T, respectively. The inclusion of spacers between the aptamer and the DTPA to eliminate possible steric effects was also investigated but not found to improve the relaxation enhancement achieved in comparison to the unaltered aptamer conjugate.

The cell labeling efficacy, cytotoxicity and relaxivity of copper-activated MRI/PET imaging contrast agents.

PubMed

Patel, Daksha; Kell, Arnold; Simard, Benoit; Xiang, Bo; Lin, Hung Yu; Tian, Ganghong

2011-02-01

A new class of nanoparticle-based dual-modality positron emission tomography/magnetic resonance imaging (PET/MRI) contrast agents has been developed. The probe consists of a superparamagnetic iron oxide (SPIO) or manganese oxide core coated with 3,4-dihydroxy-D,L-phenylalanine (DL-DOPA). The chelator 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) was conjugated to DOPA termini. The DOTA modified nanoparticles allow chelation of copper for PET imaging. These surface functionalized nanoparticle-based probes have been characterized by various analytical techniques. The cell-labeling efficacy, cytotoxicity and relaxivity of these nanoparticles have been evaluated and compared with the same properties of one of the most commonly utilized MRI contrast agents, Feridex(®). Evidently, this new nanoparticle has a great potential for use in cell tracking with MRI and PET in the absence of transfecting agent. It is noteworthy that there is a sharp increase in r(2) relaxivity of these nanoparticles on coordination with Cu(2+) ions. Thus these iron oxide nanoparticles can also be explored as the smart magnetic resonance (MR) sensor for the detection of micromolar changes in copper concentration for neurodegenerative diseases such as Alzheimer's disease, Menkes and Wilson's diseases, amyotrophic lateral sclerosis and prion diseases. Crown Copyright © 2010. Published by Elsevier Ltd. All rights reserved.

Deferiprone for the treatment of transfusional iron overload in thalassemia.

PubMed

Belmont, Ami; Kwiatkowski, Janet L

2017-06-01

Transfusional iron overload can lead to hepatic fibrosis, arrhythmias and congestive heart failure and a number of endocrinopathies. Deferiprone is an oral iron chelator approved for use in the United States as a second line agent for the treatment of transfusional iron overload in patients with thalassemia. Areas covered: This article will review the data regarding the efficacy of deferiprone for iron chelation and prevention and reversal of iron related complications, the drug's adverse effect profile, and the use of this drug in combination regimens. Expert commentary: Extensive data support that deferiprone is particularly efficacious at cardiac iron removal and therefore, a chelator regimen that contains deferiprone is generally recommended when there is significant cardiac iron loading and/or in the setting of iron-related cardiac disease. The most concerning side effects of deferiprone are agranulocytosis and milder forms of neutropenia, which require appropriate monitoring and patient/provider education.

O-Hydroxyl- or o-amino benzylamine-tacrine hybrids: multifunctional biometals chelators, antioxidants, and inhibitors of cholinesterase activity and amyloid-β aggregation.

PubMed

Mao, Fei; Huang, Ling; Luo, Zonghua; Liu, Anqiu; Lu, Chuanjun; Xie, Zhiyong; Li, Xingshu

2012-10-01

In an effort to identify novel multifunctional drug candidates for the treatment of Alzheimer's disease (AD), a series of hybrid molecules were synthesised by reacting N-(aminoalkyl)tacrine with salicylic aldehyde or derivatives of 2-aminobenzaldehyde. These compounds were then evaluated as multifunctional anti-Alzheimer's disease agents. All of the hybrids are potential biometal chelators, and in addition, most of them were better antioxidants and inhibitors of cholinesterases and amyloid-β (Aβ) aggregation than the lead compound tacrine. Compound 7c has the potential to be a candidate for AD therapy: it is a much better inhibitor of acetylcholinesterase (AChE) than tacrine (IC(50): 0.55 nM vs 109 nM), has good biometal chelation ability, is able to inhibit Aβ aggregation and has moderate antioxidant activity (1.22 Trolox equivalents). Copyright © 2012 Elsevier Ltd. All rights reserved.

Aluminium Involvement in Neurotoxicity

PubMed Central

Fulgenzi, Alessandro; Vietti, Daniele; Ferrero, Maria Elena

2014-01-01

The aetiology of neurodegenerative diseases (ND) seems to involve susceptibility genes and environmental factors. Toxic metals are considered major environmental pollutants. Following our study of a case of multiple sclerosis (MS) improvement due to removal of aluminium (Al) and other toxic metals, we have examined the possible relationship between Al intoxication and ND. We used the slow intravenous treatment with the chelating agent EDTA (calcium disodium ethylene diamine tetraacetic acid) (chelation test) to remove Al and detected it in the urine collected from the patients for 12 hours. Patients affected by MS represented 85.6% of total ND. Al was present in 44.8% of cases comprehensive of ND and healthy patients. Al levels were significantly higher in ND patients than in healthy subjects. We here show that treatment of patients affected by Al burden with ten EDTA chelation therapies (EDTA intravenous administration once a week) was able to significantly reduce Al intoxication. PMID:25243176

Triamines and their derivatives as bifunctional chelating agents

DOEpatents

Troutner, David E.; John, Christy S.; Pillai, Maroor R. A.

1992-03-31

A group of functionalized triamine chelants and their derivatives that form complexes with radioactive metal ions are disclosed. The complexes can be covalently attached to a protein or an antibody or antibody fragment and used for therapeutic and/or diagnostic purposes.

Lead-203 as a label for radioimaging

DOEpatents

Srivastava, Suresh C.; Meinken, George E.

1990-01-01

A radiopharmaceutical composition comprising a radioactive isotope of lead (Pb-203) in combination with a pharmaceutical or an antibody or antibody fragment and a bifunctional chelating agent. These compositions are especially useful in the imaging and diagnosis of tumors and tumor metastases.

Lead-203 as a label for radioimaging

DOEpatents

Srivastava, Suresh C.; Meinken, George E.

1990-02-06

A radiopharmaceutical composition comprising a radioactive isotope of lead (Pb-203) in combination with a pharmaceutical or an antibody or antibody fragment and a bifunctional chelating agent. These compositions are especially useful in the imaging and diagnosis of tumors and tumor metastases.

Effect of transfusional iron intake on response to chelation therapy in beta-thalassemia major.

PubMed

Cohen, Alan R; Glimm, Ekkehard; Porter, John B

2008-01-15

The success of chelation therapy in controlling iron overload in patients with thalassemia major is highly variable and may partly depend on the rate of transfusional iron loading. Using data from the 1-year phase III study of deferasirox, including volumes of transfused red blood cells and changes in liver iron concentration (LIC) in 541 patients, the effect of iron loading on achieving neutral or negative iron balance was assessed in patients receiving different doses of deferasirox and the comparator deferoxamine. After dose adjustment, reductions in LIC after 1 year of deferasirox or deferoxamine therapy correlated with transfusional iron intake. At a deferasirox dose of 20 mg/kg per day, neutral or negative iron balance was achieved in 46% and 75% of patients with the highest and lowest transfusional iron intake, respectively; 30 mg/kg per day produced successful control of iron stores in 96% of patients with a low rate of transfusional iron intake. Splenectomized patients had lower transfusional iron intake and greater reductions in iron stores than patients with intact spleens. Transfusional iron intake should be monitored on an ongoing basis in thalassemia major patients, and the rate of transfusional iron loading should be considered when choosing the appropriate dose of an iron-chelating agent. This study is registered at http://clinicaltrials.gov as NCT00061750.

Biocompatible, Biodegradable, and Enzymatic-Cleavable MRI Contrast Agents for Early Detection of Bone Metastatic Breast cancer

DTIC Science & Technology

2013-04-01

metastasis from breast cancer. The proposed imaging agent is consist of bone targeting moiety of Asp8 and MRI imaging moiety of DOTA (Gd) with a cathepsin K...the Gd chelator of DOTA . Asp8 has a high affinity for bone mineral and has been used as bone-targeting moiety in molecular therapeutics.(1-6) The use...findings in literature.(4, 7, 17) To obtain imaging agents for MRI studies, the above mentioned peptides were allowed to react with DOTA -NHS

Characterizing RecA-Independent Induction of Shiga toxin2-Encoding Phages by EDTA Treatment

PubMed Central

Imamovic, Lejla; Muniesa, Maite

2012-01-01

Background The bacteriophage life cycle has an important role in Shiga toxin (Stx) expression. The induction of Shiga toxin-encoding phages (Stx phages) increases toxin production as a result of replication of the phage genome, and phage lysis of the host cell also provides a means of Stx toxin to exit the cell. Previous studies suggested that prophage induction might also occur in the absence of SOS response, independently of RecA. Methodology/Principal Findings The influence of EDTA on RecA-independent Stx2 phage induction was assessed, in laboratory lysogens and in EHEC strains carrying Stx2 phages in their genome, by Real-Time PCR. RecA-independent mechanisms described for phage λ induction (RcsA and DsrA) were not involved in Stx2 phage induction. In addition, mutations in the pathway for the stress response of the bacterial envelope to EDTA did not contribute to Stx2 phage induction. The effect of EDTA on Stx phage induction is due to its chelating properties, which was also confirmed by the use of citrate, another chelating agent. Our results indicate that EDTA affects Stx2 phage induction by disruption of the bacterial outer membrane due to chelation of Mg2+. In all the conditions evaluated, the pH value had a decisive role in Stx2 phage induction. Conclusions/Significance Chelating agents, such as EDTA and citrate, induce Stx phages, which raises concerns due to their frequent use in food and pharmaceutical products. This study contributes to our understanding of the phenomenon of induction and release of Stx phages as an important factor in the pathogenicity of Shiga toxin-producing Escherichia coli (STEC) and in the emergence of new pathogenic strains. PMID:22393404

The presence of lead decreases the availability of meso-2, 3-dimercaptosuccinic acid for analysis in the monobromobimane assay.

PubMed

Lever, S Z; Parsons, T L

1999-11-01

meso-2,3-Dimercaptosuccinic acid is a suitable chelating agent for routine pharmacotherapy of lead poisoning in children. Administration of meso-2,3-dimercaptosuccinic acid presumably permits complexation of lead in vivo, allowing excretion through urine or feces. Quantification of the lead is achieved independently from the analysis of meso-2,3-dimercaptosuccinic acid and metabolites from the monobromobimane assay. To date, no direct chemical characterization of the Pb species excreted in urine has been successful. Pharmacokinetic correlation of lead excretion with excretion of meso-2,3-dimercaptosuccinic acid and metabolites has been utilized as an indirect method to draw conclusions regarding the identity of the active chelating agent. In this study, we hypothesized that the Pb-coordinated thiols are not reactive with respect to monobromobimane, and thus, the active chelator contained in the lead complex escapes detection. We performed variations of the assay and found that (1) the fluorescence detector response for the meso-2,3-dimercaptosuccinic acid-monobromobimane adduct was clearly attenuated as a function of added Pb, (2) when meso-2, 3-dimercaptosuccinic acid and monobromobimane were mixed prior to the addition of lead, the lead had no effect on detector response, (3) the addition of dithiothreitol does not affect the ability of Pb to react with meso-2,3-dimercaptosuccinic acid and verifies that oxidation of meso-DMSA had not occurred, and (4) the addition of ethylenediaminetetraacetic acid to the assay reverses the result found in point 1, presumably through trans chelation of the Pb-DMSA complex. Indirect quantification of the Pb-DMSA complexes found in urine might be accomplished through modification of the standard monobromobimane assay for analysis of meso-2,3-dimercaptosuccinic acid.

The iron chelator Dp44mT inhibits the proliferation of cancer cells but fails to protect from doxorubicin-induced cardiotoxicity in spontaneously hypertensive rats.

PubMed

Rao, V Ashutosh; Zhang, Jun; Klein, Sarah R; Espandiari, Parvaneh; Knapton, Alan; Dickey, Jennifer S; Herman, Eugene; Shacter, Emily B

2011-11-01

The iron chelator Dp44mT is a potent topoisomerase IIα inhibitor with novel anticancer activity. Doxorubicin (Dox), the current front-line therapy for breast cancer, induces a dose-limiting cardiotoxicity, in part through an iron-mediated pathway. We tested the hypothesis that Dp44mT can improve clinical outcomes of treatment with Dox by alleviating cardiotoxicity. The general cardiac and renal toxicities induced by Dox were investigated in the presence and absence of Dp44mT. The iron chelating cardioprotectant Dexrazoxane (Drz), which is approved for this indication, was used as a positive control. In vitro studies were carried out with H9c2 rat cardiomyocytes and in vivo studies were performed using spontaneously hypertensive rats. Testing of the GI(50) profile of Dp44mT in the NCI-60 panel confirmed activity against breast cancer cells. An acute, toxic dose of Dox caused the predicted cellular and cardiac toxicities, such as cell death and DNA damage in vitro and elevated cardiac troponin T levels, tissue damage, and apoptosis in vivo. Dp44mT alone caused insignificant changes in hematological and biochemical indices in rats, indicating that Dp44mT is not significantly cardiotoxic as a single agent. In contrast to Drz, Dp44mT failed to mitigate Dox-induced cardiotoxicity in vivo. We conclude that although Dp44mT is a potent iron chelator, it is unlikely to be an appropriate cardioprotectant against Dox-induced toxicity. However, it should continue to be evaluated as a potential anticancer agent as it has a novel mechanism for inhibiting the growth of a broad range of malignant cell types while exhibiting very low intrinsic toxicity to healthy tissues.

Radiolabeled technetium chelates for use in renal function determinations

DOEpatents

Fritzberg, Alan; Kasina, Sudhaker; Johnson, Dennis L.

1994-01-01

The present invention is directed to novel radiopharmaceutical imaging agents incorporating Tc-99m as a radiolabel. In particular, the novel imaging agents disclosed herein have relatively high renal extraction efficiencies, and hence are useful for conducting renal function imaging procedures. The novel Tc-99m compounds of a present invention have the following general formula: ##STR1## wherein X is S or N; and wherein Y is --H or wherein Y is ##STR2## and where R.sub.1 is --H, --CH.sub.3, or --CH.sub.2 CH.sub.3 ; R.sub.2 is --H, --CH.sub.2 CO.sub.2 H, --CH.sub.2 CONH.sub.2, --CH.sub.2 CH.sub.2 CO.sub.2 H, --CH.sub.2 CH.sub.2 CONH.sub.2, --CH.sub.3, --CH.sub.2 CH.sub.3, CH.sub.2 C.sub.6 H.sub.5, or --CH.sub.2 OH; and Z is --H, --CO.sub.2 H, --CONH.sub.2, --SO.sub.3 H, --SO.sub.2 NH.sub.2, or --CONHCH.sub.2 CO.sub.2 H; and the Tc is Tc-99m; and water-soluble salts thereof. Of the foregoing, the presently preferred Tc-99m compound of the present invention is Tc-99m-mercaptoacetylglycylglycylglycine (Tc-99m-MAGGG). The present invention is also directed to novel chelating agents that may be reacted with Tc-99m to form the foregoing compounds. Such novel chelating agents have the following general formula. ##STR3## where X and Y have the same definitions as above, and wherein Y' is --H.sub.2 when X is N, or wherein Y' is --H, or a suitable protective group such as --COCH.sub.3, --COC.sub.6 H.sub.5, --CH.sub.2 NHCOCH.sub.3, --COCF.sub.3, or --COCH.sub.2 OH when X is S. The present invention also provides methods for preparing and using the novel Tc-99m compounds.

Radiolabeled technetium chelates for use in renal function determinations

DOEpatents

Fritzberg, Alan; Kasina, Sudhakar; Johnson, Dennis L.

1990-01-01

The present invention is directed to novel radiopharmaceutical imaging agents incorporating Tc-99m as a radiolabel. In particular, the novel imaging agents disclosed herein have relatively high renal extraction efficiencies, and hence are useful for conducting renal function imaging procedures. The novel Tc-99m compounds of a present invention have the following general formula: ##STR1## wherein X is S or N; and wherein Y is--H or wherein Y is ##STR2## and where R.sub.1 is --H, --CH.sub.3, or --CH.sub.2 CH.sub.3 ; R.sub.2 is --H, --CH.sub.2 CO.sub.2 H, --CH.sub.2 CONH.sub.2, --CH.sub.2 CH.sub.2 CO.sub.2 H, --CH.sub.2 CH.sub.2 CONH.sub.2, --CH.sub.3, --CH.sub.2 CH.sub.3, CH.sub.2 C.sub.6 H.sub.5, or --CH.sub.2 OH; and Z is --H, --CO.sub.2 H, --CONH.sub.2, --SO.sub.3 H, --SO.sub.2 NH.sub.2, or --CONHCH.sub.2 CO.sub.2 H; and the Tc is Tc-99m; and water-soluble salts thereof. Of the foregoing, the presently preferred Tc-99m compound of the present invention is Tc-99m-mercaptoacetylglycylglycylglycine (Tc-99m-MAGGG). The present invention is also directed to novel chelating agents that may be reacted with Tc-99m to form the foregoing compounds. Such novel chelating agents have the following general formula. ##STR3## where X and Y have the same definitions as above, and wherein Y' is --H.sub.2 when X is N, or wherein Y' is --H, or a suitable protective group such as --COCH.sub.3, --COC.sub.6 H.sub.5, --CH.sub.2 NHCOCH.sub.3, --COCF.sub.3, or --COCH.sub.2 OH when X is S. The present invention also provides methods for preparing and using the novel Tc-99m compounds.

Gadolinium released by the linear gadolinium-based contrast-agent Gd-DTPA decreases the activity of human epithelial Na+ channels (ENaCs).

PubMed

Knoepp, Fenja; Bettmer, Joerg; Fronius, Martin

2017-05-01

Gadolinium-based-contrast-agents (GBCAs) are used for magnetic-resonance-imaging and associated with renal and cardiovascular adverse reactions caused by released Gd 3+ ions. Gd 3+ is also a modulator of mechano-gated ion channels, including the epithelial Na + channel (ENaC) that is expressed in kidney epithelium and the vasculature. ENaC is important for salt-/water homeostasis and blood pressure regulation and a likely target of released Gd 3+ from GBCAs causing the above-mentioned adverse reactions. Therefore this study examined the effect of Gd 3+ and GBCAs on ENaC's activity. Human αβγENaC was expressed in Xenopus laevis oocytes and exposed to Gd 3+ , linear (Gd-DTPA, Magnevist) or cyclic (Dotarem) GBCAs. Transmembrane ion-currents (I M ) were recorded by the two-electrode-voltage-clamp technique and Gd 3+ -release by Gd-DTPA was confirmed by inductively coupled plasma-mass spectrometry. Gd 3+ exerts biphasic effects on ENaC's activity: ≤0.3mmol/l decreased I M which was preventable by DEPC (modifies histidines). Strikingly Gd 3+ ≥0.4mmol/l increased I M and this effect was prevented by cysteine-modifying MTSEA. Linear Gd-DTPA and Magnevist mimicked the effect of ≤0.3mmol/l Gd 3+ , whereas the chelator DTPA showed no effect. Gd 3+ and Gd-DTPA increased the IC 50 for amiloride, but did not affect ENaC's self-inhibition. Interestingly, cyclic Gd-DOTA (Dotarem) increased I M to a similar extent as its chelator DOTA, suggesting that the chelator rather than released Gd 3+ is responsible for this effect. These results confirm Gd 3+ -release from linear Gd-DTPA and indicate that the released Gd 3+ amount is sufficient to interfere with ENaC's activity to provide putative explanations for GBCA-related adverse effects. Copyright © 2017 Elsevier B.V. All rights reserved.

Study of Anti-Fatigue Effect in Rats of Ferrous Chelates Including Hairtail Protein Hydrolysates

PubMed Central

Huang, Saibo; Lin, Huimin; Deng, Shang-gui

2015-01-01

The ability of ferrous chelates including hairtail protein hydrolysates to prevent and reduce fatigue was studied in rats. After hydrolysis of hairtail surimi with papain, the hairtail protein hydrolysates (HPH) were separated into three groups by range of relative molecular weight using ultrafiltration membrane separation. Hairtail proteins were then chelated with ferrous ions, and the antioxidant activity, the amino acid composition and chelation rate of the three kinds of ferrous chelates including hairtail protein hydrolysates (Fe-HPH) were determined. Among the three groups, the Fe-HPH chelate showing the best conditions was selected for the anti-fatigue animal experiment. For it, experimental rats were randomly divided into seven groups. Group A was designated as the negative control group given distilled water. Group B, the positive control group, was given glutathione. Groups C, D and E were designated as the Fe-HPH chelate treatment groups and given low, medium, and high doses, respectively. Group F was designated as HPH hydrolysate treatment group, and Group G was designated as FeCl2 treatment group. The different diets were orally administered to rats for 20 days. After that time, rats were subjected to forced swimming training after 1 h of gavage. Rats given Fe-FPH chelate had higher haemoglobin regeneration efficiency (HRE), longer exhaustive swimming time and higher SOD activity. Additionally, Fe-FPH chelate was found to significantly decrease the malondialdehyde content, visibly enhance the GSH-Px activity in liver and reduce blood lactic acid of rats. Fe-HPH chelate revealed an anti-fatigue effect, similar to or better than the positive control substance and superior to HPH or Fe when provided alone. PMID:26633476

Novel multifunctional neuroprotective iron chelator-monoamine oxidase inhibitor drugs for neurodegenerative diseases: in vitro studies on antioxidant activity, prevention of lipid peroxide formation and monoamine oxidase inhibition.

PubMed

Zheng, Hailin; Gal, Shunit; Weiner, Lev M; Bar-Am, Orit; Warshawsky, Abraham; Fridkin, Mati; Youdim, Moussa B H

2005-10-01

Iron-dependent oxidative stress, elevated levels of iron and of monoamine oxidase (MAO)-B activity, and depletion of antioxidants in the brain may be major pathogenic factors in Parkinson's disease, Alzheimer's disease and related neurodegenerative diseases. Accordingly, iron chelators, antioxidants and MAO-B inhibitors have shown efficacy in a variety of cellular and animal models of CNS injury. In searching for novel antioxidant iron chelators with potential MAO-B inhibitory activity, a series of new iron chelators has been designed, synthesized and investigated. In this study, the novel chelators were further examined for their activity as antioxidants, MAO-B inhibitors and neuroprotective agents in vitro. Three of the selected chelators (M30, HLA20 and M32) were the most effective in inhibiting iron-dependent lipid peroxidation in rat brain homogenates with IC50 values (12-16 microM), which is comparable with that of desferal, a prototype iron chelator that is not has orally active. Their antioxidant activities were further confirmed using electron paramagnetic resonance spectroscopy. In PC12 cell culture, the three novel chelators at 0.1 microM were able to attenuate cell death induced by serum deprivation and by 6-hydroxydopamine. M30 possessing propargyl, the MAO inhibitory moiety of the anti-Parkinson drug rasagiline, displayed greater neuroprotective potency than that of rasagiline. In addition, in vitro, M30 was a highly potent non-selective MAO-A and MAO-B inhibitor (IC50 < 0.1 microM). However, HLA20 was more selective for MAO-B but had poor MAO inhibition, with an IC50 value of 64.2 microM. The data suggest that M30 and HLA20 might serve as leads in developing drugs with multifunctional activities for the treatment of various neurodegenerative disorders.

Synthesis and radiolabeling of chelator-RNA aptamer bioconjugates with copper-64 for targeted molecular imaging

PubMed Central

Rockey, William M.; Huang, Ling; Kloepping, Kyle C.; Baumhover, Nicholas J.; Giangrande, Paloma H.; Schultz, Michael K.

2014-01-01

Ribonucleic acid (RNA) aptamers with high affinity and specificity for cancer-specific cell-surface antigens are promising reagents for targeted molecular imaging of cancer using positron emission tomography (PET). For this application, aptamers must be conjugated to chelators capable of coordinating PET-radionuclides (e.g. copper-64, 64Cu) to enable radiolabeling for in vivo imaging of tumors. This study investigates the choice of chelator and radiolabeling parameters such as pH and temperature for the development of 64Cu-labeled RNA-based targeted agents for PET imaging. The characterization and optimization of labeling conditions are described for four chelator-aptamer complexes. Three commercially available bifunctional macrocyclic chelators (1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid mono N-hydroxysuccinimide [DOTA-NHS]; S-2-(4-isothiocyanatobenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid [p-SCN-Bn-NOTA]; and p-SCN-Bn-3,6,9,15-tetraazabicyclo [9.3.1]pentadeca-1(15),11,13-triene-3,6,9-triacetic acid [p-SCN-Bn-PCTA]), as well as the polyamino-macrocyclic diAmSar (3,6,10,13,16,19-hexaazabicyclo[6.6.6] icosane-1,8-diamine) were conjugated to A10–3.2, a RNA aptamer which has been shown to bind specifically to a prostate cancer-specific cell-surface antigen (PSMA). Although a commercial bifunctional version of diAmSar was not available, RNA conjugation with this chelator was achieved in a two-step reaction by the addition of a disuccinimidyl suberate linker. Radiolabeling parameters (e.g. pH, temperature, and time) for each chelator-RNA conjugate were assessed in order to optimize specific activity and RNA stability. Furthermore, the radiolabeled chelator-coupled RNA aptamers were evaluated for binding specificity to their target antigen. In summary, key parameters were established for optimal radiolabeling of RNA aptamers for eventual PET imaging with 64Cu. PMID:21658962

Triamines and their derivatives as bifunctional chelating agents

DOEpatents

Troutner, D.E.; John, C.S.; Pillai, M.R.A.

1992-03-31

A group of functionalized triamine chelants and their derivatives that form complexes with radioactive metal ions are disclosed. The complexes can be covalently attached to a protein or an antibody or antibody fragment and used for therapeutic and/or diagnostic purposes. No Drawings

Separation of heavy metals: Removal from industrial wastewaters and contaminated soil

DOE Office of Scientific and Technical Information (OSTI.GOV)

Peters, R.W.; Shem, L.

1993-01-01

This paper reviews the applicable separation technologies relating to removal of heavy metals from solution and from soils in order to present the state-of-the-art in the field. Each technology is briefly described and typical operating conditions and technology performance are presented. Technologies described include chemical precipitation (including hydroxide, carbonate, or sulfide reagents), coagulation/flocculation, ion exchange, solvent extraction, extraction with chelating agents, complexation, electrochemical operation, cementation, membrane operations, evaporation, adsorption, solidification/stabilization, and vitrification. Several case histories are described, with a focus on waste reduction techniques and remediation of lead-contaminated soils. The paper concludes with a short discussion of important research needsmore » in the field.« less

Separation of heavy metals: Removal from industrial wastewaters and contaminated soil

DOE Office of Scientific and Technical Information (OSTI.GOV)

Peters, R.W.; Shem, L.

1993-03-01

This paper reviews the applicable separation technologies relating to removal of heavy metals from solution and from soils in order to present the state-of-the-art in the field. Each technology is briefly described and typical operating conditions and technology performance are presented. Technologies described include chemical precipitation (including hydroxide, carbonate, or sulfide reagents), coagulation/flocculation, ion exchange, solvent extraction, extraction with chelating agents, complexation, electrochemical operation, cementation, membrane operations, evaporation, adsorption, solidification/stabilization, and vitrification. Several case histories are described, with a focus on waste reduction techniques and remediation of lead-contaminated soils. The paper concludes with a short discussion of important research needsmore » in the field.« less

Intracellular bimodal nanoparticles based on quantum dots for high-field MRI at 21.1 T.

PubMed

Rosenberg, Jens T; Kogot, Joshua M; Lovingood, Derek D; Strouse, Geoffrey F; Grant, Samuel C

2010-09-01

Multimodal, biocompatible contrast agents for high magnetic field applications represent a new class of nanomaterials with significant potential for tracking of fluorescence and MR in vitro and vivo. Optimized for high-field MR applications-including biomedical imaging at 21.1 T, the highest magnetic field available for MRI-these nanoparticles capitalize on the improved performance of chelated Dy(3+) with increasing magnetic field coupled to a noncytotoxic Indium Phosphide/Zinc Sulfide (InP/ZnS) quantum dot that provides fluorescence detection, MR responsiveness, and payload delivery. By surface modifying the quantum dot with a cell-penetrating peptide sequence coupled to an MR contrast agent, the bimodal nanomaterial functions as a self-transfecting high-field MR/optical contrast agent for nonspecific intracellular labeling. Fluorescent images confirm sequestration in perinuclear vesicles of labeled cells, with no apparent cytotoxicity. These techniques can be extended to impart cell selectivity or act as a delivery vehicle for genetic or pharmaceutical interventions. 2010 Wiley-Liss, Inc.

Efficacy of a novel chelator BPCBG for removing uranium and protecting against uranium-induced renal cell damage in rats and HK-2 cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bao, Yizhong; Wang, Dan; Li, Zhiming

2013-05-15

Chelation therapy is a known effective method to increase the excretion of U(VI) from the body. Until now, no any uranium chelator has been approved for emergency medical use worldwide. The present study aimed to evaluate the efficacy of new ligand BPCBG containing two catechol groups and two aminocarboxylic acid groups in decorporation of U(VI) and protection against acute U(VI) nephrotoxicity in rats, and further explored the detoxification mechanism of BPCBG for U(VI)-induced nephrotoxicity in HK-2 cells with comparison to DTPA-CaNa{sub 3}. Chelating agents were administered at various times before or after injections of U(VI) in rats. The U(VI) levelsmore » in urine, kidneys and femurs were measured 24 h after U(VI) injections. Histopathological changes in the kidney and serum urea and creatinine and urine protein were examined. After treatment of U(VI)-exposed HK-2 cells with chelating agent, the intracellular U(VI) contents, formation of micronuclei, lactate dehydrogenase (LDH) activity and production of reactive oxygen species (ROS) were assessed. It was found that prompt, advanced or delayed injections of BPCBG effectively increased 24 h-urinary U(VI) excretion and decreased the levels of U(VI) in kidney and bone. Meanwhile, BPCBG injection obviously reduced the severity of the U(VI)-induced histological alterations in the kidney, which was in parallel with the amelioration noted in serum indicators, urea and creatinine, and urine protein of U(VI) nephrotoxicity. In U(VI)-exposed HK-2 cells, immediate and delayed treatment with BPCBG significantly decreased the formation of micronuclei and LDH release by inhibiting the cellular U(VI) intake, promoting the intracellular U(VI) release and inhibiting the production of intracellular ROS. Our data suggest that BPCBG is a novel bi-functional U(VI) decorporation agent with a better efficacy than DTPA-CaNa{sub 3}. - Highlights: ► BPCBG accelerated the urine U(VI) excretion and reduced the tissues U(VI) in rats. ► BPCBG can effectively protect against the U(VI)-induced nephrotoxicity in rats. ► BPCBG increased the U(VI) release and reduced the U(VI) uptake in HK-2 cells. ► BPCBG decreased the U(VI)-induced MN formation and LDH release in HK-2 cells. ► BPCBG eliminated the U(VI)-induced intracellular ROS in HK-2 cells.« less

Evaluation of nitrogen-rich macrocyclic ligands for the chelation of therapeutic bismuth radioisotopes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wilson, Justin J.; Ferrier, Maryline; Radchenko, Valery

The use of α-emitting isotopes for radionuclide therapy is a promising treatment strategy for small micro-metastatic disease. The radioisotope ²¹³Bi is a nuclide that has found substantial use for targeted α-therapy (TAT). The relatively unexplored aqueous chemistry of Bi³⁺, however, hinders the development of bifunctional chelating agents that can successfully deliver these Bi radioisotopes to the tumor cells. Here, a novel series of nitrogen-rich macrocyclic ligands is explored for their potential use as Bi-selective chelating agents. The ligands, 1,4,7,10-tetrakis(pyridin-2-ylmethyl)-1,4,7,10-tetraazacyclododecane (L py), 1,4,7,10-tetrakis(3-pyridazylmethyl)-1,4,7,10-tetraazacyclododecane (L pyd), 1,4,7,10-tetrakis(4-pyrimidylmethyl)-1,4,7,10-tetraazacyclododecane (L pyr), and 1,4,7,10-tetrakis(2-pyrazinylmethyl)-1,4,7,10-tetraazacyclododecane (L pz), were prepared by a previously reported method and investigatedmore » here for their abilities to bind Bi radioisotopes. The commercially available and commonly used ligands 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) and N-[ (R)-2-amino-3-( p-isothiocyanato-phenyl)propyl]- trans-(S,S)- cyclohexane-1,2-diamine- N,N,N',N",N"-pentaacetic acid (CHX-A''-DTPA) were also explored for comparative purposes. Radio-thin-layer chromatography (TLC) was used to measure the binding kinetics and stabilities of the complexes formed. The long-lived isotope, ²⁰⁷Bi (t 1/2 = 32 years), was used for these studies. Density functional theory (DFT) calculations were also employed to probe the ligand interactions with Bi³⁺ and the generator parent ion Ac³⁺.In contrast to DOTA and CHX-A''-DTPA, these nitrogen-rich macrocycles selectively chelate Bi³⁺ in the presence of the parent isotope Ac³⁺. Among the four tested, L py was found to exhibit optimal Bi³⁺-binding kinetics and complex stability. L py complexes Bi³⁺ more rapidly than DOTA, yet the resulting complexes are of similar stability. DFT calculations corroborate the experimentally observed selectivity of these ligands for Bi³⁺ over Ac³⁺. Taken together, these data implicate L py as a valuable chelating agent for the delivery of ²¹³Bi. Its selectivity for Bi³⁺ and rapid and stable labeling properties warrant further investigation and biological studies.« less

Evaluation of nitrogen-rich macrocyclic ligands for the chelation of therapeutic bismuth radioisotopes

DOE PAGES

Wilson, Justin J.; Ferrier, Maryline; Radchenko, Valery; ...

2015-05-01

The use of α-emitting isotopes for radionuclide therapy is a promising treatment strategy for small micro-metastatic disease. The radioisotope ²¹³Bi is a nuclide that has found substantial use for targeted α-therapy (TAT). The relatively unexplored aqueous chemistry of Bi³⁺, however, hinders the development of bifunctional chelating agents that can successfully deliver these Bi radioisotopes to the tumor cells. Here, a novel series of nitrogen-rich macrocyclic ligands is explored for their potential use as Bi-selective chelating agents. The ligands, 1,4,7,10-tetrakis(pyridin-2-ylmethyl)-1,4,7,10-tetraazacyclododecane (L py), 1,4,7,10-tetrakis(3-pyridazylmethyl)-1,4,7,10-tetraazacyclododecane (L pyd), 1,4,7,10-tetrakis(4-pyrimidylmethyl)-1,4,7,10-tetraazacyclododecane (L pyr), and 1,4,7,10-tetrakis(2-pyrazinylmethyl)-1,4,7,10-tetraazacyclododecane (L pz), were prepared by a previously reported method and investigatedmore » here for their abilities to bind Bi radioisotopes. The commercially available and commonly used ligands 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) and N-[ (R)-2-amino-3-( p-isothiocyanato-phenyl)propyl]- trans-(S,S)- cyclohexane-1,2-diamine- N,N,N',N",N"-pentaacetic acid (CHX-A''-DTPA) were also explored for comparative purposes. Radio-thin-layer chromatography (TLC) was used to measure the binding kinetics and stabilities of the complexes formed. The long-lived isotope, ²⁰⁷Bi (t 1/2 = 32 years), was used for these studies. Density functional theory (DFT) calculations were also employed to probe the ligand interactions with Bi³⁺ and the generator parent ion Ac³⁺.In contrast to DOTA and CHX-A''-DTPA, these nitrogen-rich macrocycles selectively chelate Bi³⁺ in the presence of the parent isotope Ac³⁺. Among the four tested, L py was found to exhibit optimal Bi³⁺-binding kinetics and complex stability. L py complexes Bi³⁺ more rapidly than DOTA, yet the resulting complexes are of similar stability. DFT calculations corroborate the experimentally observed selectivity of these ligands for Bi³⁺ over Ac³⁺. Taken together, these data implicate L py as a valuable chelating agent for the delivery of ²¹³Bi. Its selectivity for Bi³⁺ and rapid and stable labeling properties warrant further investigation and biological studies.« less

The influence of EDDS on the uptake of heavy metals in hydroponically grown sunflowers.

PubMed

Tandy, Susan; Schulin, Rainer; Nowack, Bernd

2006-03-01

Phytoextraction is an environmentally friendly in situ technique for cleaning up metal contaminated land. Unfortunately, efficient metal uptake by remediation plants is often limited by low phytoavailability of the targeted metals. Chelant assisted phytoextraction has been proposed to improve the efficiency of phytoextraction. Phytoremediation involves several subsequent steps: transfer of metals from the bulk soil to the root surfaces, uptake into the roots and translocation to the shoots. Nutrient solution experiments address the latter two steps. In this context we investigated the influence of the biodegradable chelating agent SS-EDDS on uptake of essential (Cu and Zn) and non-essential (Pb) metals by sunflowers from nutrient solution. EDDS was detected in shoots and xylem sap for the first time, proving that it is taken up into the above ground biomass of plants. The essential metals Cu and Zn were decreased in shoots in the presence of EDDS whereas uptake of the non-essential Pb was enhanced. We suggest that in the presence of EDDS all three metals were taken up by the non-selective apoplastic pathway as the EDDS complexes, whereas in the absence of EDDS essential metal uptake was primarily selective along the symplastic pathway. This shows that synthetic chelating agents do not necessarily increase uptake of heavy metals, when soluble concentrations are equal in the presence and absence of chelates.

Effect of EDTA, EDDS, NTA and citric acid on electrokinetic remediation of As, Cd, Cr, Cu, Ni, Pb and Zn contaminated dredged marine sediment.

PubMed

Song, Yue; Ammami, Mohamed-Tahar; Benamar, Ahmed; Mezazigh, Salim; Wang, Huaqing

2016-06-01

In recent years, electrokinetic (EK) remediation method has been widely considered to remove metal pollutants from contaminated dredged sediments. Chelating agents are used as electrolyte solutions to increase metal mobility. This study aims to investigate heavy metal (HM) (As, Cd, Cr, Cu, Ni, Pb and Zn) mobility by assessing the effect of different chelating agents (ethylenediaminetetraacetic acid (EDTA), ethylenediaminedisuccinic acid (EDDS), nitrilotriacetic acid (NTA) or citric acid (CA)) in enhancing EK remediation efficiency. The results show that, for the same concentration (0.1 mol L(-1)), EDTA is more suitable to enhance removal of Ni (52.8 %), Pb (60.1 %) and Zn (34.9 %). EDDS provides effectiveness to increase Cu removal efficiency (52 %), while EDTA and EDDS have a similar enhancement removal effect on As EK remediation (30.5∼31.3 %). CA is more suitable to enhance Cd removal (40.2 %). Similar Cr removal efficiency was provided by EK remediation tests (35.6∼43.5 %). In the migration of metal-chelate complexes being directed towards the anode, metals are accumulated in the middle sections of the sediment matrix for the tests performed with EDTA, NTA and CA. But, low accumulation of metal contamination in the sediment was observed in the test using EDDS.

Synthesis of polymers containing 3-hydroxypyridin-4-one bidentate ligands for treatment of iron overload

PubMed Central

Saghaie, Lotfollah; Liu, Dy; Hider, Robert C

2015-01-01

Iron overload is a clinical problem which can be prevented by using iron chelating agents. An alternative method of relieving iron overload is to reduce iron absorption from the intestine by administering specific iron chelating agents, which can bind iron to form nonabsorbable complexes. Based on this strategy, a series of polymeric ligands containing the chelating moiety 3-hydroxypyridin-4-ones (HPOs) were synthesized. The synthetic route involves the benzylation of hydroxyl group of (2-methyl-3-hydroxypyran-4-one (maltol) and conversion of benzylated maltol to 3-benzyloxypyridin-4-one derivatives by using three suitable primary amines (2,6-diaminohexanoic acid (lysine) and 1,6-diaminohexane and 5-aminopentanol). The resulted compounds incorporated into polymer by copolymerization with acryloyl chloride using 2, 2’-azobisisobutyronitrile (AIBN) as the initiator. Finally, the benzyl groups of polymers were removed by catalytic hydrogenation (Pd/C). In this work, three final polymers of HPO derivatives namely poly-2-propylamido-6-(3- hydroxy -1,4-dihydro-2-methy-4-oxopyrid-1-yl) hexanoic acid, 6-(3-hydroxy-1, 4-dihydro-2-methyl-4-oxopyrid-1-yl) hexyl-1-polypropylamide and 5-(3-hydroxy-1-,4-dihydro-2-methyl-4-oxopyrid-1-yl)-1-polyacrylate pentane were synthesized. Identification and structural elucidation of compounds were achieved by proton nuclear magnetic resonance (1H NMR), carbon nuclear magnetic resonance (13C NMR) and infrared (IR) spectroscopy. PMID:26600863

Assessment of water-soluble thiourea-formaldehyde (WTF) resin for stabilization/solidification (S/S) of heavy metal contaminated soils.

PubMed

Liu, She-Jiang; Jiang, Jia-Yu; Wang, Shen; Guo, Yu-Peng; Ding, Hui

2018-03-15

Stabilization/Solidification (S/S) can be regarded as necessary for remediation of heavy metal contaminated soil. There is, however, solid agent is not very convenient to use. Water-soluble thiourea-formaldehyde (WTF) is a novel chelating agent, which has more practical applications. The process of WTF resin for S/S process of heavy metal contaminated soils was studied. Laboratory-prepared slurries, made of field soils spiked with Cd 2+ and Cr 6+ were treated with WTF resin. The toxicity characteristic leaching procedure (TCLP) showed that with 2 wt% WTF, in the neutral condition of soil after treatment for 7 d, the leaching concentrations of Cd 2+ and Cr 6+ in contaminated soil were decreased by 80.3% and 92.6% respectively. Moreover, Tessier sequence extraction procedure showed WTF resin reduced the leaching concentration by transforming heavy metal from exchange form to organic form. The structure of WTF is obtained according to elemental analysis result and reaction mechanism. Through analysis of the infrared spectrogram of WTF and WTF heavy mental chelating precipitation, WTF can form stable chelate with heavy mental through coordination. The significant groups are hydroxyl, nitrogen and sulphur function groups in WTF mainly. Toxicology test revealed that the WTF resin is nontoxic to microorganism in the soils. Copyright © 2017 Elsevier B.V. All rights reserved.

Critical current densities in superconducting Y-Ba-Cu-O prepared by chelating method

NASA Astrophysics Data System (ADS)

Fujisawa, Tadashi; Okuyama, Katsuro; Ohshima, Shigetoshi; Takagi, Akira

1990-10-01

The IDA, NTA, HEDTA, EDTA, TTHA, and DTPA chelating agents have been used to prepare the Y-Ba-Cu-O compounds whose critical current is presently investigated. It is noted that the precursor YBCO prepared from large stability-constant metal complexes (HEDTA, EDTA, DTPA, and TTHA) exhibited very fine and homogeneous particles. The critical current density of a 1 x 4 x 15 mm block of YBCO sintered at 880-910 C for 24 h and subsequently annealed at 500 C in an O2 flow was approximately 500 A/sq cm at 77 K, in zero magnetic field.

Polycatecholamide chelating agents

DOEpatents

Weitl, F.L.; Raymond, K.N.

1984-04-10

Novel polybenzamide compounds useful for in vitro or in vivo chelation are described. The compounds have the formula given in patent. Polyamines are reacted with 2,3-dimethoxy benzoyl chloride unsubstituted or substituted with SO[sub 3]H, SO[sub 3]M, NO[sub 2], CO[sub 2]H or CO[sub 2]M as desired is reacted with a polyamine in an inert solvent then demethylated with BBr[sub 3] or BCl[sub 3] in an inert solvent. Where compounds symmetrically substituted on the terminal N's are desired, the polyamine is first reductively alkylated by reaction with an aldehyde or ketone and the resulting Schiff base is hydrogenated. No Drawings

Novel polycatecholamide chelating agents

DOEpatents

Weitl, F.L.; Raymond, K.N.

1981-08-24

Novel polybenzamide compounds useful for in vitro or in vivo chelation are described. Formulas of the compounds are given. To prepare them polyamines are reacted with 2,3-dimethoxy benzoyl chloride unsubstituted or substituted with SO/sub 3/H, SO/sub 3/M, NO/sub 2/, CO/sub 2/H or CO/sub 2/M as desired is reacted with a polyamine in an inert solvent then demethylated with BBr/sub 3/ or BCl/sub 3/ in an inert solvent. Where compounds symmetrically substituted on the terminal N's are desired, the polyamine is first reductively alkylated by reaction with an aldehyde or ketone and the resulting Schiff base is hydrogenated.

A neutral polydisulfide containing Gd(III) DOTA monoamide as a redox-sensitive biodegradable macromolecular MRI contrast agent.

PubMed

Ye, Zhen; Zhou, Zhuxian; Ayat, Nadia; Wu, Xueming; Jin, Erlei; Shi, Xiaoyue; Lu, Zheng-Rong

2016-01-01

This work aims to develop safe and effective gadolinium (III)-based biodegradable macromolecular MRI contrast agents for blood pool and cancer imaging. A neutral polydisulfide containing macrocyclic Gd-DOTA monoamide (GOLS) was synthesized and characterized. In addition to studying the in vitro degradation of GOLS, its kinetic stability was also investigated in an in vivo model. The efficacy of GOLS for contrast-enhanced MRI was examined with female BALB/c mice bearing 4T1 breast cancer xenografts. The pharmacokinetics, biodistribution, and metabolism of GOLS were also determined in mice. GOLS has an apparent molecular weight of 23.0 kDa with T1 relaxivities of 7.20 mM(-1) s(-1) per Gd at 1.5 T, and 6.62 mM(-1) s(-1) at 7.0 T. GOLS had high kinetic inertness against transmetallation with Zn(2+) ions, and its polymer backbone was readily cleaved by L-cysteine. The agent showed improved efficacy for blood pool and tumor MR imaging. The structural effect on biodistribution and in vivo chelation stability was assessed by comparing GOLS with Gd(HP-DO3A), a negatively charged polydisulfide containing Gd-DOTA monoamide GODC, and a polydisulfide containing Gd-DTPA-bisamide (GDCC). GOLS showed high in vivo chelation stability and minimal tissue deposition of gadolinium. The biodegradable macromolecular contrast agent GOLS is a promising polymeric contrast agent for clinical MR cardiovascular imaging and cancer imaging. Copyright © 2015 John Wiley & Sons, Ltd.

Copper chelators: chemical properties and bio-medical applications.

PubMed

Tegoni, M; Valensin, D; Toso, L; Remelli, M

2014-01-01

Copper is present in different concentrations and chemical forms throughout the earth crust, surface and deep water and even, in trace amounts, in the atmosphere itself. Copper is one of the first metals used by humans, the first artifacts dating back 10,000 years ago. Currently, the world production of refined copper exceeds 16,000 tons/year. Copper is a micro-element essential to life, principally for its red-ox properties that make it a necessary cofactor for many enzymes, like cytochrome-c oxidase and superoxide dismutase. In some animal species (e.g. octopus, snails, spiders, oysters) copper-hemocyanins also act as carriers of oxygen instead of hemoglobin. However, these red-ox properties also make the pair Cu(+)/Cu(2+) a formidable catalyst for the formation of reactive oxygen species, when copper is present in excess in the body or in tissues. The treatment of choice in cases of copper overloading or intoxication is the chelation therapy. Different molecules are already in clinical use as chelators or under study or clinical trial. It is worth noting that chelation therapy has also been suggested to treat some neurodegenerative diseases or cardiovascular disorders. In this review, after a brief description of the homeostasis and some cases of dyshomeostasis of copper, the main (used or potential) chelators are described; their properties in solution, even in relation to the presence of metal or ligand competitors, under physiological conditions, are discussed. The legislation of the most important Western countries, regarding both the use of chelating agents and the limits of copper in foods, drugs and cosmetics, is also outlined.

Greener approach for the extraction of copper metal from electronic waste.

PubMed

Jadhao, Prashant; Chauhan, Garima; Pant, K K; Nigam, K D P

2016-11-01

Technology innovations resulted into a major move from agricultural to industrial economy in last few decades. Consequently, generation of waste electronic and electrical equipments (WEEE) has been increased at a significant rate. WEEE contain large amount of precious and heavy metals and therefore, can be considered a potential secondary resource to overcome the scarcity of metals. Also, presence of these metals may affect the ecosystem due to lack of adequate management of WEEE. Building upon our previous experimental investigations for metal extraction from spent catalyst, present study explores the concept of green technology for WEEE management. Efforts have been made to recover base metal from a printed circuit board using eco-friendly chelation technology and results were compared with the conventional acid leaching method. 83.8% recovery of copper metal was achieved using chelation technology whereas only 27% could be recovered using acid leaching method in absence of any oxidant at optimum reaction conditions. Various characterization studies (energy dispersive X-ray analysis, scanning electron microscopy, X-ray diffraction, inductive coupled plasma spectrophotometry) of Printed Circuit Board (PCB) and residues were performed for qualitative and quantitative analysis of samples. Significant metal extraction, more than 96% recovery of chelating agent, recycling of reactant in next chelation cycle and nearly zero discharge to the environment are the major advantages of the proposed green process which articulate the transcendency of chelation technology over other conventional approaches. Kinetic investigation suggests diffusion controlled process as the rate determining step for the chelate assisted recovery of copper from WEEE with activation energy of 22kJ/mol. Copyright © 2015 Elsevier Ltd. All rights reserved.

Aceruloplasminaemia with progressive atrophy without brain iron overload: treatment with oral chelation.

PubMed

Skidmore, F M; Drago, V; Foster, P; Schmalfuss, I M; Heilman, K M; Streiff, R R

2008-04-01

Hereditary aceruloplasminaemia is a disorder of iron metabolism that is characterised by iron accumulation in the brain and other visceral organs. In previously reported cases, individuals with the disorder were noted to have evidence of iron accumulation in the brain. Oral chelating agents have not been used in neurological diseases of iron metabolism. A 54-year-old woman who presented with ataxia, lower extremity spasticity and chorea was evaluated for evidence of the source of neurological dysfunction. Blood studies revealed no detectable ceruloplasmin. Marked iron overload was defined by a liver biopsy, which showed a variegated pattern consistent with a primary cause of iron overload. Review of MRI scans showed progressive brain atrophy without visible iron accumulation occurring over a 5-year period. The history suggested that neurodegeneration was coincident with aggressive oral iron replacement. Oral chelation improved many symptoms. Our findings in this patient suggest that disorders of iron transport such as aceruloplasminaemia can be a cause of neurological symptoms such as chorea and cognitive decline, as well as progressive neurodegeneration in the absence of visible iron on MRI scans. We found that oral iron chelation was effective at improving symptoms.

Optimization of isolation of cellulose from orange peel using sodium hydroxide and chelating agents.

PubMed

Bicu, Ioan; Mustata, Fanica

2013-10-15

Response surface methodology was used to optimize cellulose recovery from orange peel using sodium hydroxide (NaOH) as isolation reagent, and to minimize its ash content using ethylenediaminetetraacetic acid (EDTA) as chelating agent. The independent variables were NaOH charge, EDTA charge and cooking time. Other two constant parameters were cooking temperature (98 °C) and liquid-to-solid ratio (7.5). The dependent variables were cellulose yield and ash content. A second-order polynomial model was used for plotting response surfaces and for determining optimum cooking conditions. The analysis of coefficient values for independent variables in the regression equation showed that NaOH and EDTA charges were major factors influencing the cellulose yield and ash content, respectively. Optimum conditions were defined by: NaOH charge 38.2%, EDTA charge 9.56%, and cooking time 317 min. The predicted cellulose yield was 24.06% and ash content 0.69%. A good agreement between the experimental values and the predicted was observed. Copyright © 2013 Elsevier Ltd. All rights reserved.

Alkaline Sodium Hypochlorite Irrigant and Its Chemical Interactions

PubMed Central

Kahler, Bill; Walsh, Laurence J.

2017-01-01

Endodontic irrigating solutions may interact chemically with one another. This is important, because even when solutions are not admixed, they will come into contact with one another during an alternating irrigation technique, forming unwanted by-products, which may be toxic or irritant. Mixing or alternating irrigants can also reduce their ability to clean and disinfect the root canal system of teeth by changing their chemical structure with subsequent loss of the active agent, or by inducing precipitate formation in the root canal system. Precipitates occlude dental tubules, resulting in less penetration of antimicrobials and a loss of disinfection efficacy. Sodium hypochlorite is not only a very reactive oxidizing agent, but is also the most commonly used endodontic irrigant. As such, many interactions occurring between it and other irrigants, chelators and other antimicrobials, may occur. Of particular interest is the interaction between sodium hypochlorite and the chelators EDTA, citric acid and etidronate and between sodium hypochlorite and the antimicrobials chlorhexidine, alexidine, MTAD and octenisept. PMID:28961175

Blood-Brain Barrier Permeable Gold Nanoparticles: An Efficient Delivery Platform for Enhanced Malignant Glioma Therapy and Imaging

PubMed Central

Cheng, Yu; Dai, Qing; Morshed, Ramin; Fan, Xiaobing; Wegscheid, Michelle L.; Wainwright, Derek A.; Han, Yu; Zhang, Lingjiao; Auffinger, Brenda; Tobias, Alex L.; Rincón, Esther; Thaci, Bart; Ahmed, Atique U.; Warnke, Peter; He, Chuan

2014-01-01

The blood-brain barrier (BBB) remains a formidable obstacle in medicine, preventing efficient penetration of chemotherapeutic and diagnostic agents to malignant gliomas. Here, we demonstrate that a transactivator of transcription (TAT) peptide-modified gold nanoparticle platform (TAT-Au NP) with a 5 nm core size is capable of crossing the BBB efficiently and delivering cargoes such as the anticancer drug doxorubicin (Dox) and Gd3+ contrast agents to brain tumor tissues. Treatment of mice bearing intracranial glioma xenografts with pH-sensitive Dox-conjugated TAT-Au NPs via a single intravenous administration leads to significant survival benefit when compared to the free Dox. Furthermore, we demonstrate that TAT-Au NPs are capable of delivering Gd3+ chelates for enhanced brain tumor imaging with a prolonged retention time of Gd3+ when compared to the free Gd3+ chelates. Collectively, these results show promising applications of the TAT-Au NPs for enhanced malignant brain tumor therapy and non-invasive imaging. PMID:25104165

Biomolecule conjugation strategy using novel water-soluble phosphine-based chelating agents

DOEpatents

Katti, Kattesh V.; Gali, Hariprasad; Volkert, Wynn A.

2004-08-24

This invention describes a novel strategy to produce phosphine-functionalized biomolecules (e.g. peptides or proteins) for potential use in the design and development of site-specific radiopharmaceuticals for diagnosis or therapy of specific cancers. Hydrophilic alkyl phosphines, in general, tend to be oxidatively unstable. Therefore, incorporation of such phosphine functionalities on peptide (and other biomolecule) backbones, without oxidizing the P.sup.III centers, is difficult. In this context this discovery reports on a new technology by which phosphines, in the form of bifunctional chelating agents, can be directly incorporated on biomolecular backbones using manual synthetic or solid phase peptide synthesis methodologies. The superior ligating abilities of phosphine ligands, with various diagnostically (e.g. TC-99m) or therapeutically (e.g. Re186/188, Rh-105, Au-199) useful radiometals, coupled with the findings that the resulting complexes demonstrate high in vivo stability makes this approach useful in the development of radiolabeled biomolecules for applications in the design of tumor-specific radiopharmaceuticals.

Phosphonate Pendant Armed Propylene Cross-Bridged Cyclam: Synthesis and Evaluation as a Chelator for Cu-64

PubMed Central

2015-01-01

A propylene cross-bridged macrocyclic chelator with two phosphonate pendant arms (PCB-TE2P) was synthesized from cyclam. Various properties of the synthesized chelator, including Cu-complexation, Cu-complex stability, 64Cu-radiolabeling, and in vivo behavior, were studied and compared with those of a previously reported propylene cross-bridged chelator (PCB-TE2A). PMID:26617972

Radiolabeling Silica-Based Nanoparticles via Coordination Chemistry: Basic Principles, Strategies, and Applications.

PubMed

Ni, Dalong; Jiang, Dawei; Ehlerding, Emily B; Huang, Peng; Cai, Weibo

2018-03-20

As one of the most biocompatible and well-tolerated inorganic nanomaterials, silica-based nanoparticles (SiNPs) have received extensive attention over the last several decades. Recently, positron emission tomography (PET) imaging of radiolabeled SiNPs has provided a highly sensitive, noninvasive, and quantitative readout of the organ/tissue distribution, pharmacokinetics, and tumor targeting efficiency in vivo, which can greatly expedite the clinical translation of these promising NPs. Encouraged by the successful PET imaging of patients with metastatic melanoma using 124 I-labeled ultrasmall SiNPs (known as Cornell dots or C dots) and their approval as an Investigational New Drug (IND) by the United States Food and Drug Administration, different radioisotopes ( 64 Cu, 89 Zr, 18 F, 68 Ga, 124 I, etc.) have been reported to radiolabel a wide variety of SiNPs-based nanostructures, including dense silica (dSiO 2 ), mesoporous silica (MSN), biodegradable mesoporous silica (bMSN), and hollow mesoporous silica nanoparticles (HMSN). With in-depth knowledge of coordination chemistry, abundant silanol groups (-Si-O-) on the silica surface or inside mesoporous channels not only can be directly used for chelator-free radiolabeling but also can be readily modified with the right chelators for chelator-based labeling. However, integrating these labeling strategies for constructing stably radiolabeled SiNPs with high efficiency has proven difficult because of the complexity of the involved key parameters, such as the choice of radioisotopes and chelators, nanostructures, and radiolabeling strategy. In this Account, we present an overview of recent progress in the development of radiolabeled SiNPs for cancer theranostics in the hope of speeding up their biomedical applications and potential translation into the clinic. We first introduce the basic principles and mechanisms for radiolabeling SiNPs via coordination chemistry, including general rules of selecting proper radioisotopes, engineering silica nanoplatforms (e.g., dSiO 2 , MSN, HMSN) accordingly, and chelation strategies for enhanced labeling efficiency and stability, on which our group has focused over the past decade. Generally, the medical applications guide the choice of specific SiNPs for radiolabeling by considering the inherent functionality of SiNPs. The radioisotopes can then be determined according to the amenability of the particular SiNPs for chelator-based or chelator-free radiolabeling to obtain high labeling stability in vivo, which is a prerequisite for PET to truly reflect the behavior of SiNPs since PET imaging detects the isotopes rather than nanoparticles. Next, we highlight several recent representative biomedical applications of radiolabeled SiNPs including molecular imaging to detect specific lesions, PET-guided drug delivery, SiNP-based theranostic cancer agents, and clinical studies. Finally, the challenges and prospects of radiolabeled SiNPs are briefly discussed toward clinical cancer research. We hope that this Account will clarify the recent progress on the radiolabeling of SiNPs for specific medical applications and generate broad interest in integrating nanotechnology and PET imaging. With several ongoing clinical trials, radiolabeled SiNPs offer great potential for future patient stratification and cancer management in clinical settings.

Gadolinium-conjugated PLA-PEG nanoparticles as liver targeted molecular MRI contrast agent.

PubMed

Chen, Zhijin; Yu, Dexin; Liu, Chunxi; Yang, Xiaoyan; Zhang, Na; Ma, Chunhong; Song, Jibin; Lu, Zaijun

2011-09-01

A nanoparticle magnetic resonance imaging (MRI) contrast agent targeted to liver was developed by conjugation of gadolinium (Gd) chelate groups onto the biocompatible poly(l-lactide)-block-poly (ethylene glycol) (PLA-PEG) nanoparticles. PLA-PEG conjugated with diethylenetriaminopentaacetic acid (DTPA) was used to formulate PLA-PEG-DTPA nanoparticles by solvent diffusion method, and then Gd was loaded onto the nanoparticles by chelated with the unfolding DTPA on the surface of the PLA-PEG-DTPA nanoparticles. The mean size of the nanoparticles was 265.9 ± 6.7 nm. The relaxivity of the Gd-labeled nanoparticles was measured, and the distribution in vivo was evaluated in rats. Compared with conventional contrast agent (Magnevist), the Gd-labeled PLA-PEG nanoparticles showed significant enhancement both on liver targeting ability and imaging signal intensity. The T(1) and T(2) relaxivities per [Gd] of the Gd-labeled nanoparticles was 18.865 mM(-1) s(-1) and 24.863 mM(-1) s(-1) at 3 T, respectively. In addition, the signal intensity in vivo was stronger comparing with the Gd-DTPA and the T(1) weight time was lasting for 4.5 h. The liver targeting efficiency of the Gd-labeled PLA-PEG nanoparticles in rats was 14.57 comparing with Magnevist injection. Therefore, the Gd-labeled nanoparticles showed the potential as targeting molecular MRI contrast agent for further clinical utilization.

Spectroscopic properties and Judd-Ofelt theory analysis of erbium chelates.

PubMed

Wang, Huaishan; Qian, Guodong; Wang, Zhiyu; Wang, Minquan

2005-11-01

Erbium chelates including tris(acetylacetonato) erbium(III) monohydrate, tris(acetylacetonato)(1,10-phenanthroline) erbium(III) and tris(trifluoroacetylacetonato)(1,10-phenanthroline) erbium(III) are synthesized. Judd-Ofelt theory is employed on basis of the UV-Vis-NIR absorption spectra of erbium chelates dissolved in methanol. Judd-Ofelt parameters of erbium chelates are determined by a least square fitting and dealt with the chemical structure of erbium chelates. Photoluminescence characteristics of erbium chelates are investigated upon excitation at 488 nm by an Ar(+) laser. The qualitative correlation of Judd-Ofelt parameters with photoluminescence properties for erbium chelates is also discussed. It is found that larger Omega(6) value for erbium chelate is and larger photoluminescence intensity at 1.54 microm is, and Omega(2) value should contribute to the photoluminescence full width at half maximum (FWHM) at 1.54 microm. The changes of Judd-Ofelt parameters result from the introduction of the second ligand phenathroline or the substitution of electron-drawing group CF(3) in beta-diketone for erbium chelates.

Liver transplantation for Wilson disease

PubMed Central

Catana, Andreea M; Medici, Valentina

2012-01-01

The aim of this paper is to review the current status of liver transplantation (LT) for Wilson disease (WD), focusing on indications and controversies, especially in patients with neuropsychiatric disease, and on identification of acute liver failure (ALF) cases related to WD. LT remains the treatment of choice for patients with ALF, as initial presentation of WD or when anti-copper agents are stopped, and for patients with chronic liver disease progressed to cirrhosis, unresponsive to chelating medications or not timely treated with copper chelating agents. The indication for LT in WD remains highly debated in patients with progressive neurological deterioration and failure to improve with appropriate medical treatment. In case of Wilsonian ALF, early identification is key as mortality is 100% without emergency LT. As many of the copper metabolism parameters are believed to be less reliable in ALF, simple biochemical tests have been proposed for diagnosis of acute WD with good sensitivity and specificity. LT corrects copper metabolism and complications resulting from WD with excellent 1 and 5 year survival. Living related liver transplantation represents an alternative to deceased donor LT with excellent long-term survival, without disease recurrence. Future options may include hepatocyte transplantation and gene therapy. Although both of these have shown promising results in animal models of WD, prospective human studies are much needed to demonstrate their long-term beneficial effects and their potential to replace the need for medical therapy and LT in patients with WD. PMID:22312450

Thin film composition with biological substance and method of making

DOEpatents

Campbell, Allison A.; Song, Lin

1999-01-01

The invention provides a thin-film composition comprising an underlying substrate of a first material including a plurality of attachment sites; a plurality of functional groups chemically attached to the attachment sites of the underlying substrate; and a thin film of a second material deposited onto the attachment sites of the underlying substrate, and a biologically active substance deposited with the thin-film. Preferably the functional groups are attached to a self assembling monolayer attached to the underlying substrate. Preferred functional groups attached to the underlying substrate are chosen from the group consisting of carboxylates, sulfonates, phosphates, optionally substituted, linear or cyclo, alkyl, alkene, alkyne, aryl, alkylaryl, amine, hydroxyl, thiol, silyl, phosphoryl, cyano, metallocenyl, carbonyl, and polyphosphate. Preferred materials for the underlying substrate are selected from the group consisting of a metal, a metal alloy, a plastic, a polymer, a proteic film, a membrane, a glass or a ceramic. The second material is selected from the group consisting of inorganic crystalline structures, inorganic amorphus structures, organic crystalline structures, and organic amorphus structures. Preferred second materials are phosphates, especially calcium phosphates and most particularly calcium apatite. The biologically active molecule is a protein, peptide, DNA segment, RNA segment, nucleotide, polynucleotide, nucleoside, antibiotic, antimicrobal, radioisotope, chelated radioisotope, chelated metal, metal salt, anti-inflamatory, steriod, nonsteriod anti-inflammatory, analgesic, antihistamine, receptor binding agent, or chemotherapeutic agent, or other biologically active material. Preferably the biologically active molecule is an osteogenic factor the compositions listed above.

Macromolecular and Dendrimer Based Magnetic Resonance Contrast Agents

PubMed Central

Bumb, Ambika; Brechbiel, Martin W.; Choyke, Peter

2010-01-01

Magnetic resonance imaging (MRI) is a powerful imaging modality that can provide an assessment of function or molecular expression in tandem with anatomic detail. Over the last 20–25 years, a number of gadolinium based MR contrast agents have been developed to enhance signal by altering proton relaxation properties. This review explores a range of these agents from small molecule chelates, such as Gd-DTPA and Gd-DOTA, to macromolecular structures composed of albumin, polylysine, polysaccharides (dextran, inulin, starch), poly(ethylene glycol), copolymers of cystamine and cystine with GD-DTPA, and various dendritic structures based on polyamidoamine and polylysine (Gadomers). The synthesis, structure, biodistribution and targeting of dendrimer-based MR contrast agents are also discussed. PMID:20590365

TPEN, a Specific Zn2+ Chelator, Inhibits Sodium Dithionite and Glucose Deprivation (SDGD)-Induced Neuronal Death by Modulating Apoptosis, Glutamate Signaling, and Voltage-Gated K+ and Na+ Channels.

PubMed

Zhang, Feng; Ma, Xue-Ling; Wang, Yu-Xiang; He, Cong-Cong; Tian, Kun; Wang, Hong-Gang; An, Di; Heng, Bin; Xie, Lai-Hua; Liu, Yan-Qiang

2017-03-01

Hypoxia-ischemia-induced neuronal death is an important pathophysiological process that accompanies ischemic stroke and represents a major challenge in preventing ischemic stroke. To elucidate factors related to and a potential preventative mechanism of hypoxia-ischemia-induced neuronal death, primary neurons were exposed to sodium dithionite and glucose deprivation (SDGD) to mimic hypoxic-ischemic conditions. The effects of N,N,N',N'-tetrakis (2-pyridylmethyl) ethylenediamine (TPEN), a specific Zn 2+ -chelating agent, on SDGD-induced neuronal death, glutamate signaling (including the free glutamate concentration and expression of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptor (GluR2) and N-methyl-D-aspartate (NMDA) receptor subunits (NR2B), and voltage-dependent K + and Na + channel currents were also investigated. Our results demonstrated that TPEN significantly suppressed increases in cell death, apoptosis, neuronal glutamate release into the culture medium, NR2B protein expression, and I K as well as decreased GluR2 protein expression and Na + channel activity in primary cultured neurons exposed to SDGD. These results suggest that TPEN could inhibit SDGD-induced neuronal death by modulating apoptosis, glutamate signaling (via ligand-gated channels such as AMPA and NMDA receptors), and voltage-gated K + and Na + channels in neurons. Hence, Zn 2+ chelation might be a promising approach for counteracting the neuronal loss caused by transient global ischemia. Moreover, TPEN could represent a potential cell-targeted therapy.

Predicting the efficiencies of 2-mercaptobenzothiazole collectors used as chelating agents in flotation processes: a density-functional study.

PubMed

Yekeler, Hülya; Yekeler, Meftuni

2006-09-01

In recent years, several new chelating reagents have been synthesized and tested for their collecting power in sulfide and non-sulfide minerals flotation. Many researchers have indicated that chelating reagents have the advantage of offering better selectivity and specificity as flotation collectors. Therefore, density functional theory (DFT) calculations at the B3LYP/6-31G(d,p) level were performed to investigate the observed activities of 2-mercaptobenzothiazole, 6-methyl-2-mercaptobenzothiazole and 6-methoxy-2-mercaptobenzothiazole as the most popular flotation collectors. The molecular properties and activity relationships were determined by the HOMO localizations, the HOMO energies, Mulliken charges and the electrostatic potentials at the thioamide functional group, which is the key site in the forming efficiency of the collectors studied. It is concluded that these quantities can be used successfully for understanding the collecting abilities of 2-mercaptobenzothiazoles. The results obtained theoretically are consistent with the experimental data reported in the literature.

ENHANCED BIOACCUMULATION OF HEAVY METAL BY BACTERIA CELLS DISPLAYING SYNTHETIC PHYTOCHELATINS. (R827227)

EPA Science Inventory

A novel strategy using synthetic phytochelatins is described for the purpose of developing microbial agents for enhanced bioaccumulation of toxic metals. Synthetic genes encoding for several metal-chelating phytochelatin analogs (Glu-Cys)_nGly (EC8 (n = 8), EC11 (n = 11...

Aromatic triamide-lanthanide complexes

DOEpatents

Raymond, Kenneth N; Petoud, Stephane; Xu, Jide

2013-10-08

The present invention provides luminescent lanthanide metal chelates comprising a metal ion of the lanthanide series and a complexing agent comprising at least one phthalamidyl moiety. Also provided are probes incorporating the phthalamidyl ligands of the invention and methods utilizing the ligands of the invention and probes comprising the ligands of the invention.

Using T2-Exchange from Ln3+DOTA-Based Chelates for Contrast-Enhanced Molecular Imaging of Prostate Cancer with MRI

DTIC Science & Technology

2015-04-01

antigen ( PSMA ) of prostate cancer cells would then be synthesized and tested with both in vitro and in vivo experiments. Major Findings: We found that the...simplified chemistry. 15. SUBJECT TERMS MRI Contrast Agent, T2 contrast, Prostate Cancer, PSMA Targeted Agent, Early Detection and Diagnosis, Dysprosium... PSMA ), which is significantly over-expressed by prostate cancer cells, has proven to be an excellent target for imaging prostate cancer in mouse

Chelation technology: a promising green approach for resource management and waste minimization.

PubMed

Chauhan, Garima; Pant, K K; Nigam, K D P

2015-01-01

Green chemical engineering recognises the concept of developing innovative environmentally benign technologies to protect human health and ecosystems. In order to explore this concept for minimizing industrial waste and for reducing the environmental impact of hazardous chemicals, new greener approaches need to be adopted for the extraction of heavy metals from industrial waste. In this review, a range of conventional processes and new green approaches employed for metal extraction are discussed in brief. Chelation technology, a modern research trend, has shown its potential to develop sustainable technology for metal extraction from various metal-contaminated sites. However, the interaction mechanism of ligands with metals and the ecotoxicological risk associated with the increased bioavailability of heavy metals due to the formation of metal-chelant complexes is still not sufficiently explicated in the literature. Therefore, a need was felt to provide a comprehensive state-of-the-art review of all aspects associated with chelation technology to promote this process as a green chemical engineering approach. This article elucidates the mechanism and thermodynamics associated with metal-ligand complexation in order to have a better understanding of the metal extraction process. The effects of various process parameters on the formation and stability of complexes have been elaborately discussed with respect to optimizing the chelation efficiency. The non-biodegradable attribute of ligands is another important aspect which is currently of concern. Therefore, biotechnological approaches and computational tools have been assessed in this review to illustrate the possibility of ligand degradation, which will help the readers to look for new environmentally safe mobilizing agents. In addition, emerging trends and opportunities in the field of chelation technology have been summarized and the diverse applicability of chelation technology in metal extraction from contaminated sites has also been reviewed.

Thermodynamic stability and relaxation studies of small, triaza-macrocyclic Mn(II) chelates.

PubMed

de Sá, Arsénio; Bonnet, Célia S; Geraldes, Carlos F G C; Tóth, Éva; Ferreira, Paula M T; André, João P

2013-04-07

Due to its favorable relaxometric properties, Mn(2+) is an appealing metal ion for magnetic resonance imaging (MRI) contrast agents. This paper reports the synthesis and characterization of three new triazadicarboxylate-type ligands and their Mn(2+) chelates (NODAHep, 1,4,7-triazacyclononane-1,4-diacetate-7-heptanil; NODABA, 1,4,7-triazacyclononane-1,4-diacetate-7-benzoic acid; and NODAHA, 1,4,7-triazacyclononane-1,4-diacetate-7-hexanoic acid). The protonation constants of the ligands and the stability constants of the chelates formed with Mn(2+) and the endogenous Zn(2+) ion have been determined by potentiometry. In overall, the thermodynamic stability of the chelates is lower than that of the corresponding NOTA analogues (NOTA = 1,4,7-triazacyclononane-1,4,7-triacetate), consistent with the decreased number of coordinating carboxylate groups. Variable temperature (1)H NMRD and (17)O NMR measurements have been performed on the paramagnetic chelates to provide information on the water exchange rates and the rotational dynamics. The values of the (17)O chemical shifts are consistent with the presence of one water molecule in the first coordination sphere of Mn(2+). The three complexes are in the slow to intermediate regime for the water exchange rate, and they all display relatively high rotational correlation times, which explain the relaxivity values between 4.7 and 5.8 mM(-1) s(-1) (20 MHz and 298 K). These relaxivities are higher than expected for Mn(2+) chelates of such size and comparable to those of small monohydrated Gd(3+) complexes. The amphiphilic [Mn(NODAHep)] forms micelles above 22 mM (its critical micellar concentration was determined by relaxometry and fluorescence), and interacts with HSA via its alkylic carbon chain providing a 60% relaxivity increase at 20 MHz due to a longer tumbling time.

Comparison of DOTA and NODAGA as chelators for (64)Cu-labeled immunoconjugates.

PubMed

Ghosh, Sukhen C; Pinkston, Kenneth L; Robinson, Holly; Harvey, Barrett R; Wilganowski, Nathaniel; Gore, Karen; Sevick-Muraca, Eva M; Azhdarinia, Ali

2015-02-01

Bifunctional chelators have been shown to impact the biodistribution of monoclonal antibody (mAb)-based imaging agents. Recently, radiolabeled 1,4,7-triazacyclononane,1-glutaric acid-4,7-acetic acid (NODAGA)-peptide complexes have demonstrated improved in vivo stability and performance compared to their 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) counterparts. Here, we investigated if similar utility could be achieved with mAbs and compared (64)Cu-labeled DOTA and NODAGA-immunoconjugates for the detection of epithelial cell adhesion molecule (EpCAM) in a prostate cancer model. DOTA and NODAGA-immunoconjugates of an EpCAM targeting mAb (mAb7) were synthesized and radiolabeled with (64)Cu (DOTA: 40°C for 1hr; NODAGA: 25°C for 1hr). The average number of chelators per mAb was quantified by isotopic dilution, and the biological activity of the immunoconjugates was evaluated by flow cytometry and ELISA. Radioligand assays were performed to compare cellular uptake and determine the dissociation constant (Kd) and maximum number of binding sites (Bmax) for the immunoconjugates using DsRed-transfected PC3-cells. A PC3-DsRed xenograft tumor model was established in nude mice and used to perform biodistribution studies to compare organ uptake and pharmacokinetics. (64)Cu-DOTA-mAb7 and (64)Cu-NODAGA-mAb7 were prepared with chelator/protein ratios of 2-3 and obtained in comparable radiochemical yields ranging from 59 to 71%. Similar immunoreactivity was observed with both agents, and mock labeling studies indicated that incubation at room temperature or 40°C did not affect potency. (64)Cu-NODAGA-mAb7 demonstrated higher in vitro cellular uptake while (64)Cu-DOTA-mAb7 had higher Kd and Bmax values. From the biodistribution data, we found similar tumor uptake (13.44±1.21%ID/g and 13.24±4.86%ID/g for (64)Cu-DOTA-mAb7 and (64)Cu-NODAGA-mAb7, respectively) for both agents at 24hr, although normal prostate tissue was significantly lower for (64)Cu-NODAGA-mAb7. (64)Cu-NODAGA-mAb7 also had less accumulation in the liver, suggesting excellent retention of the chelation complex in vivo. This was further confirmed by the higher blood activity of (64)Cu-NODAGA-mAb7, which corresponds to increased bioavailability afforded by the enhanced in vivo stability of the agent. Although tumor/muscle ratios were comparable, tumor/prostate ratios were >2-fold and 1.5-fold higher for (64)Cu-NODAGA-mAb7 at 24 and 48hr, respectively, and suggest better ability to discriminate tumor tissue with (64)Cu-NODAGA-mAb7 in our prostate cancer model. To the best of our knowledge, this study represents the first comparison of (64)Cu-labeled DOTA and NODAGA immunoconjugates in vivo. Our results show favorable in vivo performance for (64)Cu-NODAGA-mAb7 which builds upon previous data on our hybrid mAb7 imaging agent by increasing the detection sensitivity for metastatic prostate tumors, as well as for other types of cancer that express EpCAM. Copyright © 2014 Elsevier Inc. All rights reserved.

Reaction of gadolinium chelates with ozone and hydroxyl radicals.

PubMed

Cyris, Maike; Knolle, Wolfgang; Richard, Jessica; Dopp, Elke; von Sonntag, Clemens; Schmidt, Torsten C

2013-09-03

Gadolinium chelates are used in increasing amounts as contrast agents in magnetic resonance imaging, and their fate in wastewater treatment has recently become the focus of research. Oxidative processes, in particular the application of ozone, are currently discussed or even implemented for advanced wastewater treatment. However, reactions of the gadolinium chelates with ozone are not yet characterized. In this study, therefore, rate constants with ozone were determined for the three commonly used chelates Gd-DTPA, Gd-DTPA-BMA, and Gd-BT-DO3A, which were found to be 4.8 ± 0.88, 46 ± 2.5, and 24 ± 1.5 M(-1) s(-1), respectively. These low rate constants indicate that a direct reaction with ozone in wastewater is negligible. However, application of ozone in wastewater leads to substantial yields of (•)OH. Different methods have been applied and compared for determination of k((•)OH+Gd chelate). From rate constants determined by pulse radiolysis experiments (k((•)OH+Gd-DTPA) = 2.6 ± 0.2 × 10(9) M(-1) s(-1), k((•)OH+Gd-DTPA-BMA) = 1.9 ± 0.7 × 10(9) M(-1) s(-1), k((•)OH+Gd-BT-DO3A) = 4.3 ± 0.2 × 10(9) M(-1) s(-1)), it is concluded that a reaction in wastewater via (•)OH radicals is feasible. Toxicity has been tested for educt and product mixtures of both reactions. Cytotoxicity (MTT test) and genotoxicity (micronuclei assay) were not detectable.

Iron supply to soybean plants through the foliar application of IDHA/Fe3+: effect of plant nutritional status and adjuvants.

PubMed

Rodríguez-Lucena, Patricia; Ropero, Edgar; Hernández-Apaolaza, Lourdes; Lucena, Juan J

2010-12-01

Synthetic Fe chelates are commonly used to overcome Fe deficiencies in crops, but most of them are scarcely biodegradable. Iminodisuccinic acid (IDHA) is a biodegradable chelating agent that is currently being evaluated as an alternative to EDTA. In this work, the efficacy of the foliar application of IDHA/Fe(3+) to soybean chlorotic plants under controlled conditions was studied, testing the influence of the adjuvant used and of the plant nutritional status. When IDHA/Fe(3+) was applied to soybean plants with severe Fe chlorosis and the foliar sprays were the sole source of Fe, this chelate behaved similarly to the EDTA/Fe(3+) and the recovery of the plants was slight in both cases. The same chelates were tested when foliar sprays were an additional source of Fe for mildly chlorotic plants, which were also being supplied with low concentrations of Fe applied to the nutrient solution. Then, plant recovery was appreciable in all cases, and the IDHA/Fe(3+) was as effective as EDTA/Fe(3+). Among the adjuvants studied, a urea-based product was the only one that did not damage the leaf surface and that could improve the efficiency of IDHA/Fe(3+) up tp the level of EDTA/Fe(3+). Thus, it was concluded the foliar application of IDHA/Fe(3+) can be an environmentally friendly alternative to the non-biodegradable chelate EDTA/Fe(3+) when the appropriate adjuvant is used. Copyright © 2010 Society of Chemical Industry.

Chelation of hippocampal zinc enhances long-term potentiation and synaptic tagging/capture in CA1 pyramidal neurons of aged rats: implications to aging and memory.

PubMed

Shetty, Mahesh Shivarama; Sharma, Mahima; Sajikumar, Sreedharan

2017-02-01

Aging is associated with decline in cognitive functions, prominently in the memory consolidation and association capabilities. Hippocampus plays a crucial role in the formation and maintenance of long-term associative memories, and a significant body of evidence shows that impairments in hippocampal function correlate with aging-related memory loss. A number of studies have implicated alterations in hippocampal synaptic plasticity, such as long-term potentiation (LTP), in age-related cognitive decline although exact mechanisms underlying are not completely clear. Zinc deficiency and the resultant adverse effects on cognition have been well studied. However, the role of excess of zinc in synaptic plasticity, especially in aging, is not addressed well. Here, we have investigated the hippocampal zinc levels and the impairments in synaptic plasticity, such as LTP and synaptic tagging and capture (STC), in the CA1 region of acute hippocampal slices from 82- to 84-week-old male Wistar rats. We report increased zinc levels in the hippocampus of aged rats and also deficits in the tetani-induced and dopaminergic agonist-induced late-LTP and STC. The observed deficits in synaptic plasticity were restored upon chelation of zinc using a cell-permeable chelator. These data suggest that functional plasticity and associativity can be successfully established in aged neural networks by chelating zinc with cell-permeable chelating agents. © 2016 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

PET/CT Based In Vivo Evaluation of 64Cu Labelled Nanodiscs in Tumor Bearing Mice.

PubMed

Huda, Pie; Binderup, Tina; Pedersen, Martin Cramer; Midtgaard, Søren Roi; Elema, Dennis Ringkjøbing; Kjær, Andreas; Jensen, Mikael; Arleth, Lise

2015-01-01

64Cu radiolabelled nanodiscs based on the 11 α-helix MSP1E3D1 protein and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylcholine lipids were, for the first time, followed in vivo by positron emission tomography for evaluating the biodistribution of nanodiscs. A cancer tumor bearing mouse model was used for the investigations, and it was found that the approximately 13 nm nanodiscs, due to their size, permeate deeply into cancer tissue. This makes them promising candidates for both drug delivery purposes and as advanced imaging agents. For the radiolabelling, a simple approach for 64Cu radiolabelling of proteins via a chelating agent, DOTA, was developed. The reaction was performed at sufficiently mild conditions to be compatible with labelling of the protein part of a lipid-protein particle while fully conserving the particle structure including the amphipathic protein fold.

Bench-scale evaluation of in situ bioremediation strategies for soil at a former manufactured gas plant site.

PubMed

Li, Jun; Pignatello, Joseph J; Smets, Barth F; Grasso, Domenico; Monserrate, Esteban

2005-03-01

We examined the biodegradation and desorption of a set of 15 polycyclic aromatic hydrocarbon (PAH) compounds in coal tar-contaminated soil at a former manufactured gas plant site to evaluate the feasibility of in situ bioremediation. Experiments were conducted in well-mixed aerobic soil suspensions containing various additives over a 93- to 106-d period. In general, both biotransformation and desorption decreased with PAH ring size, becoming negligible for the six-ring PAH compounds. Biodegradation by indigenous microorganisms was strongly accelerated by addition of inorganic nutrients (N, P, K, and trace metals). The rates of biotransformation of PAH compounds by indigenous microorganisms in nutrient-amended flasks outpaced their maximum (i.e., chelate-enhanced) rates of desorption to an infinite sink (Tenax) in sterilized systems run in parallel, suggesting that indigenous organisms facilitated desorption. Biodegradation by indigenous organisms in nutrient-amended flasks appeared to be unaffected by the addition of a site-derived bacterial enrichment culture, resulting in approximately 100-fold higher aromatic dioxygenase levels, and by the addition of 0.01 M chelating agent (citrate or pyrophosphate), although such chelating agents greatly enhanced desorption in microbially inactivated flasks. The strong ability of nutrients to enhance degradation of the bioavailable PAHs indicates that their persistence for many decades at this site likely results from nutrient-limited natural biodegradation, and it also suggests that an effective strategy for their bioremediation could consist simply of adding inorganic nutrients.

Targeting hypoxia in tumors using 2-nitroimidazoles with peptidic chelators for technetium-99m: effect of lipophilicity.

PubMed

Zhang, X; Su, Z F; Ballinger, J R; Rauth, A M; Pollak, A; Thornback, J R

2000-01-01

Tumor hypoxia is an important prognostic factor for response to therapy. Radiolabeled 2-nitroimidazoles have been used for imaging hypoxia, and the octanol/water partition coefficient (P) of these compounds appears to play a crucial role in their suitability for imaging. A series of 11 2-nitroimidazoles coupled to peptidic chelators for (99m)Tc with divergent P was developed and evaluated in an in vitro system. Two classes of N(3)S chelators were used: dialkyl-Gly-Ser-Cys-linker-2-nitroimidazole (Class I) and dialkyl-Gly-Lys(2-nitroimidazole)-Cys (Class II). The chelators were prepared by automated solid-phase peptide synthesis. Xanthine oxidase was able to reduce the 2-nitroimidiazole moiety on the ligands, but the rate of reduction varied 5-fold among the different chelators. The chelators were labeled by transchelation from [(99m)Tc]gluconate at temperatures between 22 and 100 degrees C. The reaction mixtures were analyzed by HPLC and their P values determined. The accumulation of each complex in suspension cultures of Chinese hamster ovary cells incubated under aerobic or extremely hypoxic conditions was determined. Radiochemical yields ranged from 5 to 80% for the 11 compounds. HPLC showed that some of the compounds formed two complexes with (99m)Tc, possibly syn and anti conformations with respect to the Tc=O bond. In general, the Class I chelators labeled more readily than the class II chelators. The P values of the (99m)Tc complexes varied from 0.0002 to 5 and were generally in accordance with predictions based on structure. There were also differences in P as a function of pH; the free acids had a lower P at pH 7.4 than at pH 2.0 due to ionization, whereas the amides did not show this effect. Accumulation levels in aerobic cells were related to P but varied over a narrow range. Four of the 11 compounds showed selective accumulation in hypoxic cells. The peptidic class of 2-nitroimidazoles, with flexible design and convenient solid-phase synthesis, deserves further study as agents for imaging hypoxia in tumors.

Heavy Metal Displacement in Chelate-Assisted Phytoremediation of Biosolids Soil

NASA Astrophysics Data System (ADS)

Kirkham, M. B.; Liphadzi, M. S.

2005-05-01

Heavy metals in biosolids (sewage sludge) applied to land contaminate the soil. Phytoremediation, the use of plants to clean up toxic heavy metals, might remove them. Chelating agents are added to soil to solubilize the metals for enhanced phytoextraction. Yet no studies follow the displacement and leaching of heavy metals in soil with biosolids following solubilization with chelates. The objective of this work was to determine the mobility of heavy metals, as affected by a chelate, in soil (Haynie very fine sandy loam) from a 25-year old sludge farm. Soil columns (105 cm long; 39 cm in diameter) either had a plant (hybrid poplar; Populus deltoides Marsh. x P. nigra L.) or no plant. When the poplars were 144 days old, the tetrasodium salt of the chelating agent EDTA (ethylenediamine-tetraacetic acid) was irrigated onto the soil at a rate of 1 g per kg of soil. Drainage water, soil, and plants were analyzed for three toxic heavy metals (Cd, Ni, Pb) and four essential heavy metals (Cu, Fe, Mn, Zn). Without EDTA, concentrations of the seven heavy metals in the leachate from columns with or without plants were low or below detection limits. With or without plants, the EDTA mobilized all heavy metals and increased their concentration in drainage water. Without plants, the concentrations of Cd, Cu, Fe, Pb, and Zn in the leachate from columns with EDTA were above drinking-water standards. (There is no drinking-water standard for Ni.) The presence of poplar plants in the soil reduced the concentrations of Cu, Fe, and Zn in the leachate so it fell within drinking-water standards. Concentrations of Cd and Pb in the leachate remained above drinking-water standards with or without plants. At harvest (124 days after the EDTA application), total concentration of each heavy metal in the soil at different depths in the columns with EDTA was similar to that in the columns without EDTA. The chelate did not affect the concentration of heavy metals in the roots, stems, or leaves. However, the wood, which contains the xylem, from plants grown with EDTA had a higher concentration of Ni and Pb than did wood from plants grown with no EDTA. The results showed that heavy metals in soil with sludge treated with EDTA could contaminate ground water, even in the presence of plant roots. (This research is part of the dissertation of M.S. Liphadzi, who was supported by a Fulbright Fellowship.)

Retinal abnormalities in β-thalassemia major.

PubMed

Bhoiwala, Devang L; Dunaief, Joshua L

2016-01-01

Patients with beta (β)-thalassemia (β-TM: β-thalassemia major, β-TI: β-thalassemia intermedia) have a variety of complications that may affect all organs, including the eye. Ocular abnormalities include retinal pigment epithelial degeneration, angioid streaks, venous tortuosity, night blindness, visual field defects, decreased visual acuity, color vision abnormalities, and acute visual loss. Patients with β-thalassemia major are transfusion dependent and require iron chelation therapy to survive. Retinal degeneration may result from either retinal iron accumulation from transfusion-induced iron overload or retinal toxicity induced by iron chelation therapy. Some who were never treated with iron chelation therapy exhibited retinopathy, and others receiving iron chelation therapy had chelator-induced retinopathy. We will focus on retinal abnormalities present in individuals with β-thalassemia major viewed in light of new findings on the mechanisms and manifestations of retinal iron toxicity. Copyright © 2016 Elsevier Inc. All rights reserved.

Influence of irradiation time and solution concentration on the photochemical degradation of EDDHA/Fe3+: effect of its photodecomposition products on soybean growth.

PubMed

Hernández-Apaolaza, Lourdes; Lucena, Juan J

2011-08-30

Ethylenediamine-N, N'-bis(2-hydroxyphenylacetic acid (EDDHA) is one of the most efficient iron-chelating agents employed to relieve iron chlorosis in plants. It has been well known for decades that this compound is photosensitive, but in spite of this fact its degradation pathways are virtually unknown. The aim of this work was to evaluate how the length of sunlight exposure and the concentration of irradiated EDDHA/Fe(3+) solutions influence the photostability of the chelate at constant pH. Moreover, the possible toxic effect of the chelate photodegradation products, elsewhere proposed, on soybean growth has been tested. The photodecomposition of the chelate increased as the time of sunlight exposure increased, and resulted in a partial decomposition of the organic ligand. Moreover, EDDHA/Fe(3+) photodecomposition was highly correlated with the concentration of solution exposed. Plants did not present differences in recovery from chlorosis among treatments with and without decomposition products. EDDHA/Fe(3+) undergoes photodegradation, like other aminopolycarboxylic acids, being more degraded as solution concentration decreases and exposure time increases. The photodecomposition products salicylic acid, salicylaldehide and Salicylaldehyde ethylenediamine diimine tested did not have negative effects on soybean growth, at least in the short-term hydroponic experimental design tested. Copyright © 2011 Society of Chemical Industry.

Multivalent Protein Polymer MRI Contrast Agents: Controlling Relaxivity via Modulation of Amino Acid Sequence

PubMed Central

Karfeld-Sulzer, Lindsay S.; Waters, Emily A.; Davis, Nicolynn E.; Meade, Thomas J.; Barron, Annelise E.

2010-01-01

Magnetic Resonance Imaging (MRI) is a noninvasive imaging modality with high spatial and temporal resolution. Contrast agents (CAs) are frequently used to increase the contrast between tissues of interest. To increase the effectiveness of MR agents, small molecule CAs have been attached to macromolecules. We have created a family of biodegradable, macromolecular CAs based on protein polymers, allowing control over the CA properties. The protein polymers are monodisperse, random coil, and contain evenly spaced lysines that serve as reactive sites for Gd(III) chelates. The exact sequence and length of the protein can be specified, enabling controlled variation in lysine spacing and molecular weight. Relaxivity could be modulated by changing protein polymer length and lysine spacing. Relaxivities of up to ∼14 mM-1s-1 per Gd(III) and ∼461 mM-1s-1 per conjugate were observed. These CAs are biodegradable by incubation with plasmin, such that they can be easily excreted after use. They do not reduce cell viability, a prerequisite for future in vivo studies. The protein polymer CAs can be customized for different clinical diagnostic applications, including biomaterial tracking, as a balanced agent with high relaxivity and appropriate molar mass. PMID:20420441

Inorganic nanoparticle-based T1 and T1/T2 magnetic resonance contrast probes

NASA Astrophysics Data System (ADS)

Hu, Fengqin; Zhao, Yong Sheng

2012-09-01

Magnetic resonance imaging (MRI) yields high spatially resolved contrast with anatomical details for diagnosis, deeper penetration depth and rapid 3D scanning. To improve imaging sensitivity, adding contrast agents accelerates the relaxation rate of water molecules, thereby greatly increasing the contrast between specific issues or organs of interest. Currently, the majority of T1 contrast agents are paramagnetic molecular complexes, typically Gd(iii) chelates. Various nanoparticulate T1 and T1/T2 contrast agents have recently been investigated as novel agents possessing the advantages of both the T1 contrast effect and nanostructural characteristics. In this minireview, we describe the recent progress of these inorganic nanoparticle-based MRI contrast agents. Specifically, we mainly report on Gd and Mn-based inorganic nanoparticles and ultrasmall iron oxide/ferrite nanoparticles.

Synthesis of internally functionalized silica nanoparticles for theranostic applications

NASA Astrophysics Data System (ADS)

Walton, Nathan Isaac

This thesis addresses the synthesis and characterization of novel inorganic silica nanoparticle hybrids. It focuses in large part on their potential applications in the medical field. Silica acts as a useful carrier for a variety of compounds and this thesis silica will demonstrate its use as a carrier for boron or gadolinium. Boron-10 and gadolinium-157 have been suggested for the radiological treatment of tumor cells through the process called neutron capture therapy (NCT). Gadolinium is also commonly used as a Magnetic Resonance Imaging (MRI) contrast agent. Particles that carry it have potential theranostic applications of both imaging and treating tumors. Chapter 1 presents a background on synthetic strategies and usages of silica nanoparticles, and NCT theory. Chapter 2 describes a procedure to create mesoporous metal chelating silica nanoparticles, mDTTA. This is achieved via a co-condensation of tetraethoxysilane (TEOS) and 3-trimethoxysilyl-propyl diethylenetriamine (SiDETA) followed by a post-synthesis modification step with bromoacetic acid (BrAA). These particles have a large surface area and well-defined pores of ~2 nm. The mDTTA nanoparticles were used to chelate the copper(II), cobalt(II) and gadolinium(III). The chelating of gadolinium is the most interesting since it can be used as a MRI contrast agent and a neutron capture therapeutic. The synthetic procedure developed also allows for the attachment of a fluorophore that gives the gadolinium chelating mDTTA nanoparticles a dual imaging modality. Chapter 3 presents the synthetic method used to produce two classes of large surface area organically modified silica (ORMOSIL) nanoparticles. Condensating the organosilane vinyltrimethoxysilane in a micellar solution results in nanoparticles that are either surface rough (raspberry-like) or mesoporous nanoparticles, which prior to this thesis has not been demonstrated in ORMOSIL chemistry. Furthermore, the vinyl functionalities are modified, using hydroboration, to make the nanoparticles into water-dispersible boron carriers that also have potential boron neutron capture therapy (BNCT) applications. Lastly, Chapter 4 provides a general description of NCT, specifically that involving boron-10 and gadolinium-157. It further describes the synthetic methodology used in producing fatty acid coated boron nanoparticles (BNPs). The BNPs are encapsulated with silica to add a hydrophilic shell so that they can potentially be used in biological systems as BNCT agents. The silica shell is also modified with a fluorophore, dansyl chloride, so that the particle hybrid could be imaged during cell studies.

Early transcriptomic response to Fe supply in Fe-deficient tomato plants is strongly influenced by the nature of the chelating agent.

PubMed

Zamboni, Anita; Zanin, Laura; Tomasi, Nicola; Avesani, Linda; Pinton, Roberto; Varanini, Zeno; Cesco, Stefano

2016-01-07

It is well known that in the rhizosphere soluble Fe sources available for plants are mainly represented by a mixture of complexes between the micronutrient and organic ligands such as carboxylates and phytosiderophores (PS) released by roots, as well as fractions of humified organic matter. The use by roots of these three natural Fe sources (Fe-citrate, Fe-PS and Fe complexed to water-extractable humic substances, Fe-WEHS) have been already studied at physiological level but the knowledge about the transcriptomic aspects is still lacking. The (59)Fe concentration recorded after 24 h in tissues of tomato Fe-deficient plants supplied with (59)Fe complexed to WEHS reached values about 2 times higher than those measured in response to the supply with Fe-citrate and Fe-PS. However, after 1 h no differences among the three Fe-chelates were observed considering the (59)Fe concentration and the root Fe(III) reduction activity. A large-scale transcriptional analysis of root tissue after 1 h of Fe supply showed that Fe-WEHS modulated only two transcripts leaving the transcriptome substantially identical to Fe-deficient plants. On the other hand, Fe-citrate and Fe-PS affected 728 and 408 transcripts, respectively, having 289 a similar transcriptional behaviour in response to both Fe sources. The root transcriptional response to the Fe supply depends on the nature of chelating agents (WEHS, citrate and PS). The supply of Fe-citrate and Fe-PS showed not only a fast back regulation of molecular mechanisms modulated by Fe deficiency but also specific responses due to the uptake of the chelating molecule. Plants fed with Fe-WEHS did not show relevant changes in the root transcriptome with respect to the Fe-deficient plants, indicating that roots did not sense the restored cellular Fe accumulation.

Comparative Evaluation of Using NOTA and DOTA Derivatives as Bifunctional Chelating Agents in the Preparation of 68Ga-Labeled Porphyrin: Impact on Pharmacokinetics and Tumor Uptake in a Mouse Model.

PubMed

Guleria, Mohini; Das, Tapas; Amirdhanayagam, Jeyachitra; Sarma, Haladhar D; Dash, Ashutosh

2018-02-01

Both NOTA (1,4,7-triazacyclononane-1,4,7-triacetic acid) and DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) derivatives have been used as bifunctional chelating agents (BFCAs) for the preparation of 68 Ga-labeled target-specific agents having potential for positron emission tomography (PET) imaging of cancerous lesions. In the present work, the authors have attempted a comparative pharmacokinetic evaluation between 68 Ga-labeled porphyrins prepared using NOTA and DOTA derivatives as the BFCAs. A symmetrical porphyrin derivative, 5,10,15,20-tetrakis(p-carboxymethyleneoxyphenyl)porphyrin, was synthesized and coupled with two different BFCAs viz. p-NH 2 -benzyl-NOTA and p-NH 2 -benzyl-DOTA. Both the porphyrin-BFCA conjugates were radiolabeled with 68 Ga. A comparative bioevaluation involving pharmacokinetics and tumor affinity was performed in a tumor-bearing small animal model. Gallium-68-labeled porphyrin-amido-benzyl-NOTA and porphyrin-amido-benzyl-DOTA complexes were prepared with high radiochemical purity. Both radiolabeled complexes exhibited almost similar stability in human serum and near-identical tumor affinity and pharmacokinetic behavior in animal studies. The present study demonstrates that the pharmacokinetic behavior of 68 Ga-labeled porphyrin derivatives, prepared using either NOTA or DOTA derivatives as BFCAs, remains almost identical and hence both NOTA and DOTA derivatives could be considered equivalent for developing 68 Ga-based PET agents for imaging of tumorous lesions.

76 FR 6347 - (S,S)-Ethylenediamine Disuccinic Acid Trisodium Salt; Exemption From the Requirement of a Tolerance

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-04

... pesticide formulations applied to growing crops or to raw agricultural commodities after harvest under EPA... chelating agent in pesticide formulations applied to growing crops or to raw agricultural commodities after... pesticide formulations applied to growing crops or to raw agricultural commodities after harvest is safe...

Salicylamide-lanthanide complexes for use as luminescent markers

DOEpatents

Raymond, Kenneth N.; Petoud, Stephane; Cohen, Seth; Xu, Jide

2002-01-01

The present invention provides luminescent lanthanide metal chelates comprising a metal ion of the lanthanide series and a complexing agent comprising at least one salicylamidyl moiety. Also provided are probes incorporating the salicylamidyl ligands of the invention and methods utilizing the ligands of the invention and probes comprising the ligands of the invention.

Salicylamide-lanthanide complexes for use as luminescent markers

DOEpatents

Raymond, Kenneth N [Berkeley, CA; Petoud, Stephane [Berkeley, CA; Cohen, Seth [Boston, MA; Xu, Jide [Berkeley, CA

2008-07-29

The present invention provides luminescent lanthanide metal chelates comprising a metal ion of the lanthanide series and a complexing agent comprising at least one salicylamidyl moiety. Also provided are probes incorporating the salicylamidyl ligands of the invention and methods utilizing the ligands of the invention and probes comprising the ligands of the invention.

Detection and quantification of unbound phytochelatin 2 in plant extracts of Brassica napus grown with different levels of mercury.

PubMed

Iglesia-Turiño, Santiago; Febrero, Anna; Jauregui, Olga; Caldelas, Cristina; Araus, Jose Luis; Bort, Jordi

2006-10-01

The mercury (Hg) accumulation mechanism was studied in rape (Brassica napus) plants grown under a Hg concentration gradient (0 microm-1,000 microm). Hg mainly accumulated in roots. Therefore, the presence of phytochelatins (PCs) was studied in the roots of the plants. The high stability of the PC-Hg multicomplexes (mPC-nHg) seems to be the main reason for the lack of previous Hg-PC characterization studies. We propose a modification of the method to detect and quantify unbound PC of Hg in plant extracts via high-performance liquid chromatography coupled to electrospray tandem mass spectrometry and inductively coupled plasma mass spectrometry in parallel. We separated the PC from the Hg by adding the chelating agent sodium 2,3-dimercaptopropanesulfonate monohydrate. We only detected the presence of PC after the addition of the chelating agent. Some multicomplexes mPC-nHg could be formed but, due to their large sizes, could not be detected. In this study, only PC(2) was observed in plant samples. Hg accumulation was correlated with PC(2) concentration (r(2) = 0.98).

Copper activates HIF-1α/GPER/VEGF signalling in cancer cells

PubMed Central

Rigiracciolo, Damiano Cosimo; Scarpelli, Andrea; Lappano, Rosamaria; Pisano, Assunta; Santolla, Maria Francesca; De Marco, Paola; Cirillo, Francesca; Cappello, Anna Rita; Dolce, Vincenza; Belfiore, Antonino; Maggiolini, Marcello; De Francesco, Ernestina Marianna

2015-01-01

Copper promotes tumor angiogenesis, nevertheless the mechanisms involved remain to be fully understood. We have recently demonstrated that the G-protein estrogen receptor (GPER) cooperates with hypoxia inducible factor-1α (HIF-1α) toward the regulation of the pro-angiogenic factor VEGF. Here, we show that copper sulfate (CuSO4) induces the expression of HIF-1α as well as GPER and VEGF in breast and hepatic cancer cells through the activation of the EGFR/ERK/c-fos transduction pathway. Worthy, the copper chelating agent TEPA and the ROS scavenger NAC prevented the aforementioned stimulatory effects. We also ascertained that HIF-1α and GPER are required for the transcriptional activation of VEGF induced by CuSO4. In addition, in human endothelial cells, the conditioned medium from breast cancer cells treated with CuSO4 promoted cell migration and tube formation through HIF-1α and GPER. The present results provide novel insights into the molecular mechanisms involved by copper in triggering angiogenesis and tumor progression. Our data broaden the therapeutic potential of copper chelating agents against tumor angiogenesis and progression. PMID:26415222

Design, synthesis and biological evaluation of multifunctional tacrine-curcumin hybrids as new cholinesterase inhibitors with metal ions-chelating and neuroprotective property.

PubMed

Liu, Zhikun; Fang, Lei; Zhang, Huan; Gou, Shaohua; Chen, Li

2017-04-15

Total sixteen tacrine-curcumin hybrid compounds were designed and synthesized for the purpose of searching for multifunctional anti-Alzheimer agents. In vitro studies showed that these hybrid compounds showed good cholinesterase inhibitory activity. Particularly, the potency of K 3-2 is even beyond tacrine. Some of the compounds exhibited different selectivity on acetylcholinesterase or butyrylcholinesterase due to the structural difference. Thus, the structure and activity relationship is summarized and further discussed based on molecular modeling studies. The ORAC and MTT assays indicated that the hybrid compounds possessed pronounced antioxidant activity and could effectively protect PC12 cells from the H 2 O 2 /Aβ42-induced toxicity. Moreover, the hybrid compounds also showed positive metal ions-chelating ability in vitro, suggesting a potential to halt ion-induced Aβ aggregation. All the obtained results demonstrated that the tacrine-curcumin hybrid compounds, in particular compound K 3-2 , can be considered as potential therapeutic agents for Alzheimer's disease. Copyright © 2017 Elsevier Ltd. All rights reserved.

Synthesis, 99m Tc-labeling, and preliminary biological evaluation of DTPA-melphalan conjugates.

PubMed

Wang, Jianjun; Yang, Wenjiang; Xue, Jinquan; Zhang, Yanhua; Liu, Yu

2017-12-01

Melphalan (MFL) is a typical nitrogen mustard for the treatment of many types of cancer. For the purpose to develop novel 99m Tc-labeled tumor imaging agents with SPECT, MFL was directly labeled by 99m Tc using diethylene triamine pentacetate acid (DTPA) as bifunctional chelating agent. The novel ligands were successfully synthesized by conjugation of DTPA to MFL to get monosubstituted DTPA-MFL and bis-substituted DTPA-2MFL. Radiolabeling was performed in high yield to get 99m Tc-DTPA-MFL and 99m Tc-DTPA-2MFL, respectively, which were hydrophilic and stable at room temperature. The high initial tumor uptake with retention, good tumor/muscle ratios, and satisfactory scintigraphic images suggested the potential of 99m Tc-DTPA-MFL and 99m Tc-DTPA-2MFL for tumor imaging. However, the slow normal tissue clearance would be a great obstacle. Further modification on the linker and/or 99m Tc-chelate to improve the tumor targeting efficacy and in vivo kinetic profiles is currently in progress. Copyright © 2017 John Wiley & Sons, Ltd.

Derivatizations of Sgc8-c aptamer to prepare metallic radiopharmaceuticals as imaging diagnostic agents: Syntheses, isolations, and physicochemical characterizations.

PubMed

Sicco, Estefanía; Báez, Jessica; Margenat, Jimena; García, Fernanda; Ibarra, Manuel; Cabral, Pablo; Moreno, María; Cerecetto, Hugo; Calzada, Victoria

2018-03-01

Aptamers, oligonucleotides with the capability to bind to a target through non-covalent bonds with high affinity and specificity, have a great number of advantages as scaffold to prepare molecular imaging agents. In this sense, we have performed post-SELEX modifications of a truncated aptamer, Sgc8-c, which bind to protein tyrosine kinase 7 to obtain a specific molecular targeting probe for in vivo diagnosis and in vivo therapy. Herein, we describe the synthetic efforts to prepare conjugates between Sgc8-c and different metallic ions chelator moieties in short times, high purities, and adequate yields. The selected chelator moieties, derived from 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid, 2-benzyl-1,4,7-triazacyclononane-1,4,7-triacetic acid, and 6-hydrazinonicotinic acid, were covalently attached at the 5'-aptamer position yielding the expected products which were stable in aqueous solution up to 75°C and in typical aptamer storage conditions at least for 30 days. © 2017 John Wiley & Sons A/S.

Copper activates HIF-1α/GPER/VEGF signalling in cancer cells.

PubMed

Rigiracciolo, Damiano Cosimo; Scarpelli, Andrea; Lappano, Rosamaria; Pisano, Assunta; Santolla, Maria Francesca; De Marco, Paola; Cirillo, Francesca; Cappello, Anna Rita; Dolce, Vincenza; Belfiore, Antonino; Maggiolini, Marcello; De Francesco, Ernestina Marianna

2015-10-27

Copper promotes tumor angiogenesis, nevertheless the mechanisms involved remain to be fully understood. We have recently demonstrated that the G-protein estrogen receptor (GPER) cooperates with hypoxia inducible factor-1α (HIF-1α) toward the regulation of the pro-angiogenic factor VEGF. Here, we show that copper sulfate (CuSO4) induces the expression of HIF-1α as well as GPER and VEGF in breast and hepatic cancer cells through the activation of the EGFR/ERK/c-fos transduction pathway. Worthy, the copper chelating agent TEPA and the ROS scavenger NAC prevented the aforementioned stimulatory effects. We also ascertained that HIF-1α and GPER are required for the transcriptional activation of VEGF induced by CuSO4. In addition, in human endothelial cells, the conditioned medium from breast cancer cells treated with CuSO4 promoted cell migration and tube formation through HIF-1α and GPER. The present results provide novel insights into the molecular mechanisms involved by copper in triggering angiogenesis and tumor progression. Our data broaden the therapeutic potential of copper chelating agents against tumor angiogenesis and progression.

Experimental Investigation on the Mechanism of Chelation-Assisted, Copper(II) Acetate-Accelerated Azide-Alkyne Cycloaddition

PubMed Central

Kuang, Gui-Chao; Guha, Pampa M.; Brotherton, Wendy S.; Simmons, J. Tyler; Stankee, Lisa A.; Nguyen, Brian T.; Clark, Ronald J.; Zhu, Lei

2011-01-01

A mechanistic model is formulated to account for the high reactivity of chelating azides (organic azides capable of chelation-assisted metal coordination at the alkylated azido nitrogen position) and copper(II) acetate (Cu(OAc)2) in copper(II)-mediated azide-alkyne cycloaddition (AAC) reactions. Fluorescence and 1H NMR assays are developed for monitoring the reaction progress in two different solvents – methanol and acetonitrile. Solvent kinetic isotopic effect and pre-mixing experiments give credence to the proposed different induction reactions for converting copper(II) to catalytic copper(I) species in methanol (methanol oxidation) and acetonitrile (alkyne oxidative homocoupling), respectively. The kinetic orders of individual components in a chelation-assisted, copper(II)-accelerated AAC reaction are determined in both methanol and acetonitrile. Key conclusions resulting from the kinetic studies include (1) the interaction between copper ion (either in +1 or +2 oxidation state) and a chelating azide occurs in a fast, pre-equilibrium step prior to the formation of the in-cycle copper(I)-acetylide, (2) alkyne deprotonation is involved in several kinetically significant steps, and (3) consistent with prior experimental and computational results by other groups, two copper centers are involved in the catalysis. The X-ray crystal structures of chelating azides with Cu(OAc)2 suggest a mechanistic synergy between alkyne oxidative homocoupling and copper(II)-accelerated AAC reactions, in which both a bimetallic catalytic pathway and a base are involved. The different roles of the two copper centers (a Lewis acid to enhance the electrophilicity of the azido group and a two-electron reducing agent in oxidative metallacycle formation, respectively) in the proposed catalytic cycle suggest that a mixed valency (+2 and +1) dinuclear copper species be a highly efficient catalyst. This proposition is supported by the higher activity of the partially reduced Cu(OAc)2 in mediating a 2-picolylazide-involved AAC reaction than the fully reduced Cu(OAc)2. Finally, the discontinuous kinetic behavior that has been observed by us and others in copper(I/II)-mediated AAC reactions is explained by the likely catalyst disintegration during the course of a relatively slow reaction. Complementing the prior mechanistic conclusions drawn by other investigators which primarily focus on the copper(I)/alkyne interactions, we emphasize the kinetic significance of copper(I/II)/azide interaction. This work not only provides a mechanism accounting for the fast Cu(OAc)2-mediated AAC reactions involving chelating azides, which has apparent practical implications, but suggests the significance of mixed-valency dinuclear copper species in catalytic reactions where two copper centers carry different functions. PMID:21809811

A functional form for injected MRI Gd-chelate contrast agent concentration incorporating recirculation, extravasation and excretion

NASA Astrophysics Data System (ADS)

Horsfield, Mark A.; Thornton, John S.; Gill, Andrew; Jager, H. Rolf; Priest, Andrew N.; Morgan, Bruno

2009-05-01

A functional form for the vascular concentration of MRI contrast agent after intravenous bolus injection was developed that can be used to model the concentration at any vascular site at which contrast concentration can be measured. The form is based on previous models of blood circulation, and is consistent with previously measured data at long post-injection times, when the contrast agent is fully and evenly dispersed in the blood. It allows the first-pass and recirculation peaks of contrast agent to be modelled, and measurement of the absolute concentration of contrast agent at a single time point allows the whole time course to be rescaled to give absolute contrast agent concentration values. This measure of absolute concentration could be performed at a long post-injection time using either MRI or blood-sampling methods. In order to provide a model that is consistent with measured data, it was necessary to include both rapid and slow extravasation, together with excretion via the kidneys. The model was tested on T1-weighted data from the descending aorta and hepatic portal vein, and on T*2-weighted data from the cerebral arteries. Fitting of the model was successful for all datasets, but there was a considerable variation in fit parameters between subjects, which suggests that the formation of a meaningful population-averaged vascular concentration function is precluded.

Copper chelation by tetrathiomolybdate inhibits lipopolysaccharide-induced inflammatory responses in vivo

PubMed Central

Wei, Hao; Beckman, Joseph S.; Zhang, Wei-Jian

2011-01-01

Redox-active transition metal ions, such as iron and copper, may play an important role in vascular inflammation, which is an etiologic factor in atherosclerotic vascular diseases. In this study, we investigated whether tetrathiomolybdate (TTM), a highly specific copper chelator, can act as an anti-inflammatory agent, preventing lipopolysaccharide (LPS)-induced inflammatory responses in vivo. Female C57BL/6N mice were daily gavaged with TTM (30 mg/kg body wt) or vehicle control. After 3 wk, animals were injected intraperitoneally with 50 μg LPS or saline buffer and killed 3 h later. Treatment with TTM reduced serum ceruloplasmin activity by 43%, a surrogate marker of bioavailable copper, in the absence of detectable hepatotoxicity. The concentrations of both copper and molybdenum increased in various tissues, whereas the copper-to-molybdenum ratio decreased, consistent with reduced copper bioavailability. TTM treatment did not have a significant effect on superoxide dismutase activity in heart and liver. Furthermore, TTM significantly inhibited LPS-induced inflammatory gene transcription in aorta and heart, including vascular and intercellular adhesion molecule-1 (VCAM-1 and ICAM-1, respectively), monocyte chemotactic protein-1 (MCP-1), interleukin-6, and tumor necrosis factor (TNF)-α (ANOVA, P < 0.05); consistently, protein levels of VCAM-1, ICAM-1, and MCP-1 in heart were also significantly lower in TTM-treated animals. Similar inhibitory effects of TTM were observed on activation of nuclear factor-κB (NF-κB) and activator protein-1 (AP-1) in heart and lungs. Finally, TTM significantly inhibited LPS-induced increases of serum levels of soluble ICAM-1, MCP-1, and TNF-α (ANOVA, P < 0.05). These data indicate that copper chelation with TTM inhibits LPS-induced inflammatory responses in aorta and other tissues of mice, most likely by inhibiting activation of the redox-sensitive transcription factors, NF-κB and AP-1. Therefore, copper appears to play an important role in vascular inflammation, and TTM may have value as an anti-inflammatory or anti-atherogenic agent. PMID:21724870

Nitrogen-doped mesoporous carbon-armored cobalt nanoparticles as efficient hydrogen evolving electrocatalysts.

PubMed

Tang, Duihai; Li, Kuo; Zhang, Wenting; Qiao, Zhen-An; Zhu, Junjiang; Zhao, Zhen

2018-03-15

A series of Co nanoparticles embedded, N-doped mesoporous carbons have been synthesized through chelate-assisted co-assembly strategy followed by thermal treatment. The preparation is based on an assembly process, with evaporation of an ethanol-water solution containing melamine formaldehyde resin (MF resin) as carbon source, nitrogen source, and chelating agent. Moreover, F127 and Co(NO 3 ) 2 are used as template and metallic precursor, respectively. The Co nanoparticles embedded, N-doped mesoporous carbon annealed at 800 °C (denoted as MFCo800) shows high electrocatalytic activity for hydrogen evolution reaction (HER) with high current density and low overpotential, which has the ability to operate in both acidic and alkaline electrolytes. Copyright © 2017. Published by Elsevier Inc.

Characterization of commercial iron chelates and their behavior in an alkaline and calcareous soil.

PubMed

Cantera, Rodrigo G; Zamarreño, Angel M; García-Mina, José M

2002-12-18

Iron deficiency is a common problem for many plants grown in alkaline and calcareous soils. To correct this problem, iron is supplied to plants as chelates. Several iron chelates are sold under diverse trademarks with different characteristics. This work evaluated 18 commercial products containing the most representative chelated iron sources used in agricultural practice in Spain when the study was done, namely the ferric chelates of EDDHA, EDDHMA, EDDCHA, EDDHSA, EDTA, and DTPA. The chelates were comprehensively characterized and quantitated by several techniques, including several chromatographic methods. Iron and chelate dynamics in soil were also studied in a model alkaline and calcareous soil. Results indicate that, in this model soil, among the different iron compounds studied only FeEDDHA and analogues have the capacity to maintain soluble iron in soil solution over time. These results are in agreement with general experience under field conditions. Furthermore, among the different ortho-ortho isomers of FeEDDHA's, FeEDDHSA and FeEDDCHA showed greater capacity than FeEDDHA and FeEDDHMA to maintain the chelated iron in soil solution over time.

Fate of metals before and after chemical extraction of incinerated sewage sludge ash.

PubMed

Li, Jiang-Shan; Tsang, Daniel C W; Wang, Qi-Ming; Fang, Le; Xue, Qiang; Poon, Chi Sun

2017-11-01

Chemical extraction of incinerated sewage sludge ash (ISSA) can effectively recycle P, but it may change the speciation and mobility of the remaining metals. This study investigated the changes of the leaching potential and distribution of metals in the chemically extracted ISSA. Batch extraction experiments with different extractants, including inorganic acids, organic acids, and chelating agents, were conducted on the ISSA collected from a local sewage sludge incinerator. The extraction of Zn, Cu, Pb, Ni, Cd, Ba, Cr and As from the ISSA and the corresponding changes of the mobility and speciation were examined. The results showed that the metals in ISSA were naturally stable because large portions of metals were associated with the residual fraction. The inorganic (HNO 3 and H 2 SO 4 ) and organic acids (citric acid and oxalic acid) significantly co-dissolved the metals through acid dissolution, but the reduction in the total concentrations did not tally the leaching potential of the residual metals. The increase in the exchangeable fraction due to destabilization by the extractants significantly enhanced the mobility and leachability of the metals in the residual ISSA. Chelating agents (EDTA and EDTMP) only extracted a small quantity of metals and had a marginal effect on the fate of the residual metals, but they significantly reduced the Fe/Mn oxide-bound fraction. In comparison, the bioaccessibility of residual metals were reduced to varying extent. Therefore, the disposal or reuse of chemically extracted ISSA should be carefully evaluated in view of possible increase in mobility of residual metals in the environment. Copyright © 2017 Elsevier Ltd. All rights reserved.

The crystal structure of the Yersinia pestis iron chaperone YiuA reveals a basic triad binding motif for the chelated metal

PubMed Central

2017-01-01

Biological chelating molecules called siderophores are used to sequester iron and maintain its ferric state. Bacterial substrate-binding proteins (SBPs) bind iron–siderophore complexes and deliver these complexes to ATP-binding cassette (ABC) transporters for import into the cytoplasm, where the iron can be transferred from the siderophore to catalytic enzymes. In Yersinia pestis, the causative agent of plague, the Yersinia iron-uptake (Yiu) ABC transporter has been shown to improve iron acquisition under iron-chelated conditions. The Yiu transporter has been proposed to be an iron–siderophore transporter; however, the precise siderophore substrate is unknown. Therefore, the precise role of the Yiu transporter in Y. pestis survival remains uncharacterized. To better understand the function of the Yiu transporter, the crystal structure of YiuA (YPO1310/y2875), an SBP which functions to present the iron–siderophore substrate to the transporter for import into the cytoplasm, was determined. The 2.20 and 1.77 Å resolution X-ray crystal structures reveal a basic triad binding motif at the YiuA canonical substrate-binding site, indicative of a metal-chelate binding site. Structural alignment and computational docking studies support the function of YiuA in binding chelated metal. Additionally, YiuA contains two mobile helices, helix 5 and helix 10, that undergo 2–3 Å shifts across crystal forms and demonstrate structural breathing of the c-clamp architecture. The flexibility in both c-clamp lobes suggest that YiuA substrate transfer resembles the Venus flytrap mechanism that has been proposed for other SBPs. PMID:29095164

Modular Carbon and Gold Nanoparticles for High Field MR Imaging and Theranostics

NASA Astrophysics Data System (ADS)

Rammohan, Nikhil

The ability to track labeled cancer cells in vivo would allow researchers to study their distribution, growth and metastatic potential within the intact organism. Magnetic Resonance (MR) imaging is invaluable for tracking cancer cells in vivo as it benefits from high spatial resolution and absence of ionizing radiation. However, many MR contrast agents (CAs) required to label cells either do not significantly accumulate in cells or are not biologically compatible for translational studies. Accordingly, we have developed carbon- and gold-nanoparticles coupled to gadolinium(III) [Gd(III)] chelates for T1-weighted MR imaging that demonstrated remarkable properties for cell tracking in vitro and in vivo.. We created nanodiamond-Gd(III) aggregates (NDG) by peptide coupling Gd(III) chelates to aminated nanodiamonds. NDG had high relaxivity independent of field strength (unprecedented for Gd(III)-nanoparticle conjugates), and demonstrated a 300-fold increase in cellular delivery of Gd(III) compared to clinical Gd(III) chelates. Further, we were able to monitor the tumor growth of NDG-labeled flank tumors by T1-weighted MRI for 26 days in vivo, longer than reported for other MR CAs or nuclear agents. Further, theranostic nanodiamond-gadolinium(III)-doxorubicin (ND-Gd-Dox) aggregates were generated by conjugating doxorubicin (ND-Gd-Dox), which enabled efficient cancer chemotherapy in breast cancer cells. Further, we synthesized Gd(III)-gold nanoconjugates (Gd AuNPs) with varied chelate structure and nanoparticle-chelate linker length. Significantly enhanced cell labeling was demonstrated compared to previous gadolinium-gold-DNA nanoconstructs. Differences in Gd(III) loading, surface packing and cell uptake were observed between four different Gd AuNP formulations suggesting that linker length and surface charge play an important role in cell labeling. The best performing Gd AuNPs afforded 23.6 +/- 3.6 fmol of Gd(III) per cell at an incubation concentration of 27.5 microM. This efficiency of Gd(III) payload delivery (Gd(III)/cell normalized to dose) exceeds that of previously Gd(III)-Au conjugates and most other Gd(III)-nanoparticle formulations. Finally, Gd AuNPs were the first MR CAs of any type to effectively image the pancreas in vivo. . In summary, both Gd AuNPs and NDG support future MR-mediated cell tracking and theranostic applications in whole-animal models.

The efficacies of pure LICAM(C) and DTPA for enhancing the elimination of plutonium-238 and americium-241 from rats after their inhalation as nitrate.

PubMed

Stradling, G N; Stather, J W; Gray, S A; Moody, J C; Ellender, M; Hodgson, A

1989-01-01

After the inhalation of 238Pu and 241Am as nitrate, the repeated administration of DTPA is far superior to that of LICAM(C) for enhancing their elimination from the body. The therapeutic efficacies of these chelating agents are however similar after intravenous injection of 238Pu as citrate. It is concluded that DTPA should remain the agent of choice for treating persons contaminated internally with transportable forms of these actinides.

Reactivity-based drug discovery using vitamin B(6)-derived pharmacophores.

PubMed

Wondrak, Georg T

2008-05-01

Endogenous reactive intermediates including photoexcited states of tissue chromophores, reactive oxygen species (ROS), reactive carbonyl species (RCS), transition metal ions, and Schiff bases have been implicated in the initiation and progression of diverse human pathologies including tumorigenesis, atherosclerosis, diabetes, and neurodegenerative disease. In contrast to structure-based approaches that target macromolecules by selective ligands, reactivity-based drug discovery uses chemical reagents as therapeutics that target reactive chemical species involved in human pathology. Reactivity-based design of prototype agents that effectively antagonize, modulate, and potentially even reverse the chemistry underlying tissue damage from oxidative and carbonyl stress therefore holds great promise in delivering significant therapeutic benefit. Apart from its established role as an essential cofactor for numerous enzymes, a large body of evidence suggests that B(6)-vitamers contain reactive pharmacophores that mediate therapeutically useful non-vitamin drug actions as potent antioxidants, metal chelators, carbonyl scavengers, Schiff base forming agents, and photosensitizers. Based on the fascinating chemical versatility of B(6)-derived pharmacophores, B(6)-vitamers are therefore promising lead compounds for reactivity-based drug design.

Functionalization of Platinum Complexes for Biomedical Applications.

PubMed

Wang, Xiaoyong; Wang, Xiaohui; Guo, Zijian

2015-09-15

Platinum-based anticancer drugs are the mainstay of chemotherapy regimens in clinic. Nevertheless, the efficacy of platinum drugs is badly affected by serious systemic toxicities and drug resistance, and the pharmacokinetics of most platinum drugs is largely unknown. In recent years, a keen interest in functionalizing platinum complexes with bioactive molecules, targeting groups, photosensitizers, fluorophores, or nanomaterials has been sparked among chemical and biomedical researchers. The motivation for functionalization comes from some of the following demands: to improve the tumor selectivity or minimize the systemic toxicity of the drugs, to enhance the cellular accumulation of the drugs, to overcome the tumor resistance to the drugs, to visualize the drug molecules in vitro or in vivo, to achieve a synergistic anticancer effect between different therapeutic modalities, or to add extra functionality to the drugs. In this Account, we present different strategies being used for functionalizing platinum complexes, including conjugation with bisphosphonates, peptides, receptor-specific ligands, polymers, nanoparticles, magnetic resonance imaging contrast agents, metal chelators, or photosensitizers. Among them, bisphosphonates, peptides, and receptor-specific ligands are used for actively targeted drug delivery, polymers and nanoparticles are for passively targeted drug delivery, magnetic resonance imaging contrast agents are for theranostic purposes, metal chelators are for the treatment or prevention of Alzheimer's disease (AD), and photosensitizers are for photodynamic therapy of cancers. The rationales behind these designs are explained and justified at the molecular or cellular level, associating with the requirements for diagnosis, therapy, and visualization of biological processes. To illustrate the wide range of opportunities and challenges that are emerging in this realm, representative examples of targeted drug delivery systems, anticancer conjugates, anticancer theranostic agents, and anti-AD compounds relevant to functionalized platinum complexes are provided. All the examples exhibit new potential of platinum complexes for future applications in biomedical areas. The emphases of this Account are placed on the functionalization for targeted drug delivery and theranostic agents. In the end, a general assessment of various strategies has been made according to their major shortcomings and defects. The original information in this Account comes entirely from literature appearing since 2010.

Towards a unifying, systems biology understanding of large-scale cellular death and destruction caused by poorly liganded iron: Parkinson’s, Huntington’s, Alzheimer’s, prions, bactericides, chemical toxicology and others as examples

PubMed Central

2010-01-01

Exposure to a variety of toxins and/or infectious agents leads to disease, degeneration and death, often characterised by circumstances in which cells or tissues do not merely die and cease to function but may be more or less entirely obliterated. It is then legitimate to ask the question as to whether, despite the many kinds of agent involved, there may be at least some unifying mechanisms of such cell death and destruction. I summarise the evidence that in a great many cases, one underlying mechanism, providing major stresses of this type, entails continuing and autocatalytic production (based on positive feedback mechanisms) of hydroxyl radicals via Fenton chemistry involving poorly liganded iron, leading to cell death via apoptosis (probably including via pathways induced by changes in the NF-κB system). While every pathway is in some sense connected to every other one, I highlight the literature evidence suggesting that the degenerative effects of many diseases and toxicological insults converge on iron dysregulation. This highlights specifically the role of iron metabolism, and the detailed speciation of iron, in chemical and other toxicology, and has significant implications for the use of iron chelating substances (probably in partnership with appropriate anti-oxidants) as nutritional or therapeutic agents in inhibiting both the progression of these mainly degenerative diseases and the sequelae of both chronic and acute toxin exposure. The complexity of biochemical networks, especially those involving autocatalytic behaviour and positive feedbacks, means that multiple interventions (e.g. of iron chelators plus antioxidants) are likely to prove most effective. A variety of systems biology approaches, that I summarise, can predict both the mechanisms involved in these cell death pathways and the optimal sites of action for nutritional or pharmacological interventions. PMID:20967426

Chelator-Free 64Cu-Integrated Gold Nanomaterials for Positron Emission Tomography Imaging Guided Photothermal Cancer Therapy

PubMed Central

2015-01-01

Using positron emission tomography (PET) imaging to monitor and quantitatively analyze the delivery and localization of Au nanomaterials (NMs), a widely used photothermal agent, is essential to optimize therapeutic protocols to achieve individualized medicine and avoid side effects. Coupling radiometals to Au NMs via a chelator faces the challenges of possible detachment of the radiometals as well as surface property changes of the NMs. In this study, we reported a simple and general chelator-free 64Cu radiolabeling method by chemically reducing 64Cu on the surface of polyethylene glycol (PEG)-stabilized Au NMs regardless of their shape and size. Our 64Cu-integrated NMs are proved to be radiochemically stable and can provide an accurate and sensitive localization of NMs through noninvasive PET imaging. We further integrated 64Cu onto arginine-glycine-aspartic acid (RGD) peptide modified Au nanorods (NRs) for tumor theranostic application. These NRs showed high tumor targeting ability in a U87MG glioblastoma xenograft model and were successfully used for PET image-guided photothermal therapy. PMID:25019252

Characterization of changes in floc morphology, extracellular polymeric substances and heavy metals speciation of anaerobically digested biosolid under treatment with a novel chelated-Fe2+ catalyzed Fenton process.

PubMed

He, Juanjuan; Yang, Peng; Zhang, Weijun; Cao, Bingdi; Xia, Hua; Luo, Xi; Wang, Dongsheng

2017-11-01

A novel chelated-Fe 2+ catalyzed Fenton process (CCFP) was developed to enhance dewatering performance of anaerobically digested biosolid, and changes in floc morphology, extracellular polymeric substances (EPS) and heavy metals speciation were also investigated. The results showed that addition of chelating agents caused EPS solubilization by binding multivalent cations. Like traditional Fenton, CCFP performed well in improving anaerobically digested sludge dewatering property. The highly active radicals (OH, O 2 - ) produced in classical Fenton and CCFP were responsible for sludge flocs destruction and consequently degradation of biopolymers into small molecules. Furthermore, more plentiful pores and channels were presented in cake after Fenton treatment, which was conducive to water drainage under mechanical compression. Additionally, a portion of active heavy metals in the form of oxidizable and reducible states were dissolved under CCFP. Therefore, CCFP could greatly simplify the operating procedure of Fenton conditioning and improve its process adaptability for harmless treatment of biological sludge. Copyright © 2017 Elsevier Ltd. All rights reserved.

Procaspase-activating compound 1 induces a caspase-3-dependent cell death in cerebellar granule neurons

DOE Office of Scientific and Technical Information (OSTI.GOV)

Aziz, Gulzeb; Akselsen, Oyvind W.; Hansen, Trond V.

2010-09-15

Procaspase-activating compound 1, PAC-1, has been introduced as a direct activator of procaspase-3 and has been suggested as a therapeutic agent against cancer. Its activation of procaspase-3 is dependent on the chelation of zinc. We have tested PAC-1 and an analogue of PAC-1 as zinc chelators in vitro as well as their ability to activate caspase-3 and induce cell death in chicken cerebellar granule neuron cultures. These neurons are non-dividing, primary cells with normal caspase-3. The results reported herein show that PAC-1 chelates zinc, activates procaspase-3, and leads to caspase-3-dependent cell death in neurons, as the specific caspase-3-inhibitor Ac-DEVD-cmk inhibitedmore » both the caspase-3 activity and cell death. Thus, chicken cerebellar granule neurons is a suitable model to study mechanisms of interference with apoptosis of PAC-1 and similar compounds. Furthermore, the present study also raises concern about potential neurotoxicity of PAC-1 if used in cancer therapy.« less

Chelation of heavy group 2 (radio)metals by p-tert-butylcalix[4]arene-1,3-crown-6 and logK determination via NMR

NASA Astrophysics Data System (ADS)

Bauer, David; Gott, Matthew; Steinbach, Jörg; Mamat, Constantin

2018-06-01

A crown-bridged calix[4]arene scaffold was investigated as lead compound for the ligation of heavy alkaline earth metals such as strontium and barium, which appear to be useful for radiopharmaceutical applications in diagnosis as well as in radiotherapy. In particular barium, due to its chemical similarities, could serve as a surrogate for radium, a metal of high radiopharmaceutical interest. The ability of p-tert-butylcalix[4]arene-1,3-crown-6 (1) in particular to chelate cations, such as group 1 and 2 metal ions or ammonium ions is well known. Also, the manifold possibilities of structural modification on the upper- and lower-rim as well as on the crown itself produce properties that may lead to a highly selective and effective chelating agent. In this work, titration experiments of the perchlorate salts of Ba2+, Sr2+ and Pb2+ with ligand 1 were performed to determine their stability constants (logK = 4.7, 4.3, and 3.3, respectively) by 1H NMR measurements in acetonitrile-d3.

Reducing surface tension in endodontic chelator solutions has no effect on their ability to remove calcium from instrumented root canals.

PubMed

Zehnder, Matthias; Schicht, Olivier; Sener, Beatrice; Schmidlin, Patrick

2005-08-01

The aim of this study was to evaluate the effect of reducing surface tension in endodontic chelator solutions on their ability to remove calcium from instrumented root canals. Aqueous solutions containing 15.5% EDTA, 10% citric acid, or 18% 1- hydroxyethylidene-1, 1-bisphosphonate (HEBP) were prepared with and without 1% (wt/wt) polysorbate (Tween) 80 and 9% propylene glycol. Surface tension in these solutions was measured using the Wilhelmy method. Sixty-four extracted, single-rooted human teeth of similar length were instrumented and irrigated with a 1% sodium hypochlorite solution and then randomly assigned (n = 8 per group) to receive a final one-minute rinse with 5 ml of test solutions, water, or the pure aqueous Tween/propylene glycol solution. Calcium concentration in eluates was measured using atomic absorption spectrometry. Incorporation of wetting agents resulted in a reduction of surface tension values by approximately 50% in all tested solutions. However, none of the solutions with reduced surface tension chelated more calcium from canals than their pure counterparts (p > 0.05).

Use of EDTA in modified kinetic testing for contaminated drainage prediction from waste rocks: case of the Lac Tio mine.

PubMed

Plante, Benoît; Benzaazoua, Mostafa; Bussière, Bruno; Kandji, El-Hadji-Babacar; Chopard, Aurélie; Bouzahzah, Hassan

2015-05-01

The tools developed for acid mine drainage (AMD) prediction were proven unsuccessful to predict the geochemical behavior of mine waste rocks having a significant chemical sorption capacity, which delays the onset of contaminated neutral drainage (CND). The present work was performed in order to test a new approach of water quality prediction, by using a chelating agent solution (0.03 M EDTA, or ethylenediaminetetraacetic acid) in kinetic testing used for the prediction of the geochemical behavior of geologic material. The hypothesis underlying the proposed approach is that the EDTA solution should chelate the metals as soon as they are released by sulfide oxidation, inhibiting their sorption or secondary precipitation, and therefore reproduce a worst-case scenario where very low metal attenuation mechanisms are present in the drainage waters. Fresh and weathered waste rocks from the Lac Tio mine (Rio tinto, Iron and Titanium), which are known to generate Ni-CND at the field scale, were submitted to small-scale humidity cells in control tests (using deionized water) and using an EDTA solution. Results show that EDTA effectively prevents the metals to be sorbed or to precipitate as secondary minerals, therefore enabling to bypass the delay associated with metal sorption in the prediction of water quality from these materials. This work shows that the use of a chelating agent solution is a promising novel approach of water quality prediction and provides general guidelines to be used in further studies, which will help both practitioners and regulators to plan more efficient management and disposal strategies of mine wastes.

Extraction of vanadium into isobutyl methyl ketone1 1 Publication authorized by the Director, U.S. Geological Survey.

USGS Publications Warehouse

Crump-Wiesner, Hans J.; Purdy, W.C.

1969-01-01

Because of its advantages in atomic-absorption spectroscopy, isobutyl methyl ketone was chosen as organic solvent for an extraction study on vanadium. Of eight chelating agents which were evaluated for completeness of extraction, ease of use, working pH range, and freedom from interference, cupferron was judged best. ?? 1969.

Functional, mesoporous, superparamagnetic colloidal sorbents for efficient removal of toxic metals.

PubMed

Sinha, Arjyabaran; Jana, Nikhil R

2012-09-25

γ-Fe(2)O(3) incorporated mesoporous silica particles of 50-100 nm size have been synthesized which are functionalized with chelating agents of metal ions. These particles are water dispersible but aggregate in response to the external magnetic field and have been used for high performance and selective removal of Cd, Pb, Hg and As.

Bioaugmentation for Groundwater Remediation

DTIC Science & Technology

2010-02-01

in biofouling control. Citric acid is optimal as it serves as an acid and a metal chelating agent • Daily application of chlorine dioxide or other...26 6.6.4.1 Chlorinated Ethenes and Ethene ............................................. 26 6.6.4.2 Volatile Fatty Acids ...47 8.3.2 Passive Bioaugmentation and Passive Biostimulation Comparison ......... 48 8.3.2.1 Site Description

Development of PCR-Based DNA markers flanking three low phytic acid mutant loci in barley

USDA-ARS?s Scientific Manuscript database

Phytic acid (PA) is the most abundant form of phosphorus (P) in cereal grains. PA chelates mineral cations to form an indigestible salt, and is thus regarded as an antinutritional agent and a contributor to water pollution. Grain with low phytic acid (lpa) genotypes could aid in mitigating this prob...

Synthesis of DTPA analogues derived from piperidine and azepane: potential contrast enhancement agents for magnetic resonance imaging.

PubMed

Chong, H S; Garmestani, K; Bryant, L H; Brechbiel, M W

2001-11-16

Two DTPA derivatives (PIP-DTPA and AZEP-DTPA) as potential contrast enhancement agents in MRI are synthesized. The T1 and T2 relaxivities of their corresponding Gd(III) complexes are reported. At clinically relevant field strengths, the relaxivities of the complexes are comparable to that of the contrast agent, Gd(DTPA) which is in clinical use. The serum stability of the (153)Gd-labeled complexes is assessed by measuring the release of (153)Gd from the ligands. The radiolabeled Gd chelates are found to be kinetically stable in human serum for up to at least 14 days without any measurable loss of radioactivity.

Exploration of the medical periodic table: towards new targets.

PubMed

Barry, Nicolas P E; Sadler, Peter J

2013-06-07

Metallodrugs offer potential for unique mechanisms of drug action based on the choice of the metal, its oxidation state, the types and number of coordinated ligands and the coordination geometry. We discuss recent progress in identifying new target sites and elucidating the mechanisms of action of anti-cancer, anti-bacterial, anti-viral, anti-parasitic, anti-inflammatory, and anti-neurodegenerative agents, as well as in the design of metal-based diagnostic agents. Progress in identifying and defining target sites has been accelerated recently by advances in proteomics, genomics and metal speciation analysis. Examples of metal compounds and chelating agents (enzyme inhibitors) currently in clinical use, clinical trials or preclinical development are highlighted.

Remediation and desorption kinetics of pyrene from kaolinite co-contaminated with heavy metals at various organic matter contents

NASA Astrophysics Data System (ADS)

Saeedi, Mohsen; Li, Loretta Y.; Grace, John R.

2017-04-01

Soils co-contaminated with polycyclic aromatic hydrocarbons (PAHs) and heavy metals are challenging for remediation. In the present study desorption of pyrene in kaolinite, co-contaminated by Ni, Pb and Zn, was examined by combinations of surfactants and chelating agents such as Triton X-100, Tween 80, Ethylene diamine tetra acetic acid (EDTA) and citric acid. Results showed that a combination of Triton X-100 (7.5 % w/w) + EDTA (0.01 M) and Tween 80 (7.5 % w/w) + EDTA (0.01 M) were effective in simultaneously desorbing both types of contaminants. Batch desorption tests were conducted using single and combined enhancing agents containing Triton X-100 and Tween 80 as non-ionic surfactants, EDTA as a chelating agent, and citric acid as an organic acid. The solution with the highest removal efficiency was the combined solution containing Triton X-100 (7.5 % w/w) + EDTA (0.01M). Triton X-100 (7.5% w/w) + EDTA (0.01M) led to removal efficiencies of 88% for pyrene in base kaolinite. Batch desorption kinetic experiments were performed using Triton X-100 (7.5% w/w) + EDTA (0.01M). During the first 24 h, desorption was rapid. Organic matter content in the kaolinite led to a reduction in the desorption rate of the contaminants. The desorption kinetic data were well fitted by a pseudo-second-order kinetic model.

The fast method of Cu-porphyrin complex synthesis for potential use in positron emission tomography imaging

NASA Astrophysics Data System (ADS)

Kilian, Krzysztof; Pęgier, Maria; Pyrzyńska, Krystyna

2016-04-01

Porphyrin based photosensitizers are useful agents for photodynamic therapy and fluorescence imaging of cancer. Additionally, porphyrins are excellent metal chelators, forming stable metalo-complexes and 64Cu isotope can serve as a positron emitter (t1/2 = 12.7 h). The other advantage of 64Cu is its decay characteristics that facilitates the use of 64Cu-porphyrin complex as a therapeutic agent. Thus, 64Cu chelation with porphyrin photosensitizer may become a simple and versatile labeling strategy for clinical positron emission tomography. The present study reports a convenient method for the synthesis of Cu complex with tetrakis(4-carboxyphenyl)porphyrin (TCPP). The experimental conditions for labeling, such as the metal-to-ligand molar ratio, pH and time of reaction were optimized to achieve a high complexation efficiency in a short period of time as possible. In order to accelerate the metallation, the use of substitution reactions of cadmium or lead porphyrin and the presence of reducing agent, such as ascorbic acid, hydroxylamine and flavonoid - morin, were evaluated. The optimum conditions for the synthesis of the copper complex were borate buffer at pH 9 with the addition of 10-fold molar excess, with respect to Cu2 + ions and TCPP and ascorbic acid which resulted in reduction of the reaction time from 30 min to below 1 min.

Evaluation of technetium-99m decay on Escherichia coli inactivation: effects of physical or chemical agents.

PubMed Central

Silva, C. R.; Valsa, J. O.; Caniné, M. S.; Caldeira-de-Araújo, A.; Bernardo-Filho, M.

1998-01-01

Technetium-99m (99mTc) has been used in nuclear medicine and in biomedical research to label molecular and cellular structures employed as radiotracers. Here, we have evaluated, on a DNA repair proficient Escherichia coli strain, the 99mTc decay inactivation and the influence of the (i) pre-treatment with metal ion chelators or of the (ii) treatment with a free radical scavenger on the protection of the cells against the lethal effect of the 99mTc. As SnCl2 is frequently used as a reducing agent in the 99mTc-labeling process, we have also studied the capability of SnCl2 to alter the biological effects induced by the 99mTc decay. As we are exposed to either chemical or physical agents in the nature, we have decided to study a possible influence of the ultraviolet solar radiation in the biological phenomena induced by the 99mTc decay. Our data point out (i) a very important role of the Auger and/or conversion electrons in the cytotoxicity induced by the 99mTc decay; (ii) SnCl2, the metal ion chelators and the free radical scavenger protect the cells against the lethal effect of the 99mTc; and (iii) near-UV does not alter the lethal effect of the 99mTc decay. PMID:9713950

Aminothiol Receptors for Decorporation of Intravenously Administered 60Co in the Rat

DOE Office of Scientific and Technical Information (OSTI.GOV)

Levitskaia, Tatiana G.; Morris, James E.; Creim, Jeffrey A.

2010-01-01

The reported investigation provides a comparison of the oral decorporation efficacy of L-glutathione (GSH), L-cysteine (Cys), and a liposomal GSH formulation (ReadiSorb) toward systemic cobalt-60 (60Co) to that observed following intravenous administration of GSH and Cys in F344 rats. L-histidine (His) was tested intravenously to compare in vivo efficacy of the aminothiol GSH and Cys chelators with that of aminoimidazole (His) chelator. 60Co was administered to animals by intravenous injection, followed by intravenous or oral gavage doses of a chelator repeated at 24 hour intervals for a total of 5 doses. The results suggest that GSH and Cys are potentmore » decorporation agents for 60Co in the rat model, although the efficacy of treatment depends largely on systemic availability of a chelator. The intravenous GSH or Cys were most effective in reducing tissue 60Co levels and in increasing excretion of radioactivity compared to control animals. Liposomal encapsulation was found to markedly enhance the oral bioavailability of GSH compared to non-formulated GSH. Oral administration of ReadiSorb reduced 60Co levels in nearly all tissues by 12-43% compared to that observed for non-formulated GSH. Efficacy of oral Cys was only slightly reduced in comparison with intravenous Cys. Further studies to optimize the dosing regimen in order to maximize decorporation efficiency are warranted.« less

Enhanced stability of catalase covalently immobilized on functionalized titania submicrospheres.

PubMed

Wu, Hong; Liang, Yanpeng; Shi, Jiafu; Wang, Xiaoli; Yang, Dong; Jiang, Zhongyi

2013-04-01

In this study, a novel approach combing the chelation and covalent binding was explored for facile and efficient enzyme immobilization. The unique capability of titania to chelate with catecholic derivatives at ambient conditions was utilized for titania surface functionalization. The functionalized titania was then used for enzyme immobilization. Titania submicrospheres (500-600 nm) were synthesized by a modified sol-gel method and functionalized with carboxylic acid groups through a facile chelation method by using 3-(3,4-dihydroxyphenyl) propionic acid as the chelating agent. Then, catalase (CAT) was covalently immobilized on these functionalized titania submicrospheres through 1-ethyl-3-[3-dimethylaminopropyl] carbodiimide hydrochloride/N-hydroxysuccinimide (EDC/NHS) coupling reaction. The immobilized CAT retained 65% of its free form activity with a loading capacity of 100-150 mg/g titania. The pH stability, thermostability, recycling stability and storage stability of the immobilized CAT were evaluated. A remarkable enhancement in enzyme stability was achieved. The immobilized CAT retained 90% and 76% of its initial activity after 10 and 16 successive cycles of decomposition of hydrogen peroxide, respectively. Both the Km and the Vmax values of the immobilized CAT (27.4 mM, 13.36 mM/min) were close to those of the free CAT (25.7 mM, 13.46 mM/min). Copyright © 2012 Elsevier B.V. All rights reserved.

Synthesis and Characterization of Tricarbonyl-Re/Tc(I) Chelate Probes Targeting the G Protein-Coupled Estrogen Receptor GPER/GPR30

PubMed Central

Burai, Ritwik; Ramesh, Chinnasamy; Nayak, Tapan K.; Dennis, Megan K.; Bryant, Bj K.; Prossnitz, Eric R.; Arterburn, Jeffrey B.

2012-01-01

The discovery of the G protein-coupled estrogen receptor GPER (also GPR30) and the resulting development of selective chemical probes have revealed new aspects of estrogen receptor biology. The potential clinical relevance of this receptor has been suggested from numerous studies that have identified GPER expression in breast, endometrial, ovarian and other cancers. Thus GPER can be considered a candidate biomarker and target for non-invasive imaging and therapy. We have designed and synthesized a series of organometallic tricarbonyl-rhenium complexes conjugated to a GPER-selective small molecule derived from tetrahydro-3H-cyclopenta[c]quinoline. The activity and selectivity of these chelates in GPER-mediated signaling pathways were evaluated. These results demonstrate that GPER targeting characteristics depend strongly on the structure of the chelate and linkage. Ethanone conjugates functioned as agonists, a 1,2,3-triazole spacer yielded an antagonist, and derivatives with increased steric volume exhibited decreased activities. Promising GPER selectivity was observed, as none of the complexes interacted with the nuclear estrogen receptors. Radiolabeling with technetium-99m in aqueous media was efficient and gave radioligands with high radiochemical yields and purity. These chelates have favorable physicochemical properties, show excellent stability in biologically relevant media, exhibit receptor specificity and are promising candidates for continuing development as diagnostic imaging agents targeting GPER expression in cancer. PMID:23077529

Optical response measurements of a new class of upconverting luminescent reporters

NASA Astrophysics Data System (ADS)

Xiao, Xudong; Haushalter, Jeanne P.; Weiss, Michael; Faris, Gregory W.

2004-06-01

We have prepared and characterized several lanthanide ion complexes of multidentate ligands or chelates in an effort to develop new luminescent reporters that will be immune to autofluorescence and photobleaching. Our study has involved the characterization of various chelates of Eu, Er, and Tm with respect to relative luminescent efficiency and excited state lifetimes. Included in the list of chelates studied are TTFA, EDTA, DPA, DOTA and DTPA as well as mixed and double chelates. In addition to determining the relative efficiencies and luminescence lifetimes of the lanthanide chelates, we have explored various excitation mechanisms and determined optimum excitation wavelengths. This paper will address the various hurdles encountered in the development of this new class of reporters.

Gallium(III) chelates of mixed phosphonate-carboxylate triazamacrocyclic ligands relevant to nuclear medicine: Structural, stability and in vivo studies.

PubMed

Prata, Maria I M; André, João P; Kovács, Zoltán; Takács, Anett I; Tircsó, Gyula; Tóth, Imre; Geraldes, Carlos F G C

2017-12-01

Three triaza macrocyclic ligands, H 6 NOTP (1,4,7-triazacyclononane-N,N',N″-trimethylene phosphonic acid), H 4 NO2AP (1,4,7-triazacyclononane-N-methylenephosphonic acid-N',N″-dimethylenecarboxylic acid), and H 5 NOA2P (1,4,7-triazacyclononane-N,N'-bis(methylenephosphonic acid)-N″-methylene carboxylic acid), and their gallium(III) chelates were studied in view of their potential interest as scintigraphic and PET (Positron Emission Tomography) imaging agents. A 1 H, 31 P and 71 Ga multinuclear NMR study gave an insight on the structure, internal dynamics and stability of the chelates in aqueous solution. In particular, the analysis of 71 Ga NMR spectra gave information on the symmetry of the Ga 3+ coordination sphere and the stability of the chelates towards hydrolysis. The 31 P NMR spectra afforded information on the protonation of the non-coordinated oxygen atoms from the pendant phosphonate groups and on the number of species in solution. The 1 H NMR spectra allowed the analysis of the structure and the number of species in solution. 31 P and 1 H NMR titrations combined with potentiometry afforded the measurement of the protonation constants (log K Hi ) and the microscopic protonation scheme of the triaza macrocyclic ligands. The remarkably high thermodynamic stability constant (log K GaL =34.44 (0.04) and stepwise protonation constants of Ga(NOA2P) 2- were determined by potentiometry and 69 Ga and 31 P NMR titrations. Biodistribution and gamma imaging studies have been performed on Wistar rats using the radiolabeled 67 Ga(NO2AP) - and 67 Ga(NOA2P) 2- chelates, having both demonstrated to have renal excretion. The correlation of the molecular properties of the chelates with their pharmacokinetic properties has been analysed. Copyright © 2017 Elsevier Inc. All rights reserved.

Progressing Toward a Cohesive Pediatric 18F-FDG PET/MR Protocol: Is Administration of Gadolinium Chelates Necessary?

PubMed

Klenk, Christopher; Gawande, Rakhee; Tran, Vy Thao; Leung, Jennifer Trinh; Chi, Kevin; Owen, Daniel; Luna-Fineman, Sandra; Sakamoto, Kathleen M; McMillan, Alex; Quon, Andy; Daldrup-Link, Heike E

2016-01-01

With the increasing availability of integrated PET/MR scanners, the utility and need for MR contrast agents for combined scans is questioned. The purpose of our study was to evaluate whether administration of gadolinium chelates is necessary for evaluation of pediatric tumors on (18)F-FDG PET/MR images. First, in 119 pediatric patients with primary and secondary tumors, we used 14 diagnostic criteria to compare the accuracy of several MR sequences: unenhanced T2-weighted fast spin-echo imaging; unenhanced diffusion-weighted imaging; and-before and after gadolinium chelate contrast enhancement-T1-weighted 3-dimensional spoiled gradient echo LAVA (liver acquisition with volume acquisition) imaging. Next, in a subset of 36 patients who had undergone (18)F-FDG PET within 3 wk of MRI, we fused the PET images with the unenhanced T2-weighted MR images (unenhanced (18)F-FDG PET/MRI) and the enhanced T1-weighted MR images (enhanced (18)F-FDG PET/MRI). Using the McNemar test, we compared the accuracy of the two types of fused images using the 14 diagnostic criteria. We also evaluated the concordance between (18)F-FDG avidity and gadolinium chelate enhancement. The standard of reference was histopathologic results, surgical notes, and follow-up imaging. There was no significant difference in diagnostic accuracy between the unenhanced and enhanced MR images. Accordingly, there was no significant difference in diagnostic accuracy between the unenhanced and enhanced (18)F-FDG PET/MR images. (18)F-FDG avidity and gadolinium chelate enhancement were concordant in 30 of the 36 patients and 106 of their 123 tumors. Gadolinium chelate administration is not necessary for accurate diagnostic characterization of most solid pediatric malignancies on (18)F-FDG PET/MR images, with the possible exception of focal liver lesions. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Effect of Iron Chelation Therapy on Glucose Metabolism in Non-Transfusion-Dependent Thalassaemia.

PubMed

Chuansumrit, Ampaiwan; Pengpis, Pimprae; Mahachoklertwattana, Pat; Sirachainan, Nongnuch; Poomthavorn, Preamrudee; Sungkarat, Witaya; Kadegasem, Praguywan; Khlairit, Patcharin; Wongwerawattanakoon, Pakawan

2017-01-01

To compare insulin sensitivity, β-cell function and iron status biomarkers in non-transfusion-dependent thalassaemia (NTDT) with iron excess during pre- and post-iron chelation. Subjects with NTDT, aged older than 10 years, with serum ferritin >300 ng/ml, were included. Iron chelation with deferasirox (10 mg/kg/day) was prescribed daily for 6 months. Ten patients with a median age of 17.4 years were enrolled. The comparison between pre- and post-chelation demonstrated significantly lower iron load: median serum ferritin (551.4 vs. 486.2 ng/ml, p = 0.047), median TIBC (211.5 vs. 233.5 µg/dl, p = 0.009) and median non-transferrin binding iron (5.5 vs. 1.4 µM, p = 0.005). All patients had a normal oral glucose tolerance test (OGTT) both pre- and post-chelation. However, fasting plasma glucose was significantly reduced after iron chelation (85.0 vs.79.5 mg/dl, p = 0.047). MRI revealed no significant changes of iron accumulation in the heart and liver after chelation, but there was a significantly lower iron load in the pancreas, assessed by higher T2* at post-chelation compared with pre-chelation (41.9 vs. 36.7 ms, p = 0.047). No adverse events were detected. A trend towards improving insulin sensitivity and β-cell function as well as a reduced pancreatic iron load was observed following 6 months of iron chelation (TCTR20160523003). © 2016 S. Karger AG, Basel.

Gastrin Receptor-Avid Peptide Conjugates

DOEpatents

Hoffman, Timothy J.; Volkert, Wynn A.; Li, Ning; Sieckman, Gary; Higginbotham, Chrys-Ann

2005-07-26

A compound for use as a therapeutic or diagnostic radiopharmaceutical includes a group capable of complexing a medically useful metal attached to a moiety which is capable of binding to a gastrin releasing peptide receptor. A method for treating a subject having a neoplastic disease includes administering to the subject an effective amount of a radiopharmaceutical having a metal chelated with a chelating group attached to a moiety capable of binding to a gastrin releasing peptide receptor expressed on tumor cells with subsequent internalization inside of the cell. A method of forming a therapeutic or diagnostic compound includes reacting a metal synthon with a chelating group covalently linked with a moiety capable of binding a gastrin releasing peptide receptor.

Gastrin receptor-avid peptide conjugates

DOEpatents

Hoffman, Timothy J.; Volkert, Wynn A.; Li, Ning; Sieckman, Gary; Higginbotham, C. A.

2001-01-01

A compound for use as a therapeutic or diagnostic radiopharmaceutical includes a group capable of complexing a medically useful metal attached to a moiety which is capable of binding to a gastrin releasing peptide receptor. A method for treating a subject having a neoplastic disease includes administering to the subject an effective amount of a radiopharmaceutical having a metal chelated with a chelating group attached to a moiety capable of binding to a gastrin releasing peptide receptor expressed on tumor cells with subsequent internalization inside of the cell. A method of forming a therapeutic or diagnostic compound includes reacting a metal synthon with a chelating group covalently linked with a moiety capable of binding a gastrin releasing peptide receptor.

Gastrin receptor-avid peptide conjugates

DOEpatents

Hoffman, Timothy J.; Volkert, Wynn A.; Sieckman, Gary; Smith, Charles J.; Gali, Hariprasad

2006-06-13

A compound for use as a therapeutic or diagnostic radiopharmaceutical includes a group capable of complexing a medically useful metal attached to a moiety which is capable of binding to a gastrin releasing peptide receptor. A method for treating a subject having a neoplastic disease includes administering to the subject an effective amount of a radiopharmaceutical having a metal chelated with a chelating group attached to a-moiety capable of binding to a gastrin releasing peptide receptor expressed on tumor cells with subsequent internalization inside of the cell. A method of forming a therapeutic or diagnostic compound includes reacting a metal synthon with a chelating group covalently linked with a moiety capable of binding a gastrin releasing peptide receptor.

Gastrin receptor-avid peptide conjugates

DOEpatents

Hoffman, Timothy J.; Volkert, Wynn A.; Li, Ning; Sieckman, Gary; Higginbotham, Chrys-Ann

2006-12-12

A compound for use as a therapeutic or diagnostic radiopharmaceutical includes a group capable of complexing a medically useful metal attached to a moiety which is capable of binding to a gastrin releasing peptide receptor. A method for treating a subject having a neoplastic disease includes administering to the subject an effective amount of a radiopharmaceutical having a metal chelated with a chelating group attached to a moiety capable of binding to a gastrin releasing peptide receptor expressed on tumor cells with subsequent internalization inside of the cell. A method of forming a therapeutic or diagnostic compound includes reacting a metal synthon with a chelating group covalently linked with a moiety capable of binding a gastrin releasing peptide receptor.

Zinc chelation decreases IFN-β-induced STAT1 upregulation and iNOS expression in RAW 264.7 macrophages.

PubMed

Reiber, Cathleen; Brieger, Anne; Engelhardt, Gabriela; Hebel, Silke; Rink, Lothar; Haase, Hajo

2017-12-01

One consequence of lipopolysaccharide (LPS)-induced stimulation of macrophages is the release of Interferon (IFN)-β, and subsequently the activation of the JAK-STAT1 pathway, resulting in the expression of inducible nitric oxide synthase (iNOS). Free intracellular zinc ions (Zn 2+ ) have a profound impact as a second messenger in LPS-dependent gene expression. Previous work had indicated a Zn 2+ -dependent upregulation of STAT1 mRNA in response to LPS and IFN-β, potentially affecting STAT1-dependent downstream signaling upon pre-incubation with these agents. The aim of the present study was to investigate the long-term influence of Zn 2+ chelation on cellular STAT1 levels and their effect on protein levels and activity of iNOS. The LPS- and IFN-β-mediated increase of STAT1 mRNA and protein levels was abrogated by chelation of Zn 2+ with the membrane permeable chelator N,N,N',N'-Tetrakis(2-pyridylmethyl)ethylenediamine (TPEN) in RAW 264.7 macrophages. After 48h pre-incubation together with IFN-β, TPEN also led to reduced nitric monoxide formation in response to a second stimulation with LPS. Nonetheless, the latter was observed regardless of any pre-incubation with IFN-β, suggesting that the effect of treatment with TPEN negatively affects iNOS induction independently from cellular STAT1 levels. In conclusion, long term Zn 2+ chelation does affect STAT1 protein expression, but interferes with NO production by a different, yet unknown pathway not involving STAT1. However, as there are many additional STAT1-dependent genes, there might still be effects on targets other than iNOS. Copyright © 2017 Elsevier GmbH. All rights reserved.

Method of producing catalytic material for fabricating nanostructures

DOE Office of Scientific and Technical Information (OSTI.GOV)

Seals, Roland D.; Menchhofer, Paul A.; Howe, Jane Y.

Methods of fabricating nano-catalysts are described. In some embodiments the nano-catalyst is formed from a powder-based substrate material and is some embodiments the nano-catalyst is formed from a solid-based substrate material. In some embodiments the substrate material may include metal, ceramic, or silicon or another metalloid. The nano-catalysts typically have metal nanoparticles disposed adjacent the surface of the substrate material. The methods typically include functionalizing the surface of the substrate material with a chelating agent, such as a chemical having dissociated carboxyl functional groups (--COO), that provides an enhanced affinity for metal ions. The functionalized substrate surface may then bemore » exposed to a chemical solution that contains metal ions. The metal ions are then bound to the substrate material and may then be reduced, such as by a stream of gas that includes hydrogen, to form metal nanoparticles adjacent the surface of the substrate.« less

Method of producing catalytic materials for fabricating nanostructures

DOEpatents

Seals, Roland D; Menchhofer, Paul A; Howe, Jane Y; Wang, Wei

2013-02-19

Methods of fabricating nano-catalysts are described. In some embodiments the nano-catalyst is formed from a powder-based substrate material and is some embodiments the nano-catalyst is formed from a solid-based substrate material. In some embodiments the substrate material may include metal, ceramic, or silicon or another metalloid. The nano-catalysts typically have metal nanoparticles disposed adjacent the surface of the substrate material. The methods typically include functionalizing the surface of the substrate material with a chelating agent, such as a chemical having dissociated carboxyl functional groups (--COO), that provides an enhanced affinity for metal ions. The functionalized substrate surface may then be exposed to a chemical solution that contains metal ions. The metal ions are then bound to the substrate material and may then be reduced, such as by a stream of gas that includes hydrogen, to form metal nanoparticles adjacent the surface of the substrate.

Organic contaminants in onsite wastewater treatment systems

USGS Publications Warehouse

Conn, K.E.; Siegrist, R.L.; Barber, L.B.; Brown, G.K.

2007-01-01

Wastewater from thirty onsite wastewater treatment systems was sampled during a reconnaissance field study to quantify bulk parameters and the occurrence of organic wastewater contaminants including endocrine disrupting compounds in treatment systems representing a variety of wastewater sources and treatment processes and their receiving environments. Bulk parameters ranged in concentrations representative of the wide variety of wastewater sources (residential vs. non-residential). Organic contaminants such as sterols, surfactant metabolites, antimicrobial agents, stimulants, metal-chelating agents, and other consumer product chemicals, measured by gas chromatography/mass spectrometry were detected frequently in onsite system wastewater. Wastewater composition was unique between source type likely due to differences in source water and chemical usage. Removal efficiencies varied by engineered treatment type and physicochemical properties of the contaminant, resulting in discharge to the soil treatment unit at ecotoxicologically-relevant concentrations. Organic wastewater contaminants were detected less frequently and at lower concentrations in onsite system receiving environments. Understanding the occurrence and fate of organic wastewater contaminants in onsite wastewater treatment systems will aid in minimizing risk to ecological and human health.

Brain tumor enhancement in magnetic resonance imaging at 3 tesla: intraindividual comparison of two high relaxivity macromolecular contrast media with a standard extracellular gd-chelate in a rat brain tumor model.

PubMed

Fries, Peter; Runge, Val M; Bücker, Arno; Schürholz, Hellmut; Reith, Wolfgang; Robert, Philippe; Jackson, Carney; Lanz, Titus; Schneider, Günther

2009-04-01

The aim of this study was to evaluate lesion enhancement (LE) and contrast-to-noise ratio (CNR) properties of P846, a new intermediate sized, high relaxivity Gd-based contrast agent at 3 Tesla in a rat brain glioma model, and to compare this contrast agent with a high relaxivity, macromolecular compound (P792), and a standard extracellular Gd-chelate (Gd-DOTA). Seven rats with experimental induced brain glioma were evaluated using 3 different contrast agents, with each MR examination separated by at least 24 hours. The time between injections assured sufficient clearance of the agent from the tumor, before the next examination. P792 (Gadomelitol, Guerbet, France) and P846 (a new compound from Guerbet Research) are macromolecular and high relaxivity contrast agents with no protein binding, and were compared with the extracellular agent Gd-DOTA (Dotarem, Guerbet, France). T1w gradient echo sequences (TR/TE 200 milliseconds/7.38 milliseconds, flip angle = 90 degrees , acquisition time: 1:42 minutes:sec, voxel size: 0.2 x 0.2 x 2.0 mm, FOV = 40 mm, acquisition matrix: 256 x 256) were acquired before and at 5 consecutive time points after each intravenous contrast injection in the identical slice orientation, using a dedicated 4-channel head array animal coil. The order of contrast media injection was randomized, with however Gd-DOTA used either as the first or second contrast agent. Contrast agent dose was adjusted to compensate for the different T1 relaxivities of the 3 agents. Signal-to-noise ratio, CNR, and LE were evaluated using region-of-interest analysis. A veterinary histopathologist confirmed the presence of a glioma in each subject, after completion of the imaging study. P792 showed significantly less LE as compared with Gd-DOTA within the first 7 minutes after contrast agent injection (P < 0.05) with, however, reaching comparable LE values at 9 minutes after injection (P = 0.07). However, P792 provided significantly less CNR as compared with Gd-DOTA (P < 0.05) for all examination time points. P846 provided comparable but persistent LE as compared with Gd-DOTA (P < 0.05) and demonstrated significantly greater LE and CNR when compared with P792 (P < 0.05). No statistically significant differences between CNR values for Gd-DOTA and P846 were noted for all examination time points (P < 0.05), with P846 administered at one-fourth the dose as compared with Gd-DOTA. The intravascular contrast medium P792 showed significantly less LE and CNR in comparison to Gd-DOTA and P846, suggesting that it does not show marked extravasation from tumor neocapillaries and does not significantly cross the disrupted blood brain-barrier in this rat glioma model. In distinction, P846 provides comparable enhancement properties at a field strength of 3 Tesla to the extracellular contrast agent Gd-DOTA, using the adjusted dose, suggesting that it crosses the disrupted blood-brain-barrier and tumor capillaries, most likely based on the decreased molecular weight as compared with P792. At the same time, the high relaxivity of this compound allows for decreasing the injected gadolinium dose by a factor of 4 whereas providing comparable enhancement properties when compared with a standard extracellular Gd-chelate (Gd-DOTA) at a dose of 0.1 mmol/kg body weight.

Effects of soil applications of micro-nutrients and chelating agent citric acid on mineral nutrients in soybean seeds

USDA-ARS?s Scientific Manuscript database

Micro-nutrients deficiency in soil result in crop yield loss and poor seed quality. Correcting this deficiency is normally conducted by foliar or soil application. The objective of this research was to determine the effects of soil applications of five micro-nutrients (Mn, Cu, Zn, Mo, and B) with a ...

Molecular Innovations Toward Theranostics of Aggressive Prostate Cancer

DTIC Science & Technology

2015-09-01

therapeutic agents assisted with new imaging probe is expect to bring a new frontier for prostate cancer management. Our objective is to develop dendrimer ...selective dendrimer nanoparticle platform with both targeted imaging and drug delivery capabilities to target metastatic PCa. Using this unique...constructing dendrimer conjugated with therapeutic peptide, determining the mechanism of action and preparing chelator for conjugating PET tracer and

Molecular Innovations Toward Theranostics of Aggressive Prostate Cancer

DTIC Science & Technology

2014-09-01

to develop dendrimer -based theranostic agent with prostate cancer specificity and positron emission tomography imaging capability that can prevent...laboratories to develop a new molecular medicine. The goal of this project is to construct dendrimer nanoconjuate containing a prostate specific...cell permeation peptide, peptide therapeutic(s) and bifunctional chelator for PET imaging. Dr. Simanek’s laboratory will make dendrimers that bear

Molecular Innovations Toward Theranostics of Aggressive Prostate Cancer

DTIC Science & Technology

2013-09-01

objective is to develop dendrimer -based theranostic agent with prostate cancer specificity and positron emission tomography imaging capability that...The goal of this project is to construct dendrimer nanoconjuate containing a prostate specific cell permeation peptide, peptide therapeutic(s) and...bifunctional chelator for PET imaging. Dr. Simanek’s laboratory will make dendrimers that bear functional handles for conjugation with imaging

Chelating agent-assisted heat treatment of a carbon-supported iron oxide nanoparticle catalyst for PEMFC.

PubMed

Liu, Shyh-Jiun; Huang, Chia-Hung; Huang, Chun-Kai; Hwang, Weng-Sing

2009-08-28

Iron complexes were supported on commercial carbon black and heat treated to create FeO(x)/C catalysts that showed a larger normalized current density and normalized power density than commercial Pt/C catalysts; the coordination number of the iron complexes used affected the formation of the active site for oxygen reduction in PEMFC.

Removal of nano- and micronized-copper from treated wood by chelating agents

Treesearch

S. Nami Kartal; Evren Terzi; Bessie Woodward; Carol A. Clausen; Stan T. Lebow

2013-01-01

Micronized and nano-copper (Cu)-based and arsenic and chromium-free systems have received much attention for wood protection in recent years. Because they have different fixation, and micro-distribution properties, such copper systems may be more or less subject to release using known remediation methods than soluble forms of Cu. This study evaluated Cu recovery from...

Dynamic NMR of Intramolecular Exchange Processes in EDTA Complexes of Sc[superscript 3+], Y[superscript 3+], and La[superscript 3+

ERIC Educational Resources Information Center

Ba, Yong; Han, Steven; Ni, Lily; Su, Tony; Garcia, Andres

2006-01-01

Dynamic NMR makes use of the effect of chemical exchanges on NMR spectra to study kinetics and thermodynamics. An advanced physical chemistry lab experiment was developed to study the intramolecular exchange processes of EDTA (the disodium salt of ethylenediaminetetraacetic acid) metal complexes. EDTA is an important chelating agent, used in…

Detection and Quantification of Unbound Phytochelatin 2 in Plant Extracts of Brassica napus Grown with Different Levels of Mercury1

PubMed Central

Iglesia-Turiño, Santiago; Febrero, Anna; Jauregui, Olga; Caldelas, Cristina; Araus, Jose Luis; Bort, Jordi

2006-01-01

The mercury (Hg) accumulation mechanism was studied in rape (Brassica napus) plants grown under a Hg concentration gradient (0 μm–1,000 μm). Hg mainly accumulated in roots. Therefore, the presence of phytochelatins (PCs) was studied in the roots of the plants. The high stability of the PC-Hg multicomplexes (mPC-nHg) seems to be the main reason for the lack of previous Hg-PC characterization studies. We propose a modification of the method to detect and quantify unbound PC of Hg in plant extracts via high-performance liquid chromatography coupled to electrospray tandem mass spectrometry and inductively coupled plasma mass spectrometry in parallel. We separated the PC from the Hg by adding the chelating agent sodium 2,3-dimercaptopropanesulfonate monohydrate. We only detected the presence of PC after the addition of the chelating agent. Some multicomplexes mPC-nHg could be formed but, due to their large sizes, could not be detected. In this study, only PC2 was observed in plant samples. Hg accumulation was correlated with PC2 concentration (r2 = 0.98). PMID:16920879

Type of MRI contrast, tissue gadolinium, and fibrosis.

PubMed

Do, Catherine; Barnes, Jeffrey L; Tan, Chunyan; Wagner, Brent

2014-10-01

It has been presupposed that the thermodynamic stability constant (K(therm)) of gadolinium-based MRI chelates relate to the risk of precipitating nephrogenic systemic fibrosis. The present study compared low-K(therm) gadodiamide with high-K(therm) gadoteridol in cultured fibroblasts and rats with uninephrectomies. Gadolinium content was assessed using scanning electron microscopy equipped with energy-dispersive X-ray spectroscopy in paraffin-embedded tissues. In vitro, fibroblasts demonstrated dose-dependent fibronectin generation, transforming growth factor-β production, and expression of activated myofibroblast stress fiber protein α-smooth muscle actin. There were negligible differences with respect to toxicity or proliferation between the two contrast agents. In the rodent model, gadodiamide treatment led to greater skin fibrosis and dermal cellularity than gadoteridol. In the kidney, both contrast agents led to proximal tubule vacuolization and increased fibronectin accumulation. Despite large detectable gadolinium signals in the spleen, skin, muscle, and liver from the gadodiamide-treated group, contrast-induced fibrosis appeared to be limited to the skin and kidney. These findings support the hypothesis that low-K(therm) chelates have a greater propensity to elicit nephrogenic systemic fibrosis and demonstrate that certain tissues are resistant to these effects.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ogawa, E.; Suzuki, S.; Tsuzuki, H.

Mice were subcutaneoulsy injected with Sr/sup 90/ or Sr/sup 85/, and effects of various drugs on their 3-day excretion and retention on the 4th day were investigated. Among chelating agents, NaCa citrate, NaMg citrate, NaSr citrate, Achromycin (or tetracycline), and aspartic MgK (alone or in combination with NH/sub 4/Cl) displayed Sr-eliminating effects. ATP increased only the excretion without diminishing the retention in bone. EDTA, DTPA, BADE, tricarballylate, Na citrate and NaPb citrate were not effective. Among salts, Mg salt, sulfite, and thiosulfate were effective in eliminating Sr. The last exerted a greater effect when given concurrently with Mg, Ca, ormore » Sr salt. Ca and Sr salt exerted no effect, and ammonium chloride promoted only urinary secretion, not extending to local or total excretion. Such salts as induce alkalosis conversely exerted inhibitory effects. Among hormones, glucocorticoids had Sreliminating effects. TSH was effective, and antithyroidal drugs conversely seemed to have excretion-diminishing effects. Among vitamins, cocarboxylase increased Sr excretion, but did not decrease the retention in bone. Also metabolic inhibitors were ineffective, and NaF conversely increased bone deposition of Sr. Among diuretics, SHdrugs, and weak chelating agents, there were no effective drugs. (JAIF)« less

Influence of pH, buffers and role of quinolinic acid, a novel iron chelating agent, in the determination of hydroxyl radical scavenging activity of plant extracts by Electron Paramagnetic Resonance (EPR).

PubMed

Fadda, Angela; Barberis, Antonio; Sanna, Daniele

2018-02-01

The Fenton reaction is used to produce hydroxyl radicals for the evaluation of the antioxidant activity of plant extracts. In this paper the parameters affecting the production of hydroxyl radicals and their spin trapping with DMPO were studied. The use of quinolinic acid (Quin) as an Fe(II) ligand was proposed for antioxidant activity determination of Green tea, orange juice and asparagus extracts. Quin, buffers and pH affect the DMPO-OH signal intensity of the EPR spectra. Quin/Fe(II) and low pH enhance the OH generation. Phosphate and Tris-HCl buffers decrease the signal intensity measured in Fe(II)-sulfate and Fe(II)-Quin systems. The extracts were analyzed with Fenton systems containing Fe(II)-sulfate and Fe(II)-Quin with and without buffer. The highest activity was shown with Fe(II)-Quin without buffer, this system being less influenced by pH and chelating agents present in the extracts. This paper will help researchers to better design spin trapping experiments for food matrices. Copyright © 2017 Elsevier Ltd. All rights reserved.

Use of a Genetically Engineered Protein for the Design of a Multivalent MRI Contrast Agent

PubMed Central

Karfeld, Lindsay S.; Bull, Steve R.; Davis, Nicolynn E.; Meade, Thomas J.; Barron, Annelise E.

2008-01-01

The majority of clinically used contrast agents (CAs) for magnetic resonance imaging have low relaxivities and thus require high concentrations for signal enhancement. Research has turned to multivalent, macromolecular CAs to increase CA efficiency. However, previously developed macromolecular CAs do not provide high relaxivities, have limited biocompatibility, and/or do not have a structure that is readily modifiable to tailor to particular applications. We report a new family of multivalent, biomacromolecular, genetically engineered protein polymer-based CAs; the protein backbone contains evenly spaced lysines that are derivatized with gadolinium (Gd(III)) chelators. The protein's length and repeating amino acid sequence are genetically specified. We reproducibly obtained conjugates with an average of 8 – 9 Gd(III) chelators per protein. These multivalent CAs reproducibly provide a high relaxivity of 7.3 mM-1s-1 per Gd(III) and 62.6 mM-1s-1 per molecule. Furthermore, they can be incorporated into biomaterial hydrogels via chemical crosslinking of remaining free lysines, and provide a dramatic contrast enhancement. Thus, these protein polymer CAs could be a useful tool for following the evolution of tissue engineering scaffolds. PMID:17927227

Synthesis of Nanometric-Sized Barium Titanate Powders Using Acetylacetone as the Chelating Agent in a Sol-Precipitation Process

NASA Astrophysics Data System (ADS)

Hung, Kun Ming; Hsieh, Ching Shieh; Yang, Wein Duo; Tsai, Hui Ju

2007-03-01

Nanometric-sized barium titanate powders were prepared by using titanium isopropoxid as the raw material and acetylacetone as a chelating agent, in a strong alkaline solution (pH > 13) through the sol-precipitation method. The preparatory variables affect the extent of cross-linking in the structure, change the mode of condensation of the gels, and even control the particle size of the powder. The reaction rate of forming powder, at a higher temperature such as 100°C and more water content (the molar ratio of water to titanium isopropoxide is 25) or fewer acetylacetone (the molar ratio of acetylacetone to titanium isopropoxide is 1), is rapid and the particle size formed is finer at 60 80 nm. On the contrary, that of forming powder, at lower temperature (40°C) and less water content (molar ratio of water/titanium isopropoxide = 5) or higher acetylacetone (acetylacetone/titanium isopropoxide = 7), is slow and the particle size of the powder is larger. The optimal preparatory conditions were obtained by using the experimental statistical method; as a result, nanometric-sized BaTiO3 powder with an average particle size of about 50 nm was prepared.

Poisoning of a Silica-Supported Cobalt Catalyst due to Presence of Sulfur Impurities in Syngas during Fischer–Tropsch Synthesis: Effects of Chelating Agent

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bambal, Ashish S.; Guggilla, Vidya S.; Kugler, Edwin L.

2014-04-09

The effects of sulfur impurities on the performance of cobalt-based Fischer–Tropsch catalysts are evaluated under industrially relevant operating conditions of temperature, pressure, and impurity levels. Chelating agents (CAs) were used to modify the SiO 2 support, and the performances of the CA-modified catalysts are compared with conventional Co/SiO 2 catalysts. For both the Co/SiO 2 and CA-modified catalysts, the presence of sulfur in the inlet syngas results in a notable drop in the CO conversion, an undesired shift in the hydrocarbon selectivity toward short-chain hydrocarbons, more olefins in the products, and lower product yields. In the post-poisoning stage, i.e., aftermore » termination of sulfur introduction in the inlet syngas, the CA-modified catalysts recover activity and selectivity (to some extent at least), whereas such trends are not observed for the base-case, i.e., unmodified Co/SiO 2 catalyst. Finally, the improved performance of the CA-modified catalysts in the presence of sulfur is attributed to higher densities of active sites.« less

Calixarene cleansing formulation for uranium skin contamination.

PubMed

Phan, Guillaume; Semili, Naïma; Bouvier-Capely, Céline; Landon, Géraldine; Mekhloufi, Ghozlene; Huang, Nicolas; Rebière, François; Agarande, Michelle; Fattal, Elias

2013-10-01

An oil-in-water cleansing emulsion containing calixarene molecule, an actinide specific chelating agent, was formulated in order to improve the decontamination of uranium from the skin. Commonly commercialized cosmetic ingredients such as surfactants, mineral oil, or viscosifying agents were used in preparing the calixarene emulsion. The formulation was characterized in terms of size and apparent viscosity measurements and then was tested for its ability to limit uranyl ion permeation through excoriated pig-ear skin explants in 24-h penetration studies. Calixarene emulsion effectiveness was compared with two other reference treatments consisting of DTPA and EHBP solutions. Application of calixarene emulsion induced the highest decontamination effect with an 87% decrease in uranium diffusion flux. By contrast, EHBP and DTPA solutions only allowed a 50% and 55% reduction of uranium permeation, respectively, and had the same effect as a simple dilution of the contamination by pure water. Uranium diffusion decrease was attributed to uranyl ion-specific chelation by calixarene within the formulation, since no significant effect was obtained after application of the same emulsion without calixarene. Thus, calixarene cleansing emulsion could be considered as a promising treatment in case of accidental contamination of the skin by highly diffusible uranium compounds.

Ocular pharmacokinetic study using T₁ mapping and Gd-chelate- labeled polymers.

PubMed

Shi, Xianfeng; Liu, Xin; Wu, Xueming; Lu, Zheng-Rong; Li, S Kevin; Jeong, Eun-Kee

2011-12-01

Recent advances in drug discovery have led to the development of a number of therapeutic macromolecules for treatment of posterior eye diseases. We aimed to investigate the clearance of macromolecular contrast probes (polymers conjugated with Gd-chelate) in the vitreous after intravitreal injections with the recently developed ms-DSEPI-T12 MRI and to examine the degradation of disulfide-containing biodegradable polymers in the vitreous humor in vivo. Intravitreal injections of model contrast agents poly[N-(2-hydroxypropyl)methacrylamide]-GG-1,6-hexanediamine-(Gd-DO3A), biodegradable (Gd-DTPA)-cystine copolymers, and MultiHance were performed in rabbits; their distribution and elimination from the vitreous after injections were determined by MRI. Times for macromolecular contrast agents to decrease to half their initial concentrations in the vitreous ranged from 0.4-1.3 days post-injection. Non-biodegradable polymers demonstrated slower vitreal clearance than those of disulfide-biodegradable polymers. Biodegradable polymers had similar clearance as MultiHance. Usefulness of T(1) mapping and ms-DSEPI-T12 MRI to study ocular pharmacokinetics was demonstrated. Results suggest an enzymatic degradation mechanism for the disulfide linkage in polymers in the vitreous leading to breakup of polymers in vitreous humor over time.

Robust superhydrophobic needle-like nanostructured ZnO surfaces prepared without post chemical-treatment

NASA Astrophysics Data System (ADS)

Velayi, Elmira; Norouzbeigi, Reza

2017-12-01

Robust superhydrophobic ZnO surfaces with micro/nano hybrid hierarchical structures were synthesized on the stainless steel mesh by a facile single-step chemical bath deposition (CBD) method without using further low surface energy materials. The Taguchi L16 experimental design was applied to evaluate the effects of reaction time, type and concentration of the additive, type of the chelating agent, and the molar ratio of the chelating agent to the initial zinc (II) ions. The prepared sample at the optimal conditions exhibited a sustainable and time-independent superhydrophobic behavior with the water contact angle (WCA) of 162.8° ± 2.5° and contact angle hysteresis (CAH) of 1.8° ± 0.5°. The XRD, SEM, TEM and FTIR analyses were used to characterize the prepared samples. Surface characterization using scanning electron microscopy (SEM) indicated accumulation of micro/nano branched ZnO needles on the substrate with the average diameters of ∼85 nm. After 20 abrasion cycles the optimum sample indicated an excellent mechanical robustness via exposure to the pressure of 4.7 kPa. A suitable chemical resistance to the acidic and basic droplets with the pH range of 4 and 9 was observed.

Sequential application of chelating agents and innovative surfactants for the enhanced electroremediation of real sediments from toxic metals and PAHs.

PubMed

Hahladakis, John N; Lekkas, Nikolaos; Smponias, Andreas; Gidarakos, Evangelos

2014-06-01

This study focused on the sequential application of a chelating agent (citric acid) followed by a surfactant in the simultaneous electroremediation of real contaminated sediments from toxic metals and Polycyclic Aromatic Hydrocarbons (PAHs). Furthermore, the efficiency evaluation of two innovative non-ionic surfactants, commercially known as Poloxamer 407 and Nonidet P40, was investigated. The results indicated a removal efficacy of approximately 43% and 48% for the summation of PAHs (SUM PAHs), respectively for the aforementioned surfactants, much better than the one obtained by the use of Tween 80 (nearly 21%). Individual PAHs (e.g. fluorene) were removed in percentages that reached almost 84% and 92% in the respective electrokinetic experiments when these new surfactants were introduced. In addition, the combined-enhanced sequential electrokinetic treatment with citric acid improved dramatically the removal of Zn and As, compared to the unenhanced run, but did not favor the other toxic metals examined. Since no improvement in metal removal percentages occurred when Tween 80 was used, significant contribution to this matter should also be attributed to the solubilization capacity of these innovative, in electrokinetic remediation, non-ionic surfactants. Copyright © 2013 Elsevier Ltd. All rights reserved.

Investigations into Alternative Desorption Agents for Amidoxime-Based Polymeric Uranium Adsorbents

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gill, Gary A.; Kuo, Li-Jung; Strivens, Jonathan E.

2015-06-01

Amidoxime-based polymeric braid adsorbents that can extract uranium (U) from seawater are being developed to provide a sustainable supply of fuel for nuclear reactors. A critical step in the development of the technology is to develop elution procedures to selectively remove U from the adsorbents and to do so in a manner that allows the adsorbent material to be reused. This study investigates use of high concentrations of bicarbonate along with targeted chelating agents as an alternative means to the mild acid elution procedures currently in use for selectively eluting uranium from amidoxime-based polymeric adsorbents.

Magnetomotive room temperature dicationic ionic liquid: a new concept toward centrifuge-less dispersive liquid-liquid microextraction.

PubMed

Beiraghi, Asadollah; Shokri, Masood; Seidi, Shahram; Godajdar, Bijan Mombani

2015-01-09

A new centrifuge-less dispersive liquid-liquid microextraction technique based on application of magnetomotive room temperature dicationic ionic liquid followed by electrothermal atomic absorption spectrometry (ETAAS) was developed for preconcentration and determination of trace amount of gold and silver in water and ore samples, for the first time. Magnetic ionic liquids not only have the excellent properties of ionic liquids but also exhibit strong response to an external magnetic field. These properties provide more advantages and potential application prospects for magnetic ionic liquids than conventional ones in the fields of extraction processes. In this work, thio-Michler's ketone (TMK) was used as chelating agent to form Ag/Au-TMK complexes. Several important factors affecting extraction efficiency including extraction time, rate of vortex agitator, pH of sample solution, concentration of the chelating agent, volume of ionic liquid as well as effects of interfering species were investigated and optimized. Under the optimal conditions, the limits of detection (LOD) were 3.2 and 7.3ngL(-1) with the preconcentration factors of 245 and 240 for Au and Ag, respectively. The precision values (RSD%, n=7) were 5.3% and 5.8% at the concentration level of 0.05μgL(-1) for Au and Ag, respectively. The relative recoveries for the spiked samples were in the acceptable range of 96-104.5%. The results demonstrated that except Hg(2+), no remarkable interferences are created by other various ions in the determination of Au and Ag, so that the tolerance limits (WIon/WAu or Ag) of major cations and anions were in the range of 250-1000. The validated method was successfully applied for the analysis of Au and Ag in some water and ore samples. Copyright © 2014 Elsevier B.V. All rights reserved.

A small MRI contrast agent library of gadolinium(III)-encapsulated supramolecular nanoparticles for improved relaxivity and sensitivity**

PubMed Central

Chen, Kuan-Ju; Wolahan, Stephanie M.; Wang, Hao; Hsu, Chao-Hsiung; Chang, Hsing-Wei; Durazo, Armando; Hwang, Lian-Pin; Garcia, Mitch A.; Jiang, Ziyue Karen; Wu, Lily

2010-01-01

We introduce a new category of nanoparticle-based T1 MRI contrast agents (CAs) by encapsulating paramagnetic chelated gadolinium(III), i.e., Gd3+·DOTA, through supramolecular assembly of molecular building blocks that carry complementary molecular recognition motifs, including adamantane (Ad) and β-cyclodextrin (CD). A small library of Gd3+·DOTA-encapsulated supramolecular nanoparticles (Gd3+·DOTA⊂SNPs) was produced by systematically altering the molecular building block mixing ratios. A broad spectrum of relaxation rates was correlated to the resulting Gd3+·DOTA⊂SNP library. Consequently, an optimal synthetic formulation of Gd3+·DOTA⊂SNPs with an r1 of 17.3 s−1mM−1 (ca. 4-fold higher than clinical Gd3+ chelated complexes at high field strengths) was identified. T1-weighted imaging of Gd3+·DOTA⊂SNPs exhibits an enhanced sensitivity with a contrast-to-noise ratio (C/N ratio) ca. 3.6 times greater than that observed for free Gd3+·DTPA. A Gd3+·DOTA⊂SNPs solution was injected into foot pads of mice, and MRI was employed to monitor dynamic lymphatic drainage of the Gd3+·DOTA⊂SNPs-based CA. We observe an increase in signal intensity of the brachial lymph node in T1-weighted imaging after injecting Gd3+·DOTA⊂SNPs but not after injecting Gd3+·DTPA. The MRI results are supported by ICP-MS analysis ex vivo. These results show that Gd3+·DOTA⊂SNPs not only exhibits enhanced relaxivity and high sensitivity but also can serve as a potential tool for diagnosis of cancer metastasis. PMID:21167594

Sulphur-containing Amino Acids: Protective Role Against Free Radicals and Heavy Metals.

PubMed

Colovic, Mirjana B; Vasic, Vesna M; Djuric, Dragan M; Krstic, Danijela Z

2018-01-30

Sulphur is an abundant element in biological systems, which plays an important role in processes essential for life as a constituent of proteins, vitamins and other crucial biomolecules. The major source of sulphur for humans is plants being able to use inorganic sulphur in the purpose of sulphur-containing amino acids synthesis. Sulphur-containing amino acids include methionine, cysteine, homocysteine, and taurine. Methionine and cysteine are classified as proteinogenic, canonic amino acids incorporated in protein structure. Sulphur amino acids are involved in the synthesis of intracellular antioxidants such as glutathione and N-acetyl cysteine. Moreover, naturally occurring sulphur-containing ligands are effective and safe detoxifying agents, often used in order to prevent toxic metal ions effects and their accumulation in human body. Literature search for peer-reviewed articles was performed using PubMed and Scopus databases, and utilizing appropriate keywords. This review is focused on sulphur-containing amino acids - methionine, cysteine, taurine, and their derivatives - glutathione and N-acetylcysteine, and their defense effects as antioxidant agents against free radicals. Additionally, the protective effects of sulphur-containing ligands against the toxic effects of heavy and transition metal ions, and their reactivation role towards the enzyme inhibition are described. Sulphur-containing amino acids represent a powerful part of cell antioxidant system. Thus, they are essential in the maintenance of normal cellular functions and health. In addition to their worthy antioxidant action, sulphur-containing amino acids may offer a chelating site for heavy metals. Accordingly, they may be supplemented during chelating therapy, providing beneficial effects in eliminating toxic metals. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Synthetic and natural iron chelators: therapeutic potential and clinical use

PubMed Central

Hatcher, Heather C; Singh, Ravi N; Torti, Frank M; Torti, Suzy V

2013-01-01

Iron-chelation therapy has its origins in the treatment of iron-overload syndromes. For many years, the standard for this purpose has been deferoxamine. Recently, considerable progress has been made in identifying synthetic chelators with improved pharmacologic properties relative to deferoxamine. Most notable are deferasirox (Exjade®) and deferiprone (Ferriprox®), which are now available clinically. In addition to treatment of iron overload, there is an emerging role for iron chelators in the treatment of diseases characterized by oxidative stress, including cardiovascular disease, atherosclerosis, neurodegenerative diseases and cancer. While iron is not regarded as the underlying cause of these diseases, it does play an important role in disease progression, either through promotion of cellular growth and proliferation or through participation in redox reactions that catalyze the formation of reactive oxygen species and increase oxidative stress. Thus, iron chelators may be of therapeutic benefit in many of these conditions. Phytochemicals, many of which bind iron, may also owe some of their beneficial properties to iron chelation. This review will focus on the advances in iron-chelation therapy for the treatment of iron-overload disease and cancer, as well as neurodegenerative and chronic inflammatory diseases. Established and novel iron chelators will be discussed, as well as the emerging role of dietary plant polyphenols that effectively modulate iron biochemistry. PMID:21425984

Guidelines on iron chelation therapy in patients with myelodysplastic syndromes and transfusional iron overload.

PubMed

Gattermann, Norbert

2007-12-01

Experts believe that iron overload is an important problem which could be avoided with suitable treatment. Guidelines on treating myelodysplastic syndromes (MDS) include sections on using iron chelation therapy to prevent or ameliorate transfusional iron overload. The proportion of MDS patients who may benefit from iron chelation therapy is 35-55%, depending on the length of survival necessary for iron to accumulate to a detrimental level. Candidates for iron chelation are mainly patients with dyserythropoietic and cytopenic subtypes of disease, which fall into the International Prognostic Scoring System (IPSS) Low-risk or Intermediate-1-risk categories, with median survival of 3-6 years.

Gd-labeled glycol chitosan as a pH-responsive magnetic resonance imaging agent for detecting acidic tumor microenvironments.

PubMed

Nwe, Kido; Huang, Ching-Hui; Tsourkas, Andrew

2013-10-24

Neoplastic lesions can create a hostile tumor microenvironment with low extracellular pH. It is commonly believed that these conditions can contribute to tumor progression as well as resistance to therapy. We report the development and characterization of a pH-responsive magnetic resonance imaging contrast agent for imaging the acidic tumor microenvironment. The preparation included the conjugation of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid 1-(2,5-dioxo-1-pyrrolidinyl) ester (DOTA-NHS) to the surface of a water-soluble glycol chitosan (GC) polymer, which contains pH-titrable primary amines, followed by gadolinium complexation (GC-NH2-GdDOTA). GC-NH2-GdDOTA had a chelate-to-polymer ratio of approximately1:24 and a molar relaxivity of 9.1 mM(-1) s(-1). GC-NH2-GdDOTA demonstrated pH-dependent cellular association in vitro compared to the control. It also generated a 2.4-fold enhancement in signal in tumor-bearing mice 2 h postinjection. These findings suggest that glycol chitosan coupled with contrast agents can provide important diagnostic information about the tumor microenvironment.

Synthesis of functional materials in combustion reactions

NASA Astrophysics Data System (ADS)

Zhuravlev, V. D.; Bamburov, V. G.; Ermakova, L. V.; Lobachevskaya, N. I.

2015-12-01

The conditions for obtaining oxide compounds in combustion reactions of nitrates of metals with organic chelating-reducing agents such as amino acids, urea, and polyvinyl alcohol are reviewed. Changing the nature of internal fuels and the reducing agent-to-oxidizing agent ratio makes possible to modify the thermal regime of the process, fractal dimensionality, morphology, and dispersion of synthesized functional materials. This method can be used to synthesize simple and complex oxides, composites, and metal powders, as well as ceramics and coatings. The possibilities of synthesis in combustion reactions are illustrated by examples of αand γ-Al2O3, YSZ composites, uranium oxides, nickel powder, NiO and NiO: YSZ composite, TiO2, and manganites, cobaltites, and aluminates of rare earth elements.

Aptamer-Targeted Magnetic Resonance Imaging Contrast Agents and Their Applications.

PubMed

Zhang, Yajie; Zhang, Tingting; Liu, Min; Kuang, Ye; Zu, Guangyue; Zhang, Kunchi; Cao, Yi; Pei, Renjun

2018-06-01

Magnetic resonance imaging is a powerful diagnostic technology with high spatial resolution and non-invasion. The contrast agents have significant effect on the resolution of the MR imaging. However, the commercial contrast agents (CAs) usually consist of individual Gd3+ chelated with a low molecular weight acyclic or cyclic ligand, and these small-molecule CAs are usually subjected to nonspecificity, thus leading to rapid renal clearance and modest contrast enhancement for tumor imaging. In recent years, the nanostructured materials conjugated with aptamers were widely used and opened a new door in biomedical imaging due to excellent specificity, non-immunogenicity, easily synthesis and chemical modification of aptamers. This review summarizes all kinds of aptamertargeted MRI CAs and their applications.

An ABC Transporter System of Yersinia pestis Allows Utilization of Chelated Iron by Escherichia coli SAB11

PubMed Central

Bearden, Scott W.; Staggs, Teanna M.; Perry, Robert D.

1998-01-01

The acquisition of iron is an essential component in the pathogenesis of Yersinia pestis, the agent of bubonic and pneumonic plague. A cosmid library derived from the genomic DNA of Y. pestis KIM6+ was used for transduction of an Escherichia coli mutant (SAB11) defective in the biosynthesis of the siderophore enterobactin. Recombinant plasmids which had a common 13-kb BamHI fragment were isolated from SAB11 transductants in which growth but not enterobactin synthesis was restored on media containing the iron chelator EDDA [ethylenediamine-di(o-hydroxyphenyl acetic acid)]. Subcloning and transposon mutagenesis revealed a 5.6-kb region, designated yfe, essential for SAB11 growth stimulation. In vitro transcription-translation analysis identified polypeptides of 18, 29.5, 32, and 33 kDa encoded by the yfe locus. Sequence analysis shows this locus to be comprised of five genes in two separate operons which have potential Fur-binding sequences in both promoters. A putative polycistronic operon, yfeABCD, is Fur regulated and responds to iron and manganese. A functional Fur protein is required for the observed manganese repression of this operon. This operon encodes polypeptides which have strong similarity to the ATP-binding cassette (ABC) family of transporters and include a periplasmic binding protein (YfeA), an ATP-binding protein (YfeB), and two integral membrane proteins (YfeC and -D), which likely function in the acquisition of inorganic iron and possibly other ions. The ∼21-kDa protein encoded by the separately transcribed yfeE gene may be located in the cell envelope, since a yfeE::TnphoA fusion is PhoA+. Mutations in this gene abrogate growth of SAB11 on iron-chelated media. PMID:9495751

An ABC transporter system of Yersinia pestis allows utilization of chelated iron by Escherichia coli SAB11.

PubMed

Bearden, S W; Staggs, T M; Perry, R D

1998-03-01

The acquisition of iron is an essential component in the pathogenesis of Yersinia pestis, the agent of bubonic and pneumonic plague. A cosmid library derived from the genomic DNA of Y. pestis KIM6+ was used for transduction of an Escherichia coli mutant (SAB11) defective in the biosynthesis of the siderophore enterobactin. Recombinant plasmids which had a common 13-kb BamHI fragment were isolated from SAB11 transductants in which growth but not enterobactin synthesis was restored on media containing the iron chelator EDDA [ethylenediamine-di(o-hydroxyphenyl acetic acid)]. Subcloning and transposon mutagenesis revealed a 5.6-kb region, designated yfe, essential for SAB11 growth stimulation. In vitro transcription-translation analysis identified polypeptides of 18, 29.5, 32, and 33 kDa encoded by the yfe locus. Sequence analysis shows this locus to be comprised of five genes in two separate operons which have potential Fur-binding sequences in both promoters. A putative polycistronic operon, yfeABCD, is Fur regulated and responds to iron and manganese. A functional Fur protein is required for the observed manganese repression of this operon. This operon encodes polypeptides which have strong similarity to the ATP-binding cassette (ABC) family of transporters and include a periplasmic binding protein (YfeA), an ATP-binding protein (YfeB), and two integral membrane proteins (YfeC and -D), which likely function in the acquisition of inorganic iron and possibly other ions. The approximately 21-kDa protein encoded by the separately transcribed yfeE gene may be located in the cell envelope, since a yfeE::TnphoA fusion is PhoA+. Mutations in this gene abrogate growth of SAB11 on iron-chelated media.

Microreactor and method for preparing a radiolabeled complex or a biomolecule conjugate

DOEpatents

Reichert, David E; Kenis, Paul J. A.; Wheeler, Tobias D; Desai, Amit V; Zeng, Dexing; Onal, Birce C

2015-03-17

A microreactor for preparing a radiolabeled complex or a biomolecule conjugate comprises a microchannel for fluid flow, where the microchannel comprises a mixing portion comprising one or more passive mixing elements, and a reservoir for incubating a mixed fluid. The reservoir is in fluid communication with the microchannel and is disposed downstream of the mixing portion. A method of preparing a radiolabeled complex includes flowing a radiometal solution comprising a metallic radionuclide through a downstream mixing portion of a microchannel, where the downstream mixing portion includes one or more passive mixing elements, and flowing a ligand solution comprising a bifunctional chelator through the downstream mixing portion. The ligand solution and the radiometal solution are passively mixed while in the downstream mixing portion to initiate a chelation reaction between the metallic radionuclide and the bifunctional chelator. The chelation reaction is completed to form a radiolabeled complex.

Curcumin derivatives as metal-chelating agents with potential multifunctional activity for pharmaceutical applications.

PubMed

Ferrari, Erika; Benassi, Rois; Sacchi, Stefania; Pignedoli, Francesca; Asti, Mattia; Saladini, Monica

2014-10-01

Curcuminoids represent new perspectives for the development of novel therapeutics for Alzheimer's disease (AD), one probable mechanism of action is related to their metal complexing ability. In this work we examined the metal complexing ability of substituted curcuminoids to propose new chelating molecules with biological properties comparable with curcumin but with improved stability as new potential AD therapeutic agents. The K2T derivatives originate from the insertion of a -CH2COOC(CH3)3 group on the central atom of the diketonic moiety of curcumin. They retain the diketo-ketoenol tautomerism which is solvent dependent. In aqueous solution the prevalent form is the diketo one but the addition of metal ion (Ga(3+), Cu(2+)) causes the dissociation of the enolic proton creating chelate complexes and shifting the tautomeric equilibrium towards the keto-enol form. The formation of metal complexes is followed by both NMR and UV-vis spectroscopy. The density functional theory (DFT) calculations on K2T21 complexes with Ga(3+) and Cu(2+) are performed and compared with those on curcumin complexes. [Ga(K2T21)2(H2O)2](+) was found more stable than curcumin one. Good agreement is detected between calculated and experimental (1)H and (13)C NMR data. The calculated OH bond dissociation energy (BDE) and the OH proton dissociation enthalpy (PDE), allowed to predict the radical scavenging ability of the metal ion complexed with K2T21, while the calculated electronic affinity (EA) and ionization potential (IP) represent yardsticks of antioxidant properties. Eventually theoretical calculations suggest that the proton-transfer-associated superoxide-scavenging activity is enhanced after binding metal ions, and that Ga(3+) complexes display possible superoxide dismutase (SOD)-like activity. Copyright © 2014 Elsevier Inc. All rights reserved.

Antibody-dendrimer conjugates: the number, not the size of the dendrimers, determines the immunoreactivity.

PubMed

Wängler, C; Moldenhauer, G; Eisenhut, M; Haberkorn, U; Mier, W

2008-04-01

Radioimmunotherapy using antibodies with favorable tumor targeting properties and high binding affinity is increasingly applied in cancer therapy. The potential of this valuable cancer treatment modality could be further improved by increasing the specific activity of the labeled proteins. This can be done either by coupling a large number of chelators which leads to a decreased immunoreactivity or by conjugating a small number of multimeric chelators. In order to systematically investigate the influence of conjugations on immunoreactivity with respect to size and number of the conjugates, the anti-EGFR antibody hMAb425 was reacted with PAMAM dendrimers of different size containing up to 128 chelating agents per conjugation site. An improved dendrimer synthesis protocol was established to obtain compounds of high homogeneity suitable for the formation of defined protein conjugates. The quantitative derivatization of the PAMAM dendrimers with DOTA moieties and the characterization of the products by isotopic dilution titration using (111)In/(nat)In are shown. The DOTA-containing dendrimers were conjugated with high efficiency to hMAb425 by applying Sulfo-SMCC as cross-linking agent and a 10- to 25-fold excess of the thiol-containing dendrimers. The determination of the immunoreactivities of the antibody-dendrimer conjugates by FACS analysis revealed a median retained immunoreactivity of 62.3% for 1.7 derivatization sites per antibody molecule, 55.4% for 2.8, 27.9% for 5.3, and 17.1% for 10.0 derivatization sites per antibody but no significant differences in immunoreactivity for different dendrimer sizes. These results show that the dendrimer size does not influence the immunoreactivity of the derivatized antibody significantly over a wide molecular weight range, whereas the number of derivatization sites has a crucial effect.

Lanthanide Oleates: Chelation, Self-assembly, and Exemplification of Ordered Nanostructured Colloidal Contrast Agents for Medical Imaging

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Guozhen; Conn, Charlotte E.; Drummond, Calum J.

2010-01-12

Eight lanthanide(III) oleates have been prepared and characterized. The chelation and self-assembly structures of these rare-earth oleates have been studied by elemental analysis, Fourier transfer infrared spectroscopy (FTIR), and X-ray powder diffraction (XRD) analysis. Elemental analysis and FTIR results indicate that three oleate anions are complexed with one lanthanide cation and, with the exception of anhydrous cerium(III) oleate, form either a mono- or a hemihydrate. The X-ray analysis showed that the neat lanthanide soaps have a lamellar bilayer structure at room temperature. The thermal behavior has been investigated by cross-polarized optical microscopy (POM), differential scanning calorimetry (DSC), and thermogravimetric analysismore » (TGA). POM scans showed that all the lanthanide oleates form a lamellar phase in the presence of excess water. Small-angle X-ray scattering (SAXS) and XRD were used to investigate the internal structure of the bulk lanthanide oleates in excess water, and these X-ray results confirmed that the lanthanide oleates do not swell in water. Select lanthanide oleates were dispersed in water to form nonswelling lamellar submicrometer particles, confirmed by dynamic light scattering (DLS) and synchrotron SAXS measurements. NMR results indicated that colloidal dispersions of lanthanide oleates containing paramagnetic ions, such as gadolinium(III), terbium(III), and dysprosium(III), have a significant effect on the longitudinal (T{sub 1}) and transverse (T{sub 2}) relaxation times of protons in water. Time-resolved fluorescence measurements have demonstrated that colloidal dispersions of europium(III) oleate exhibit strong luminescence. The rare earth metal soaps exemplify the potential of self-assembled chelating amphiphiles as contrast agents in medical imaging modalities such as magnetic resonance imaging (MRI) and fluorescence imaging.« less

Compliance assessed by the Medication Event Monitoring System.

PubMed Central

Olivieri, N F; Matsui, D; Hermann, C; Koren, G

1991-01-01

The accurate assessment of patient compliance is especially crucial in evaluating the efficacy of a new treatment. Because of the problems associated with parenteral desferrioxamine, the development of a safe, effective, and convenient iron chelator is of high priority. The high morbidity and mortality associated with iron overload requires careful evaluation of the ability of any new agent to promote long term effective iron chelation. Patients' compliance with an orally available chelating agent, 1,2,-dimethyl-3-hydroxypyrid-4-one (L1), that has been demonstrated to induce in vivo iron excretion equivalent to that of desferrioxamine during supervised short term administration, was examined. Compliance was assessed in seven patients by patient interview, by daily diaries reviewed monthly with each patient, and with the use of the Medication Event Monitoring System (MEMS) standard pill bottles with microprocessors in the cap that record the timing and frequency of bottle openings. L1 was dispensed in MEMS containers to the patients, who, unaware of their significance, recorded compliance using a daily diary. Overall compliance rate (% of prescribed doses taken) measured by MEMS was 88.7 +/- 6.8%. When 'doubling of doses' was accounted for, significantly poorer compliance with L1 was noted by MEMS (91.7 +/- 7.4%) than by patients' diaries (95.7 +/- 5.2%). There was no significant difference in patient compliance recorded between the first and last 30 day period of drug administration. MEMS can eliminate the confounding variable of erratic patient compliance in the evaluation of a new drug's efficacy. As MEMS cannot distinguish a missed dose from one doubled at the next bottle opening, the use of patient diaries is a useful adjunct to the accurate assessment of compliance and should be combined with the use of MEMS. PMID:1776885

Evaluation and treatment of transfusional iron overload in children.

PubMed

Ware, Hannah M; Kwiatkowski, Janet L

2013-12-01

Red blood cell transfusions are increasingly used in the management of various anemias, including thalassemia and sickle cell disease. Because the body lacks physiologic mechanisms for removing excess iron, transfusional iron overload is a common complication in children receiving regular transfusions. Iron chelation is necessary to remove the excess iron that causes injury to the heart, liver, and endocrine organs. Three chelators, deferoxamine, deferasirox, and deferiprone, are currently available in the United States. When choosing a chelator regimen, patients, parents, and providers may consider a variety of factors, including the severity of iron overload, administration schedule, and adverse effect profile. Copyright © 2013 Elsevier Inc. All rights reserved.

Nuclear and radiological terrorism: continuing education article.

PubMed

Anderson, Peter D; Bokor, Gyula

2013-06-01

Terrorism involving radioactive materials includes improvised nuclear devices, radiation exposure devices, contamination of food sources, radiation dispersal devices, or an attack on a nuclear power plant or a facility/vehicle that houses radioactive materials. Ionizing radiation removes electrons from atoms and changes the valence of the electrons enabling chemical reactions with elements that normally do not occur. Ionizing radiation includes alpha rays, beta rays, gamma rays, and neutron radiation. The effects of radiation consist of stochastic and deterministic effects. Cancer is the typical example of a stochastic effect of radiation. Deterministic effects include acute radiation syndrome (ARS). The hallmarks of ARS are damage to the skin, gastrointestinal tract, hematopoietic tissue, and in severe cases the neurovascular structures. Radiation produces psychological effects in addition to physiological effects. Radioisotopes relevant to terrorism include titrium, americium 241, cesium 137, cobalt 60, iodine 131, plutonium 238, califormium 252, iridium 192, uranium 235, and strontium 90. Medications used for treating a radiation exposure include antiemetics, colony-stimulating factors, antibiotics, electrolytes, potassium iodine, and chelating agents.

In Vitro Inhibition of Leishmania Attachment to Sandfly Midguts and LL-5 Cells by Divalent Metal Chelators, Anti-gp63 and Phosphoglycans.

PubMed

Soares, Rodrigo Pedro; Altoé, Ellen Cristina Félix; Ennes-Vidal, Vítor; da Costa, Simone M; Rangel, Elizabeth Ferreira; de Souza, Nataly Araújo; da Silva, Vanderlei Campos; Volf, Petr; d'Avila-Levy, Claudia Masini

2017-07-01

Leishmania braziliensis and Leishmania infantum are the causative agents of cutaneous and visceral leishmaniasis, respectively. Several aspects of the vector-parasite interaction involving gp63 and phosphoglycans have been individually assayed in different studies. However, their role under the same experimental conditions was not studied yet. Here, the roles of divalent metal chelators, anti-gp63 antibodies and purified type I phosphoglycans (PGs) were evaluated during in vitro parasite attachment to the midgut of the vector. Parasites were treated with divalent metal chelators or anti-gp63 antibodies prior to the interaction with Lutzomyia longipalpis/Lutzomyia intermedia midguts or sand fly LL-5 cells. In vitro binding system was used to examine the role of PG and gp63 in parallel. Treatment with divalent metal chelators reduced Le. infantum adhesion to the Lu. longipalpis midguts. The most effective compound (Phen) inhibited the binding in both vectors. Similar results were observed in the interaction between both Leishmania species and the cell line LL-5. Finally, parallel experiments using anti-gp63-treated parasites and PG-incubated midguts demonstrated that both approaches substantially inhibited attachment in the natural parasite-vector pairs Le. infantum/Lu. longipalpis and Le. braziliensis/Lu. intermedia. Our results suggest that gp63 and/or PG are involved in parasite attachment to the midgut of these important vectors. Copyright © 2017 Elsevier GmbH. All rights reserved.

Potassium fulvate-modified graft copolymer of acrylic acid onto cellulose as efficient chelating polymeric sorbent.

PubMed

Mohamed, Magdy F; Essawy, Hisham A; Ammar, Nabila S; Ibrahim, Hanan S

2017-01-01

Acrylic acid (AA) was graft copolymerized from cellulose (Cell) in presence of potassium fulvate (KF) in order to enhance the chemical activity of the resulting chelating polymer and the handling as well. Fourier transform infrared (FTIR) proved that KF was efficiently inserted and became a permanent part of the network structure of the sorbent in parallel during the grafting copolymerization. Scanning electron microscopy (SEM) revealed intact homogeneous structure with uniform surface. This indicates improvement of the handling, however, it was not the case for the graft copolymer of acrylic acid onto cellulose in absence of KF, which is known to be brittle and lacks mechanical integrity. Effective insertion of this co-interpenetrating agent provided more functional groups, such as OH and COOH, which improved the chelating power of the produced sorbent as found for the removal of Cu 2+ ions from its aqueous solutions (the removal efficiency reached ∼98.9%). Different models were used to express the experimental data. The results corroborated conformity of the pseudo-second order kinetic model and Langmuir isotherm model to the sorption process, which translates into dominance of the chemisorption. Regeneration of the chelating polymers under harsh conditions did not affect the efficiency of copper ions uptake up to three successive cycles. A thermodynamic investigation ensured exothermic nature of the adsorption process that became less favourable at higher temperatures. Copyright © 2016 Elsevier B.V. All rights reserved.

Structure and in vitro activities of a Copper II-chelating anionic peptide from the venom of the scorpion Tityus stigmurus.

PubMed

Melo, Menilla M A; Daniele-Silva, Alessandra; Teixeira, Diego G; Estrela, Andréia B; Melo, Karolline R T; Oliveira, Verônica S; Rocha, Hugo A O; Ferreira, Leandro de Santis; Pontes, Daniel L; Lima, João P M S; Silva-Júnior, Arnóbio A; Barbosa, Euzebio G; Carvalho, Eneas; Fernandes-Pedrosa, Matheus F

2017-08-01

Anionic Peptides are molecules rich in aspartic acid (Asp) and/or glutamic acid (Glu) residues in the primary structure. This work presents, for the first time, structural characterization and biological activity assays of an anionic peptide from the venom of the scorpion Tityus stigmurus, named TanP. The three-dimensional structure of TanP was obtained by computational modeling and refined by molecular dynamic (MD) simulations. Furthermore, we have performed circular dichroism (CD) analysis to predict TanP secondary structure, and UV-vis spectroscopy to evaluate its chelating activity. CD indicated predominance of random coil conformation in aqueous medium, as well as changes in structure depending on pH and temperature. TanP has chelating activity on copper ions, which modified the peptide's secondary structure. These results were corroborated by MD data. The molar ratio of binding (TanP:copper) depends on the concentration of peptide: at lower TanP concentration, the molar ratio was 1:5 (TanP:Cu 2+ ), whereas in concentrated TanP solution, the molar ratio was 1:3 (TanP:Cu 2+ ). TanP was not cytotoxic to non-neoplastic or cancer cell lines, and showed an ability to inhibit the in vitro release of nitric oxide by LPS-stimulated macrophages. Altogether, the results suggest TanP is a promising peptide for therapeutic application as a chelating agent. Copyright © 2017 Elsevier Inc. All rights reserved.

Evaluation of the chelating performance of biopolyelectrolyte green complexes (NIBPEGCs) for wastewater treatment from the metal finishing industry.

PubMed

López-Maldonado, Eduardo A; Zavala García, Oscar Gabriel; Escobedo, Kevin Cruz; Oropeza-Guzman, Mercedes T

2017-08-05

In this paper nonstoichiometric interbiopolyelectrolyte green complexes (NIBPEGCs) were prepared using chitosan (Ch), alginate (AG) and poly(acrylic acid)(PAA). They are proposed as innovative formulations (polyelectrolytes and chelating agents) suitable for the elimination heavy metals contained in wastewater. This application may represent an integral solution for industries rejecting solid and aqueous metallic materials; however, it has not been previously reported. NIBPEGCs physicochemical performance was evaluated based on pH, particle size, surface charge, isoelectric point, dose, coagulation-flocculation kinetics and chemical affinity with seven metal ions. The experimental results showed that NIBPEGCs composed by AG/Ch and PAA/Chitosan have all the three complementary functions: chemical affinity, electrostatic interaction and particle entrapment anticipating more simple operation units to remove heavy metals. Complexes of AG/Ch (negative) were higher performance in removing heavy metals, with a dose window (150-180mg/L), lower dose of 410mg/L PAA/Ch (negative). Investigation of chelating performances of NIBPEGCs show that the efficiency of metal removal is: Ca˃Cr˃Cu˃Pb˃Ni˃Zn˃Cd. Transmittance vs time profiles, metals and zeta potential analysis showed that chelation capacity is the crucial factor to ensure metallic species removal, followed by physical entrapment of the metallic colloids. Integrating all presented results allow to sustain the development of excellent metals removal formulations. Copyright © 2017 Elsevier B.V. All rights reserved.

Characterization of the activity of L-ascorbic acid 2-[3,4-dihydro-2,5,7,8-tetramethyl-2-(4,8,12-trimethyltridecyl)-2H-1-be nzopyran-6-yl-hydrogen phosphate] potassium salt in hydroxyl radical elimination.

PubMed

Tomita, T; Kashima, M; Tsujimoto, Y

2000-03-01

The effect of L-ascorbic acid 2-[3,4-dihydro-2,5,7,8-tetramethyl-2-(4,8,12-trimethyltridecyl)-2H -1-benzopyran-6-yl-hydrogen phosphate] potassium salt (EPC-K1) on hydroxyl radical (*OH) elimination was studied using electron spin resonance (ESR) and spectrophotometric experiments. The addition of EPC-K, and *OH scavengers eliminated the *OH generated from Cu2+/H2O2, Fe2+/H2O2 and H2O2/UV-irradiation reaction systems. However, in competitive reactions using different concentrations of a spin-trap agent, the addition of the *OH scavenger altered the IC50 values, whereas the addition of EPC-K1 and a metal chelater did not change the value in the Cu2+/H2O2 and Fe2+/H2O2 reaction systems. The addition of EPC-K1 and metal chelater changed the ESR signal for free Cu2+. The spectrophotometric experiments confirmed that the addition of EPC-K1 and metal chelater altered the absorption spectra due to CuCl2 and FeSO4, whereas the *OH scavenger did not alter the spectra. Therefore, it was demonstrated that EPC-K, has the ability both to scavenge *OH directly and to inhibit the generation of *OH by the chelation of Cu2+ and Fe2+.

Relaxivity enhancement of aquated Tris(β-diketonate)gadolinium(III) chelates by confinement within ultrashort single-walled carbon nanotubes.

PubMed

Law, Justin J; Guven, Adem; Wilson, Lon J

2014-01-01

Ultrashort single-walled carbon nanotubes loaded with gadolinium ions (gadonanotubes) have been previously shown to exhibit extremely high T1 -weighted relaxivities (>100 mm(-1) s(-1) ). To further examine the effect of nanoconfinement on the relaxivity of gadolinium-based contrast agents for magnetic resonance imaging, a series of ultrashort single-walled carbon nanotube (US-tube) materials internally loaded with gadolinium chelates have been prepared and studied. US-tubes were loaded with Gd(acac)3  · 2H2 O, Gd(hfac)3  · 2H2 O, and Gd(thd)3 (acac = acetylacetone, hfac = hexafluoroacetylacetone, thd = tetramethylheptanedione). The longitudinal relaxivities of the prepared materials determined at 25°C in a 1.5 T field were 103 mm(-1) s(-1) for Gd(acac)3  · 2H2 O@US-tubes, 105 mm(-1) s(-1) for Gd(hfac)3  · 2H2 O@US-tubes and 26 mm(-1) s(-1) for Gd(thd)3 @US-tubes. Compared with the relaxivities obtained for the unloaded chelates (<10 mm(-1) s(-1) ) as well as accounting for the T1 reduction observed for the empty US-tubes, the boost in relaxivity for chelate-loaded US-tubes is attributed to confinement within the nanotube and depends on the number of coordinated water molecules. Copyright © 2014 John Wiley & Sons, Ltd.

"Off-the-Shelf" K2-EDTA for Calcific Band Keratopathy.

PubMed

Lee, Marco E; Ouano, Dean P; Shapiro, Brett; Fong, Andrew; Coroneo, Minas T

2018-07-01

To explore the effectiveness of "off-the-shelf" dipotassium-ethylenediaminetetraacetic acid (K2-EDTA) as an alternative to sodium EDTA as chelation therapy in removal of calcific band keratopathy (CBK). This study was a retrospective case series involving 4 patients with CBK who underwent superficial keratectomy and subsequent chelation therapy with K2-EDTA in a single center (Coastal Eye Clinic) by the same surgeon. Visual acuity and symptomatic relief were the main outcomes measured in our study. All 4 participants in this study were female with an average age of 80.3 years. Three of the patients with reasonable baseline visual acuity experienced improved visual acuity at 1 month. The other patient with multiple ocular comorbidities and severely reduced visual potential reported symptomatic pain relief at 1-month follow-up after the intervention. K2-EDTA seems to be an effective alternative to disodium EDTA in its ability to clear calcific plaques and restore visual function. Because of the logistical difficulties associated with acquiring disodium EDTA, and the relative abundance of K2-EDTA in health-care facilities, we believe that our findings warrant further investigation into its use as a more accessible and cost-effective chelating agent in CBK.

Modelling dimercaptosuccinic acid (DMSA) plasma kinetics in humans.

PubMed

van Eijkeren, Jan C H; Olie, J Daniël N; Bradberry, Sally M; Vale, J Allister; de Vries, Irma; Meulenbelt, Jan; Hunault, Claudine C

2016-11-01

No kinetic models presently exist which simulate the effect of chelation therapy on lead blood concentrations in lead poisoning. Our aim was to develop a kinetic model that describes the kinetics of dimercaptosuccinic acid (DMSA; succimer), a commonly used chelating agent, that could be used in developing a lead chelating model. This was a kinetic modelling study. We used a two-compartment model, with a non-systemic gastrointestinal compartment (gut lumen) and the whole body as one systemic compartment. The only data available from the literature were used to calibrate the unknown model parameters. The calibrated model was then validated by comparing its predictions with measured data from three different experimental human studies. The model predicted total DMSA plasma and urine concentrations measured in three healthy volunteers after ingestion of DMSA 10 mg/kg. The model was then validated by using data from three other published studies; it predicted concentrations within a factor of two, representing inter-human variability. A simple kinetic model simulating the kinetics of DMSA in humans has been developed and validated. The interest of this model lies in the future potential to use it to predict blood lead concentrations in lead-poisoned patients treated with DMSA.

Supportive therapies for prevention of hepatocellular carcinoma recurrence and preservation of liver function

PubMed Central

Takami, Taro; Yamasaki, Takahiro; Saeki, Issei; Matsumoto, Toshihiko; Suehiro, Yutaka; Sakaida, Isao

2016-01-01

Hepatocellular carcinoma (HCC) is one of the deadliest cancers in the world and is associated with a high risk of recurrence. The development of a wide range of new therapies is therefore essential. In this study, from the perspective of supportive therapy for the prevention of HCC recurrence and preservation of liver function in HCC patients, we surveyed a variety of different therapeutic agents. We show that branched chain amino acids (BCAA) supplementation and late evening snack with BCAA, strategies that address issues of protein-energy malnutrition, are important for liver cirrhotic patients with HCC. For chemoprevention of HCC recurrence, we show that viral control after radical treatment is important. We also reviewed the therapeutic potential of antiviral drugs, sorafenib, peretinoin, iron chelators. Sorafenib is a kinase inhibitor and a standard therapy in the treatment of advanced HCC. Peretinoin is a vitamin A-like molecule that targets the retinoid nuclear receptor to induce apoptosis and inhibit tumor growth in HCC cells. Iron chelators, such as deferoxamine and deferasirox, act to prevent cancer cell growth. These chelators may have potential as combination therapies in conjunction with peretinoin. Finally, we review the potential inhibitory effect of bone marrow cells on hepatocarcinogenesis. PMID:27621572

Removal of heavy metal species from industrial sludge with the aid of biodegradable iminodisuccinic acid as the chelating ligand.

PubMed

Wu, Qing; Duan, Gaoqi; Cui, Yanrui; Sun, Jianhui

2015-01-01

High level of heavy metals in industrial sludge was the obstacle of sludge disposal and resource recycling. In this study, iminodisuccinic acid (IDS), a biodegradable chelating ligand, was used to remove heavy metals from industrial sludge generated from battery industry. The extraction of cadmium, copper, nickel, and zinc from battery sludge with aqueous solution of IDS was studied under various conditions. It was found that removal efficiency greatly depends on pH, chelating agent's concentration, as well as species distribution of metals. The results showed that mildly acidic and neutral systems were not beneficial to remove cadmium. About 68 % of cadmium in the sample was extracted at the molar ratio of IDS to heavy metals 7:1 without pH adjustment (pH 11.5). Copper of 91.3 % and nickel of 90.7 % could be removed by IDS (molar ratio, IDS: metals = 1:1) with 1.2 % phosphoric acid effectively. Removal efficiency of zinc was very low throughout the experiment. Based on the experimental results, IDS could be a potentially useful chelant for heavy metal removal from battery industry sludge.

Non-invasive magnetic resonance imaging follow-up of sono-sensitive liposome tumor delivery and controlled release after high-intensity focused ultrasound.

PubMed

Fowler, Robert Andrew; Fossheim, Sigrid L; Mestas, Jean-Louis; Ngo, Jacqueline; Canet-Soulas, Emmanuelle; Lafon, Cyril

2013-12-01

This work examines the use of lanthanide-based contrast agents and magnetic resonance imaging in monitoring liposomal behavior in vivo. Dysprosium (Dy) and gadolinium (Gd) chelates, Dy-diethylenetriaminepentaacetic acid bismethylamide (Dy-DTPA-BMA) and Gd-DTPA-BMA, were encapsulated in pegylated distearoylphosphatidylethanolamine-based (saturated) liposomes, and then intravenously injected into Copenhagen rats with subcutaneous Dunning AT2 xenografts. Liposome-encapsulated Dy chelate shortens transverse relaxation times (T(2) and T(2)*) of tissue; thus, liposomal accumulation in the tumor can be monitored by observing the decrease in T(2)* relaxation time over time. The tumor was treated at the time of maximum liposomal accumulation (48 h) with confocal, cavitating high-intensity focused ultrasound to induce liposomal payload release. Using liposome-encapsulated Gd chelate at high enough concentrations and saturated liposomal phospholipids induces an exchange-limited longitudinal (T(1)) relaxation when the liposomes are intact; when the liposomes are released, exchange limitation is relieved, thus allowing in vivo observation of payload release as a decrease in tumor T(1). Copyright © 2013 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Setting up an emergency stock for metabolic diseases.

PubMed

Fernandez-Llamazares, C M; Serrano, M L; Manrique-Rodríguez, S; Sanjurjo-Sáez, M

2010-01-01

Therapeutic management of inborn errors of metabolism (IEMs) is complicated. The drugs involved are classified as orphan, and their supply depends on whether they are orphan medicines, investigational drugs, or need to be prepared as a compounded formula. We analyzed emergency criteria, availability, and permanent location of metabolic drugs within the hospital. Information on therapeutic usage, administration, and dosage was also recorded. A stock for treating IEMs should include chelating agents, drugs to treat deficiencies, enzyme supplements, and other specific treatments. Hyperammonemia was considered to be life-threatening; therefore, an emergency supply of drugs to treat this condition should be kept permanently in the hospitalization unit. Emergency drug stocks are highly recommended in tertiary hospitals in order to improve care for patients susceptible to IEM.

On the Anticataractogenic Effects of L-Carnosine: Is It Best Described as an Antioxidant, Metal-Chelating Agent or Glycation Inhibitor?

PubMed Central

Alany, Raid G.

2016-01-01

Purpose. L-Carnosine is a naturally occurring dipeptide which recently gained popularity as an anticataractogenic agent due to its purported antioxidant activities. There is a paucity of research and conclusive evidence to support such claims. This work offers compelling data that help clarify the mechanism(s) behind the anticataract properties of L-carnosine. Methods. Direct in vitro antioxidant free radical scavenging properties were assayed using three different antioxidant (TEAC, CUPRAC, and DPPH) assays. Indirect in vitro and ex vivo antioxidant assays were studied by measuring glutathione bleaching capacity and total sulfhydryl (SH) capacity of bovine lens homogenates as well as hydrogen-peroxide-stress assay using human lens epithelial cells. Whole porcine lenses were incubated in high galactose media to study the anticataract effects of L-carnosine. MTT cytotoxicity assays were conducted on human lens epithelial cells. Results. The results showed that L-carnosine is a highly potent antiglycating agent but with weak metal chelating and antioxidant properties. There were no significant decreases in lens epithelial cell viability compared to negative controls. Whole porcine lenses incubated in high galactose media and treated with 20 mM L-carnosine showed a dramatic inhibition of advanced glycation end product formation as evidenced by NBT and boronate affinity chromatography assays. Conclusion. L-Carnosine offers prospects for investigating new methods of treatment for diabetic cataract and any diseases that are caused by glycation. PMID:27822337

Production, Labeling and In Vivo Studies with the Theranostic Positron-Emitting Radiometals 44Sc, 55/58m/58gCo, 61/64Cu, 86Y and 69Ge =

NASA Astrophysics Data System (ADS)

Valdovinos, Hector Francisco

In this dissertation, novel radiochemical separation methods for these radiometals that satisfy such requirements are presented, including a detailed characterization of the separated radionuclide in terms of radionuclidic purity, specific activity and spatial resolution in a small animal PET scanner. This dissertation also presents novel targetry and radiochemical separation methods for the production of less conventional radiometals that constitute "theranostic" (therapeutic and diagnostic) pairs, namely the Auger electron emitters 58mCo and 71Ge and their positron emitting complements 55Co and 69Ge. The theranostic potential of each radiometal is demonstrated first by collecting biodistribution data from PET imaging of tumor-bearing mice intravenously injected with radiolabeled agents, followed by internal dosimetry calculations focusing on the therapeutic and radiotoxic implications caused by the agent. Special attention is given to the radionuclides with intrinsic theranostic properties in themselves: 64Cu and the parent-daughter pair 58m/58gCo. The radiolabeled agents that are employed include the radiometal by itself, that is, weakly bound to a simple ligand in solution (all radiometals), as well as strongly bound to a chelator-conjugated tumor-targeting antibody called TRC105 (55Co, 58mCo, 58gCo, 64Cu and 86Y) or incorporated into the structure of a super paramagnetic iron oxide nanoparticle (69Ge).

EDTA a novel inducer of pisatin, a phytoalexin indicator of the non-host resistance in peas.

PubMed

Hadwiger, Lee A; Tanaka, Kiwamu

2014-12-23

Pea pod endocarp suppresses the growth of an inappropriate fungus or non-pathogen by generating a "non-host resistance response" that completely suppresses growth of the challenging fungus within 6 h. Most of the components of this resistance response including pisatin production can be elicited by an extensive number of both biotic and abiotic inducers. Thus this phytoalexin serves as an indicator to be used in evaluating the chemical properties of inducers that can initiate the resistance response. Many of the pisatin inducers are reported to interact with DNA and potentially cause DNA damage. Here we propose that EDTA (ethylenediaminetetraacetic acid) is an elicitor to evoke non-host resistance in plants. EDTA is manufactured as a chelating agent, however at low concentration it is a strong elicitor, inducing the phytoalexin pisatin, cellular DNA damage and defense-responsive genes. It is capable of activating complete resistance in peas against a pea pathogen. Since there is also an accompanying fragmentation of pea DNA and alteration in the size of pea nuclei, the potential biochemical insult as a metal chelator may not be its primary action. The potential effects of EDTA on the structure of DNA within pea chromatin may assist the transcription of plant defense genes.

The biogeochemical fate of nickel during microbial ISA degradation; implications for nuclear waste disposal.

PubMed

Kuippers, Gina; Boothman, Christopher; Bagshaw, Heath; Ward, Michael; Beard, Rebecca; Bryan, Nicholas; Lloyd, Jonathan R

2018-06-08

Intermediate level radioactive waste (ILW) generally contains a heterogeneous range of organic and inorganic materials, of which some are encapsulated in cement. Of particular concern are cellulosic waste items, which will chemically degrade under the conditions predicted during waste disposal, forming significant quantities of isosaccharinic acid (ISA), a strongly chelating ligand. ISA therefore has the potential to increase the mobility of a wide range of radionuclides via complex formation, including Ni-63 and Ni-59. Although ISA is known to be metabolized by anaerobic microorganisms, the biodegradation of metal-ISA complexes remains unexplored. This study investigates the fate of a Ni-ISA complex in Fe(III)-reducing enrichment cultures at neutral pH, representative of a microbial community in the subsurface. After initial sorption of Ni onto Fe(III)oxyhydroxides, microbial ISA biodegradation resulted in >90% removal of the remaining Ni from solution when present at 0.1 mM, whereas higher concentrations of Ni proved toxic. The microbial consortium associated with ISA degradation was dominated by close relatives to Clostridia and Geobacter species. Nickel was preferentially immobilized with trace amounts of biogenic amorphous iron sulfides. This study highlights the potential for microbial activity to help remove chelating agents and radionuclides from the groundwater in the subsurface geosphere surrounding a geodisposal facility.

A Chelator-Free Multifunctional [64Cu]-CuS Nanoparticle Platform for Simultaneous Micro-PET/CT Imaging and Photothermal Ablation Therapy

PubMed Central

Zhou, Min; Zhang, Rui; Huang, Miao; Lu, Wei; Song, Shaoli; Melancon, Marites P.; Tian, Mei; Liang, Dong; Li, Chun

2010-01-01

We synthesized and evaluated a novel class of chelator-free [64Cu]-CuS nanoparticles (NPs) suitable for both PET imaging and as photothermal coupling agents for photothermal ablation. [64Cu]-CuS NPs were simple to make, possessed excellent stability, and allowed robust noninvasive micro-PET imaging. Furthermore, CuS NPs displayed strong absorption in the near-infrared (NIR) region (peak 930 nm), passive targeting prefers the tumor site, and mediated ablation of U87 tumor cells upon exposure to NIR light both in vitro and in vivo after either intratumoral or intravenous injection. The combination of small diameter (~11 nm diameter), strong NIR absorption, and integration of 64Cu as a structural component makes [64Cu]-CuS NPs ideally suited for multifunctional molecular imaging and therapy. PMID:20942456

Phytochelators Intended for Clinical Use in Iron Overload, Other Diseases of Iron Imbalance and Free Radical Pathology.

PubMed

Kontoghiorghe, Christina N; Kolnagou, Annita; Kontoghiorghes, George J

2015-11-23

Iron chelating drugs are primarily and widely used in the treatment of transfusional iron overload in thalassaemia and similar conditions. Recent in vivo and clinical studies have also shown that chelators, and in particular deferiprone, can be used effectively in many conditions involving free radical damage and pathology including neurodegenerative, renal, hepatic, cardiac conditions and cancer. Many classes of phytochelators (Greek: phyto (φυτό)-plant, chele (χηλή)-claw of the crab) with differing chelating properties, including plant polyphenols resembling chelating drugs, can be developed for clinical use. The phytochelators mimosine and tropolone have been identified to be orally active and effective in animal models for the treatment of iron overload and maltol for the treatment of iron deficiency anaemia. Many critical parameters are required for the development of phytochelators for clinical use including the characterization of the therapeutic targets, ADMET, identification of the therapeutic index and risk/benefit assessment by comparison to existing therapies. Phytochelators can be developed and used as main, alternative or adjuvant therapies including combination therapies with synthetic chelators for synergistic and or complimentary therapeutic effects. The development of phytochelators is a challenging area for the introduction of new pharmaceuticals which can be used in many diseases and also in ageing. The commercial and other considerations for such development have great advantages in comparison to synthetic drugs and could also benefit millions of patients in developing countries.

Method of forming catalyst layer by single step infiltration

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gerdes, Kirk; Lee, Shiwoo; Dowd, Regis

Provided herein is a method for electrocatalyst infiltration of a porous substrate, of particular use for preparation of a cathode for a solid oxide fuel cell. The method generally comprises preparing an electrocatalyst infiltrate solution comprising an electrocatalyst, surfactant, chelating agent, and a solvent; pretreating a porous mixed ionic-electric conductive substrate; and applying the electrocatalyst infiltration solution to the porous mixed ionic-electric conductive substrate.

Cyclohexyl EDTA monoanhydride

DOEpatents

Mease, Ronnie C.; Srivastava, Suresh C.

1991-01-01

The present invention relates to new rigid chelating structures, to methods for preparing these materials, and to their use in preparing radiometal labeled immunoconjugates. These new chelates include cyclohexyl EDTA monohydride, the transforms of cyclohexyl DTPA and TTHA and derivatives of these cyclohexyl polyaminocarboxylate materials.

Radiopharmaceutical stannic Sn-117m chelate compositions and methods of use

DOEpatents

Srivastava, Suresh C.; Meinken, George E.

2001-01-01

Radiopharmaceutical compositions including .sup.117m Sn labeled stannic (Sn.sup.4+) chelates are provided. The chelates are preferably polyhydroxycarboxylate, such as oxalates, tartrates, citrates, malonates, gluconates, glucoheptonates and the like. Methods of making .sup.117m Sn-labeled (Sn.sup.4+) polyhydroxycarboxylic chelates are also provided. The foregoing pharmaceutical compositions can be used in methods of preparing bone for scintigraphical analysis, for radiopharmaceutical skeletal imaging, treatment of pain resulting from metastatic bone involvement, treatment of primary bone cancer, treatment of cancer resulting from metastatic spread to bone from other primary cancers, treatment of pain resulting from rheumatoid arthritis, treatment of bone/joint disorders and to monitor radioactively the skeletal system.

Cyclohexyl EDTA monoanhydride

DOEpatents

Mease, R.C.; Srivastava, S.C.

1991-06-04

The present invention relates to new rigid chelating structures, to methods for preparing these materials, and to their use in preparing radiometal labeled immunoconjugates. These new chelates include cyclohexyl EDTA monohydride, the transforms of cyclohexyl DTPA and TTHA and derivatives of these cyclohexyl polyaminocarboxylate materials. No Drawings

Cyclohexyl-triethylenetetraamine hexacetic acid

DOEpatents

Mease, Ronnie C.; Srivastava, Suresh C.; Gestin, Jean-Francois

1992-01-01

The present invention relates to new rigid chelating structures, to methods for preparing these materials, and to their use in preparing radiometal labeled immunoconjugates. These new chelates include cyclohexyl EDTA monohydride, the trans forms of cyclohexyl DTPA and TTHA, and derivatives of these cyclohexyl polyaminocarboxylate materials.

Stable radiometal antibody immunoconjugates

DOEpatents

Mease, Ronnie C.; Srivastava, Suresh C.; Gestin, Jean-Francois

1994-01-01

The present invention relates to new rigid chelating structures, to methods for preparing these materials, and to their use in preparing radiometal labeled immunoconjugates. These new chelates include cyclohexyl EDTA monohydride, the trans forms of cyclohexyl DTPA and TTHA, and derivatives of these cyclohexyl polyaminocarboxylate materials.

Simple method for quantification of gadolinium magnetic resonance imaging contrast agents using ESR spectroscopy.

PubMed

Takeshita, Keizo; Kinoshita, Shota; Okazaki, Shoko

2012-01-01

To develop an estimation method of gadolinium magnetic resonance imaging (MRI) contrast agents, the effect of concentration of Gd compounds on the ESR spectrum of nitroxyl radical was examined. A solution of either 4-oxo-2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPONE) or 4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPOL) was mixed with a solution of Gd compound and the ESR spectrum was recorded. Increased concentration of gadolinium-diethylenetriamine pentaacetic acid chelate (Gd-DTPA), an MRI contrast agent, increased the peak-to-peak line widths of ESR spectra of the nitroxyl radicals, in accordance with a decrease of their signal heights. A linear relationship was observed between concentration of Gd-DTPA and line width of ESR signal, up to approximately 50 mmol/L Gd-DTPA, with a high correlation coefficient. Response of TEMPONE was 1.4-times higher than that of TEMPOL as evaluated from the slopes of the lines. The response was slightly different among Gd compounds; the slopes of calibration curves for acua[N,N-bis[2-[(carboxymethyl)[(methylcarbamoyl)methyl]amino]ethyl]glycinato(3-)]gadolinium hydrate (Gd-DTPA-BMA) (6.22 μT·L/mmol) and gadolinium-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid chelate (Gd-DOTA) (6.62 μT·L/mmol) were steeper than the slope for Gd-DTPA (5.45 μT·L/mmol), whereas the slope for gadolinium chloride (4.94 μT·L/mmol) was less steep than that for Gd-DTPA. This method is simple to apply. The results indicate that this method is useful for rough estimation of the concentration of Gd contrast agents if calibration is carried out with each standard compound. It was also found that the plot of the reciprocal square root of signal height against concentrations of contrast agents could be useful for the estimation if a constant volume of sample solution is taken and measured at the same position in the ESR cavity every time.

Relevant interactions of antimicrobial iron chelators and membrane models revealed by nuclear magnetic resonance and molecular dynamics simulations.

PubMed

Coimbra, João T S; Moniz, Tânia; Brás, Natércia F; Ivanova, Galya; Fernandes, Pedro A; Ramos, Maria J; Rangel, Maria

2014-12-18

The dynamics and interaction of 3-hydroxy-4-pyridinone fluorescent iron chelators, exhibiting antimicrobial properties, with biological membranes were evaluated through NMR and molecular dynamics simulations. Both NMR and MD simulation results support a strong interaction of the chelators with the lipid bilayers that seems to be strengthened for the rhodamine containing compounds, in particular for compounds that include ethyl groups and a thiourea link. For the latter type of compounds the interaction reaches the hydrophobic core of the lipid bilayer. The molecular docking and MD simulations performed for the potential interaction of the chelators with DC-SIGN receptors provide valuable information regarding the cellular uptake of these compounds since the results show that the fluorophore fragment of the molecular framework is essential for an efficient binding. Putting together our previous and present results, we put forward the hypothesis that all the studied fluorescent chelators have access to the cell, their uptake occurs through different pathways and their permeation properties correlate with a better access to the cell and its compartments and, consequently, with the chelators antimicrobial properties.