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Sample records for bifunctional chelator alternative

  1. Macrocyclic bifunctional chelating agents

    DOEpatents

    Meares, Claude F.; DeNardo, Sally J.; Cole, William C.; Mol, Min K.

    1987-01-01

    A copper chelate conjugate which is stable in human serum. The conjugate includes the copper chelate of a cyclic tetraaza di-, tri-, or tetra-acetic acid, a linker attached at one linker end to a ring carbon of the chelate, and a biomolecule joined at the other end of the linker. The conjugate, or the linker-copper chelate compound used in forming the conjugate, are designed for use in diagnostic and therapeutic applications which involve Cu(II) localization via the systemic route.

  2. Rigid bifunctional chelating agents

    DOEpatents

    Sweet, Mark P.; Mease, Ronnie C.; Srivastava, Suresh C.

    1998-07-21

    Bicyclo›2.2.2! octane-2,3 diamine-N,N,N',N'-tetraacetic acids (BODTA) and bicyclo›2.2.1! heptane-2,3 diamine-N,N,N',N'-tetraacetic acid (BHDTA) are chelating agents useful in forming detectably labeled bioconjugate compounds for diagnostic and therapeutic purposes. New compounds and processes of forming BODTA and BHDTA are disclosed. Radioimmunoconjugates of the present invention show high and prolonged tumor uptake with low normal tissue uptakes.

  3. Rigid bifunctional chelating agents

    DOEpatents

    Sweet, Mark P.; Mease, Ronnie C.; Srivastava, Suresh C.

    2000-02-08

    Bicyclo[2.2.2]octane-2,3 diamine-N,N,N',N'-tetraacetic acids (BODTA) and bicyclo[2.2.1]heptane-2,3 diamine-N,N,N',N'-tetraacetic acid (BHDTA) are chelating agents useful in forming detectably labeled bioconjugate compounds for diagnostic and therapeutic purposes. New compounds and processes of forming BODTA and BHDTA are disclosed. Radioimmunoconjugates of the present invention show high and prolonged tumor uptake with low normal tissue uptakes.

  4. Rigid bifunctional chelating agents

    DOEpatents

    Sweet, M.P.; Mease, R.C.; Srivastava, S.C.

    1998-07-21

    Bicyclo[2.2.2] octane-2,3 diamine-N,N,N`,N`-tetraacetic acids (BODTA) and bicyclo[2.2.1] heptane-2,3 diamine-N,N,N`,N`-tetraacetic acid (BHDTA) are chelating agents useful in forming detectably labeled bioconjugate compounds for diagnostic and therapeutic purposes. New compounds and processes of forming BODTA and BHDTA are disclosed. Radioimmunoconjugates of the present invention show high and prolonged tumor uptake with low normal tissue uptakes.

  5. Bifunctional Gallium-68 Chelators: Past, Present, and Future.

    PubMed

    Spang, Philipp; Herrmann, Christian; Roesch, Frank

    2016-09-01

    This article reviews the development of bifunctional chelates for synthesising (68)Ga radiopharmaceuticals. It structures the chelates into groups of macrocycles, nonmacrocycles, and chimeric derivatives. The most relevant bifunctional chelates are discussed in chelate structure, parameters of (68)Ga-labeling, and stability of the (68)Ga-chelate complexes. Furthermore those derivatives are included, where (67)Ga was applied instead of (68)Ga. A particular feature discussed is the ability of certain bifunctional chelate structures to function in kit-type preparation of the (68)Ga radiopharmaceuticals. Currently, nonmacrocyclic and chimeric derivates attract particular attention such as THP-derivates and DATA-derivates. PMID:27553464

  6. An enzymatic approach to bifunctional chelating agents.

    PubMed

    Minazzi, Paolo; Lattuada, Luciano; Menegotto, Ivan G; Giovenzana, Giovanni B

    2014-09-21

    Bifunctional chelating agents (BFCAs) combine the complexing properties of a multidentate ligand with the presence of a free reactive functional group, mainly devoted to conjugation purposes. Indeed, products obtained by conjugation of a BFCA to a biomolecule and coordination of a suitable metal ion are widely applied in medicine nowadays as diagnostic and therapeutic agents. BFCAs are generally prepared through multi-step syntheses and with extensive application of protection-deprotection strategies, due to the large number of functional groups involved. Hydrolytic enzymes, with their unique chemoselectivity, provided the best results in the preparation of three different BFCAs based on very useful and well known ligand platforms. PMID:25060174

  7. 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

  8. Bifunctional Chelates Optimized for Molecular MRI

    PubMed Central

    2015-01-01

    Important requirements for exogenous dyes or contrast agents in magnetic resonance imaging (MRI) include an effective concentration of paramagnetic or superparamagnetic ions at the target to be imaged. We report the concise synthesis and characterization of several new enantiopure bifunctional derivatives of (α1R,α4R,α7R,α10R)-α1,α4,α7,α10-tetramethyl-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTMA) (and their 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) analogues as controls) that can be covalently attached to a contrast agent delivery system using either click or peptide coupling chemistry. Gd complexes of these derivatives can be attached to delivery systems while maintaining optimal water residence time for increased molecular imaging sensitivity. Long chain biotin (LC-biotin) derivatives of the Eu(III) and Gd(III) chelates associated with avidin are used to demonstrate higher efficiencies. Variable-temperature relaxometry, 17O NMR, and nuclear magnetic resonance dispersion (NMRD) spectroscopy used on the complexes and biotin–avidin adducts measure the influence of water residence time and rotational correlation time on constrained and unconstrained systems. The Gd(III)-DOTMA derivative has a shorter water residence time than the Gd(III)-DOTA derivative. Compared to the constrained Gd(III)-DOTA derivatives, the rotationally constrained Gd(III)-DOTMA derivative has ∼40% higher relaxivity at 37 °C, which could increase its sensitivity as an MRI agent as well as reduce the dose of the targeting agent. PMID:24933389

  9. Clickable bifunctional radiometal chelates for peptide labeling†

    PubMed Central

    Lebedev, Artem Y.; Holland, Jason P.; Lewis, Jason S.

    2016-01-01

    Novel synthetic methods for producing an array of chelates for use in “click”-radiolabeling of peptides are described, and their reactivity with regards to subsequent conjugation and radiolabeling is discussed. PMID:20177623

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

    SciTech Connect

    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).

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

    SciTech Connect

    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).

  12. 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.

  13. Bifunctional chelates of RH-105 and AU199 as potential radiotherapeutic agents

    SciTech Connect

    Droege, P.

    1997-03-01

    Research is presented on new bifunctional chelating ligand systems with stability on the macroscopic and radiochemical levels. The synthesis of the following complexes are described: rhodium 105, palladium 109, and gold 198.

  14. Liposomal Cu-64 labeling method using bifunctional chelators: polyethylene glycol spacer and chelator effects

    PubMed Central

    Seo, Jai Woong; Mahakian, Lisa M.; Kheirolomoom, Azadeh; Zhang, Hua; Meares, Claude F.; Ferdani, Riccardo; Anderson, Carolyn J.; Ferrara, Katherine W.

    2010-01-01

    Two bifunctional Cu-64 chelators (BFCs), (6-(6-(3-(2-pyridyldithio)propionamido)hexanamido)benzyl)-1,4,8,11-tetraazacyclotetradecane- 1,4,8,11-tetraacetic acid (TETA-PDP) and 4-(2-(2-pyridyldithioethyl)ethanamido)-11-carboxymethyl-1,4,8,11-tetraazabicyclo(6.6.2)hexadecane (CB-TE2A-PDEA), were synthesized and conjugated to long circulating liposomes (LCLs) via attachment to a maleimide lipid. An in vitro stability assay of 64Cu-TETA, 64Cu-TETA-PEG2k, and 64Cu-CB-TE2A-PEG2k liposomes showed that more than 86% of the radioactivity remains associated with the liposomal fraction after 48 hours of incubation with mouse serum. The in vivo time activity curves (TAC) for the three liposomal formulations showed that ~50% of the radioactivity cleared from the blood pool in 16 - 18 hours. As expected, the in vivo biodistribution and TAC data obtained at 48 hours demonstrate that the clearance of radioactivity from the liver slows with the incorporation of a polyethylene glycol-2k (PEG2k) brush. Our data suggest that 64Cu-TETA and 64Cu-CB-TE2A are similarly stable in the blood pool and accumulation of radioactivity in the liver and spleen is not related to the stability of Cu-64 chelator complex; however clearance of Cu-64 from the liver and spleen are faster when injected as 64Cu-TETA-chelated liposomes rather than 64Cu-CB-TE2A-chelated liposomes. PMID:20568726

  15. Novel Bifunctional Cyclic Chelator for 89Zr Labeling–Radiolabeling and Targeting Properties of RGD Conjugates

    PubMed Central

    2015-01-01

    Within the last years 89Zr has attracted considerable attention as long-lived radionuclide for positron emission tomography (PET) applications. So far desferrioxamine B (DFO) has been mainly used as bifunctional chelating system. Fusarinine C (FSC), having complexing properties comparable to DFO, was expected to be an alternative with potentially higher stability due to its cyclic structure. In this study, as proof of principle, various FSC-RGD conjugates targeting αvß3 integrins were synthesized using different conjugation strategies and labeled with 89Zr. In vitro stability, biodistribution, and microPET/CT imaging were evaluated using [89Zr]FSC-RGD conjugates or [89Zr]triacetylfusarinine C (TAFC). Quantitative 89Zr labeling was achieved within 90 min at room temperature. The distribution coefficients of the different radioligands indicate hydrophilic character. Compared to [89Zr]DFO, [89Zr]FSC derivatives showed excellent in vitro stability and resistance against transchelation in phosphate buffered saline (PBS), ethylenediaminetetraacetic acid solution (EDTA), and human serum for up to 7 days. Cell binding studies and biodistribution as well as microPET/CT imaging experiments showed efficient receptor-specific targeting of [89Zr]FSC-RGD conjugates. No bone uptake was observed analyzing PET images indicating high in vivo stability. These findings indicate that FSC is a highly promising chelator for the development of 89Zr-based PET imaging agents. PMID:25941834

  16. Synthesis and Evaluation of New Generation Cross-Bridged Bifunctional Chelator for (64)Cu Radiotracers.

    PubMed

    Dale, Ajit V; An, Gwang Il; Pandya, Darpan N; Ha, Yeong Su; Bhatt, Nikunj; Soni, Nisarg; Lee, Hochun; Ahn, Heesu; Sarkar, Swarbhanu; Lee, Woonghee; Huynh, Phuong Tu; Kim, Jung Young; Gwon, Mi-Ri; Kim, Sung Hong; Park, Jae Gyu; Yoon, Young-Ran; Yoo, Jeongsoo

    2015-09-01

    Bifunctional chelators have been successfully used to construct (64)Cu-labeled radiopharmaceuticals. Previously reported chelators with cross-bridged cyclam backbones have various essential features such as high stability of the copper(II) complex, high efficiency of radiolabeling at room temperature, and good biological inertness of the radiolabeled complex, along with rapid body clearance. Here, we report a new generation propylene-cross-bridged chelator with hybrid acetate/phosphonate pendant groups (PCB-TE1A1P) developed with the aim of combining these key properties in a single chelator. The PCB-TE1A1P was synthesized from cyclam with good overall yield. The Cu(II) complex of our chelator showed good robustness in kinetic stability evaluation experiments, such as acidic decomplexation and cyclic voltammetry studies. The Cu(II) complex of PCB-TE1A1P remained intact under highly acidic conditions (12 M HCl, 90 °C) for 8 d and showed quasi-reversible reduction/oxidation peaks at -0.77 V in electrochemical studies. PCB-TE1A1P was successfully radiolabeled with (64)Cu ions in an acetate buffer at 60 °C within 60 min. The electrophoresis study revealed that the (64)Cu-PCB-TE1A1P complex has net negative charge in aqueous solution. The biodistribution and in vivo stability study profiles of (64)Cu-PCB-TE1A1P indicated that the radioactive complex was stable under physiological conditions and cleared rapidly from the body. A whole body positron emission tomography (PET) imaging study further confirmed high in vivo stability and fast clearance of the complex in mouse models. In conclusion, PCB-TE1A1P has good potential as a bifunctional chelator for (64)Cu-based radiopharmaceuticals, especially those involving peptides. PMID:26286436

  17. Preparation of Ga-67 labeled monoclonal antibodies using deferoxamine as a bifunctional chelating agent

    SciTech Connect

    Endo, K.; Furukawa, T.; Ohmomo, Y.; Sakahara, H.; Ohta, H.; Nakashima, T.; Okada, K.; Yoshida, O.; Yokoyama, A.; Torizuka, K.

    1984-01-01

    Ga-67 labeled monoclonal IgG or F(ab')/sub 2/ fragments against ..cap alpha..-fetoprotein and ..beta..-subunit of human choriogonadotropin (HCG), were prepared using Deferoxamine (DFO) as a bifunctional chelating agent. DFO, a well-known iron chelating agent, was conjugated with monoclonal antibodies (Ab) by a glutaraldehyde two step method and the effect of conjugation on the Ab activities was examined by RIA and Scatchard plot analysis. In both monoclonal Ab preparations, the conjugation reaction was favored as the pH increased. However, Ab-binding activities decreased as the molecular ratios of DFO to Ab increased. Preserved Ab activities were observed when Ab contained DFO per Ab molecule less than 2.1. At a ratio of over 3.3 DFO molecules per Ab, the maximal binding capacity rather than the affinity constant decreased. The inter-molecular cross linkage seemed to be responsible for the deactivation of binding activities. The obtained DFO-Ab conjugates, were then easily labeled with high efficiency and reproducibility and Ga-67 DFO-Ab complexes were highly stable both in vitro and in vivo. Thus, biodistribution of Ga-67 labeled F(ab')/sub 2/ fragments of monoclonal Ab to HCG ..beta..-subunit was attempted in nude mice transplanted with HCG-producing human teratocarcinoma. Tumor could be visualized, in spite of relatively high background imaging of liver, kidney and spleen. The use of DFO as a bifunctional chelating agent provided good evidence for its applicability to labeling monoclonal Ab with almost full retention of Ab activities. Further, availability of Ga-68 will make Ga-68 DFO-monoclonal Ab a very useful tool for positron tomography imaging of various tumors.

  18. The determination of the rate of conjugation immunoglobuline with bifunctional chelator

    NASA Astrophysics Data System (ADS)

    Málek, Z.; Miler, V.; Budský, F.

    2006-01-01

    The work was performed under the GACR project: "Technology of preparation of radionuclides and their labelled compounds for nuclear medicine and pharmacy with the use of the reactor LVR-15" reg. no. 104/03/0499. Imaging of cell’s antigens with the use of labelled immunoglobulines allows imaging of specific receptors on cell membrane and specific tumours. It is necessary to carry out the labelling of the immunoglobulines with radionuclides of suitable physical properties, which form cations (e.g., 111In, 90Y, 177Lu) that form very strong chelates of sufficiently high stability constant preventing the dissociation of complexes or the radionuclide under “in-vivo” conditions. The immunoglobuline must be conjugated with the bifunctional chelator (BCH), which contains both chelating unit and reactive group for binding to the immunoglobuline. In our laboratory we have conjugated human IgG and monoclonal antibody CD20 with diethylenetriamine pentaacetic acid dianhydride (cDTPAA). Radionuclides 90Y and 177Lu prepared on the LVR-15 reactor in NRI Rez were used for labelling. After conjugation and labelling the yields in relation to the amount of isotopic carrier have been determined.

  19. 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.

  20. Fusarinine C, a novel siderophore-based bifunctional chelator for radiolabeling with Gallium-68

    PubMed Central

    Zhai, Chuangyan; Summer, Dominik; Rangger, Christine; Haas, Hubertus; Haubner, Roland; Decristoforo, Clemens

    2015-01-01

    Fusarinine C (FSC), a siderophore-based chelator coupled with the model peptide c(RGDfK) (FSC(succ-RGD)3), revealed excellent targeting properties in vivo using positron emission tomography (PET). Here, we report the details of radiolabeling conditions and specific activity as well as selectivity for 68Ga. 68Ga labeling of FSC(succ-RGD)3 was optimized regarding peptide concentration, pH, temperature, reaction time, and buffer system. Specific activity (SA) of [68Ga]FSC(succ-RGD)3 was compared with 68Ga-1,4,7-triazacyclononane, 1-glutaric acid-4,7 acetic acid RGD ([68Ga]NODAGA-RGD). Stability was evaluated in 1000-fold ethylenediaminetetraacetic acid (EDTA) solution (pH 7) and phosphate-buffered saline (PBS). Metal competition tests (Fe, Cu, Zn, Al, and Ni) were carried out using [68Ga]-triacetylfusarinine C. High radiochemical yield was achieved within 5 min at room temperature, in particular allowing labeling with 68Ga up to pH 8 with excellent stability in 1000-fold EDTA solution and PBS. The 10-fold to 20-fold lower concentrations of FSC(succ-RGD)3 led to the same radiochemical yield compared with [68Ga]NODAGA-RGD with SA up to 1.8 TBq/μmol. Metal competition tests showed high selective binding of 68Ga to FSC. FSC is a multivalent siderophore-based bifunctional chelator allowing fast and highly selective labeling with 68Ga in a wide pH range and results in stable complexes with high SA. Thus it is exceptionally well suited for the development of new 68Ga-tracers for in vivo molecular imaging with PET. PMID:25874571

  1. Synthesis, characterization, and evaluation of a novel bifunctional chelating agent for the lead isotopes 203Pb and 212Pb.

    PubMed

    Chappell, L L; Dadachova, E; Milenic, D E; Garmestani, K; Wu, C; Brechbiel, M W

    2000-01-01

    Radioisotopes of Pb(II) have been of some interest in radioimmunotherapy and radioimmunoimaging (RII). However, the absence of a kinetically stable bifunctional chelating agent for Pb(II) has hampered its use for these applications. 203Pb (T(1/2) = 52.02 h) has application potential in RII, with a gamma-emission that is ideal for single photon emission computerized tomography, whereas 212Pb (T(1/2) = 10 h) is a source of highly cytotoxic alpha-particles via its decay to its 212Bi (T(1/2) = 60 min) daughter. The synthesis of the novel bifunctional chelating agent 2-(4-isothiocyanotobenzyl)-1,4,7,10-tetraaza-1,4,7,10-tetra- (2-carbamoyl methyl)-cyclododecane (4-NCS-Bz-TCMC) is reported herein. The Pb[TCMC]2+ complex was less labile to metal ion release than Pb[DOTA]2- at pH 3.5 and below in isotopic exchange experiments. In addition to increased stability to Pb2+ ion release at low pH, the bifunctional TCMC ligand was found to have many other advantages over the bifunctional 1,4,7,10-tetraazacyclodocane-1,4,7,10-tetraacetic acid (DOTA) ligand. These include a shorter and more straightforward synthetic route, a more efficient conjugation reaction to a monoclonal antibody (mAb), with a higher chelate to protein ratio, a higher percent immuroreactivity, and a more efficient radiolabeling reaction of the mAb-ligand conjugate with 203Pb. PMID:10755652

  2. Hexadentate bispidine derivatives as versatile bifunctional chelate agents for copper(II) radioisotopes.

    PubMed

    Juran, Stefanie; Walther, Martin; Stephan, Holger; Bergmann, Ralf; Steinbach, Jörg; Kraus, Werner; Emmerling, Franziska; Comba, Peter

    2009-02-01

    The preparation and use of bispidine derivatives (3,7-diazabicyclo[3.3.1]nonane) as chelate ligands for radioactive copper isotopes for diagnosis (64Cu) or therapy (67Cu) are reported. Starting from the hexadentate bispidine-based bis(amine)tetrakis(pyridine) ligand 1 with a keto and two ester substituents, the corresponding mono-ol 2 and two dicarboxylic acid derivatives 3 and 5 have been synthesized. A range of techniques, including single-crystal X-ray structure analysis, UV/vis spectroscopy, cyclic voltammetry, thin-layer- (TLC), and high-performance liquid chromatography (HPLC), have been used to characterize the structure and stability of the copper(II)-bispidine complexes. A rapid formation (within 1 min) of stable copper(II)-bispidine complexes under mild conditions (ambient temperature, aqueous solution) has been observed. Challenge experiments of these complexes in the presence of a high excess of competing ligands, such as glutathione, cyclam, or superoxide dismutase (SOD), as well as in rat plasma, gave no evidence of demetalation or transchelation. The bifunctional bispidine derivative 5 can be readily functionalized with biologically active molecules at the pendant carboxylate groups. The coupling of a bombesin analogue betahomo-Glu-betaAla-betaAla-[Cha(13),Nle(14)]BBN(7-14), by condensation of a carboxylate of the bispidine backbone with the N-terminus of the peptide produced the bifunctional ligand 6. The radiocopper(II) complex of this bombesin-bispidine conjugate has a considerable hydrophilicity (log D(o/w) < -2.4), and this leads to a very fast blood clearance (blood: 0.28 +/- 0.02 SUV, 1 h p.i.), low liver tissue accumulation (liver: 1.20 +/- 0.27 SUV, 1 h p.i.), and rapid renal-urinary excretion (kidneys: 6.06 +/- 2.96 SUV, 1 h p.i.) as shown by biodistribution studies of 64Cu-6 in Wistar rats. Preliminary in vivo studies of 64Cu-6 in NMRI nu/nu mice, bearing the human prostate tumor PC-3 showed an accumulation of the conjugate in the tumor (2

  3. Propylene cross-bridged macrocyclic bifunctional chelator: a new design for facile bioconjugation and robust (64)Cu complex stability.

    PubMed

    Pandya, Darpan N; Bhatt, Nikunj; An, Gwang Il; Ha, Yeong Su; Soni, Nisarg; Lee, Hochun; Lee, Yong Jin; Kim, Jung Young; Lee, Woonghee; Ahn, Heesu; Yoo, Jeongsoo

    2014-09-11

    The first macrocyclic bifunctional chelator incorporating propylene cross-bridge was efficiently synthesized from cyclam in seven steps. After the introduction of an extra functional group for facile conjugation onto the propylene cross-bridge, the two carboxylic acid pendants could contribute to strong coordination of Cu(II) ions, leading to a robust Cu complex. The cyclic RGD peptide conjugate of PCB-TE2A-NCS was prepared and successfully radiolabeled with (64)Cu ion. The radiolabeled peptide conjugate was evaluated in vivo through a biodistribution study and animal PET imaging to demonstrate high tumor uptake with low background. PMID:25137619

  4. Promising bifunctional chelators for copper 64-PET imaging: practical (64)Cu radiolabeling and high in vitro and in vivo complex stability.

    PubMed

    Wu, Ningjie; Kang, Chi Soo; Sin, Inseok; Ren, Siyuan; Liu, Dijie; Ruthengael, Varyanna C; Lewis, Michael R; Chong, Hyun-Soon

    2016-04-01

    Positron emission tomography (PET) using copper-64 is a sensitive and non-invasive imaging technique for diagnosis and staging of cancer. A bifunctional chelator that can present rapid radiolabeling kinetics and high complex stability with (64)Cu is a critical component for targeted PET imaging. Bifunctional chelates 3p-C-NE3TA, 3p-C-NOTA, and 3p-C-DE4TA were evaluated for complexation kinetics and stability with (64)Cu in vitro and in vivo. Hexadentate 3p-C-NOTA and heptadentate 3p-C-NE3TA possess a smaller TACN-based macrocyclic backbone, while nonadentate 3p-C-DE4TA is constructed on a larger CYCLEN-based ring. The frequently explored chelates of (64)Cu, octadentate C-DOTA and hexadentate C-NOTA were also comparatively evaluated. Radiolabeling kinetics of bifunctional chelators with (64)Cu was assessed under mild conditions. All bifunctional chelates instantly bound to (64)Cu in excellent radiolabeling efficiency at room temperature. C-DOTA was less efficient in binding (64)Cu than all other chelates. All (64)Cu-radiolabeled bifunctional chelates remained stable in human serum without any loss of (64)Cu for 2 days. When challenged by an excess amount of EDTA, (64)Cu complexes of C-NOTA, 3p-C-NE3TA and 3p-C-NOTA were shown to be more stable than (64)Cu-C-DOTA and (64)Cu-3p-C-DE4TA. (64)Cu complexes of the new chelates 3p-C-NE3TA and 3p-C-NOTA displayed comparable in vitro and in vivo complex stability to (64)Cu-C-NOTA. In vivo biodistribution result indicates that the (64)Cu-radiolabeled complexes of 3p-C-NOTA and 3p-C-NE3TA possess excellent in vivo complex stability, while (64)Cu-3p-C-DE4TA was dissociated as evidenced by high renal and liver retention in mice. The results of in vitro and in vivo studies suggest that the bifunctional chelates 3p-C-NE3TA and 3p-C-NOTA offer excellent chelation chemistry with (64)Cu for potential PET imaging applications. PMID:26666778

  5. Isothiocyanate-functionalized bifunctional chelates and fac-[MI(CO)3]+ (M = Re, 99mTc) complexes for targeting uPAR in prostate cancer

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Developing strategies to rapidly incorporate the fac-[MI(CO)3]+ (M = Re, 99mTc) core into biological targeting vectors is a growing realm in radiopharmaceutical development. This work presents the preparation of a novel isothiocyanate-functionalized bifunctional chelate based on 2,2´-dipicolylamine ...

  6. Synthesis of a new bifunctional chelating agent for radioimmunotherapy: Cyclohexyl fused tetraazacyclodo-decanetetraacetic acid

    SciTech Connect

    Sweet, M.P.; Mease, R.C.; Lambert, C.; Srivastava, S.C.

    1996-05-01

    Preorganization of the coordinating groups within a chelating agent increases the stability of its metal-ligand complexes. For example, 1,2-diaminocyclo-hexanetetraacetic acid (CDTA) forms metal complexes with stability constants 1-3 orders of magnitude higher than the corresponding complexes of EDTA. Incorporation of a cyclohexyl group into a macrocyclic ligand produces a similar effect; stability constants of Cu complexes of tetrathiocyclotetradecanes are increased by 1.5 orders of magnitude by incorporating one cyclohexyl group into the macrocyclic ring and 3 orders of magnitude by incorporating two cyclohexyl moieties. In this study, we have synthesized cycohexyl DOTA (C-DOTA) in which the cyclohexyl group is fused to two carbons of the macrocyclic ring. Alkylation of disodium ethylene ditosylamide with trans-1,2-di(bromoacetamido)cyclohexane afforded the C{sub 8}N{sub 4} macrocycle. Reduction with lithium aluminum hydride not only reduced the amide moieties to amines but also removed the tosyl protecting groups affording the cyclohexylcyclen. Cyanomethylation followed by hydrolysis gave C-DOTA in an overall yield of 9.4%. C-DOTA is expected to offer improvements in the biodistribution of radiometal immunoconjugates for radioimmunotherapy, in particular with Sc-47, Y-90, and Sm-153 that have given encouraging results using the plain DOTA ligand.

  7. New Tris(hydroxypyridinone) Bifunctional Chelators Containing Isothiocyanate Groups Provide a Versatile Platform for Rapid One-Step Labeling and PET Imaging with 68Ga3+

    PubMed Central

    2015-01-01

    Two new bifunctional tris(hydroxypyridinone) (THP) chelators designed specifically for rapid labeling with 68Ga have been synthesized, each with pendant isothiocyanate groups and three 1,6-dimethyl-3-hydroxypyridin-4-one groups. Both compounds have been conjugated with the primary amine group of a cyclic integrin targeting peptide, RGD. Each conjugate can be radiolabeled and formulated by treatment with generator-produced 68Ga3+ in over 95% radiochemical yield under ambient conditions in less than 5 min, with specific activities of 60–80 MBq nmol–1. Competitive binding assays and in vivo biodistribution in mice bearing U87MG tumors demonstrate that the new 68Ga3+-labeled THP peptide conjugates retain affinity for the αvβ3 integrin receptor, clear within 1–2 h from circulation, and undergo receptor-mediated tumor uptake in vivo. We conclude that bifunctional THP chelators can be used for simple, efficient labeling of 68Ga biomolecules under mild conditions suitable for peptides and proteins. PMID:26286399

  8. Imaging Cancer Using PET – the Effect of the Bifunctional Chelator on the Biodistribution of a 64Cu-Labeled Antibody

    PubMed Central

    Dearling, Jason L.J.; Voss, Stephan D.; Dunning, Patricia; Snay, Erin; Fahey, Frederic; Smith, Suzanne V.; Huston, James S.; Meares, Claude F.; Treves, S. Ted; Packard, Alan B.

    2010-01-01

    Introduction Use of copper radioisotopes in antibody radiolabeling is challenged by reported loss of the radionuclide from the bifunctional chelator used to label the protein. The objective of this study was to investigate the relationship between the thermodynamic stability of the 64Cu-complexes of five commonly used bifunctional chelators (BFCs) and the biodistribution of an antibody labeled with 64Cu using these chelators in tumor-bearing mice. Methods The chelators (p-NH2-Bn-NOTA, BAT-6, p-NH2-Bn-DOTA, DOTA, and SarAr) were conjugated to the anti-GD2 antibody ch14.18, and the conjugated antibody was labeled with 64Cu and injected into mice bearing subcutaneous human melanoma tumors (M21) (n = 3-5 for each study). Biodistribution data were obtained from PET images acquired at 1, 24 and 48 hours post-injection, and at 48 hours post-injection a full ex vivo biodistribution study was carried out. Results The biodistribution, including tumor targeting, was similar for all the radioimmunoconjugates. At 48 h post-injection, the only statistically significant differences in radionuclide uptake (p < 0.05) were between blood, liver, spleen and kidney. For example, liver uptake of [64Cu]ch14.18-p-NH2-Bn-NOTA was 4.74 ± 0.77 per cent of the injected dose per gram of tissue (%ID/g), and for [64Cu]ch14.18-SarAr was 8.06 ± 0.77 %ID/g. Differences in tumor targeting correlated with variations in tumor size rather than which BFC was used. Conclusions The results of this study indicate that differences in the thermodynamic stability of these chelator-Cu(II) complexes were not associated with significant differences in uptake of the tracer by the tumor. However, there were significant differences in tracer concentration in other tissues, including those involved in clearance of the radioimmunoconjugate (e.g., liver and spleen). PMID:21220127

  9. Deferasirox-TAT(47-57) peptide conjugate as a water soluble, bifunctional iron chelator with potential use in neuromedicine.

    PubMed

    Goswami, Dibakar; Vitorino, Hector A; Alta, Roxana Y P; Silvestre, Daniel M; Nomura, Cassiana S; Machini, M Teresa; Espósito, Breno P

    2015-10-01

    Deferasirox (DFX), an orally active and clinically approved iron chelator, is being used extensively for the treatment of iron overload. However, its water insolubility makes it cumbersome for practical use. In addition to this, the low efficacy of DFX to remove brain iron prompted us to synthesize and evaluate a DFX-TAT(47-57) peptide conjugate for its iron chelation properties and permeability across RBE4 cell line, an in vitro model of the blood-brain barrier. The water-soluble conjugate was able to remove labile iron from buffered solution as well as from iron overloaded sera, and the permeability of DFX-TAT(47-57) conjugate into RBE4 cells was not affected compared to parent deferasirox. The iron bound conjugate was also able to translocate through the cell membrane. PMID:26164834

  10. Inhibition of Cu-amyloid-β by using bifunctional peptides with β-sheet breaker and chelator moieties.

    PubMed

    Jensen, Madeleine; Canning, Anne; Chiha, Sabri; Bouquerel, Pierre; Pedersen, Jeppe Trudslev; Østergaard, Jesper; Cuvillier, Olivier; Sasaki, Isabelle; Hureau, Christelle; Faller, Peter

    2012-04-16

    Breaking the mold: Inhibition of toxic amyloid-β (Aβ) aggregates and disruption of Cu-Aβ with subsequent redox-silencing of Cu have been considered promising strategies against Alzheimer's disease. The design and proof of concept of simple peptides containing a Cu-chelating/redox-silencing unit and an Aβ-aggregation inhibition unit (β-sheet breaker) is described (see scheme). PMID:22422637

  11. p-carboxyethyl-phenylglyoxal bis(n-methylthiosemicarbazone) (CE-DTS), a bifunctional chelating agent for Tc-99m labeled monoclonal antibody

    SciTech Connect

    Arano, Y.; Yokoyama, A.; Furukawa, T.; Saji, H.; Endo, K.; Torizaka, K.

    1985-05-01

    In the search for bifunctional chelating agents (BCA) with better affinity, selectivity and stability as for Tc-99m, synthesis of a novel BCA containing di-thio-semicarbazone as for Tc-99m chelating site has offered interesting characteristics for the labeling of macromolecules. In the present paper, monoclonal IgG (MoAb) against human thyroglobulin was selected as a model and conditions for coupling, labeling reactions were tested along with immunological reactivity. CE-DTS was coupled to MoAb by the azido method and effect of conjugation on the MoAb immunoreactivity was followed by RIA. When CE-DTS was coupled to MoAb at the molar ratio of 1:1, no loss of its original immunoreactivity was observed. Tc-99m labeling, using the stannous ion reducing method, indicated the reaction pH as being a determinant parameter. The reducing agent prepared in tartrate buffer (pH 3) offered high yield and stable Tc-99m-CE-DTS-MoAb, as evidence by HPLC. In vivo studies in mice indicated percent of injected dose and blood clearance alike the I-131-MoAb. This good labeled state of Tc-99m-CE-DTS-MoAb was also demonstrated by using second antibody reaction in serum of mice. The newly synthesized CE-DTS offered good basis for the Tc-99m labeling of monclonal antibodies with preserved immunological properties, as desirable for the radioimmunodetection. Work with tumor related monoclonal antibodies is under progress.

  12. Bifunctional drug derivatives of MAO-B inhibitor rasagiline and iron chelator VK-28 as a more effective approach to treatment of brain ageing and ageing neurodegenerative diseases.

    PubMed

    Youdim, Moussa B H; Fridkin, Mati; Zheng, Hailin

    2005-02-01

    and other propargylamines have been demonstrated to have neuroprotective activity in several in vitro and in vivo models, which have been shown be associated with propargylamines moiety, since propargylamines itself possess these properties. The mechanism of neuroprotective activity has been attributed to the ability of propargylamines-inducing the antiapoptotic family proteins Bcl-2 and Bcl-xl, while decreasing Bad and Bax and preventing opening of mitochondrial permeability transition pore. Iron accumulates in brain regions associated with neurodegenerative diseases of PD, AD, amyotrophic lateral sclerosis and Huntington disease. It is thought to be involved in Fenton chemistry oxidative stress observed in these diseases. The neuroprotective activity of propargylamines led us to develop several novel bifunctional iron chelator from our prototype brain permeable iron chelators, VK-28, possessing propargylamine moiety (HLA-20, M30 and M30A) to iron out iron from the brain. These compounds have been shown to have iron chelating and monoamine oxidase A and B selective brain inhibitory and neuroprotective-antiapoptotic actions. PMID:15621213

  13. Bifunctional CYP81AA proteins catalyse identical hydroxylations but alternative regioselective phenol couplings in plant xanthone biosynthesis

    PubMed Central

    El-Awaad, Islam; Bocola, Marco; Beuerle, Till; Liu, Benye; Beerhues, Ludger

    2016-01-01

    Xanthones are natural products present in plants and microorganisms. In plants, their biosynthesis starts with regioselective cyclization of 2,3′,4,6-tetrahydroxybenzophenone to either 1,3,5- or 1,3,7-trihydroxyxanthones, catalysed by cytochrome P450 (CYP) enzymes. Here we isolate and express CYP81AA-coding sequences from Hypericum calycinum and H. perforatum in yeast. Microsomes catalyse two consecutive reactions, that is, 3′-hydroxylation of 2,4,6-trihydroxybenzophenone and C–O phenol coupling of the resulting 2,3′,4,6-tetrahydroxybenzophenone. Relative to the inserted 3′-hydroxyl, the orthologues Hc/HpCYP81AA1 cyclize via the para position to form 1,3,7-trihydroxyxanthone, whereas the paralogue HpCYP81AA2 directs cyclization to the ortho position, yielding the isomeric 1,3,5-trihydroxyxanthone. Homology modelling and reciprocal mutagenesis reveal the impact of S375, L378 and A483 on controlling the regioselectivity of HpCYP81AA2, which is converted into HpCYP81AA1 by sextuple mutation. However, the reciprocal mutations in HpCYP81AA1 barely affect its regiospecificity. Product docking rationalizes the alternative C–O phenol coupling reactions. Our results help understand the machinery of bifunctional CYPs. PMID:27145837

  14. 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

  15. Combination of deferasirox and deferoxamine in clinical practice: an alternative scheme of chelation in thalassemia major patients.

    PubMed

    Cassinerio, E; Orofino, N; Roghi, A; Duca, L; Poggiali, E; Fraquelli, M; Zanaboni, L; Cappellini, M D

    2014-09-01

    The availability of three iron chelators improved the scenario of chelation therapy for transfusion-dependent thalassemia (TDT) patients, allowing tailoring of drugs according to the goals expected for each patient. The use of Deferiprone/Deferoxamine (DFP/DFO) combined in different schemes has been reported since many years. Only recently data from combination of Deferasirox/Deferoxamine (DFX/DFO) have been reported showing that it can be safe and efficacious to remove iron overload, particularly in patients who do not respond adequately to a single chelating agent. We investigated the efficacy, tolerability and safety of combined DFX/DFO in thalassemia major patients. Ten TDT patients have started DFX/DFO for different reasons: 1) lack of efficacy in removing liver/cardiac iron with monotherapy; 2) agranulocytosis on DFP; and 3) adverse events with elevated doses of monotherapies. The study design included: cardiac and hepatic T2* magnetic resonance (CMR), transient elastography evaluation (Fibroscan), biochemical evaluation, and audiometric and ocular examinations. The drugs' starting doses were: DFO 32 ± 4 mg/kg/day for 3-4 days a week and DFX 20 ± 2 mg/kg/day. Seven patients completed the one-year follow-up period. At baseline the mean pre-transfusional Hb level was 9.4 ± 0.4 g/dl, the mean iron intake was 0.40 ± 0.10mg/kg/day, the median ferritin level was 2254 ng/ml (range 644-17,681 ng/ml). Data available at 1 year showed no alteration of renal/hepatic function and no adverse events. A marked reduction in LIC (6.54 vs 11.44 mg/g dw at baseline) and in median ferritin (1346 vs 2254 ng/ml at baseline) was achieved. A concomitant reduction of non-transferrin-bound iron (NTBI) at six months was observed (2.1 ± 1.0 vs 1.7 ± 1.2 μM). An improvement in cardiac T2* values was detected (26.34 ± 15.85 vs 19.85 ± 12.06 at baseline). At 1 year an increased dose of DFX was administered (27 ± 6 mg/kg/day vs 20 ± 2 mg/kg/day at baseline, p=0.01) with a stable

  16. Iron Chelation

    MedlinePlus

    ... iron overload and need treatment. What is iron overload? Iron chelation therapy is used when you have ... may want to perform: How quickly does iron overload happen? This is different for each person. It ...

  17. Hyperaccumulator oilcake manure as an alternative for chelate-induced phytoremediation of heavy metals contaminated alluvial soils.

    PubMed

    Mani, Dinesh; Kumar, Chitranjan; Patel, Niraj Kumar

    2015-01-01

    The ability of hyperaccumulator oilcake manure as compared to chelates was investigated by growing Calendula officinalis L for phytoremediation of cadmium and lead contaminated alluvial soil. The combinatorial treatment T6 [2.5 g kg(-1) oilcake manure+5 mmol kg(-1) EDDS] caused maximum cadmium accumulation in root, shoot and flower up to 5.46, 4.74 and 1.37 mg kg(-1) and lead accumulation up to 16.11, 13.44 and 3.17 mg kg(-1), respectively at Naini dump site, Allahabad (S3). The treatment showed maximum remediation efficiency for Cd (RR=0.676%) and Pb (RR=0.202%) at Mumfordganj contaminated site (S2). However, the above parameters were also observed at par with the treatment T5 [2.5 g kg(-1) oilcake manure +2 g kg(-1) humic acid]. Applied EDDS altered chlorophyll-a, chlorophyll-b, and carotene contents of plants while application of oilcake manure enhanced their contents in plant by 3.73-8.65%, 5.81-17.65%, and 7.04-17.19%, respectively. The authors conclude that Calendula officinalis L has potential to be safely grown in moderately Cd and Pb-contaminated soils and application of hyperaccumulator oilcake manure boosts the photosynthetic pigments of the plant, leading to enhanced clean-up of the cadmium and lead-contaminated soils. Hence, the hyperaccumulator oilcake manure should be preferred over chelates for sustainable phytoremediation through soil-plant rhizospheric process. PMID:25397984

  18. MTBE OXIDATION BY BIFUNCTIONAL ALUMINUN

    EPA Science Inventory

    Bifunctional aluminum, prepared by sulfating zero-valent aluminum with sulfuric acid, is an innovative extension of zero-valent metal (ZVM) technology for ground water remediation. Bifunctional aluminum has a dual functionality of simultaneously decomposing both reductively- an...

  19. MTBE OXIDATION BY BIFUNCTIONAL ALUMINUM

    EPA Science Inventory

    Bifunctional aluminum, prepared by sulfating zero-valent aluminum with sulfuric acid, has a dual functionality of simultaneously decomposing both reductively- and oxidatively-degradable contaminants. In this work, the use of bifunctional aluminum for the degradation of methyl te...

  20. Determination of alternative and conventional chelating agents as copper(II) complexes by capillary zone electrophoresis--the first use of didecyldimethylammonium bromide as a flow reversal reagent.

    PubMed

    Laamanen, Pirkko-Leena; Matilainen, Rose

    2007-02-12

    A capillary zone electrophoresis (CZE) method for analyzing 11 chelating agents [beta-alaninediacetic acid (beta-ADA), trans-1,2-diaminocyclohexane-N,N,N',N'-tetraacetic acid (CDTA), diethylenetriaminepentaacetic acid (DTPA), ethylenediaminetetraacetic acid (EDTA), N-(2-hydroxyethyl)ethylenediamine-N,N',N'-triacetic acid (HEDTA), N-(2-hydroxyethyl)iminodiacetic acid (HEIDA), iminodiacetic acid (IDA), methylglycinediacetic acid (MGDA), nitrilotriacetic acid (NTA), 1,3-diaminopropane-N,N,N',N'-tetraacetic acid (PDTA) and triethylenetetraaminehexaacetic acid (TTHA)] as negatively charged copper(II) complexes has been established. Both conventional and alternative chelating agents were included in this study, because they are used side by side in industrial applications. In this study, didecyldimethylammonium bromide (DMDDAB) was successfully used as a flow reversal reagent for the first time in an aqueous CZE method based on phosphate BGE with UV spectrophotometric detection. In addition this new flow modifier was compared to common TTAB. Method development was done using a fused silica capillary (61 cm x 50 microm i.d.). The optimized BGE was a 105 mmol L(-1) phosphate buffer with TTAB or DMDDAB in the concentration 0.5 mmol L(-1) at pH 7.1. The measurements were done with -20 kV voltage using direct UV detection at 254 nm. In both CZE methods all 11 analyte zones were properly separated (resolutions > or =2.4), and the calibrations gave excellent correlation coefficients (> or =0.998; linear range tested 0.5-2.0 mmol L(-1)). The limits of detection were < or =34 and < or =49 micromol L(-1) with the method of DMDDAB and TTAB, respectively. A clear benefit of both methods was the short analysis time; all 11 complexes were detected in less than 6 and 5.5 min with the methods of TTAB and DMDDAB, respectively. The two methods were tested with dishwashing detergents and paper mill wastewater samples and proved to be suitable for practical use. PMID:17386596

  1. Bifunctional alkaline oxygen electrodes

    NASA Technical Reports Server (NTRS)

    Swette, L.; Kackley, N.; Mccatty, S. A.

    1991-01-01

    The authors describe the identification and testing of electrocatalysts and supports for the positive electrode of moderate-temperature, single-unit, rechargeable alkaline fuel cells. Recent work on Na(x)Pt3O4, a potential bifunctional catalyst, is described, as well as the application of novel approaches to the development of more efficient bifunctional electrode structures. The three dual-character electrodes considered here showed similar superior performance; the Pt/RhO2 and Rh/RhO2 electrodes showed slightly better performance than the Pt/IrO2 electrode. It is concluded that Na(x)Pt3O4 continues to be a promising bifunctional oxygen electrode catalyst but requires further investigation and development.

  2. Tight bifunctional hierarchical catalyst.

    PubMed

    Højholt, Karen T; Vennestrøm, Peter N R; Tiruvalam, Ramchandra; Beato, Pablo

    2011-12-28

    A new concept to prepare tight bifunctional catalysts has been developed, by anchoring CoMo(6) clusters on hierarchical ZSM-5 zeolites for simultaneous use in HDS and hydrocracking catalysis. The prepared material displays a significant improved activity in HDS catalysis compared to the impregnated counterpart. PMID:22048337

  3. Bifunctional phosphoramidite reagents for the introduction of histidyl and dihistidyl residues into oligonucleotides.

    PubMed

    Smith, T H; LaTour, J V; Bochkariov, D; Chaga, G; Nelson, P S

    1999-01-01

    The synthesis and characterization of reagents for the incorporation of histidyl residues into oligonucleotides by automated chemical synthesis is described. Automated oligonucleotide synthesis utilizing a bifunctional reagent for the incorporation of a dihistidyl residue into oligonucleotides is described. Oligonucleotides incorporating one to three dihistidyl residues were prepared and characterized. The interaction of these oligonucleotides with a metal chelating IMAC matrix was explored. PMID:10411463

  4. 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

  5. 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.

  6. Nanoparticle Superlattices as Efficient Bifunctional Electrocatalysts for Water Splitting.

    PubMed

    Li, Jun; Wang, Yongcheng; Zhou, Tong; Zhang, Hui; Sun, Xuhui; Tang, Jing; Zhang, Lijuan; Al-Enizi, Abdullah M; Yang, Zhongqin; Zheng, Gengfeng

    2015-11-18

    The solar-driven water splitting process is highly attractive for alternative energy utilization, while developing efficient, earth-abundant, bifunctional catalysts for both oxygen evolution reaction and hydrogen evolution reaction has remained as a major challenge. Herein, we develop an ordered CoMnO@CN superlattice structure as an efficient bifunctional water-splitting electrocatalyst, in which uniform Co-Mn oxide (CoMnO) nanoparticles are coated with a thin, continuous nitrogen-doped carbon (CN) framework. The CoMnO nanoparticles enable optimized OER activity with effective electronic structure configuration, and the CN framework serves as an excellent HER catalyst. Importantly, the ordered superlattice structure is beneficial for enhanced reactive sites, efficient charge transfer, and structural stability. This bifunctional superlattice catalyst manifests optimized current densities and electrochemical stability in overall water splitting, outperforming most of the previously reported single- or bifunctional electrocatalysts. Combining with a silicon photovoltaic cell, this CoMnO@CN superlattice bifunctional catalyst enables unassisted solar water splitting continuously for ∼5 days with a solar-to-hydrogen conversion efficiency of ∼8.0%. Our discovery suggests that these transition metal oxide-based superlattices may serve as a unique structure modality for efficient bifunctional water splitting electrocatalysts with scale-up potentials. PMID:26496655

  7. Hydroxypyridonate chelating agents

    DOEpatents

    Raymond, Kenneth N.; Scarrow, Robert C.; White, David L.

    1987-01-01

    Chelating agents having 1-hydroxy-2-pyridinone (HOPO) and related moieties incorporated within their structures, including polydentate HOPO-substituted polyamines such as spermidine and spermine, and HOPO-substituted desferrioxamine. The chelating agents are useful in selectively removing certain cations from solution, and are particularly useful as ferric ion and actinide chelators. Novel syntheses of the chelating agents are provided.

  8. A new radiochemical method to study the stability of metal chelates used in radiopharmaceuticals

    SciTech Connect

    Subramanian, K.M.; Wolf, W.

    1985-05-01

    Bifunctional chelates are more and more actively used to allow radiolabeling of proteins following metal chelation. While there are data in the literature on the stability constants of the free metal chelates in solution, such methods are neither simple nor suitable for the determination of metal-chelate stability constants following coupling of the bifunctional chelate to a protein. The authors present a novel method for determining the stability constants of indium chelates, which is based on the use of ferric ions as displacement cations. Indium-111 or inium-114m labeled 1:1 In-chelates were incubated with molar equivalents of ferric ions at acidic and neutral pH. At equilibrium this mixture was analyzed by paper and cation-exchange chromatography to determine free and complexed indium. The position equilibrium constants 'K' were calculated from the above data. Using the known stability constants of the ferric chelates ..beta.. and the 'K' values, the stability constants of the indium chelates of several amino polycarboxylic acids, such as NTA, EDTA, DTPA and TTHA were determined. The results obtained were: (current work, literature value) - In-NTA: 16.0, 16.9; In-EDTA: 25.3, 25.3; In-DTPA: 28.7, 29.0; In-TTHA: 27.8, -. These results document that the values obtained by this new method agree well with the values reported in the literature determined by potentiometric titrations. The simplicity of the current method and the ease of calculation of the K values renders this procedure easy to use for the study of indium (and probably other metal) chelates. This method may find special use in determining the stability constants of indium labeled chelates conjugated to proteins, such as in monoclonal antibodies.

  9. 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

  10. Novel pendant-type macrocyclic bifunctional chelating agents: (Carboxymethyl)amino derivatives of 2-(4-nitrobenzyl)-1,4,7,10-tetraazacyclo-dodecane-N,N{prime},N{double_prime},N{prime}{double_prime}-tetraacetic acid and their complex formation with yttrium(III)

    SciTech Connect

    Takenouchi, Kazuya; Tabe, Masayasu; Watanabe, Kenzo

    1993-11-19

    The authors investigated novel synthetic routes to pendant-type {rho}-NO{sub 2}-BZ-DOTA, 1 and 2, containing a (carboxymethyl) amino group appended to the DOTA structure via a methylene (1) and an ethylene (2) spacer, respectively. The complexation of Yttrium (III) with these chelates is reported. 1 fig., 1 tab.

  11. Bifunctional DTPA-type ligand

    SciTech Connect

    Gansow, O.A.; Brechbiel, M.W.

    1990-03-26

    The subject matter of the invention relates to bifunctional cyclohexyl DTPA ligands and methods of using these compounds. Specifically, such ligands are useful for radiolabeling proteins with radioactive metals, and can consequently be utilized with respect to radioimmunoimaging and/or radioimmunotherapy.

  12. The Chelate Effect Redefined.

    ERIC Educational Resources Information Center

    da Silva, J. J. R. Frausto

    1983-01-01

    Discusses ambiguities of the accepted definition of the chelate effect, suggesting that it be defined in terms of experimental observation rather than mathematical abstraction. Indicates that the effect depends on free energy change in reaction, ligand basicity, pH of medium, type of chelates formed, and concentration of ligands in solution. (JN)

  13. Genetics Home Reference: D-bifunctional protein deficiency

    MedlinePlus

    ... Genetics Home Health Conditions D-bifunctional protein deficiency D-bifunctional protein deficiency Enable Javascript to view the ... boxes. Download PDF Open All Close All Description D-bifunctional protein deficiency is a disorder that causes ...

  14. Analyzing the Case for Bifunctional Catalysis.

    PubMed

    Andersen, Mie; Medford, Andrew J; Nørskov, Jens K; Reuter, Karsten

    2016-04-18

    Bifunctional coupling of two different catalytic site types has often been invoked to explain experimentally observed enhanced catalytic activities. We scrutinize such claims with generic scaling-relation-based microkinetic models that allow exploration of the theoretical limits for such a bifunctional gain for several model reactions. For sites at transition-metal surfaces, the universality of the scaling relations between adsorption energies largely prevents any improvements through bifunctionality. Only the consideration of systems that involve the combination of different materials, such as metal particles on oxide supports, offers hope for significant bifunctional gains. PMID:27005967

  15. (S)-5-(p-Nitrobenzyl)-PCTA, a Promising Bifunctional Ligand with Advantageous Metal Ion Complexation Kinetics

    PubMed Central

    Tircsó, Gyula; Benyó, Enikő Tircsóné; Suh, Eul Hyun; Jurek, Paul; Kiefer, Garry E.; Sherry, A. Dean; Kovács, Zoltán

    2009-01-01

    A bifunctional version of PCTA (3,6,9,15-tetraazabicyclo[9.3.1]pentadeca-1(15),11,13-triene-3,6,9,-triacetic acid) that exhibits fast complexation kinetics with the trivalent lanthanide(III) ions was synthesized in reasonable yields starting from N, N′, N″-tristosyl-(S)-2-(p-nitrobenzyl)-diethylenetriamine. pH-potentiometric studies showed that the basicities of p-nitrobenzyl-PCTA and the parent ligand PCTA were similar. The stability of M(NO2-Bn-PCTA) (M = Mg2+, Ca2+, Cu2+, Zn2+) complexes was similar to that of the corresponding PCTA complexes while the stability of Ln3+ complexes of the bifunctional ligand is somewhat lower than that of PCTA chelates. The rate of complex formation of Ln(NO2-Bn-PCTA) complexes was found to be quite similar to that of PCTA, a ligand known to exhibit the fastest formation rates among all lanthanide macrocyclic ligand complexes studied to date. The acid catalyzed decomplexation kinetic studies of the selected Ln(NO2-Bn-PCTA) complexes showed that the kinetic inertness of the complexes was comparable to that of Ln(DOTA) chelates making the bifunctional ligand NO2-Bn-PCTA suitable for labeling biological vectors with radioisotopes for nuclear medicine applications. PMID:19220012

  16. Evaluation of a 3-hydroxypyridin-2-one (2,3-HOPO) Based Macrocyclic Chelator for 89Zr4+ and Its Use for ImmunoPET Imaging of HER2 Positive Model of Ovarian Carcinoma in Mice

    PubMed Central

    N.Tinianow, Jeff; Pandya, Darpan N.; Pailloux, Sylvie L.; Ogasawara, Annie; Vanderbilt, Alexander N.; Gill, Herman S.; Williams, Simon-P.; Wadas, Thaddeus J.; Magda, Darren; Marik, Jan

    2016-01-01

    A novel octadentate 3-hydroxypyridin-2-one (2,3-HOPO) based di-macrocyclic ligand was evaluated for chelation of 89Zr; subsequently, it was used as a bi-functional chelator for preparation of 89Zr-labeled antibodies. Quantitative chelation of 89Zr4+ with the octadentate ligand forming 89ZrL complex was achieved under mild conditions within 15 minutes. The 89Zr-complex was stable in vitro in presence of DTPA, but a slow degradation was observed in serum. In vivo, the hydrophilic 89Zr-complex showed prevalently renal excretion; and an elevated bone uptake of radioactivity suggested a partial release of 89Zr4+ from the complex. The 2,3-HOPO based ligand was conjugated to the monoclonal antibodies, HER2-specific trastuzumab and an isotypic anti-gD antibody, using a p-phenylene bis-isothiocyanate linker to yield products with an average loading of less than 2 chelates per antibody. Conjugated antibodies were labeled with 89Zr under mild conditions providing the PET tracers in 60-69% yield. Despite the limited stability in mouse serum; the PET tracers performed very well in vivo. The PET imaging in mouse model of HER2 positive ovarian carcinoma showed tumor uptake of 89Zr-trastuzumab (29.2 ± 12.9 %ID/g) indistinguishable (p = 0.488) from the uptake of positive control 89Zr-DFO-trastuzumab (26.1 ± 3.3 %ID/g). In conclusion, the newly developed 3-hydroxypyridin-2-one based di-macrocyclic chelator provides a viable alternative to DFO-based heterobifunctional ligands for preparation of 89Zr-labeled monoclonal antibodies for immunoPET studies. PMID:26941844

  17. Nanoscale intimacy in bifunctional catalysts for selective conversion of hydrocarbons.

    PubMed

    Zečević, Jovana; Vanbutsele, Gina; de Jong, Krijn P; Martens, Johan A

    2015-12-10

    The ability to control nanoscale features precisely is increasingly being exploited to develop and improve monofunctional catalysts. Striking effects might also be expected in the case of bifunctional catalysts, which are important in the hydrocracking of fossil and renewable hydrocarbon sources to provide high-quality diesel fuel. Such bifunctional hydrocracking catalysts contain metal sites and acid sites, and for more than 50 years the so-called intimacy criterion has dictated the maximum distance between the two types of site, beyond which catalytic activity decreases. A lack of synthesis and material-characterization methods with nanometre precision has long prevented in-depth exploration of the intimacy criterion, which has often been interpreted simply as 'the closer the better' for positioning metal and acid sites. Here we show for a bifunctional catalyst--comprising an intimate mixture of zeolite Y and alumina binder, and with platinum metal controllably deposited on either the zeolite or the binder--that closest proximity between metal and zeolite acid sites can be detrimental. Specifically, the selectivity when cracking large hydrocarbon feedstock molecules for high-quality diesel production is optimized with the catalyst that contains platinum on the binder, that is, with a nanoscale rather than closest intimacy of the metal and acid sites. Thus, cracking of the large and complex hydrocarbon molecules that are typically derived from alternative sources, such as gas-to-liquid technology, vegetable oil or algal oil, should benefit especially from bifunctional catalysts that avoid locating platinum on the zeolite (the traditionally assumed optimal location). More generally, we anticipate that the ability demonstrated here to spatially organize different active sites at the nanoscale will benefit the further development and optimization of the emerging generation of multifunctional catalysts. PMID:26659185

  18. Nanoscale intimacy in bifunctional catalysts for selective conversion of hydrocarbons

    NASA Astrophysics Data System (ADS)

    Zecevic, Jovana; Vanbutsele, Gina; de Jong, Krijn P.; Martens, Johan A.

    2015-12-01

    The ability to control nanoscale features precisely is increasingly being exploited to develop and improve monofunctional catalysts. Striking effects might also be expected in the case of bifunctional catalysts, which are important in the hydrocracking of fossil and renewable hydrocarbon sources to provide high-quality diesel fuel. Such bifunctional hydrocracking catalysts contain metal sites and acid sites, and for more than 50 years the so-called intimacy criterion has dictated the maximum distance between the two types of site, beyond which catalytic activity decreases. A lack of synthesis and material-characterization methods with nanometre precision has long prevented in-depth exploration of the intimacy criterion, which has often been interpreted simply as ‘the closer the better’ for positioning metal and acid sites. Here we show for a bifunctional catalyst—comprising an intimate mixture of zeolite Y and alumina binder, and with platinum metal controllably deposited on either the zeolite or the binder—that closest proximity between metal and zeolite acid sites can be detrimental. Specifically, the selectivity when cracking large hydrocarbon feedstock molecules for high-quality diesel production is optimized with the catalyst that contains platinum on the binder, that is, with a nanoscale rather than closest intimacy of the metal and acid sites. Thus, cracking of the large and complex hydrocarbon molecules that are typically derived from alternative sources, such as gas-to-liquid technology, vegetable oil or algal oil, should benefit especially from bifunctional catalysts that avoid locating platinum on the zeolite (the traditionally assumed optimal location). More generally, we anticipate that the ability demonstrated here to spatially organize different active sites at the nanoscale will benefit the further development and optimization of the emerging generation of multifunctional catalysts.

  19. Nanoscale intimacy in bifunctional catalysts for selective conversion of hydrocarbons

    PubMed Central

    Zečević, Jovana; Vanbutsele, Gina; de Jong, Krijn P.; Martens, Johan A.

    2016-01-01

    The ability to precisely control nanoscale features is increasingly exploited to develop and improve monofunctional catalysts1–4. Striking effects might also be expected in the case of bifunctional catalysts, which play an important role in hydrocracking of fossil and renewable hydrocarbon sources to provide high-quality diesel fuel5–7. Such bifunctional hydrocracking catalysts contain metal sites and acid sites, and for more than 50 years the so-called ‘intimacy criterion’8 has dictated the maximum distance between the two site types beyond which catalytic activity decreases. The lack of synthesis and material characterization methods with nanometer precision has long prevented in-depth exploration of the criterion, which has often been interpreted simply as ‘the closer the better’ for positioning metal and acid sites8–11. Here we show for a bifunctional catalyst, comprised of an intimate mixture of zeolite Y and alumina binder and with platinum (Pt) metal controllably deposited20,21 on either the zeolite or the binder, that close proximity between metal and zeolite acid sites can be detrimental: the selectivity when cracking large hydrocarbon feedstock molecules for high-quality diesel production is optimized with the catalyst that contains Pt on the binder, i.e. with a larger distance between metal and acid sites. Cracking of the large and complex hydrocarbon molecules typically derived from alternative sources such as gas-to-liquid technology, vegetable oil or algal oil6–7 should thus benefit especially from bifunctional catalysts that avoid locating Pt on the zeolite as the traditionally assumed optimal location. More generally, we anticipate that the ability to spatially organize different active sites at the nanoscale demonstrated here will benefit the further development and optimization of the newly emerging generation of multifunctional catalysts12–15. PMID:26659185

  20. Liposome encapsulation of chelating agents

    DOEpatents

    Rahman, Yueh Erh

    1976-01-13

    A method for transferring a chelating agent across a cellular membrane by encapsulating the charged chelating agent within liposomes and carrying the liposome-encapsulated chelating agent to the cellular membrane where the liposomes containing the chelating agent will be taken up by the cells, thereby transferring the chelating agent across the cellular membrane. A chelating agent can be introduced into the interior of a cell of a living organism wherein the liposomes will be decomposed, releasing the chelating agent to the interior of the cell. The released chelating agent will complex intracellularly deposited toxic heavy metals, permitting the more soluble metal complex to transfer across the cellular membrane from the cell and subsequently be removed from the living organism.

  1. Cupreines and cupreidines: an established class of bifunctional cinchona organocatalysts.

    PubMed

    Bryant, Laura A; Fanelli, Rossana; Cobb, Alexander J A

    2016-01-01

    Cinchona alkaloids with a free 6'-OH functionality are being increasingly used within asymmetric organocatalysis. This fascinating class of bifunctional catalyst offers a genuine alternative to the more commonly used thiourea systems and because of the different spacing between the functional groups, can control enantioselectivity where other organocatalysts have failed. In the main, this review covers the highlights from the last five years and attempts to show the diversity of reactions that these systems can control. It is hoped that chemists developing asymmetric methodologies will see the value in adding these easily accessible, but underused organocatalysts to their screens. PMID:27340439

  2. Cupreines and cupreidines: an established class of bifunctional cinchona organocatalysts

    PubMed Central

    Bryant, Laura A; Fanelli, Rossana

    2016-01-01

    Summary Cinchona alkaloids with a free 6'-OH functionality are being increasingly used within asymmetric organocatalysis. This fascinating class of bifunctional catalyst offers a genuine alternative to the more commonly used thiourea systems and because of the different spacing between the functional groups, can control enantioselectivity where other organocatalysts have failed. In the main, this review covers the highlights from the last five years and attempts to show the diversity of reactions that these systems can control. It is hoped that chemists developing asymmetric methodologies will see the value in adding these easily accessible, but underused organocatalysts to their screens. PMID:27340439

  3. Structural basis for bifunctional peptide recognition at human δ-opioid receptor.

    PubMed

    Fenalti, Gustavo; Zatsepin, Nadia A; Betti, Cecilia; Giguere, Patrick; Han, Gye Won; Ishchenko, Andrii; Liu, Wei; Guillemyn, Karel; Zhang, Haitao; James, Daniel; Wang, Dingjie; Weierstall, Uwe; Spence, John C H; Boutet, Sébastien; Messerschmidt, Marc; Williams, Garth J; Gati, Cornelius; Yefanov, Oleksandr M; White, Thomas A; Oberthuer, Dominik; Metz, Markus; Yoon, Chun Hong; Barty, Anton; Chapman, Henry N; Basu, Shibom; Coe, Jesse; Conrad, Chelsie E; Fromme, Raimund; Fromme, Petra; Tourwé, Dirk; Schiller, Peter W; Roth, Bryan L; Ballet, Steven; Katritch, Vsevolod; Stevens, Raymond C; Cherezov, Vadim

    2015-03-01

    Bifunctional μ- and δ-opioid receptor (OR) ligands are potential therapeutic alternatives, with diminished side effects, to alkaloid opiate analgesics. We solved the structure of human δ-OR bound to the bifunctional δ-OR antagonist and μ-OR agonist tetrapeptide H-Dmt-Tic-Phe-Phe-NH2 (DIPP-NH2) by serial femtosecond crystallography, revealing a cis-peptide bond between H-Dmt and Tic. The observed receptor-peptide interactions are critical for understanding of the pharmacological profiles of opioid peptides and for development of improved analgesics. PMID:25686086

  4. Structural basis for bifunctional peptide recognition at human δ-opioid receptor

    DOE PAGESBeta

    Fenalti, Gustavo; Zatsepin, Nadia A.; Betti, Cecilia; Giguere, Patrick; Han, Gye Won; Ishchenko, Andrii; Liu, Wei; Guillemyn, Karel; Zhang, Haitao; James, Daniel; et al

    2015-02-16

    Bi-functional μ- and δ- opioid receptor (OR) ligands are potential therapeutic alternatives to alkaloid opiate analgesics with diminished side effects. We solved the structure of human δ-OR bound to the bi-functional δ-OR antagonist and μ-OR agonist tetrapeptide H-Dmt-Tic-Phe-Phe-NH2 (DIPP-NH2) by serial femtosecond crystallography, revealing a cis-peptide bond between H-Dmt and Tic. In summary, the observed receptor-peptide interactions are critical to understand the pharmacological profiles of opioid peptides, and to develop improved analgesics.

  5. Structural basis for bifunctional peptide recognition at human δ-opioid receptor

    SciTech Connect

    Fenalti, Gustavo; Zatsepin, Nadia A.; Betti, Cecilia; Giguere, Patrick; Han, Gye Won; Ishchenko, Andrii; Liu, Wei; Guillemyn, Karel; Zhang, Haitao; James, Daniel; Wang, Dingjie; Weierstall, Uwe; Spence, John C. H.; Boutet, Sébastien; Messerschmidt, Marc; Williams, Garth J.; Gati, Cornelius; Yefanov, Oleksandr M.; White, Thomas A.; Oberthuer, Dominik; Metz, Markus; Yoon, Chun Hong; Barty, Anton; Chapman, Henry N.; Basu, Shibom; Coe, Jesse; Conrad, Chelsie E.; Fromme, Raimund; Fromme, Petra; Tourwé, Dirk; Schiller, Peter W.; Roth, Bryan L.; Ballet, Steven; Katritch, Vsevolod; Stevens, Raymond C.; Cherezov, Vadim

    2015-02-16

    Bi-functional μ- and δ- opioid receptor (OR) ligands are potential therapeutic alternatives to alkaloid opiate analgesics with diminished side effects. We solved the structure of human δ-OR bound to the bi-functional δ-OR antagonist and μ-OR agonist tetrapeptide H-Dmt-Tic-Phe-Phe-NH2 (DIPP-NH2) by serial femtosecond crystallography, revealing a cis-peptide bond between H-Dmt and Tic. In summary, the observed receptor-peptide interactions are critical to understand the pharmacological profiles of opioid peptides, and to develop improved analgesics.

  6. Tailored bifunctional polymer for plutonium monitoring.

    PubMed

    Paul, Sumana; Pandey, Ashok K; Kumar, Pranaw; Kaity, Santu; Aggarwal, Suresh K

    2014-07-01

    Monitoring of actinides with sophisticated conventional methods is affected by matrix interferences, spectral interferences, isobaric interferences, polyatomic interferences, and abundance sensitivity problems. To circumvent these limitations, a self-supported disk and membrane-supported bifunctional polymer were tailored in the present work for acidity-dependent selectivity toward Pu(IV). The bifunctional polymer was found to be better than the polymer containing either a phosphate group or a sulfonic acid group in terms of (i) higher Pu(IV) sorption efficiency at 3-4 mol L(-1) HNO3, (ii) selective preconcentration of Pu(IV) in the presence of a trivalent actinide such as Am(III), and (iii) preferential sorption of Pu(IV) in the presence of a large excess of U(VI). The bifunctional polymer was formed as a self-supported matrix by bulk polymerization and also as a 1-2 μm thin layer anchored on a microporous poly(ether sulfone) by surface grafting. The proportions of sulfonic acid and phosphate groups in both the self-supported disk and membrane-supported bifunctional polymer were found to be the same as expected from the mole proportions of monomers in polymerizing solutions used for syntheses. α radiography by a solid-state nuclear track detector indicated fairly homogeneous anchoring of the bifunctional polymer on the surface of the membrane. Pu(IV) preconcentrated on a single bifunctional bead was used for determination of the Pu isotopic composition by thermal ionization mass spectrometry. The membrane-supported bifunctional polymer was used for preconcentration and subsequent quantification of Pu(IV) by α spectrometry using the absolute efficiency at a fixed counting geometry. The analytical performance of the membrane-supported-bifunctional-polymer-based α spectrometry method was found to be highly reproducible for assay of Pu(IV) in a variety of complex samples. PMID:24901969

  7. Chelating ligands for nanocrystals' surface functionalization.

    PubMed

    Querner, Claudia; Reiss, Peter; Bleuse, Joël; Pron, Adam

    2004-09-22

    A new family of ligands for the surface functionalization of CdSe nanocrystals is proposed, namely alkyl or aryl derivatives of carbodithioic acids (R-C(S)SH). The main advantages of these new ligands are as follows: they nearly quantitatively exchange the initial surface ligands (TOPO) in very mild conditions; they significantly improve the resistance of nanocrystals against photooxidation because of their ability of strong chelate-type binding to metal atoms; their relatively simple preparation via Grignard intermediates facilitates the development of new bifunctional ligands containing, in addition to the anchoring carbodithioate group, a second function, which enables the grafting of molecules or macromolecules of interest on the nanocrystal surface. To give an example of this approach, we report, for the first time, the grafting of an electroactive oligomer from the polyaniline family-aniline tetramer-on CdSe nanocrystals after their functionalization with 4-formyldithiobenzoic acid. The grafting proceeds via a condensation reaction between the aldehyde group of the ligand and the terminal primary amine group of the tetramer. The resulting organic/inorganic hybrid exhibits complete extinction of the fluorescence of its constituents, indicating efficient charge or energy transfer between the organic and the inorganic semiconductors. PMID:15366904

  8. Metal Chelating Crosslinkers Form Nanogels with High Chelation Stability.

    PubMed

    Lux, Jacques; Chan, Minnie; Elst, Luce Vander; Schopf, Eric; Mahmoud, Enas; Laurent, Sophie; Almutairi, Adah

    2013-12-14

    We present a series of hydrogel nanoparticles (nanogels) incorporating either acyclic or cyclic metal chelates as crosslinkers. These crosslinkers are used to formulate polyacrylamide-based nanogels (diameter 50 to 85 nm) yielding contrast agents with enhanced relaxivities (up to 6-fold greater than Dotarem®), because this nanogel structure slows the chelator's tumbling frequency and allows fast water exchange. Importantly, these nanogels also stabilize Gd(3+) within the chelator thermodynamically and kinetically against metal displacement through transmetallation, which should reduce toxicity associated with release of free Gd(3+). This chelation stability suggests that the chelate crosslinker strategy may prove useful for other applications of metal-chelating nanoparticles in medicine, including other imaging modalities and radiotherapy. PMID:24505553

  9. Metal Chelating Crosslinkers Form Nanogels with High Chelation Stability

    PubMed Central

    Elst, Luce Vander; Schopf, Eric; Mahmoud, Enas; Laurent, Sophie; Almutairi, Adah

    2013-01-01

    We present a series of hydrogel nanoparticles (nanogels) incorporating either acyclic or cyclic metal chelates as crosslinkers. These crosslinkers are used to formulate polyacrylamide-based nanogels (diameter 50 to 85 nm) yielding contrast agents with enhanced relaxivities (up to 6-fold greater than Dotarem®), because this nanogel structure slows the chelator's tumbling frequency and allows fast water exchange. Importantly, these nanogels also stabilize Gd3+ within the chelator thermodynamically and kinetically against metal displacement through transmetallation, which should reduce toxicity associated with release of free Gd3+. This chelation stability suggests that the chelate crosslinker strategy may prove useful for other applications of metal-chelating nanoparticles in medicine, including other imaging modalities and radiotherapy. PMID:24505553

  10. Natural chelates for radionuclide decorporation

    DOEpatents

    Premuzic, E.T.

    1983-08-25

    This invention relates to the method and resulting chelates of desorbing a radionuclide selected from thorium, uranium, and plutonium containing cultures in a bioavailable form involving pseudomonas or other microorganisms. A preferred microorganism is Pseudomonas aeruginosa which forms multiple chelates with thorium in the range of molecular weight 1000 to 1000 and also forms chelates with uranium of molecular weight in the area of 100 to 1000 and 1000 to 2000.

  11. Metal chelate process to remove pollutants from fluids

    DOEpatents

    Chang, S.G.T.

    1994-12-06

    The present invention relates to improved methods using an organic iron chelate to remove pollutants from fluids, such as flue gas. Specifically, the present invention relates to a process to remove NO[sub x] and optionally SO[sub 2] from a fluid using a metal ion (Fe[sup 2+]) chelate wherein the ligand is a dimercapto compound wherein the --SH groups are attached to adjacent carbon atoms (HS--C--C--SH) or (SH--C--CCSH) and contain a polar functional group so that the ligand of DMC chelate is water soluble. Alternatively, the DMC is covalently attached to a water insoluble substrate such as a polymer or resin, e.g., polystyrene. The chelate is regenerated using electroreduction or a chemical additive. The dimercapto compound bonded to a water insoluble substrate is also useful to lower the concentration or remove hazardous metal ions from an aqueous solution. 26 figures.

  12. Metal chelate process to remove pollutants from fluids

    DOEpatents

    Chang, Shih-Ger T.

    1994-01-01

    The present invention relates to improved methods using an organic iron chelate to remove pollutants from fluids, such as flue gas. Specifically, the present invention relates to a process to remove NO.sub.x and optionally SO.sub.2 from a fluid using a metal ion (Fe.sup.2+) chelate wherein the ligand is a dimercapto compound wherein the --SH groups are attached to adjacent carbon atoms (HS--C--C--SH) or (SH--C--CCSH) and contain a polar functional group so that the ligand of DMC chelate is water soluble. Alternatively, the DMC' is covalently attached to a water insoluble substrate such as a polymer or resin, e.g., polystyrene. The chelate is regenerated using electroreduction or a chemical additive. The dimercapto compound bonded to a water insoluble substrate is also useful to lower the concentration or remove hazardous metal ions from an aqueous solution.

  13. 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.

  14. 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

  15. 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.

  16. Fluoride ion recognition by chelating and cationic boranes.

    PubMed

    Hudnall, Todd W; Chiu, Ching-Wen; Gabbaï, François P

    2009-02-17

    Because of the ubiquity of fluoride ions and their potential toxicity at high doses, researchers would like to design receptors that selectively detect this anion. Fluoride is found in drinking water, toothpaste, and osteoporosis drugs. In addition, fluoride ions also can be detected as an indicator of uranium enrichment (via hydrolysis of UF(6)) or of the chemical warfare agent sarin, which releases the ion upon hydrolysis. However, because of its high hydration enthalpy, the fluoride anion is one of the most challenging targets for anion recognition. Among the various recognition strategies that are available, researchers have focused a great deal of attention on Lewis acidic boron compounds. These molecules typically interact with fluoride anions to form the corresponding fluoroborate species. In the case of simple triarylboranes, the fluoroborates are formed in organic solvents but not in water. To overcome this limitation, this Account examines various methods we have pursued to increase the fluoride-binding properties of boron-based receptors. We first considered the use of bifunctional boranes, which chelate the fluoride anion, such as 1,8-diborylnaphthalenes or heteronuclear 1-boryl-8-mercurio-naphthalenes. In these molecules, the neighboring Lewis acidic atoms can cooperatively interact with the anionic guest. Although the fluoride binding constants of the bifunctional compounds exceed those of neutral monofunctional boranes by several orders of magnitude, the incompatibility of these systems with aqueous media limits their utility. More recently, we have examined simple triarylboranes whose ligands are decorated by cationic ammonium or phosphonium groups. These cationic groups increase the electrophilic character of these boranes, and unlike their neutral analogs, they are able to complex fluoride in aqueous media. We have also considered cationic boranes, which form chelate complexes with fluoride anions. Our work demonstrates that Coulombic and chelate

  17. Hydroxypyridonate chelating agents and synthesis thereof

    DOEpatents

    Raymond, K.N.; Scarrow, R.C.; White, D.L.

    1985-11-12

    Chelating agents having 1-hydroxy-2-pyridinone (HOPO) and related moieties incorporated within their structures, including polydentate HOPO-substituted polyamines such as spermidine and spermine, and HOPO-substituted desferrioxamine. The chelating agents are useful in selectively removing certain cations from solution, and are particularly useful as ferric ion and actinide chelators. Novel syntheses of the chelating agents are provided. 4 tabs.

  18. Development of novel bifunctional chelating agents containing rigid cyclic hydrocarbon backbones

    SciTech Connect

    Sweet, M.P.; Joshi, V.; Mease, R.C.

    1995-05-01

    We are developing a new class of ligands in which the metal-binding polyaminocarboxylate groups are incorporated onto rigid cyclic hydrocarbon backbones. These ligands, with increased preorganization, should produce radiometal-bioconjugates with higher in-vivo stability. The synthesis of the first in this series of ligands (2,3-diaminobicyclo[2.2.2] octanetetraacetic acid, BODTA) began with a Diels-Alder reaction of 1,3-diacetylimidazolin-2-one and 1,3-cyclohexadiene. Base hydrolysis, alkylation with ethyl iodoacetate, hydrolysis of the esters, and catalytic hydrogenation gave BODTA. For conjugation to MAbs, an average of one COOH group of unsaturated BODTA was converted into an NHS ester using 0.8 equivalent of DCC. The second ligand under development is the decadentate tethered bis-cyclohexyl-EDTA (bis-CDTA) in which 2 cyclohexyl rings are tied together with an ethylene tether. Acylation of monotrityl-1,2-diaminocyclohexane with the di-NHS ester of oxalic acid, reduction of the amide moieties, and removal of the trityl groups followed by cyanomethylation has afforded a hexanitrile whose hydrolysis will produce tethered bis-CDTA. An anti-CEA F(ab{prime}){sub 2} MAb was conjugated with an average of 0.6 BODTA per MAb molecule, labeled with Co-57, and purified by size-exclusion HPLC. Stability of this radioconjugate in mouse serum at 48 h was somewhat better (2% loss) than that of the conventional DTPA-dianhydride (DTPA-DA) conjugate (8% loss). In human tumor-xenografted nude mice (LS-174T cells), tumor (T), blood (B), liver (L), and kidney (K) uptakes (% ID/g) at 24h were: TODTA, 21.6, 4.4, 4.8, 6.0; DTPA-DA, 13.6, 2.5, 5.0, 2.9. The tumor to normal tissue ratios at 48 h for BODTA and DTPA-DA respectively were: T/B, 18.0, 13.9; T/L 4.9, 2.3; T/K, 5.4, 3.9. These preliminary results show promise for using the basic BODTA structure to produce improved bioconjugates with small radiometal ions.

  19. An Efficient Bifunctional Decadentate Ligand 3p-C-DEPA for Targeted Alpha Radioimmunotherapy Applications

    PubMed Central

    Song, Hyun A; Kang, Chi Soo; Baidoo, Kwamena E.; Milenic, Diane E.; Chen, Yunwei; Dai, Anzhi; Brechbiel, M. W.; Chong, Hyun-Soon

    2011-01-01

    A new bifunctional ligand 3p-C-DEPA was synthesized and evaluated for use in targeted alpha radioimmunotherapy. 3p-C-DEPA was efficiently prepared via regiospecific ring opening of an aziridinium ion and conjugated with trastuzumab. The 3p-C-DEPA-trastuzumab conjugate was extremely rapid in binding 205/6Bi, and the corresponding 205/6Bi-3p-C-DEPA-trastuzumab complex was stable in human serum. Biodistribution studies were performed to evaluate in vivo stability and tumor targeting of 205/6Bi-3p-C-DEPA-trastuzumab conjugate in tumor bearing athymic mice. 205/6Bi-3p-C-DEPA-trastuzumab conjugate displayed excellent in vivo stability and targeting as evidenced by low organ uptake and high tumor uptake. The results of the in vitro and in vivo studies indicate that 3p-C-DEPA is a promising chelator for radioimmunotherapy of 212Bi and 213Bi. PMID:21604692

  20. Bifunctional hydrogen bonds in monohydrated cycloether complexes.

    PubMed

    Vallejos, Margarita M; Angelina, Emilio L; Peruchena, Nélida M

    2010-03-01

    In this work, the cooperative effects implicated in bifunctional hydrogen bonds (H-bonds) were studied (in monohydrated six-membered cycloether) within the framework of the atoms in molecules (AIM) theory and of the natural bond orbitals (NBO) analysis. The study was carried out in complexes formed by six-membered cycloether compounds (tetrahydropyrane, 1,4-dioxane, and 1,3-dioxane) and a water molecule. These compounds were used as model systems instead of more complicated molecules of biological importance. All the results were obtained at the second-order Møller-Plesset (MP2) level theory using a 6-311++G(d,p) basis set. Attention was focused on the indicators of the cooperative effects that arise when a water molecule interacts simultaneously with a polar and a nonpolar portion of a six-membered cycloether (via bifunctional hydrogen bonds) and compared with conventional H-bonds where the water molecule only interacts with the polar portion of the cycloether. Different indicators of H-bonds strength, such as structural and spectroscopic data, electron charge density, population analysis, hyperconjugation energy and charge transference, consistently showed significant cooperative effects in bifunctional H-bonds. From the AIM, as well as from the NBO analysis, the obtained results allowed us to state that in the monohydrated six-membered cycloether, where the water molecule plays a dual role, as proton acceptor and proton donor, a mutual reinforcement of the two interactions occurs. Because of this feature, the complexes engaged by bifunctional hydrogen bonds are more stabilized than the complexes linked by conventional hydrogen bonds. PMID:20136161

  1. Questions and Answers on Unapproved Chelation Products

    MedlinePlus

    ... OTC) to prevent or treat diseases. Companies are marketing unapproved OTC chelation therapy products to patients with ... 4. Why did FDA take this action? Companies marketing unapproved OTC chelation products with unsubstantiated treatment claims ...

  2. Hydroxypyridonate and hydroxypyrimidinone chelating agents

    SciTech Connect

    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.

  3. Natural chelating agents for radionuclide decorporation

    DOEpatents

    Premuzic, Eugene T.

    1988-01-01

    This invention relates to the preparation of new, naturally produced chelating agents as well as to the method and resulting chelates of desorbing cultures in a bioavailable form involving Pseudomonas species or other microorganisms. A preferred microorganism is Pseudomonas aeruginosa which forms multiple chelates with thorium in the range of molecular weight 100-1,000 and also forms chelates with uranium of molecular weight in the area of 100-1,000 and 1,000-2,000.

  4. Development of Cobalt Hydroxide as a Bifunctional Catalyst for Oxygen Electrocatalysis in Alkaline Solution.

    PubMed

    Zhan, Yi; Du, Guojun; Yang, Shiliu; Xu, Chaohe; Lu, Meihua; Liu, Zhaolin; Lee, Jim Yang

    2015-06-17

    Co(OH)2 in the form of hexagonal nanoplates synthesized by a simple hydrothermal reaction has shown even greater activity than cobalt oxides (CoO and Co3O4) in oxygen reduction and oxygen evolution reactions (ORR and OER) under alkaline conditions. The bifunctionality for oxygen electrocatalysis as shown by the OER-ORR potential difference (ΔE) could be reduced to as low as 0.87 V, comparable to the state-of-the-art non-noble bifunctional catalysts, when the Co(OH)2 nanoplates were compounded with nitrogen-doped reduced graphene oxide (N-rGO). The good performance was attributed to the nanosizing of Co(OH)2 and the synergistic interaction between Co(OH)2 and N-rGO. A zinc-air cell assembled with a Co(OH)2-air electrode also showed a performance comparable to that of the state-of-the-art zinc-air cells. The combination of bifunctional activity and operational stability establishes Co(OH)2 as an effective low-cost alternative to the platinum group metal catalysts. PMID:25997179

  5. A rapid assay for evaluation of iron-chelating agents in rats

    SciTech Connect

    Pippard, M.J.; Johnson, D.K.; Finch, C.A.

    1981-10-01

    The animal assay of potential new iron-chelating agents is at present dependent on cumbersome and imprecise iron balance studies in hypertransfused rodents. We report the development of a radioisotope assay in intact rats based on the transient labeling by ferritin 59Fe of the main source of chelatable iron within hepatocytes. The isotope was maximally available to chelators during the first 6 hr after its injection, nearly all the excretion being in the bile. The bile 59Fe/total iron ratio was independent of both the chelator and its dose. However, in iron-loaded rats, the ratio was reduced, and the isotope excretion was a less sensitive measure of intrahepatic chelation. In the proposed assay, test chelators were given to normal rats 2 hr after an intravenous injection of 59Fe-ferritin. Four hours later, the radioiron in the liver and in the gut gave a sensitive measure of the mobilization of hepatic iron to the bile. In addition, chemical iron determinations identified a small alternative source of urinary chelate with agents known to promote urine excretion in man. The assay gave a rapid and precise screen for chelators given by parenteral and oral routes.

  6. 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.

  7. Some Linguistic Detail on Chelation

    NASA Astrophysics Data System (ADS)

    Haworth, Daniel T.

    1998-01-01

    The term chelate was first applied by Morgan and Drew in 1920 to describe the heterocyclic rings formed from bidentate ligands bonding to a central atom. The history of the word ch_l_ is traced from its original Greek meaning through the Latin language to its anglicized form, chela. This word has a very rich history and has been cited by both Greek (Aristotle) and Latin (Cicero, Vergil) philosophers and poets.

  8. Chelating agents and cadmium intoxication

    SciTech Connect

    Shinobu, L.A.

    1985-01-01

    A wide range of conventional chelating agents have been screened for (a) antidotal activity in acute cadmium poisoning and (b) ability to reduce aged liver and kidney deposits of cadmium. Chelating agents belonging to the dithiocarbamate class have been synthesized and tested in both the acute and chronic modes of cadmium intoxication. Several dithiocarbamates, not only provide antidotal rescue, but also substantially decrease the intracellular deposits of cadmium associated with chronic cadmium intoxication. Fractionating the cytosol from the livers and kidneys of control and treated animals by Sephadex G-25 gel filtration clearly demonstrates that the dithiocarbamates are reducing the level of metallothionein-bound cadmium. However, the results of cell culture (Ehrlich ascites) studies designed to investigate the removal of cadmium from metallothionein and subsequent transport of the resultant cadmium complex across the cell membrane were inconclusive. In other in vitro investigations, the interaction between isolated native Cd, Zn-metallothionein and several chelating agents was explored. Ultracentrifugation, equilibrium dialysis, and Sephadex G-25 gel filtration studies have been carried out in an attempt to determine the rate of removal of cadmium from metallothionein by these small molecules. Chemical shifts for the relevant cadmium-dithiocarbamate complexes have been determined using natural abundance Cd-NMR.

  9. High-yielding aqueous 18F-labeling of peptides via Al18F chelation.

    PubMed

    D'Souza, Christopher A; McBride, William J; Sharkey, Robert M; Todaro, Louis J; Goldenberg, David M

    2011-09-21

    The coordination chemistry of a new pentadentate bifunctional chelator (BFC), NODA-MPAA 1, containing the 1,4,7-triazacyclononane-1,4-diacetate (NODA) motif with a methylphenylacetic acid (MPAA) backbone, and its ability to form stable Al(18)F chelates were investigated. The organofluoroaluminates were easily accessible from the reaction of 1 and AlF(3). X-ray diffraction studies revealed aluminum at the center of a slightly distorted octahedron, with fluorine occupying one of the axial positions. The tert-butyl protected prochelator 7, which can be synthesized in one step, is useful for coupling to biomolecules on solid phase or in solution. High yield (55-89%) aqueous (18)F-labeling was achieved in 10-15 min with a tumor-targeting peptide 4 covalently linked to 1. Defluorination was not observed for at least 4 h in human serum at 37 °C. These results demonstrate the facile application of Al(18)F chelation using BFC 1 as a versatile labeling method for radiofluorinating other heat-stable peptides for positron emission imaging. PMID:21805975

  10. Winged bean [Psophorcarpus tetragonolobus (L.) DC] seeds as an underutilised plant source of bifunctional proteolysate and biopeptides.

    PubMed

    Yea, Chay Shyan; Ebrahimpour, Afshin; Hamid, Azizah Abdul; Bakar, Jamilah; Muhammad, Kharidah; Saari, Nazamid

    2014-05-01

    Hypertension is one of the major causes of cardiovascular-related diseases, which is highly associated with angiotensin-I-converting enzyme (ACE) activity and oxidative stress. In this study, winged bean seed (WBS), a potential source of protein, was utilised for the production of bifunctional proteolysate and biopeptides with ACE inhibitory and antioxidative properties. An enzymatic approach was applied, coupled with pretreatment of shaking and centrifuging techniques to remove endogenous ACE inhibitors prior to proteolysis. ACE inhibition reached its highest activity, 78.5%, after 12 h proteolysis while antioxidative activities, determined using assays involving DPPH˙ radical scavenging activity and metal ion-chelating activity, reached peaks of 65.0% and 65.7% at 8 h and 14 h, respectively. The said bioactivities were proposed to share some common structural requirements among peptides. A two-dimensional approach was employed for characterisation of effective peptides based on hydrophobicity, using RP-HPLC, and isoelectric property, using isoelectric focusing technique. Results revealed that acidic and basic peptides with partially higher hydrophobicity provided higher ACE inhibition activity than did neutral peptides. Finally, by using Q-TOF mass spectrometry, two peptide sequences (YPNQKV and FDIRA) with ACE inhibitory and antioxidative activities were successfully matched with a database. This study indicates that the WBS proteolysate can be a potential bifunctional food ingredient as the identified biopeptides demonstrated both ACE inhibitory and antioxidative activities in vitro. PMID:24658538

  11. Beliefs about chelation among thalassemia patients

    PubMed Central

    2012-01-01

    Background Understanding patients’ views about medication is crucial to maximize adherence. Thalassemia is a congenital blood disorder requiring chronic blood transfusions and daily iron chelation therapy. Methods The Beliefs in Medicine Questionnaire (BMQ) was used to assess beliefs in chelation in thalassemia patients from North America and London in the Thalassemia Longitudinal Cohort (TLC) of the Thalassemia Clinical Research Network (TCRN). Chelation adherence was based on patient report of doses administered out of those prescribed in the last four weeks. Results Of 371 patients (ages 5-58y, mean 24y), 93% were transfused and 92% receiving chelation (26% deferoxamine (DFO; a slow subcutaneous infusion via portable pump), 63% oral, 11% combination). Patients expressed high “necessity” for transfusion (96%), DFO chelation (92%) and oral chelation (89%), with lower “concern” about treatment (48%, 39%, 19% respectively). Concern about oral chelation was significantly lower than that of DFO (p<0.001). Self-reported adherence to chelation was not associated with views about necessity or concerns, but negatively correlated with perceived sensitivity to DFO (Sensitive Soma scale; r=−0.23, p=0.01) and side effects of oral chelation (r=−0.14, p=0.04). High ferritin iron levels, potentially indicating lower adherence, were found in 41% of patients reporting low necessity of oral chelation compared to 24% reporting high necessity (p=0.048). Concerns about treatment were associated with lower quality of life and more symptoms of anxiety and depression. Conclusions Despite their requirement for multimodal therapy, thalassemia patients have positive views about medicine, more so than in other disease populations. Patients may benefit from education about the tolerability of chelation and strategies to effectively cope with side effects, both of which might be beneficial in lowering body iron burden. Clinicaltrials.gov identifier NCT00661804 PMID:23216870

  12. Phosphinic acid functionalized polyazacycloalkane chelators for radiodiagnostics and radiotherapeutics: unique characteristics and applications.

    PubMed

    Notni, Johannes; Šimeček, Jakub; Wester, Hans-Jürgen

    2014-06-01

    Given the wide application of positron emission tomography (PET), positron-emitting metal radionuclides have received much attention recently. Of these, gallium-68 has become particularly popular, as it is the only PET nuclide commercially available from radionuclide generators, therefore allowing local production of PET radiotracers independent of an on-site cyclotron. Hence, interest in optimized bifunctional chelators for the elaboration of (68) Ga-labeled bioconjugates has been rekindled as well, resulting in the development of improved triazacyclononane-triphosphinate (TRAP) ligand structures. The most remarkable features of these ligands are unparalleled selectivity for Ga(III) , rapid Ga(III) complexation kinetics, extraordinarily high thermodynamic stability, and kinetic inertness of the respective Ga(III) chelates. As a result, TRAP chelators exhibit very favorable (68) Ga-labeling properties. Based on the scaffolds NOPO (1,4,7-triazacyclononane-1,4-bis[methylene(hydroxymethyl)phosphinic acid]-7-[methylene(2-carboxyethyl)phosphinic acid]) and TRAP-Pr, tailored for convenient preparation of (68) Ga-labeled monomeric and multimeric bioconjugates, a variety of novel (68) Ga radiopharmaceuticals have been synthesized. These include bisphosphonates, somatostatin receptor ligands, prostate-specific membrane antigen (PSMA)-targeting peptides, and cyclic RGD pentapeptides, for in vivo PET imaging of bone, neuroendocrine tumors, prostate cancer, and integrin expression, respectively. Furthermore, TRAP-based (68) Ga-labeled gadolinium(III) complexes have been proposed as bimodal probes for PET/MRI, and a cyclen-based analogue of TRAP-Pr has been suggested for the elaboration of targeted radiotherapeutics comprising radiolanthanide ions. Thus, polyazacycloalkane-based polyphosphinic acid chelators are a powerful toolbox for pharmaceutical research, particularly for the development of (68) Ga radiopharmaceuticals. PMID:24700633

  13. 68Ga-PET radiopharmacy: A generator-based alternative to 18F-radiopharmacy.

    PubMed

    Maecke, H R; André, J P

    2007-01-01

    Positron emission tomography (PET) is becoming a dominating method in the field of molecular imaging. Most commonly used radionuclides are accelerator produced 11C and 18F. An alternative method to label biomolecules is the use of metallic positron emitters; among them 68Ga is the most promising as it can be produced from a generator system consisting of an inorganic or organic matrix immobilizing the parent radionuclide 68Ge. Germanium-68 has a long half-life of 271 days which allows the production of long-lived, potentially very cost-effective generator systems. A commercial generator from Obninsk, Russia, is available which uses TiO2 as an inorganic matrix to immobilize 68Ge in the oxidation state IV+. 68Ge(IV) is chemically sufficiently different to allow efficient separation from 68Ga(III). Ga3+ is redox-inert; its coordination chemistry is dominated by its hard acid character. A variety of mono- and bifunctional chelators were developed which allow immobilization of 68Ga3+ and convenient coupling to biomolecules. Especially peptides targeting G-protein coupled receptors overexpressed on human tumour cells have been studied preclinically and in patient studies showing high and specific tumour uptake and specific localization. 68Ga-radiopharmacy may indeed be an alternative to 18F-based radiopharmacy. Freeze-dried, kit-formulated precursors along with the generator may be provided, similar to the 99Mo/99mTc-based radiopharmacy, still the mainstay of nuclear medicine. PMID:17172157

  14. Metal ions, Alzheimer's disease and chelation therapy.

    PubMed

    Budimir, Ana

    2011-03-01

    In the last few years, various studies have been providing evidence that metal ions are critically involved in the pathogenesis of major neurological diseases (Alzheimer, Parkinson). Metal ion chelators have been suggested as potential therapies for diseases involving metal ion imbalance. Neurodegeneration is an excellent target for exploiting the metal chelator approach to therapeutics. In contrast to the direct chelation approach in metal ion overload disorders, in neurodegeneration the goal seems to be a better and subtle modulation of metal ion homeostasis, aimed at restoring ionic balance. Thus, moderate chelators able to coordinate deleterious metals without disturbing metal homeostasis are needed. To date, several chelating agents have been investigated for their potential to treat neurodegeneration, and a series of 8-hydroxyquinoline analogues showed the greatest potential for the treatment of neurodegenerative diseases. PMID:21406339

  15. Bifunctional Phosphorus Dendrimers and Their Properties.

    PubMed

    Caminade, Anne-Marie; Majoral, Jean-Pierre

    2016-01-01

    Dendrimers are hyperbranched and monodisperse macromolecules, generally considered as a special class of polymers, but synthesized step-by-step. Most dendrimers have a uniform structure, with a single type of terminal function. However, it is often desirable to have at least two different functional groups. This review will discuss the case of bifunctional phosphorus-containing dendrimers, and the consequences for their properties. Besides the terminal functions, dendritic structures may have also a function at the core, or linked off-center to the core, or at the core of dendrons (dendritic wedges). Association of two dendrons having different terminal functions leads to Janus dendrimers (two faces). The internal structure can also possess functional groups on one layer, or linked to one layer, or on several layers. Finally, there are several ways to have two types of terminal functions, besides the case of Janus dendrimers: either each terminal function bears two functions sequentially, or two different functions are linked to each terminal branching point. Examples of each type of structure will be given in this review, as well as practical uses of such sophisticated structures in the fields of fluorescence, catalysis, nanomaterials and biology. PMID:27120586

  16. Interdomain communications in bifunctional enzymes: how are different activities coordinated?

    PubMed

    Nagradova, Natalya

    2003-08-01

    Although bifunctional enzymes containing two different active centers located within separate domains are quite common in living systems, the significance of this bifunctionality is not always clear, and the molecular mechanisms of site-site interactions in such complex systems have come under the scrutiny of science only in recent years. This review summarizes recent data on the mechanisms of communication between active centers in bifunctional enzymes. Three types of enzymes are considered: (1) those catalyzing consecutive reactions of a metabolic pathway and exhibiting substrate channeling (glutamate synthase and imidazole glycerol phosphate synthase), (2) those catalyzing consecutive reactions without substrate channeling (lysine-ketoglutarate reductase/saccharopine dehydrogenase), and (3) those catalyzing opposed reactions (6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase). The functional role of interdomain communications is briefly discussed. PMID:14609201

  17. Natural chelating agents for radionuclide decorporation

    DOEpatents

    Premuzic, E.T.

    1985-06-11

    This invention relates to the production of metal-binding compounds useful for the therapy of heavy metal poisoning, for biological mining and for decorporation of radionuclides. The present invention deals with an orderly and effective method of producing new therapeutically effective chelating agents. This method uses challenge biosynthesis for the production of chelating agents that are specific for a particular metal. In this approach, the desired chelating agents are prepared from microorganisms challenged by the metal that the chelating agent is designed to detoxify. This challenge induces the formation of specific or highly selective chelating agents. The present invention involves the use of the challenge biosynthetic method to produce new complexing/chelating agents that are therapeutically useful to detoxify uranium, plutonium, thorium and other toxic metals. The Pseudomonas aeruginosa family of organisms is the referred family of microorganisms to be used in the present invention to produce the new chelating agent because this family is known to elaborate strains resistant to toxic metals.

  18. Novel bifunctional natriuretic peptides as potential therapeutics.

    PubMed

    Dickey, Deborah M; Burnett, John C; Potter, Lincoln R

    2008-12-12

    Synthetic atrial natriuretic peptide (carperitide) and B-type natriuretic peptide (BNP; nesiritide) are used to treat congestive heart failure. However, despite beneficial cardiac unloading properties, reductions in renal perfusion pressures limit their clinical effectiveness. Recently, CD-NP, a chimeric peptide composed of C-type natriuretic peptide (CNP) fused to the C-terminal tail of Dendroaspis natriuretic peptide (DNP), was shown to be more glomerular filtration rate-enhancing than BNP in dogs. However, the molecular basis for the increased responsiveness was not determined. Here, we show that the DNP tail has a striking effect on CNP, converting it from a non-agonist to a partial agonist of natriuretic peptide receptor (NPR)-A while maintaining the ability to activate NPR-B. This effect is specific for human receptors because CD-NP was only a slightly better activator of rat NPR-A due to the promiscuous nature of CNP in this species. Interesting, the DNP tail alone had no effect on any NPR even though it is effective in vivo. To further increase the potency of CD-NP for NPR-A, we converted two different triplet sequences within the CNP ring to their corresponding residues in BNP. Both variants demonstrated increased affinity and full agonist activity for NPR-A, whereas one was as potent as any NPR-A activator known. In contrast to a previous report, we found that DNP binds the natriuretic peptide clearance receptor (NPR-C). However, none of the chimeric peptides bound NPR-C with significantly higher affinity than endogenous ligands. We suggest that bifunctional chimeric peptides represent a new generation of natriuretic peptide therapeutics. PMID:18940797

  19. Novel Bifunctional Natriuretic Peptides as Potential Therapeutics*

    PubMed Central

    Dickey, Deborah M.; Burnett, John C.; Potter, Lincoln R.

    2008-01-01

    Synthetic atrial natriuretic peptide (carperitide) and B-type natriuretic peptide (BNP; nesiritide) are used to treat congestive heart failure. However, despite beneficial cardiac unloading properties, reductions in renal perfusion pressures limit their clinical effectiveness. Recently, CD-NP, a chimeric peptide composed of C-type natriuretic peptide (CNP) fused to the C-terminal tail of Dendroaspis natriuretic peptide (DNP), was shown to be more glomerular filtration rate-enhancing than BNP in dogs. However, the molecular basis for the increased responsiveness was not determined. Here, we show that the DNP tail has a striking effect on CNP, converting it from a non-agonist to a partial agonist of natriuretic peptide receptor (NPR)-A while maintaining the ability to activate NPR-B. This effect is specific for human receptors because CD-NP was only a slightly better activator of rat NPR-A due to the promiscuous nature of CNP in this species. Interesting, the DNP tail alone had no effect on any NPR even though it is effective in vivo. To further increase the potency of CD-NP for NPR-A, we converted two different triplet sequences within the CNP ring to their corresponding residues in BNP. Both variants demonstrated increased affinity and full agonist activity for NPR-A, whereas one was as potent as any NPR-A activator known. In contrast to a previous report, we found that DNP binds the natriuretic peptide clearance receptor (NPR-C). However, none of the chimeric peptides bound NPR-C with significantly higher affinity than endogenous ligands. We suggest that bifunctional chimeric peptides represent a new generation of natriuretic peptide therapeutics. PMID:18940797

  20. Bi-functional air electrodes for metal-air batteries. Final report, September 15, 1993--December 14, 1994

    SciTech Connect

    Swette, L.L.; Manoukian, M.; LaConti, A.B.

    1995-12-01

    The program was directed to the need for development of bifunctional air electrodes for Zn-Air batteries for the consumer market. The Zn-Air system, widely used as a primary cell for hearing-aid batteries and as a remote-site power source in industrial applications, has the advantage of high energy density, since it consumes oxygen from the ambient air utilizing a thin, efficient fuel-cell-type gas-diffusion electrode, and is comparatively low in cost. The disadvantages of the current technology are a relatively low rate capability, and the lack of simple reversibility. {open_quotes}Secondary{close_quotes} Zn-Air cells require a third electrode for oxygen evolution or mechanical replacement of the Zinc anodes; thus the development of a bifunctional air electrode (i.e., an electrode that can alternately consume and evolve oxygen) would be a significant advance in Zn-Air cell technology. Evaluations of two carbon-free non-noble metal perovskite-type catalyst systems, La{sub 1-x}CA{sub x}CoO{sub 3} as bifunctional catalysts for potential application in Zn-air batteries were carried out. The technical objectives were to develop higher-surface-area materials and to fabricate reversible electrodes by modifying the hydrophobic/hydrophilic balance of the catalyst-binder structures.

  1. [Purification of Cu-67 and Macrocyclic chelates for targeted therapy]. DOE annual report, 1993--94

    SciTech Connect

    DeNardo, S.J.

    1994-12-31

    {sup 67}Cu produced at the Brookhaven Linac Isotope Producer (BLIP) is purified from zinc target material and coproduced radioisotopes of cobalt, chromium, nickel, and gallium by a multi-step extraction process. This procedure introduces applicable amounts of cold copper into the sample, lowering the specific activity of the {sup 67}Cu. Because of this, the {sup 67}Cu produced at BLIP is not of high enough activity for use in radioimmunotherapy procedures. It is their goal to develop a procedure with which to purify {sup 67}Cu from the other radioisotopes produced, while at the same time minimize the amount of cold copper introduced into the system. There are two different approaches that they devised for the purification of {sup 67}Cu. They are an extraction method similar to what is used at Brookhaven already, and a copper affinity column. Bifunctional macrocyclic chelates have been developed to conjugate metals to antibodies, and metal chelated antibodies have been shown to have slower clearance from the tumor than iodinated antibodies. This provides a mechanism for increasing tumor radiation dose and the therapeutic index. Conditions for {sup 67}Cu radiolabeling of TETA immunoconjugates have been optimized, leading to rapid, quantitative complexation of metal binding sites, further contributing to high radioactive yield and to the routine production of {sup 67}Cu radiolabed immunoconjugates of therapeutic quality.

  2. Chelation therapy and cardiovascular disease: connecting scientific silos to benefit cardiac patients.

    PubMed

    Peguero, Julio G; Arenas, Ivan; Lamas, Gervasio A

    2014-08-01

    Medical practitioners have treated atherosclerotic disease with chelation therapy for over 50 years. Lack of strong of evidence led conventional practitioners to abandon its use in the 1960s and 1970s. This relegated chelation therapy to complementary and alternative medicine practitioners, who reported good anecdotal results. Concurrently, the epidemiologic evidence linking xenobiotic metals with cardiovascular disease and mortality gradually accumulated, suggesting a plausible role for chelation therapy. On the basis of the continued use of chelation therapy without an evidence base, the National Institutes of Health released a Request for Applications for a definitive trial of chelation therapy. The Trial to Assess Chelation Therapy (TACT) was formulated as a 2 × 2 factorial randomized controlled trial of intravenous EDTA-based chelation vs. placebo and high-dose oral multivitamins and multiminerals vs. oral placebo. The composite primary endpoint was death, reinfarction, stroke, coronary revascularization, or hospitalization for angina. A total of 1708 post-MI patients who were 50 years or older with a creatinine of 2.0 or less were enrolled and received 55,222 infusions of disodium EDTA or placebo with a median follow-up of 55 months. Patients were on evidence-based post-MI medications including statins. EDTA proved to be safe. EDTA chelation therapy reduced cardiovascular events by 18%, with a 5-year number needed to treat (NNT) of 18. Prespecified subgroup analysis revealed a robust benefit in patients with diabetes mellitus with a 41% reduction in the primary endpoint (5-year NNT = 6.5), and a 43% 5-year relative risk reduction in all-cause mortality (5-year NNT = 12). The magnitude of benefit is such that it suggests urgency in replication and implementation, which could, due to the excellent safety record, occur simultaneously. PMID:25106084

  3. Positron emission tomographic imaging of copper 64- and gallium 68-labeled chelator conjugates of the somatostatin agonist tyr3-octreotate.

    PubMed

    Nedrow, Jessie R; White, Alexander G; Modi, Jalpa; Nguyen, Kim; Chang, Albert J; Anderson, Carolyn J

    2014-01-01

    The bifunctional chelator and radiometal have been shown to have a direct effect on the pharmacokinetics of somatostatin receptor (SSTR)-targeted imaging agents. We evaluated three Y3-TATE analogues conjugated to NOTA-based chelators for radiolabeling with 64Cu and 68Ga for small-animal positron emission tomographic/computed tomographic (PET/CT) imaging. Two commercially available NOTA analogues, p-SCN-Bn-NOTA and NODAGA, were evaluated. The p-SCN-Bn-NOTA analogues were conjugated to Y3-TATE through β-Ala and PEG8 linkages. The NODAGA chelator was directly conjugated to Y3-TATE. The analogues labeled with 64Cu or 68Ga were analyzed in vitro for binding affinity and internalization and in vivo by PET/CT imaging, biodistribution, and Cerenkov imaging (68Ga analogues). We evaluated the effects of the radiometals, chelators, and linkers on the performance of the SSTR subtype 2--targeted imaging agents and also compared them to a previously reported agent, 64Cu-CB-TE2A-Y3-TATE. We found that the method of conjugation, particularly the length of the linkage between the chelator and the peptide, significantly impacted tumor and nontarget tissue uptake and clearance. Among the 64Cu- and 68Ga-labeled NOTA analogues, NODAGA-Y3-TATE had the most optimal in vivo behavior and was comparable to 64Cu-CB-TE2A-Y3-TATE. An advantage of NODAGA-Y3-TATE is that it allows labeling with 64Cu and 68Ga, providing a versatile PET probe for imaging SSTr subtype 2-positive tumors. PMID:25060207

  4. Biochemical and Structural Characterization of the Arabidopsis Bifunctional Enzyme Dethiobiotin Synthetase–Diaminopelargonic Acid Aminotransferase: Evidence for Substrate Channeling in Biotin Synthesis[C][W

    PubMed Central

    Cobessi, David; Dumas, Renaud; Pautre, Virginie; Meinguet, Céline; Ferrer, Jean-Luc; Alban, Claude

    2012-01-01

    Diaminopelargonic acid aminotransferase (DAPA-AT) and dethiobiotin synthetase (DTBS) catalyze the antepenultimate and the penultimate steps, respectively, of biotin synthesis. Whereas DAPA-AT and DTBS are encoded by distinct genes in bacteria, in biotin-synthesizing eukaryotes (plants and most fungi), both activities are carried out by a single enzyme encoded by a bifunctional gene originating from the fusion of prokaryotic monofunctional ancestor genes. In few angiosperms, including Arabidopsis thaliana, this chimeric gene (named BIO3-BIO1) also produces a bicistronic transcript potentially encoding separate monofunctional proteins that can be produced following an alternative splicing mechanism. The functional significance of the occurrence of a bifunctional enzyme in biotin synthesis pathway in eukaryotes and the relative implication of each of the potential enzyme forms (bifunctional versus monofunctional) in the plant biotin pathway are unknown. In this study, we demonstrate that the BIO3-BIO1 fusion protein is the sole protein form produced by the BIO3-BIO1 locus in Arabidopsis. The enzyme catalyzes both DAPA-AT and DTBS reactions in vitro and is targeted to mitochondria in vivo. Our biochemical and kinetic characterizations of the pure recombinant enzyme show that in the course of the reaction, the DAPA intermediate is directly transferred from the DAPA-AT active site to the DTBS active site. Analysis of several structures of the enzyme crystallized in complex with and without its ligands reveals key structural elements involved for acquisition of bifunctionality and brings, together with mutagenesis experiments, additional evidences for substrate channeling. PMID:22547782

  5. H4octapa-Trastuzumab: Versatile Acyclic Chelate System for 111In and 177Lu Imaging and Therapy

    PubMed Central

    Price, Eric W.; Zeglis, Brian M.; Cawthray, Jacqueline F.; Ramogida, Caterina F.; Ramos, Nicholas

    2013-01-01

    A bifunctional derivative of the versatile acyclic chelator H4octapa, p-SCNBn- H4octapa, has been synthesized for the first time. The chelator was conjugated to the HER2/neu-targeting antibody trastuzumab and labeled in high radiochemical purity and specific activity with the radioisotopes 111In and 177Lu. The in vivo behavior of the resulting radioimmunoconjugates was investigated in mice bearing ovarian cancer xenografts and compared to analogous radioimmunoconjugates employing the ubiquitous chelator DOTA. The H4octapa-trastuzumab conjugates displayed faster radiolabeling kinetics with more reproducible yields under milder conditions (15 min, RT, ~94–95%) than those based on DOTA-trastuzumab (60 min, 37 °C ~50–88%). Further, antibody integrity was better preserved in the 111In- and 177Lu-octapatrastuzumab constructs, with immunoreactive fractions of 0.99 for each compared to 0.93–0.95 for 111In- and 177Lu-DOTA-trastuzumab. These results translated to improved in vivo biodistribution profiles and SPECT imaging results for 111In- and 177Lu-octapa-trastuzumab compared to 111In- and 177Lu-DOTA-trastuzumab, with increased tumor uptake and higher tumor-to-tissue activity ratios. PMID:23901833

  6. Iron-chelating activity of chickpea protein hydrolysate peptides.

    PubMed

    Torres-Fuentes, Cristina; Alaiz, Manuel; Vioque, Javier

    2012-10-01

    Chickpea-chelating peptides were purified and analysed for their iron-chelating activity. These peptides were purified after affinity and gel filtration chromatography from a chickpea protein hydrolysate produced with pepsin and pancreatin. Iron-chelating activity was higher in purified peptide fractions than in the original hydrolysate. Histidine contents were positively correlated with the iron-chelating activity. Hence fractions with histidine contents above 20% showed the highest chelating activity. These results show that iron-chelating peptides are generated after chickpea protein hydrolysis with pepsin plus pancreatin. These peptides, through metal chelation, may increase iron solubility and bioavailability and improve iron absorption. PMID:25005984

  7. Fluid extraction using carbon dioxide and organophosphorus chelating agents

    DOEpatents

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

    1998-11-24

    Methods for extracting metalloid and metal species from a solid or liquid material by exposing the material to a fluid solvent, particularly supercritical CO{sub 2}, and a chelating agent are described. The chelating agent forms a chelate with the species, the chelate being soluble in the fluid to allow removal of the species from the material. In preferred embodiments the extraction solvent is supercritical CO{sub 2} and the chelating agent comprises an organophosphorous chelating agent, particularly sulfur-containing organophosphorous chelating agents, including mixtures of chelating agents. Examples of chelating agents include monothiophosphinic acid, di-thiophosphinic acid, phosphine sulfite, phosphorothioic acid, and mixtures thereof. The method provides an environmentally benign process for removing metal and metalloids from industrial waste solutions, particularly acidic solutions. Both the chelate and the supercritical fluid can be regenerated and the contaminant species recovered to provide an economic, efficient process. 1 fig.

  8. Fluid extraction using carbon dioxide and organophosphorus chelating agents

    DOEpatents

    Smart, Neil G.; Wai, Chien M.; Lin, Yuehe; Kwang, Yak Hwa

    1998-01-01

    Methods for extracting metalloid and metal species from a solid or liquid material by exposing the material to a fluid solvent, particularly supercritical CO.sub.2, and a chelating agent are described. The chelating agent forms a chelate with the species, the chelate being soluble in the fluid to allow removal of the species from the material. In preferred embodiments the extraction solvent is supercritical CO.sub.2 and the chelating agent comprises an organophosphorous chelating agent, particularly sulfur-containing organophosphorous chelating agents, including mixtures of chelating agents. Examples of chelating agents include monothiophosphinic acid, di-thiophosphinic acid, phosphine sulfite, phosphorothioic acid, and mixtures thereof. The method provides an environmentally benign process for removing metal and metalloids from industrial waste solutions, particularly acidic solutions. Both the chelate and the supercritical fluid can be regenerated and the contaminant species recovered to provide an economic, efficient process.

  9. Bifunctional mesoporous silicas with clearly distinguished localization of grafted groups

    NASA Astrophysics Data System (ADS)

    Roik, N. V.; Belyakova, L. A.

    2013-12-01

    Bifunctional mesoporous silicas with clearly distinguished localization of grafted groups on the surface of particles and inside their pores were obtained by means of sol-gel synthesis with postsynthetic vapor-phase treatment in vacuum. It was found that the synthesized materials have the hexagonally ordered porous structure typical of MCM-41 type silica.

  10. Clinical studies with In-111 BLEDTA, a tumor-imaging conjugate of bleomycin with a bifunctional chelating agent

    SciTech Connect

    Goodwin, D.A.; Meares, C.F.; DeRiemer, L.H.; Diamanti, C.I.; Goode, R.L.; Baumert, J.E. Jr.; Sartoris, D.J.; Lantieri, R.L.; Fawcett, H.D.

    1981-09-01

    Indium-111 BLEDTA, a bleomycin analog containing an EDTA group, was used for tumor imaging in 110 patients with cancer. Scans with In-111 BLEDTA agreed with biopsy results in 75 of 95 patients (79% accuracy). A positive scan was obtained in 71 of 88 patients with a positive biopsy (81% sensitivity). In 21 of 95 patients (22%), the scan revealed tumor sites that had not been detected. The main limitation of visualization was the size of the tumor (1.5--2.0 cm diameter was the smallest size seen). Background radioactivity in the liver, spleen, and bone marrow also made tumor detection in these areas more difficult. The cause of this background, and of false-positive uptake in sites of inflammation, is correlated with specific radiolabeling of polymorphonuclear leukocytes by In-111 BLEDTA. Means of eliminating this background are discussed.

  11. Gadolinium Nanoparticles Conjugated with Therapeutic Bifunctional Chelate as a Potential T1 Theranostic Magnetic Resonance Imaging Agent.

    PubMed

    Kang, Min-Kyoung; Lee, Gang Ho; Jung, Ki-Hye; Jung, Jae-Chang; Kim, Hee-Kyung; Kim, Yeon-Hee; Lee, Jongmin; Ryeom, Hun-Kyu; Kim, Tae-Jeong; Chang, Yongmin

    2016-05-01

    This work is directed toward the synthesis of two types of gadolinium oxide nanoparticles (Gd-oxide NPs), abbreviated as Gd@SiO2-DO3A and Gd@SiO2-DO2A-BTA, with diameters of 50-60 nm. The synthesis involves sequential coating of Gd-oxide NPs with tetraethyl orthosilicate (TEOS) and (3-aminopropyl) triethoxysilane (APTES), followed by functionalization of the aminopropylsilane group with 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) or 1,4,7,10-tetraazacyclododecane-1,4,7-trisacetic acid conjugates of benzothiazoles (DO3A-BTA). Gd@SiO2-DO3A and Gd@SiO2-DO2A-BTA exhibit high water solubility and colloidal stability. The r1 relaxivities of both Gd@SiO2-DO3A and Gd@SiO2-DO2A-BTA are higher than those of the corresponding low-molecular-weight magnetic resonance imaging contrast agents (MRI CAs), and their r2/r1 ratios are close to 1, indicating that both can be used as potential T1 MRI CAs. Biodistribution studies demonstrated that Gd@SiO2-DO2A-BTA was excreted via both hepatobiliary and renal pathways. Gd@SiO2-DO2A-BTA exhibits a strong intracellular uptake property in a series of tumor cell lines, and has significant anticancer characteristics against cell lines such as SK-HEP-1, MDA-MB-231, HeLa, and Hep-3B. PMID:27305813

  12. Bi-functional Mo-doped WO3 nanowire array electrochromism-plus electrochemical energy storage.

    PubMed

    Zhou, D; Shi, F; Xie, D; Wang, D H; Xia, X H; Wang, X L; Gu, C D; Tu, J P

    2016-03-01

    Metal-doping is considered to be an effective way for construction of advanced semiconducting metal oxides with tailored physicochemical properties. Herein, Mo-doped WO3 nanowire arrays are rationally fabricated by a sulfate-assisted hydrothermal method. Compared to the pure WO3, the optimized Mo-doped WO3 nanowire arrays exhibit improved electrochromic properties with fast switching speed (3.2s and 2.6s for coloration and bleaching, respectively), significant optical modulation (56.7% at 750nm, 83.0% at 1600nm and 48.5% at 10μm), high coloration efficiency (123.5cm(2)C(-1)) and excellent cycling stability. In addition, as a proof of concept, the Mo-doped WO3 nanowire arrays are demonstrated with electrochemical energy storage monitored by the electrochromism. This electrode design protocol can provide an alternative way for developing high-performance active materials for bi-functional electrochromic batteries. PMID:26669497

  13. Effects of chelators on mercury, iron, and lead neurotoxicity in cortical culture.

    PubMed

    Rush, Travis; Hjelmhaug, Julie; Lobner, Doug

    2009-01-01

    Chelation therapy for the treatment of acute, high dose exposure to heavy metals is accepted medical practice. However, a much wider use of metal chelators is by alternative health practitioners for so called "chelation therapy". Given this widespread and largely unregulated use of metal chelators it is important to understand the actions of these compounds. We tested the effects of four commonly used metal chelators, calcium disodium ethylenediaminetetraacetate (CaNa2EDTA), D-penicillamine (DPA), 2,3 dimercaptopropane-1-sulfonate (DMPS), and dimercaptosuccinic acid (DMSA) for their effects on heavy metal neurotoxicity in primary cortical cultures. We studied the toxicity of three forms of mercury, inorganic mercury (HgCl2), methyl mercury (MeHg), and ethyl mercury (thimerosal), as well as lead (PbCl2) and iron (Fe-citrate). DPA had the worst profile of effects, providing no protection while potentiating HgCl2, thimerosal, and Fe-citrate toxicity. DMPS and DMSA both attenuated HgCl2 toxicity and potentiated thimerosal and Fe toxicity, while DMPS also potentiated PbCl2 toxicity. CaNa2EDTA attenuated HgCl2 toxicity, but caused a severe potentiation of Fe-citrate toxicity. The ability of these chelators to attenuate the toxicity of various metals is quite restricted, and potentiation of toxicity is a serious concern. Specifically, protection is provided only against inorganic mercury, while it is lacking against the common form of mercury found in food, MeHg, and the form found in vaccines, thimerosal. The potentiation of Fe-citrate toxicity is of concern because of iron's role in oxidative stress in the body. Potentiation of iron toxicity could have serious health consequences when using chelation therapy. PMID:19027035

  14. Effect of chelating agents and solubility of cadmium complexes on uptake from soil by Brassica juncea.

    PubMed

    Van Engelen, Debra L; Sharpe-Pedler, Rachel C; Moorhead, Kevin K

    2007-06-01

    Brassica juncea, or Indian mustard, was grown in soil artificially contaminated with either a soluble salt, CdCl(2), at 186mg Cdkg(-1), or alternately an insoluble, basic salt, CdCO(3), at 90mg Cdkg(-1). These experiments study the range of Cd uptake by Indian mustard from conditions of very high Cd concentration in a soluble form to the other extreme with an insoluble Cd salt. After plants were established, four different chelating agents were applied. Chelating agents increased plant uptake of Cd from the CdCl(2) soil but did not significantly increase plant uptake of Cd from the CdCO(3) contaminated soil. Addition of ethylenediaminetetraacetic acid (EDTA) increased the plant concentration of Cd by almost 10-fold in soils contaminated with CdCl(2), with a concentration of 1283mg Cdkg(-1) in the dried EDTA-treated plants over a concentration of 131mg Cdkg(-1) in plants without added chelate. However, EDTA increased the aqueous solubility of Cd by 36 times over the soil matrix without added chelator, and thereby, increased the possibility of leaching. Other chelators used in both experiments were ethylenebis(oxyethylenenitrilo)tetraacetic acid, trans-1,2-diaminocyclohexane-N,N,N',N'-tetraacetic acid, and diethylenetriaminepentaacetic acid (DTPA) increasing Cd in plants to 1240, 962, and 437mg Cdkg(-1), respectively. The other chelating agents increased the solubility of Cd in the leachate but not to the extent of EDTA. Comparing all chelating agents studied, DTPA increased plant uptake in terms of Cd in dried plant concentration most relative to the solubility of complexed Cd in runoff water. PMID:17320931

  15. Copper Chelation in Alzheimer's Disease Protein

    NASA Astrophysics Data System (ADS)

    Rose, Frisco; Hodak, Miroslav; Bernholc, Jerry

    2013-03-01

    Alzheimer's disease (AD) is a neurodegenerative disorder affecting millions of people in the U.S. AD is primarily characterized at the cellular level by densely tangled fibrils of amyloid- β protein. These protein clusters have been found in association with elevated levels of multiple transition metals, with copper being the most egregious. Interestingly, metal chelation has shown promise in attenuating the symptoms of AD in recent clinical studies. We investigate this process by constructing an atomistic model of the amyloid- β-copper complex and profile the energetic viability in each of its subsequent disassociation stages. Our results indicate that five energetic barriers must be overcome for full metal chelation. The energy barriers are biologically viable in the presence water mediated bond and proton transfer between the metal and the protein. We model the chelation reaction using a consecutive path nudged elastic band method implemented in our ab initio real-space multi-grid code to obtain a viable sequence. This reaction model details a physically consistent explanation of the chelation process that could lead to the discovery of more effective chelation agents in the treatment of AD.

  16. Method and apparatus for back-extracting metal chelates

    DOEpatents

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

    1998-01-01

    A method of extracting metal and metalloid species from a solid or liquid substrate using a supercritical fluid solvent containing one or more chelating agents followed by back-extracting the metal and metalloid species from the metal and metalloid chelates formed thereby. The back-extraction acidic solution is performed utilizing an acidic solution. Upon sufficient exposure of the metal and metalloid chelates to the acidic solution, the metal and metalloid species are released from the chelates into the acid solution, while the chelating agent remains in the supercritical fluid solvent. The chelating agent is thereby regenerated and the metal and metalloid species recovered.

  17. Method and apparatus for back-extracting metal chelates

    DOEpatents

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

    1998-08-11

    A method is described for extracting metal and metalloid species from a solid or liquid substrate using a supercritical fluid solvent containing one or more chelating agents followed by back-extracting the metal and metalloid species from the metal and metalloid chelates formed thereby. The back-extraction acidic solution is performed utilizing an acidic solution. Upon sufficient exposure of the metal and metalloid chelates to the acidic solution, the metal and metalloid species are released from the chelates into the acid solution, while the chelating agent remains in the supercritical fluid solvent. The chelating agent is thereby regenerated and the metal and metalloid species recovered. 3 figs.

  18. Method of encapsulating polyaminopolycarboxylic acid chelating agents in liposomes

    DOEpatents

    Rahman, Yueh Erh

    1977-11-10

    A method is provided for transferring a polyaminopolycarboxylic acid chelating agent across a cellular membrane by encapsulating the charged chelating agent within liposomes, which liposomes will be taken up by the cells, thereby transferring the chelating agent across the cellular membrane. The chelating agent is encapsulated within liposomes by drying a lipid mixture to form a thin film and wetting the lipid film with a solution containing the chelating agent. Mixing then results in the formation of a suspension of liposomes encapsulating the chelating agent, which liposomes can then be separated.

  19. Trypanotoxic activity of thiosemicarbazone iron chelators.

    PubMed

    Ellis, Samuel; Sexton, Darren W; Steverding, Dietmar

    2015-03-01

    Only a few drugs are available for treating sleeping sickness and nagana disease; parasitic infections caused by protozoans of the genus Trypanosoma in sub-Saharan Africa. There is an urgent need for the development of new medicines for chemotherapy of these devastating diseases. In this study, three newly designed thiosemicarbazone iron chelators, TSC24, Dp44mT and 3-AP, were tested for in vitro activity against bloodstream forms of Trypanosoma brucei and human leukaemia HL-60 cells. In addition to their iron chelating properties, TSC24 and Dp44mT inhibit topoisomerase IIα while 3-AP inactivates ribonucleotide reductase. All three compounds exhibited anti-trypanosomal activity, with minimum inhibitory concentration (MIC) values ranging between 1 and 100 µM and 50% growth inhibition (GI50) values of around 250 nM. Although the compounds did not kill HL-60 cells (MIC values >100 µM), TSC24 and Dp44mT displayed considerable cytotoxicity based on their GI50 values. Iron supplementation partly reversed the trypanotoxic and cytotoxic activity of TSC24 and Dp44mT but not of 3-AP. This finding suggests possible synergy between the iron chelating and topoisomerase IIα inhibiting activity of the compounds. However, further investigation using separate agents, the iron chelator deferoxamine and the topoisomerase II inhibitor epirubicin, did not support any synergy for the interaction of iron chelation and topoisomerase II inhibition. Furthermore, TSC24 was shown to induce DNA degradation in bloodstream forms of T. brucei indicating that the mechanism of trypanotoxic activity of the compound is topoisomerase II independent. In conclusion, the data support further investigation of thiosemicarbazone iron chelators with dual activity as lead compounds for anti-trypanosomal drug development. PMID:25595343

  20. Glutathione production by recombinant Escherichia coli expressing bifunctional glutathione synthetase.

    PubMed

    Wang, Dezheng; Wang, Cheng; Wu, Hui; Li, Zhimin; Ye, Qin

    2016-01-01

    Glutathione (GSH) is an important bioactive substance applied widely in pharmaceutical and food industries. Due to the strong product inhibition in the GSH biosynthetic pathway, high levels of intracellular content, yield and productivity of GSH are difficult to achieve. Recently, a novel bifunctional GSH synthetase was identified to be less sensitive to GSH. A recombinant Escherichia coli strain expressing gshF encoding the bifunctional glutathione synthetase of Streptococcus thermophilus was constructed for GSH production. In this study, efficient GSH production using this engineered strain was investigated. The cultivation process was optimized by controlling dissolved oxygen (DO), amino acid addition and glucose feeding. 36.8 mM (11.3 g/L) GSH were formed at a productivity of 2.06 mM/h when the amino acid precursors (75 mM each) were added and glucose was supplied as the sole carbon and energy source. PMID:26586402

  1. Bifunctional organophosphorus liquid-liquid extraction reagents: development and applications

    SciTech Connect

    Schulz, W.W.; Navratil, J.D.

    1985-01-01

    American and Russian workers have evidenced great interest in the last decade in the potential application of certain neutral and acidic bifunctional organophosphorus compounds in solvent extraction processes. Triggering this interest is the ability of some carbamoylmethylenephosphorus (CMP) and carbamoylmethylenephosphine oxide (CMPO) compounds to extract trivalent actinides and lanthanides from strong HNO/sub 3/ (>1 M) solutions, a property which distinguishes them from monofunctional organophosphorus reagents. Investigators at several US Department of Energy laboratories have concentrated on synthesis of novel CMP and CMPO reagents and on reactions and mechanisms involved in extraction of metal ions from aqueous nitrate media; application of selected CMP and CMPO reagents in solvent extraction and supported liquid membrane recovery of metal values from nuclear waste solutions have been proposed. This paper, based upon a book now in preparation, provides a brief overview of the current status of the development and application of bifunctional organophosphorus extractants. 44 references, 4 tables.

  2. Bifunctional organophosphorus liquid-liquid extraction reagents: development and applications

    SciTech Connect

    Schulz, W.W.; Navratil, J.D.

    1984-03-13

    American and Russian workers have evidenced great interest in the last decade in the potential application of certain neutral and acidic bifunctional organophosphorus compounds in solvent extraction processes. Triggering this interest is the ability of some carbamoylmethylenephosphorus (CMP) and carbamoylmethylenephosphine oxide (CMPO) compounds to extract trivalent actinides and lanthanides from strong HNO/sub 3/ (>1M) solutions, a property which distinguishes them from monofunctional organophosphorus reagents. Investigators at several US Department of Energy laboratories have concentrated on synthesis of novel CMP and CMPO reagents and on reactions and mechanisms involved in extraction of metal ions from aqueous nitrate media; application of selected CMP and CMPO reagents in solvent extraction and supported liquid membrane recovery of metal values from nuclear waste solutions have been proposed. This paper, based upon a book now in preparation, provides a brief overview of the current status of the development and application of bifunctional organophosphorus extractants. 42 references, 4 tables.

  3. The aminoindanol core as a key scaffold in bifunctional organocatalysts

    PubMed Central

    G. Sonsona, Isaac

    2016-01-01

    Summary The 1,2-aminoindanol scaffold has been found to be very efficient, enhancing the enantioselectivity when present in organocatalysts. This may be explained by its ability to induce a bifunctional activation of the substrates involved in the reaction. Thus, it is easy to find hydrogen-bonding organocatalysts ((thio)ureas, squaramides, quinolinium thioamide, etc.) in the literature containing this favored structural core. They have been successfully employed in reactions such as Friedel–Crafts alkylation, Michael addition, Diels–Alder and aza-Henry reactions. However, the 1,2-aminoindanol core incorporated into proline derivatives has been scarcely explored. Herein, the most representative and illustrative examples are compiled and this review will be mainly focused on the cases where the aminoindanol moiety confers bifunctionality to the organocatalysts. PMID:27340443

  4. The aminoindanol core as a key scaffold in bifunctional organocatalysts.

    PubMed

    G Sonsona, Isaac; Marqués-López, Eugenia; Herrera, Raquel P

    2016-01-01

    The 1,2-aminoindanol scaffold has been found to be very efficient, enhancing the enantioselectivity when present in organocatalysts. This may be explained by its ability to induce a bifunctional activation of the substrates involved in the reaction. Thus, it is easy to find hydrogen-bonding organocatalysts ((thio)ureas, squaramides, quinolinium thioamide, etc.) in the literature containing this favored structural core. They have been successfully employed in reactions such as Friedel-Crafts alkylation, Michael addition, Diels-Alder and aza-Henry reactions. However, the 1,2-aminoindanol core incorporated into proline derivatives has been scarcely explored. Herein, the most representative and illustrative examples are compiled and this review will be mainly focused on the cases where the aminoindanol moiety confers bifunctionality to the organocatalysts. PMID:27340443

  5. Bifunctional air electrodes containing elemental iron powder charging additive

    DOEpatents

    Liu, Chia-tsun; Demczyk, Brian G.; Gongaware, Paul R.

    1982-01-01

    A bifunctional air electrode for use in electrochemical energy cells is made, comprising a hydrophilic layer and a hydrophobic layer, where the hydrophilic layer essentially comprises a hydrophilic composite which includes: (i) carbon; (ii) elemental iron particles having a particle size of between about 25 microns and about 700 microns diameter; (iii) an oxygen evolution material; (iv) a nonwetting agent; and (v) a catalyst, where at least one current collector is formed into said composite.

  6. Room Temperature Hydrosilylation of Silicon Nanocrystals with Bifunctional Terminal Alkenes

    PubMed Central

    Yu, Yixuan; Hessel, Colin M.; Bogart, Timothy; Panthani, Matthew G.; Rasch, Michael R.; Korgel, Brian A.

    2013-01-01

    H-terminated Si nanocrystals undergo room temperature hydrosilylation with bifunctional alkenes with distal polar moieties—ethyl-, methyl-ester or carboxylic acids—without the aid of light or added catalyst. The passivated Si nanocrystals exhibit bright photoluminescence (PL) and disperse in polar solvents, including water. We propose a reaction mechanism in which ester or carboxylic acid groups facilitate direct nucleophilic attack of the highly curved Si surface of the nanocrystals by the alkene. PMID:23312033

  7. Bifunctional reactivity of amidoximes observed upon nucleophilic addition to metal-activated nitriles.

    PubMed

    Bolotin, Dmitrii S; Demakova, Marina Ya; Novikov, Alexander S; Avdontceva, Margarita S; Kuznetsov, Maxim L; Bokach, Nadezhda A; Kukushkin, Vadim Yu

    2015-04-20

    Treatment of the aromatic nitrile complexes trans-[PtCl2(RC6H4CN)2] (R = p-CF3 NC1, H NC2, o-Cl NC3) with the aryl amidoximes p-R'C6H4C(NH2)=NOH (R' = Me AO1, H AO2, Br AO3, CF3 AO4, NO2 AO5) in all combinations, followed by addition of 1 equiv of AgOTf and then 5 equiv of Et3N, leads to the chelates [PtCl{HN=C(RC6H4)ON=C(C6H4R'-p)NC(RC6H4)═NH}] (1-15; 15 examples; yields 71-88% after column chromatography) derived from the platinum(II)-mediated coupling between metal-activated nitriles and amidoximes. The mechanism of this reaction was studied experimentally by trapping and identification of the reaction intermediates, and it was also investigated theoretically at the DFT level of theory. The combined experimental and theoretical results indicate that the coupling with the nitrile ligands involves both the HON and monodeprotonated NH2 groups of the amidoximes, whereas in the absence of the base, the NH2 functionality is inactive toward the coupling. The observed reaction represents the first example of bifunctional nucleophilic behavior of amidoximes. The complexes 1-16 were characterized by elemental analyses (C, H, N), high-resolution ESI(+)-MS, FTIR, and (1)H NMR techniques, whereas unstable 17 was characterized by HRESI(+)-MS and FTIR. In addition, 8·C4H8O2, 12, and 16·CHCl3 were studied by single-crystal X-ray diffraction. PMID:25822628

  8. A Manganese Alternative to Gadolinium for MRI Contrast.

    PubMed

    Gale, Eric M; Atanasova, Iliyana P; Blasi, Francesco; Ay, Ilknur; Caravan, Peter

    2015-12-16

    Contrast-enhanced computed tomography (CT) and magnetic resonance imaging (MRI) are routinely used to diagnose soft tissue and vascular abnormalities. However, safety concerns limit the use of iodinated and gadolinium (Gd)-based CT and MRI contrast media in renally compromised patients. With an estimated 14% of the US population suffering from chronic kidney disease (CKD), contrast media compatible with renal impairment is sorely needed. We present the new manganese(II) complex [Mn(PyC3A)(H2O)](-) as a Gd alternative. [Mn(PyC3A)(H2O)](-) is among the most stable Mn(II) complexes at pH 7.4 (log KML = 11.40). In the presence of 25 mol equiv of Zn at pH 6.0, 37 °C, [Mn(PyC3A)(H2O)](-) is 20-fold more resistant to dissociation than [Gd(DTPA)(H2O)](2-). Relaxivity of [Mn(PyC3A)(H2O)](-) in blood plasma is comparable to commercial Gd contrast agents. Biodistribution analysis confirms that [Mn(PyC3A)(H2O)](-) clears via a mixed renal/hepatobiliary pathway with >99% elimination by 24 h. [Mn(PyC3A)(H2O)](-) was modified to form a bifunctional chelator and 4 chelates were conjugated to a fibrin-specific peptide to give Mn-FBP. Mn-FBP binds the soluble fibrin fragment DD(E) with Kd = 110 nM. Per Mn relaxivity of Mn-FBP is 4-fold greater than [Mn(PyC3A)(H2O)](-) and increases 60% in the presence of fibrin, consistent with binding. Mn-FBP provided equivalent thrombus enhancement to the state of the art Gd analogue, EP-2104R, in a rat model of arterial thrombosis. Mn metabolite analysis reveals no evidence of dechelation and the probe was >99% eliminated after 24 h. [Mn(PyC3A)(H2O)](-) is a lead development candidate for an imaging probe that is compatible with renally compromised patients. PMID:26588204

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

    DOE PAGESBeta

    Wilson, Justin J.; Ferrier, Maryline; Radchenko, Valery; Maassen, Joel R.; Engle, Jonathan W.; Batista, Enrique R.; Martin, Richard L.; Nortier, Francois M.; Fassbender, Michael E.; John, Kevin D.; et al

    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 (Lpy), 1,4,7,10-tetrakis(3-pyridazylmethyl)-1,4,7,10-tetraazacyclododecane (Lpyd), 1,4,7,10-tetrakis(4-pyrimidylmethyl)-1,4,7,10-tetraazacyclododecane (Lpyr), and 1,4,7,10-tetrakis(2-pyrazinylmethyl)-1,4,7,10-tetraazacyclododecane (Lpz), were prepared by a previously reported method and investigated here for their abilitiesmore » 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 (t1/2 = 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, Lpy was found to exhibit optimal Bi³⁺-binding kinetics and complex stability. Lpy complexes Bi³⁺ more rapidly than DOTA, yet the resulting complexes are of similar stability. DFT

  10. In vivo kinetics of micronuclei induction by bifunctional alkylating antineoplastics.

    PubMed

    Morales-Ramírez, Pedro; Vallarino-Kelly, Teresita; Cruz-Vallejo, Virginia L; López-Iturbe, Rosario; Alvaro-Delgadillo, Horacio

    2004-05-01

    The aim of the present study was to determine in vivo the kinetics of micronucleated polychromatic erythrocyte (MN-PCE) induction in mice, as an approach for studying the mechanism of micronuclei induction by mitomycin C, cis-diamine dichloroplatinum, busulfan and bis-chloroethylnitrosourea, bifuctional alkylating antineoplastic agents having different patterns of crosslink induction. The kinetics of MN-PCE induction was established by scoring the frequency of MN-PCE in 2000 PCE in peripheral blood, for periods of 8 or 10 h after acute treatment and up to 80 h, with different doses of the agent. The kinetics of MN-PCE induction and particularly the times of maximal induction by different bifunctional alkylating agents were compared with the kinetics previously obtained for ethylnitrosourea, methylnitrosourea and 6-mercaptopurine, agents that cause MN-PCE mainly in the first, second and third divisions after exposure, respectively. The results obtained in the present study allow us to conclude that: (i) bifunctional alkylating agents have very different efficiencies of genotoxic and cytotoxic action; (ii) all assayed bifunctional alkylating agents induced micronuclei during the first cell division, owing to the mistaken repair of primary lesions, e.g. excision; (iii) busulfan and bis-chloroethylnitrosourea showed an additional late mechanism of micronuclei induction, which is expressed at the third division and seems to be related to the mismatch repair process. PMID:15123786

  11. Shadow enhancers enable Hunchback bifunctionality in the Drosophila embryo

    PubMed Central

    Staller, Max V.; Vincent, Ben J.; Bragdon, Meghan D. J.; Lydiard-Martin, Tara; Wunderlich, Zeba; Estrada, Javier; DePace, Angela H.

    2015-01-01

    Hunchback (Hb) is a bifunctional transcription factor that activates and represses distinct enhancers. Here, we investigate the hypothesis that Hb can activate and repress the same enhancer. Computational models predicted that Hb bifunctionally regulates the even-skipped (eve) stripe 3+7 enhancer (eve3+7) in Drosophila blastoderm embryos. We measured and modeled eve expression at cellular resolution under multiple genetic perturbations and found that the eve3+7 enhancer could not explain endogenous eve stripe 7 behavior. Instead, we found that eve stripe 7 is controlled by two enhancers: the canonical eve3+7 and a sequence encompassing the minimal eve stripe 2 enhancer (eve2+7). Hb bifunctionally regulates eve stripe 7, but it executes these two activities on different pieces of regulatory DNA—it activates the eve2+7 enhancer and represses the eve3+7 enhancer. These two “shadow enhancers” use different regulatory logic to create the same pattern. PMID:25564665

  12. Development of an upconverting chelate assay

    NASA Astrophysics Data System (ADS)

    Xiao, Xudong; Haushalter, Jeanne P.; Kotz, Kenneth T.; Faris, Gregory W.

    2005-04-01

    We report progress on performing a cell-based assay for the detection of EGFR on cell surfaces by using upconverting chelates. An upconversion microscope has been developed for performing assays and testing optical response. A431 cells are labeled with europium DOTA and imaged using this upconverting microscope.

  13. Thermal Stability of Chelated Indium Activable Tracers

    SciTech Connect

    Chrysikopoulos, Costas; Kruger, Paul

    1986-01-21

    The thermal stability of indium tracer chelated with organic ligands ethylenediaminetetraacetic acid (EDTA) and nitrilotriacetic acid (NTA) was measured for reservoir temperatures of 150, 200, and 240 C. Measurements of the soluble indium concentration was made as a function of time by neutron activation analysis. From the data, approximate thermal decomposition rates were estimated. At 150 C, both chelated tracers were stable over the experimental period of 20 days. At 200 C, the InEDTA concentration remained constant for 16 days, after which the thermal decomposition occurred at a measured rate constant of k = 0.09 d{sup -1}. The thermal decomposition of InNTA at 200 C showed a first order reaction with a measured rate constant of k = 0.16 d{sup -1}. At 240 C, both indium chelated tracers showed rapid decomposition with rate constants greater than 1.8 d{sup -1}. The data indicate that for geothermal reservoir with temperatures up to about 200 C, indium chelated tracers can be used effectively for transit times of at least 20 days. These experiments were run without reservoir rock media, and do not account for concomitant loss of indium tracer by adsorption processes.

  14. Determination of equilibrium constants of alkaline earth metal ion chelates with Dowex A-1 chelating resin.

    PubMed

    Harju, L; Krook, T

    1995-03-01

    A complexation chemistry model is applied to chelating ion-exchange systems and a method is presented for the determination of equilibrium constants for metal ion chelates with these resins. Protonation constants for the iminodiacetic based chelating resin Dowex A-1 were determined from potentiometric pH-data. Equilibrium constants were determined for 1:1 beryllium, magnesium, calcium, strontium and barium chelates with the resin in a wide pH range by measuring the concentrations of respective metal ions in the aqueous phase with direct current plasma atomic emission spectrometry (DCP-AES). A batch technique was used for the equilibrium experiments. At pH below 7 protonated 1:1 species were also found to be formed with the resin. From the obtained equilibrium constants, theoretical distribution coefficients were calculated as function of pH for respective metal ion resin system. PMID:18966248

  15. 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

  16. Chelator-induced phytoextraction of zinc and copper by rice seedlings.

    PubMed

    Yu, Xiao-Zhang; Wang, Dun-Qiu; Zhang, Xue-Hong

    2014-05-01

    Solution culture was carried to investigate capacity of synthetic aminopolycarboxylic acids (ethylenediamine tetraacetate, N-hydroxyethylenediaminetriacetic acid, and diethylenetriamine-pentaacetate) for enhancing botanical removal and transport of heavy metals (Cu and Zn) by plants. Biodegradable organic acids (citric acid, malic acid, and oxalic acid) were also selected as alternatives to compare them with synthesized chelating agents for effectiveness. Young rice seedlings (Oryza sativa L. cv. XZX 45) were grown in nutrient solutions treated with single or combined metal solutions in presence or absence of chelating compounds. Calculation by chemical equilibrium program VISUAL MINTEQ showed that different chelating compounds had various complex potential with Cu(2+) and Zn(2+) ions, in which synthetic chelators exhibited higher complexed capability than biodegradable organic acids. All applied synthetic aminopolycarboxylic acids significantly decreased removal of metal from nutrient solution (p < 0.01), while more or less effects of organic acids supplied on biosorptive potential were observed with all treatments (p > 0.05), compared with the treatment without metal ligands. Synthetic aminopolycarboxylic acids significantly decreased metal concentrations in plant materials in all treatments (p < 0.01). However, biodegradable organic acids decreased metal concentrations in roots (p < 0.01), but enhanced them in shoots (p < 0.01). Results obtained indicated that synthetic aminopolycarboxylic acids decreased uptake of metals by rice seedlings, but translocation of metals complexed within plant materials was evident. Although exogenous biodegradable organic acids showed negligible effect on botanical removal of metals, metals complexed with organic acids was more mobile than those complexed with other chelating agents. These information collected here had important implication for the use of biodegradable metal chelators in transport of essential micronutrients in

  17. [Functionalized Metal Chelates Based on Diethylenetriaminetetraacetic Acids for Chemical Modification of Proteins and Small Biomolecules].

    PubMed

    Kuprienko, O S; Dubovskaya, L V; Shabunya, P S; Fatykhava, S A; Sviridov, O V

    2015-01-01

    Bifunctional reagents based on diethylenetriaminetetraacetic acid containing a bound metal ion and a reactive functional group for the interaction with proteins and low-molecular-weight substances have been synthesized. An Amino-derivative of a complexonate was obtained by acylation of monosubstituted diamine with diethylenetriaminepentaacetic acid dianhydride followed by deprotection ofthe amino group, purification by anion exchange chromatography and chelation of Eu3+. This metal chelate derivative was used for labeling 17α-hydroxyprogesterone 3-(O-carboxymethyl)oxime and horseradish peroxidase. The enzyme modified with the Eu3+ complexonate at the carbohydrate component and with a cortisol derivative at the polypeptide chain was used in a dissociation-enhanced lanthanide fluorescent immunoassay (DELFIA) as well as in an enzyme immunoassay of the steroid hormone. DELFIA showed that labeled 17α-hydroxyprogesterone retained the affinity for corresponding antibodies. A Eu(3+)-complexonate carboxy-derivative N-succinimide ester was obtained by acylation of the aminochelate with p-phthalic acid di-N-succinimide ester. It was used for modification of amino groups of lysine residues in polypeptide chains of human serum albumin and some immunoglobulins G. Purification of Eu3+ complexonate-protein conjugates by gel-chromatography on a Superose- 12 column allowed to separate the modified proteins from unreacted low molecular weight Eu(3+)-derivatives and to determine a degree of lanthanide inclusion into a protein. The amount of Eu3+ covalently attached to a protein was determined by measuring the fluorescence of a conjugate in the dissociative-enhancement solution. The obtained values correlated well with the results of ICP-MS determination of Eu3+ concentration in a conjugate solution. It was shown that conjugates of monoclonal antibodies obtained by the proposed method possessed the required characteristics of fluorescence intensity, signal-to-noise ratio, sensitivity

  18. Effects of chelators on chromium and nickel uptake by Brassica juncea on serpentine-mine tailings for phytoextraction.

    PubMed

    Hsiao, Kai-Hsun; Kao, Po-Hsu; Hseu, Zeng-Yei

    2007-09-01

    This study compares the effect of synthetic aminopolycarboxylic acids ethylenediamine tetraacetate (EDTA) and diethylenetriamine pentaacetate (DTPA) with natural low-molecular-weight organic acids (LMWOAs) oxalic acid and citric acid as chelators for enhancing phytoextraction of Cr and Ni by Brassica juncea on serpentine-mine tailings. Chelator treatments were applied at doses of 0.05 and 0.10 mmolkg(-1) dry soils after seedlings were grown in pots for 56 days. Experimental results indicate that EDTA and DTPA were the most efficient chelators of increasing the levels of Cr and Ni in the soil solutions over time. Additionally, the reduction of plant shoot biomass caused by the two synthetic chelators exceeds that caused by the LMWOAs. The total uptake (mass removal from soil) of metals by plants was enhanced via the chelators. Experimental results supported the use of B. juncea for Cr and Ni phytoremediation: B. juncea improved the removal of Cr and Ni from serpentine-mine tailings. However, low plant biomass did not assist phytoextraction by using EDTA and DTPA, both of which carry environmental risk. Therefore, adding LMWOAs during phytoremediation can provide an environmentally compatible alternative, which may decrease the use of synthetic chelators. PMID:17391842

  19. Chelation: A Fundamental Mechanism of Action of AGE Inhibitors, AGE Breakers, and Other Inhibitors of Diabetes Complications

    SciTech Connect

    Nagai, Rhoji; Murray, David B.; Metz, Thomas O.; Baynes, John

    2012-03-01

    Advanced glycation or glycoxidation end-products (AGE) increase in tissue proteins with age, and their rate of accumulation is increased in diabetes, nephropathy and inflammatory diseases. AGE inhibitors include a range of compounds that are proposed to act by trapping carbonyl and dicarbonyl intermediates in AGE formation. However, some among the newer generation of AGE inhibitors lack reactive functional groups that would trap reaction intermediates, indicating an alternative mechanism of action. We propose that AGE inhibitors function primarily as chelators, inhibiting metal-catalyzed oxidation reactions. The AGE-inhibitory activity of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers is also consistent with their chelating activity. Finally, compounds described as AGE breakers, or their hydrolysis products, also have strong chelating activity, suggesting that these compounds also act through their chelating activity. We conclude that chelation is the common, and perhaps the primary, mechanism of action of AGE inhibitors and breakers, and that chronic, mild chelation therapy should prove useful in treatment of diabetes and age-related diseases characterized by oxidative stress, inflammation and increased chemical modification of tissue proteins by advanced glycoxidation and lipoxidation end-products.

  20. REDUCTIVE ACTIVATION OF DIOXYGEN FOR DEGRADATION OF METHYL TERT-BUTYL ETHER BY BIFUNCTION

    EPA Science Inventory

    Bifunctional aluminum is prepared by sulfating aluminum metal with sulfuric acid. The use of bifunctional aluminum to degrade methyl tert-butyl ether (MTBE) in the presence of dioxygen has been examined using batch systems. Primary degradation products were tert-butyl alcohol, ...

  1. Bifunctional Phage-Based Pretargeted Imaging of Human Prostate Carcinoma Bifunctional Phage Based Pretargeted Imaging

    PubMed Central

    Newton-Northup, Jessica R.; Figueroa, Said D.; Quinn, Thomas P.; Deutscher, Susan L.

    2009-01-01

    Introduction Two-step and three-step pretargeting systems utilizing biotinylated prostate tumor-homing bacteriophage (phage) and 111In-radiolabeled- streptavidin or biotin were developed for use in cancer radioimaging. The in vivo selected prostate carcinoma-specific phage (G1) displaying up to five copies of the peptide IAGLATPGWSHWLAL, was the focus of the present study. Methods The ability of G1 phage to extravasate and target prostate tumor cells was investigated using immunohistochemistry. G1 phage were biotinylated, streptavidin was conjugated to diethylenetriaminepentaacetic acid (DTPA), and biotin was conjugated to 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA). Biodistribution studies and single photon emission computed tomography (SPECT)/CT imaging of xenografted PC-3 tumors via two-step pretargeted 111In-labeled streptavidin and three-step pretargeted 111In-labeled biotin were performed in SCID mice to determine the optimal pretargeting method. Results The ability of G1 phage to extravasate the vasculature and bind directly to human PC-3 prostate carcinoma tumor cells in vivo was demonstrated via immunocytochemical analysis. Comparative biodistribution studies of the two-step and three-step pretargeting strategies indicated increased PC-3 human prostate carcinoma tumor uptake in SCID mice of 4.34 ±0.26 %ID/g at 0.5 hours post-injection of 111In radiolabeled biotin (utilized in a three-step protocol) compared to that of 0.67 ±0.06 %ID/g at twenty four hour postinjection of 111In radiolabeled streptavidin (employed in a two-step protocol). In vivo SPECT/CT imaging of xenografted PC-3 tumors in SCID mice with the three-step pretargeting method was superior to that of the two-step pretargeting method, and, importantly, blocking studies demonstrated specificity of tumor uptake of 111In-labeled biotin in the three-step pretargeting scheme. Conclusion This study demonstrates the use of multivalent bifunctional phage in a three

  2. Relationship among Chelator Adherence, Change in Chelators, and Quality of Life in Thalassemia

    PubMed Central

    Trachtenberg, Felicia L.; Gerstenberger, Eric; Xu, Yan; Mednick, Lauren; Sobota, Amy; Ware, Hannah; Thompson, Alexis A.; Neufeld, Ellis J.; Yamashita, Robert

    2015-01-01

    Purpose Thalassemia, a chronic blood disease, necessitates life-long adherence to blood transfusions and chelation therapy to reduce iron overload. We examine stability of Health-Related Quality of Life (HRQOL) in thalassemia and adherence to chelation therapy over time, especially after changes in chelator choice. Methods Thalassemia Longitudinal Cohort participants in the US, UK, and Canada completed the SF-36v2 (ages 14+), and the PF-28 CHQ (parents of children<14 years). Chelation adherence was defined as self-reported percent of doses administered in the last 4 weeks. Results 258 adults/adolescents (mean 29.7 years) and 133 children (mean 8.5 years) completed a mean of 2.8 years follow-up. Children made few chelator changes, whereas a mean of 2.2 changes was observed among the 37% of adults/adolescents who made chelator changes, mainly, due to patient preference or medical necessity. Physical HRQOL improved among those with lower iron burden (better health status) at baseline who made a single change in chelator, but declined among participants with multiple changes and/or high iron burden (worse health status). Mental health improved among participants with lower iron burden, but iron overload was negatively associated with social functioning. Adherence did not significantly change over follow-up except for an increase after a change from DFO infusion to oral deferasirox (p=0.03). Predictors of lower adherence for adults/adolescents at follow-up included side effects, smoking, younger age, problems preparing DFO, increased number of days per week DFO prescribed, and lower physical QOL. Conclusions Strategies to balance medical needs with family, work, and personal life may assist in adherence. PMID:24682717

  3. Silybin, a new iron-chelating agent.

    PubMed

    Borsari, M; Gabbi, C; Ghelfi, F; Grandi, R; Saladini, M; Severi, S; Borella, F

    2001-06-01

    Silybin, a natural occurring flavolignan isolated from the fruits of Silibum marianum, has been reported to exert antioxidant and free radical scavenging abilities. It was suggested to act also as an iron chelator. The complexation and protonation equilibria of the ferric complex of this compound have been studied by potentiometric, spectrophotometric and electrochemical techniques. The formation of the complex silybin-Ga(III) in anhydrous DMSO-d6 has been studied by 1H NMR spectroscopy. Mass spectrometry and infrared spectroscopy on silybin-Fe(III) complex confirm all data obtained by 1H NMR spectroscopy. The experimental results show that silybin binds Fe(III) even at acidic pH. Different ternary complexes were observed at increasing methoxide ion concentration and their stability constants have been calculated. The results show the possible role of silybin in relation to the chelation therapy of chronic iron overload, as occurs in the treatment of Cooley's anemia. PMID:11410232

  4. 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.

  5. Paramagnetic lanthanide chelates for multicontrast MRI.

    PubMed

    Cakić, Nevenka; Savić, Tanja; Stricker-Shaver, Janice; Truffault, Vincent; Platas-Iglesias, Carlos; Mirkes, Christian; Pohmann, Rolf; Scheffler, Klaus; Angelovski, Goran

    2016-07-28

    The preparation of a paramagnetic chelator that serves as a platform for multicontrast MRI, and can be utilized either as a T1-weighted, paraCEST or (19)F MRI contrast agent is reported. Its europium(iii) complex exhibits an extremely slow water exchange rate which is optimal for the use in CEST MRI. The potential of this platform was demonstrated through a series of MRI studies on tube phantoms and animals. PMID:27291157

  6. Organosilylated complex [Eu(TTA)3(Bpy-Si)]: a bifunctional moiety for the engeneering of luminescent silica-based nanoparticles for bioimaging.

    PubMed

    Duarte, Adriana P; Mauline, Léïla; Gressier, Marie; Dexpert-Ghys, Jeannette; Roques, Christine; Caiut, José Maurício A; Deffune, Elenice; Maia, Danielle C G; Carlos, Iracilda Z; Ferreira, Antonio A P; Ribeiro, Sidney J L; Menu, Marie-Joëlle

    2013-05-14

    A new highly luminescent europium complex with the formula [Eu(TTA)3(Bpy-Si)], where TTA stands for the thenoyltrifluoroacetone, (C4H3S)COCH2COCF3, chelating ligand and Bpy-Si, Bpy-CH2NH(CH2)3Si(OEt)3, is an organosilyldipyridine ligand displaying a triethoxysilyl group as a grafting function has been synthesized and fully characterized. This bifunctional complex has been grafted onto the surface of dense silica nanoparticles (NPs) and on mesoporous silica microparticles as well. The covalent bonding of [Eu(TTA)3(Bpy-Si)] inside uniform Stöber silica nanoparticles was also achieved. The general methodology proposed could be applied to any silica matrix, allowed high grafting ratios that overcome chelate release and the tendency to agglomerate. Luminescent silica-based nanoparticles SiO2-[Eu(TTA)3(Bpy-Si)], with a diameter of 28 ± 2 nm, were successfully tested as a luminescent labels for the imaging of Pseudomonas aeruginosa biofilms. They were also functionalized by a specific monoclonal antibody and subsequently employed for the selective imaging of Escherichia coli bacteria. PMID:23586677

  7. Invariants reveal multiple forms of robustness in bifunctional enzyme systems.

    PubMed

    Dexter, Joseph P; Dasgupta, Tathagata; Gunawardena, Jeremy

    2015-08-01

    Experimental and theoretical studies have suggested that bifunctional enzymes catalyzing opposing modification and demodification reactions can confer steady-state concentration robustness to their substrates. However, the types of robustness and the biochemical basis for them have remained elusive. Here we report a systematic study of the most general biochemical reaction network for a bifunctional enzyme acting on a substrate with one modification site, along with eleven sub-networks with more specialized biochemical assumptions. We exploit ideas from computational algebraic geometry, introduced in previous work, to find a polynomial expression (an invariant) between the steady state concentrations of the modified and unmodified substrate for each network. We use these invariants to identify five classes of robust behavior: robust upper bounds on concentration, robust two-sided bounds on concentration ratio, hybrid robustness, absolute concentration robustness (ACR), and robust concentration ratio. This analysis demonstrates that robustness can take a variety of forms and that the type of robustness is sensitive to many biochemical details, with small changes in biochemistry leading to very different steady-state behaviors. In particular, we find that the widely-studied ACR requires highly specialized assumptions in addition to bifunctionality. An unexpected result is that the robust bounds derived from invariants are strictly tighter than those derived by ad hoc manipulation of the underlying differential equations, confirming the value of invariants as a tool to gain insight into biochemical reaction networks. Furthermore, invariants yield multiple experimentally testable predictions and illuminate new strategies for inferring enzymatic mechanisms from steady-state measurements. PMID:26021467

  8. Metal chelate catalysts for fuel cells

    NASA Astrophysics Data System (ADS)

    Darby, R.; White, R.; Yamana, M.; Tsutsue, M.

    1981-07-01

    A variety of metal chelates were synthesized and evaluated for their activity as oxygen cathode electrocatalysts in strong acidic electrolytes. It was found that Cobalt tetraazaanulene (CoTAA) and iron phthalocyanine (FePc) exhibit the best activity of all the metal chelates synthesized, but have very limited stability. The proposed solution to this problem is the synthesis of polymeric forms of these chelates, with comparable active and considerably greater stability than the monomers. Three methods for stability testing were developed: (1) Potentiostatic, with periodic measurement of the current potential characteristic; (2) potentiostatic, with continuous monitoring of the current, and; (3) galvanostatic, with continuous monitoring of potential. Each method provides a good evaluation of activity versus time, and the method to be used depends upon the objective of the test. A polymeric form of Co(TAA) was synthesized by means of an acetylene terminated monomer, which in turn was made via a Co(TAA)Br2 intermediate. The activity of the polymer was found to be comparable to that of Co(TAA) monomer, and significantly greater than that of either the stacked or sheet polymeric forms of Cobalt tetraphenylporphrine (CoTPP) previously synthesized and tested.

  9. Iron Chelation Therapy in Thalassemia Syndromes

    PubMed Central

    Cianciulli, Paolo

    2009-01-01

    Transfusional hemosiderosis is a frequent complication in patients with transfusion dependent chronic diseases such as thalassemias and severe type of sickle cell diseases. As there are no physiological mechanisms to excrete the iron contained in transfused red cells (1 unit of blood contains approximately 200 mg of iron) the excess of iron is stored in various organs. Cardiomyopathy is the most severe complication covering more than 70% of the causes of death of thalassemic patients. Although the current reference standard iron chelator deferoxamine (DFO) has been used clinically for over four decades, its effectiveness is limited by a demanding therapeutic regimen that leads to poor compliance. Despite poor compliance, because of the inconvenience of subcutaneous infusion, DFO improved considerably the survival and quality of life of patients with thalassemia. Deferiprone since 1998 and Deferasirox since 2005 were licensed for clinical use. The oral chelators have a better compliance because of oral use, a comparable efficacy to DFO in iron excretion and probably a better penetration to myocardial cells. Considerable increase in iron excretion was documented with combination therapy of DFO and Deferiprone. The proper use of the three chelators will improve the prevention and treatment of iron overload, it will reduce complications, and improve survival and quality of life of transfused patients. PMID:21415999

  10. Cu-Free 1,3-Dipolar Cycloaddition Click Reactions To Form Isoxazole Linkers in Chelating Ligands for fac-[MI(CO)3]+ Centers (M = Re, 99mTc)

    PubMed Central

    2015-01-01

    Isoxazole ring formation was examined as a potential Cu-free alternative click reaction to CuI-catalyzed alkyne/azide cycloaddition. The isoxazole reaction was explored at macroscopic and radiotracer concentrations with the fac-[MI(CO)3]+ (M = Re, 99mTc) core for use as a noncoordinating linker strategy between covalently linked molecules. Two click assembly methods (click, then chelate and chelate, then click) were examined to determine the feasibility of isoxazole ring formation with either alkyne-functionalized tridentate chelates or their respective fac-[MI(CO)3]+ complexes with a model nitrile oxide generator. Macroscale experiments, alkyne-functionalized chelates, or Re complexes indicate facile formation of the isoxazole ring. 99mTc experiments demonstrate efficient radiolabeling with click, then chelate; however, the chelate, then click approach led to faster product formation, but lower yields compared to the Re analogues. PMID:24483834

  11. Spectroscopy, modeling and computation of metal chelate solubility in supercritical CO{sub 2}

    SciTech Connect

    J. F. Brennecke; M. A. Stadtherr

    1999-12-10

    The overall objectives of this project were to gain a fundamental understanding of the solubility and phase behavior of metal chelates in supercritical CO{sub 2}. Extraction with CO{sub 2} is an excellent way to remove organic compounds from soils, sludges and aqueous solutions, and recent research has demonstrated that, together with chelating agents, it is a viable way to remove metals, as well. In this project the authors sought to gain fundamental knowledge that is vital to computing phase behavior, and modeling and designing processes using CO{sub 2} to separate organics and metal compounds from DOE mixed wastes. The overall program was a comprehensive one to measure, model and compute the solubility of metal chelate complexes in supercritical CO{sub 2} and CO{sub 2}/cosolvent mixtures. Through a combination of phase behavior measurements, spectroscopy and the development of a new computational technique, the authors have achieved a completely reliable way to model metal chelate solubility in supercritical CO{sub 2} and CO{sub 2}/co-contaminant mixtures. Thus, they can now design and optimize processes to extract metals from solid matrices using supercritical CO{sub 2}, as an alternative to hazardous organic solvents that create their own environmental problems, even while helping in metals decontamination.

  12. Divergent evolution of a bifunctional de novo protein.

    PubMed

    Smith, Betsy A; Mularz, Ann E; Hecht, Michael H

    2015-02-01

    Primordial proteins, the evolutionary ancestors of modern sequences, are presumed to have been minimally active and nonspecific. Following eons of selective pressure, these early progenitors evolved into highly active and specific proteins. While evolutionary trajectories from poorly active and multifunctional generalists toward highly active specialists likely occurred many times in evolutionary history, such pathways are difficult to reconstruct in natural systems, where primordial sequences are lost to time. To test the hypothesis that selection for enhanced activity leads to a loss of promiscuity, we evolved a de novo designed bifunctional protein. The parental protein, denoted Syn-IF, was chosen from a library of binary patterned 4-helix bundles. Syn-IF was shown previously to rescue two different auxotrophic strains of E. coli: ΔilvA and Δfes. These two strains contain deletions for proteins with very different biochemical functions; IlvA is involved in isoleucine biosynthesis, while Fes is involved in iron assimilation. In two separate experiments, Syn-IF, was evolved for faster rescue of either ΔilvA or Δfes. Following multiple rounds of mutagenesis, two new proteins were selected, each capable of rescuing the selected function significantly faster than the parental protein. In each case, the evolved protein also lost the ability to rescue the unselected function. In both evolutionary trajectories, the original bifunctional generalist was evolved into a monofunctional specialist with enhanced activity. PMID:25420677

  13. Amino Acid-Derived Bifunctional Phosphines for Enantioselective Transformations.

    PubMed

    Wang, Tianli; Han, Xiaoyu; Zhong, Fangrui; Yao, Weijun; Lu, Yixin

    2016-07-19

    Even though seminal reports on phosphine catalysis appeared in the 1960s, in the last few decades of the past century trivalent phosphines were viewed primarily as useful ligands for transition-metal-mediated processes. The 1990s saw revived interest in using phosphines in organic catalysis, but the key advances in asymmetric phosphine catalysis have all come within the past decade. The uniqueness of phosphine catalysis can be attributed to the high nucleophilicity of the phosphorus atom. In typical phosphine-catalyzed reactions, nucleophilic attacks of the phosphorus atom on electron-deficient multiple bonds create different reactive ylide-type intermediates. When such structurally diverse zwitterionic species react with a variety of suitable substrates, new reaction patterns are often discovered and a diverse array of reactions can be developed. In recent years, substantial progress has been made in the field of asymmetric phosphine catalysis; many new reactions have been discovered, and numerous enantioselective processes have been reported. However, we felt that powerful and versatile phosphine catalysts that can work for a wide range of asymmetric reactions are still lacking. We therefore set our goal to develop a family of easily derived phosphine catalysts that are efficient in asymmetric induction for a broad range of phosphine-mediated transformations. This Account describes our efforts in the past few years on the development of amino acid-based bifunctional phosphines and their applications to enantioselective processes. Building upon our previous success in primary-amine-mediated enamine catalysis, we first established that bifunctional phosphines could be readily prepared from amino acids. In most of our studies, we chose threonine as the key backbone for catalyst development, and threonine-based monoamino acid or dipeptide bifunctional phosphines have displayed remarkable stereochemical control. We began our investigations by demonstrating the

  14. Chelators whose affinity for calcium is decreased by illumination

    NASA Technical Reports Server (NTRS)

    Tsien, Roger Y. (Inventor); Grynkiewicz, Grzegorz (Inventor); Minta, Akwasi (Inventor)

    1987-01-01

    The present invention discloses a group of calcium chelating compounds which have a descreased affinity for calcium following illumination. These new compounds contain a photolabile nitrobenzyl derivative coupled to a tetracarboxylate Ca.sup.2+ chelating parent compound having the octacoordinate chelating groups characteristic of EGTA or BAPTA. In a first form, the new compounds are comprised of a BAPTA-like chelator coupled to a single 2-nitrobenzyl derivative, which in turn is a photochemical precursor of a 2-nitrosobenzophenone. In a second form, the new compounds are comprised of a BAPTA-like chelator coupled to two 2-nitrobenzyl derivatives, themselves photochemical prcursors of the related 2-nitrosobenzophenones. The present invention also discloses a novel method for preparing 1-hydroxy- or 1-alkoxy-1-(2-nitroaryl)-1-aryl methanes. Methanes of this type are critical to the preparation of, or actually constitute, the photolabile Ca.sup.2+ chelating compounds disclosed and claimed herein.

  15. Metal regeneration of iron chelates in nitric oxide scrubbing

    DOEpatents

    Chang, Shih-Ger; Littlejohn, David; Shi, Yao

    1997-08-19

    The present invention relates to a process of using metal particles to reduce NO to NH.sub.3. More specifically, the invention concerns an improved process to regenerate iron (II) (CHELATE) by reduction of iron (II) (CHELATE) (NO) complex, which process comprises: a) contacting an aqueous solution containing iron (II) (CHELATE) (NO) with metal particles at between about 20.degree. and 90.degree. C. to reduce NO present, produce ammonia or an ammonium ion, and produce free iron (II) (CHELATE) at a pH of between about 3 and 8. The process is useful to remove NO from flue gas and reduce pollution.

  16. Metal regeneration of iron chelates in nitric oxide scrubbing

    DOEpatents

    Chang, S.G.; Littlejohn, D.; Shi, Y.

    1997-08-19

    The present invention relates to a process of using metal particles to reduce NO to NH{sub 3}. More specifically, the invention concerns an improved process to regenerate iron (II) (CHELATE) by reduction of iron (II) (CHELATE) (NO) complex, which process comprises: (a) contacting an aqueous solution containing iron (II) (CHELATE) (NO) with metal particles at between about 20 and 90 C to reduce NO present, produce ammonia or an ammonium ion, and produce free iron (II) (CHELATE) at a pH of between about 3 and 8. The process is useful to remove NO from flue gas and reduce pollution. 34 figs.

  17. Chemical treatment of chelated metal finishing wastes.

    PubMed

    McFarland, Michael J; Glarborg, Christen; Ross, Mark A

    2012-12-01

    This study evaluated two chemical approaches for treatment of commingled cadmium-cyanide (Cd-CN) and zinc-nickel (Zn-Ni) wastewaters. The first approach, which involved application of sodium hypochlorite (NaOCl), focused on elimination of chelating substances. The second approach evaluated the use of sodium dimethyldithiocarbamate (DMDTC) to specifically target and precipitate regulated heavy metals. Results demonstrated that by maintaining a pH of 10.0 and an oxidation-reduction potential (ORP) value of +600 mV, NaOCl treatment was effective in eliminating all chelating substances. Cadmium, chromium, nickel, and zinc solution concentrations were reduced from 0.27, 4.44, 0.06, and 0.10 ppm to 0.16, 0.17, 0.03, and 0.06 ppm, respectively. Similarly, a 1% DMDTC solution reduced these same metal concentrations in commingled wastewater to 0.009, 1.142, 0.036, and 0.320 ppm. Increasing the DMDTC concentration to 2% improved the removal of all regulated heavy metals except zinc, the removal of which at high pH values is limited by its amphotericity. PMID:23342939

  18. A bi-functional antibody-receptor domain fusion protein simultaneously targeting IGF-IR and VEGF for degradation

    PubMed Central

    Shen, Yang; Zeng, Lin; Novosyadlyy, Ruslan; Forest, Amelie; Zhu, Aiping; Korytko, Andrew; Zhang, Haifan; Eastman, Scott W; Topper, Michael; Hindi, Sagit; Covino, Nicole; Persaud, Kris; Kang, Yun; Burtrum, Douglas; Surguladze, David; Prewett, Marie; Chintharlapalli, Sudhakar; Wroblewski, Victor J; Shen, Juqun; Balderes, Paul; Zhu, Zhenping; Snavely, Marshall; Ludwig, Dale L

    2015-01-01

    Bi-specific antibodies (BsAbs), which can simultaneously block 2 tumor targets, have emerged as promising therapeutic alternatives to combinations of individual monoclonal antibodies. Here, we describe the engineering and development of a novel, human bi-functional antibody-receptor domain fusion molecule with ligand capture (bi-AbCap) through the fusion of the domain 2 of human vascular endothelial growth factor receptor 1 (VEGFR1) to an antibody directed against insulin-like growth factor – type I receptor (IGF-IR). The bi-AbCap possesses excellent stability and developability, and is the result of minimal engineering. Beyond potent neutralizing activities against IGF-IR and VEGF, the bi-AbCap is capable of cross-linking VEGF to IGF-IR, leading to co-internalization and degradation of both targets by tumor cells. In multiple mouse xenograft tumor models, the bi-AbCap improves anti-tumor activity over individual monotherapies. More importantly, it exhibits superior inhibition of tumor growth, compared with the combination of anti-IGF-IR and anti-VEGF therapies, via powerful blockade of both direct tumor cell growth and tumor angiogenesis. The unique “capture-for-degradation” mechanism of the bi-AbCap is informative for the design of next-generation bi-functional anti-cancer therapies directed against independent signaling pathways. The bi-AbCap design represents an alternative approach to the creation of dual-targeting antibody fusion molecules by taking advantage of natural receptor-ligand interactions. PMID:26073904

  19. A bi-functional antibody-receptor domain fusion protein simultaneously targeting IGF-IR and VEGF for degradation.

    PubMed

    Shen, Yang; Zeng, Lin; Novosyadlyy, Ruslan; Forest, Amelie; Zhu, Aiping; Korytko, Andrew; Zhang, Haifan; Eastman, Scott W; Topper, Michael; Hindi, Sagit; Covino, Nicole; Persaud, Kris; Kang, Yun; Burtrum, Douglas; Surguladze, David; Prewett, Marie; Chintharlapalli, Sudhakar; Wroblewski, Victor J; Shen, Juqun; Balderes, Paul; Zhu, Zhenping; Snavely, Marshall; Ludwig, Dale L

    2015-01-01

    Bi-specific antibodies (BsAbs), which can simultaneously block 2 tumor targets, have emerged as promising therapeutic alternatives to combinations of individual monoclonal antibodies. Here, we describe the engineering and development of a novel, human bi-functional antibody-receptor domain fusion molecule with ligand capture (bi-AbCap) through the fusion of the domain 2 of human vascular endothelial growth factor receptor 1 (VEGFR1) to an antibody directed against insulin-like growth factor - type I receptor (IGF-IR). The bi-AbCap possesses excellent stability and developability, and is the result of minimal engineering. Beyond potent neutralizing activities against IGF-IR and VEGF, the bi-AbCap is capable of cross-linking VEGF to IGF-IR, leading to co-internalization and degradation of both targets by tumor cells. In multiple mouse xenograft tumor models, the bi-AbCap improves anti-tumor activity over individual monotherapies. More importantly, it exhibits superior inhibition of tumor growth, compared with the combination of anti-IGF-IR and anti-VEGF therapies, via powerful blockade of both direct tumor cell growth and tumor angiogenesis. The unique "capture-for-degradation" mechanism of the bi-AbCap is informative for the design of next-generation bi-functional anti-cancer therapies directed against independent signaling pathways. The bi-AbCap design represents an alternative approach to the creation of dual-targeting antibody fusion molecules by taking advantage of natural receptor-ligand interactions. PMID:26073904

  20. Bifunctional combined aptamer for simultaneous separation and detection of thrombin.

    PubMed

    Bing, Tao; Liu, Xiangjun; Cheng, Xiaohong; Cao, Zehui; Shangguan, Dihua

    2010-02-15

    Here we report on the construction and evaluation of a bifunctional combined aptamer (BCA) that consists of a DNA streptavidin-binding aptamer (SBA), a DNA thrombin-binding aptamer (TBA) and a fluorophore. The BCA adopts a new conformation that is very different from simply linking the conformations of the two individual aptamers together, so that it does not bind to streptavidin in the absence of thrombin. Binding of this novel DNA aptamer to streptavidin is triggered by the thrombin binding and depends on the concentration of thrombin. Meanwhile, fluorescence from the streptavidin captured BCA reflects the quantity of the target molecule in the sample. This aptamer combination strategy based on the SBA holds good potential for applications in simultaneous detection and separation of targets of aptamers or certain DNA and RNA targets. PMID:19959350

  1. Enantioselective tandem reaction over a site-isolated bifunctional catalyst.

    PubMed

    Xu, Jianyou; Cheng, Tanyu; Zhang, Kun; Wang, Ziyun; Liu, Guohua

    2016-05-21

    Construction of a site-isolated heterogeneous catalyst to realize the compatibility of bimetallic complexes for a feasible tandem reaction is a significant challenge in heterogeneous asymmetric catalysis. Herein, taking advantage of yolk-shell-structured mesoporous silica, we assemble an active site-isolated bifunctional catalyst through assembly of organopalladium-functionality into silicate channels as an outer shell and chiral organoruthenium-functionality onto silicate yolk as an inner core, realizing the one-pot enantioselective tandem reaction from Pd-catalyzed Sonogashira coupling to Ru-catalyzed asymmetric transfer hydrogenation. As presented in this study, this tandem Sonogashira coupling-asymmetric transfer hydrogenation of haloacetophenones and arylacetylenes affords various chiral conjugated alkynols with high yields and up to 99% enantioselectivity. Moreover, a catalyst can also be recovered easily and recycled repeatedly, making it an interesting feature in a practical organic transformation. PMID:27063335

  2. Bifunctional magnetic-fluorescent nanoparticles: synthesis, characterization, and cell imaging.

    PubMed

    Lu, Yanjiao; Zheng, Yang; You, Shusen; Wang, Feng; Gao, Zhuo; Shen, Jie; Yang, Wantai; Yin, Meizhen

    2015-03-11

    A new type of bifunctional magnetic-fluorescent Fe3O4@SiO2-PDI-PAA/Ca(2+) nanoparticles has been prepared by coating PDI-cored star polymers (PDI-PAA) onto the surface of Fe3O4@SiO2 core-shell nanostructures. The morphology and properties of the composite nanoparticles are investigated by transmission electron microscopy, ultraviolet-visible spectrometry, fluorescence spectrometry, and vibrating sample magnetometry. The composite nanoparticles display a strong red emission and superparamagnetic behavior at room temperature. The cell viability and uptake assays reveal good biocompatibility of these hybrid nanoparticles. Hence, the composite nanoparticles are of potential to be further explored as therapeutic vector in biomedical field. PMID:25691125

  3. BIFUNCTIONAL ALUMINUN: A PERMEABLE BARRIER MATERIAL FOR THE DEGRADATION OF MTBE

    EPA Science Inventory

    Bifunctional aluminum is an innovative remedial material for the treatment of gasoline oxygenates in permeable reactive barriers (PRBs). PRBs represent a promising environmental technology for remediation of groundwater contamination. Although zero-valent metals (ZVM) have been...

  4. Synergistic Interaction within Bifunctional Ruthenium Nanoparticle/SILP Catalysts for the Selective Hydrodeoxygenation of Phenols.

    PubMed

    Luska, Kylie L; Migowski, Pedro; El Sayed, Sami; Leitner, Walter

    2015-12-21

    Ruthenium nanoparticles immobilized on acid-functionalized supported ionic liquid phases (Ru NPs@SILPs) act as efficient bifunctional catalysts in the hydrodeoxygenation of phenolic substrates under batch and continuous flow conditions. A synergistic interaction between the metal sites and acid groups within the bifunctional catalyst leads to enhanced catalytic activities for the overall transformation as compared to the individual steps catalyzed by the separate catalytic functionalities. PMID:26545408

  5. Detection and isolation of nucleic acid sequences using a bifunctional hybridization probe

    DOEpatents

    Lucas, Joe N.; Straume, Tore; Bogen, Kenneth T.

    2000-01-01

    A method for detecting and isolating a target sequence in a sample of nucleic acids is provided using a bifunctional hybridization probe capable of hybridizing to the target sequence that includes a detectable marker and a first complexing agent capable of forming a binding pair with a second complexing agent. A kit is also provided for detecting a target sequence in a sample of nucleic acids using a bifunctional hybridization probe according to this method.

  6. Reusable chelating resins concentrate metal ions from highly dilute solutions

    NASA Technical Reports Server (NTRS)

    Bauman, A. J.; Weetal, H. H.; Weliky, N.

    1966-01-01

    Column chromatographic method uses new metal chelating resins for recovering heavy-metal ions from highly dilute solutions. The absorbed heavy-metal cations may be removed from the chelating resins by acid or base washes. The resins are reusable after the washes are completed.

  7. Chelation Treatment for Autism Spectrum Disorders: A Systematic Review

    ERIC Educational Resources Information Center

    Davis, Tonya N.; O'Reilly, Mark; Kang, Soyeon; Lang, Russell; Rispoli, Mandy; Sigafoos, Jeff; Lancioni, Giulio; Copeland, Daelynn; Attai, Shanna; Mulloy, Austin

    2013-01-01

    Chelation treatment is used to eliminate specific metals from the body, such as mercury. It has been hypothesized that mercury poisoning may be a factor in autism and data suggest that perhaps 7% of individuals with autism spectrum disorder (ASD) have received chelation treatment. It would therefore seem timely to review studies investigating the…

  8. Clawing Back: Broadening the Notion of Metal Chelators in Medicine

    PubMed Central

    Franz, Katherine J.

    2013-01-01

    The traditional notion of chelation therapy is the administration of a chemical agent to remove metals from the body. But formation of a metal-chelate can have biological ramifications that are much broader than metal elimination. Exploring these other possibilities could lead to pharmacological interventions that alter the concentration, distribution, or reactivity of metals in targeted ways for therapeutic benefit. This review highlights recent examples that showcase four general strategies of using principles of metal chelation in medicinal contexts beyond the traditional notion of chelation therapy. These strategies include altering metal biodistribution, inhibiting specific metalloenzymes associated with disease, enhancing the reactivity of a metal complex to promote cytotoxicity, and conversely, passivating the reactivity of metals by site-activated chelation to prevent cytotoxicity. PMID:23332666

  9. Chelators for copper radionuclides in positron emission tomography radiopharmaceuticals†

    PubMed Central

    Cai, Zhengxin; Anderson, Carolyn J.

    2014-01-01

    The development of chelating agents for copper radionuclides in positron emission tomography radiopharmaceuticals has been a highly active and important area of study in recent years. The rapid evolution of chelators has resulted in highly specific copper chelators that can be readily conjugated to biomolecules and efficiently radiolabeled to form stable complexes in vivo. Chelators are not only designed for conjugation to monovalent biomolecules but also for incorporation into multivalent targeting ligands such as theranostic nanoparticles. These advancements have strengthened the role of copper radionuclides in the fields of nuclear medicine and molecular imaging. This review emphasizes developments of new copper chelators that have most greatly advanced the field of copper-based radiopharmaceuticals over the past 5 years. PMID:24347474

  10. Chelating Agents and the Regulation of Metal Ions

    PubMed Central

    Bulman, Robert A.

    1994-01-01

    Up to about the early 1980s it was perhaps still possible to summarize in a review of a moderate length the development of the medicinal applications of chelation chemistry and the exploitation of such chemistry in regulating the metal ion concentrations in the body. However, in the last few years there has a great surge in the development of chelation chemistry and its usage in medicine and related areas of life sciences research. It is no longer the case that such a review primarily concentrates upon the use of chelating agents in removing toxic metals from the body but it must now cover the use of chelating agents in the imaging procedures nuclear medicine and magnetic resonance imaging (MRI), the use of chelating agents in unravelling the biochemistry of reactive oxidative species (ROS) and the control and measurement of intracellular calcium ions. It is in the recent applications that there have been the greatest developments over the last ten years. PMID:18476223

  11. Chelation in metal intoxication XXI: chelation in lead intoxication during vitamin B complex deficiency

    SciTech Connect

    Not Available

    1986-09-01

    The vitamin B-complex deficiency increases the vulnerability to neuro- and systemic toxicity of Pb in young rats. Thus, the nutritional status of vitamins like that of protein or minerals seems to influence the etiology of Pb toxicity and may be expected to affect the response toward Pb chelators. 2,3 dimercaptosuccinic acid (DMSA) and N-(2-hydroxyethyl) ethylene-diamine triacetic acid (HEDTA) have been found to be effective antidotes to Pb intoxication. In the present study, these selective metal chelating agents were compared for their ability to reduce the body burden of Pb and restore the altered biochemical parameters in young developing Pb intoxicated rats maintained on normal or vitamin B-complex deficient diet. The investigation was aimed to suggest suitable prophylaxis of Pb poisoning prevalent among children who may also be suffering from vitamin deficiency in developing and poor countries.

  12. Chelating ionic liquids for reversible zinc electrochemistry.

    PubMed

    Kar, Mega; Winther-Jensen, Bjorn; Forsyth, Maria; MacFarlane, Douglas R

    2013-05-21

    Advanced, high energy-density, metal-air rechargeable batteries, such as zinc-air, are of intense international interest due to their important role in energy storage applications such as electric and hybrid vehicles, and to their ability to deal with the intermittency of renewable energy sources such as solar and wind. Ionic liquids offer a number of ideal thermal and physical properties as potential electrolytes in such large-scale energy storage applications. We describe here the synthesis and characterisation of a family of novel "chelating" ILs designed to chelate and solubilize the zinc ions to create electrolytes for this type of battery. These are based on quaternary alkoxy alkyl ammonium cations of varying oligo-ether side chains and anions such as p-toluene sulfonate, bis(trifluoromethylsulfonyl)amide and dicyanoamides. This work shows that increasing the ether chain length in the cation from two to four oxygens can increase the ionic conductivity and reduce the melting point from 67 °C to 15 °C for the tosylate system. Changing the anion also plays a significant role in the nature of the zinc deposition electrochemistry. We show that zinc can be reversibly deposited from [N(222(20201))][NTf2] and [N(222(202020201))][NTf2] beginning at -1.4 V and -1.7 V vs. SHE, respectively, but not in the case of tosylate based ILs. This indicates that the [NTf2] is a weaker coordinating anion with the zinc cation, compared to the tosylate anion, allowing the coordination of the ether chain to dominate the behavior of the deposition and stripping of zinc ions. PMID:23558696

  13. Fixation kinetics of chelated and non-chelated zinc in semi-arid alkaline soils: application to zinc management

    NASA Astrophysics Data System (ADS)

    Udeigwe, Theophilus K.; Eichmann, Madeleine; Menkiti, Matthew C.

    2016-07-01

    This study was designed to examine the fixation pattern and kinetics of zinc (Zn) in chelated (ethylenediaminetetraacetic acid, EDTA) and non-chelated mixed micronutrient systems of semi-arid alkaline soils from the Southern High Plains, USA. Soils were characterized for a suite of chemical and physical properties and data obtained from extraction experiments fitted to various kinetic models. About 30 % more plant-available Zn was fixed in the non-chelated system within the first 14 days with only about 18 % difference observed between the two systems by day 90, suggesting that the effectiveness of the chelated compounds tended to decrease over time. The strengths of the relationships of change in available Zn with respect to other micronutrients (copper, iron, and manganese) were higher and more significant in the non-chelated system (average R2 of 0.83), compared to the chelated (average R2 of 0.42). Fixation of plant-available Zn was best described by the power-function model (R2 = 0.94, SE = 0.076) in the non-chelated system, and was poorly described by all the models examined in the chelated system. Reaction rate constants and relationships generated from this study can serve as important tools for micronutrient management and for future micronutrient modeling studies on these soils and other semi-arid regions of the world.

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

    SciTech Connect

    Wilson, Justin J.; Ferrier, Maryline; Radchenko, Valery; Maassen, Joel R.; Engle, Jonathan W.; Batista, Enrique R.; Martin, Richard L.; Nortier, Francois M.; Fassbender, Michael E.; John, Kevin D.; Birnbaum, Eva R.

    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 (Lpy), 1,4,7,10-tetrakis(3-pyridazylmethyl)-1,4,7,10-tetraazacyclododecane (Lpyd), 1,4,7,10-tetrakis(4-pyrimidylmethyl)-1,4,7,10-tetraazacyclododecane (Lpyr), and 1,4,7,10-tetrakis(2-pyrazinylmethyl)-1,4,7,10-tetraazacyclododecane (Lpz), were prepared by a previously reported method and investigated 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 (t1/2 = 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, Lpy was found to exhibit optimal Bi³⁺-binding kinetics and complex stability. Lpy complexes

  15. Chelation: Harnessing and Enhancing Heavy Metal Detoxification—A Review

    PubMed Central

    Sears, Margaret E.

    2013-01-01

    Toxic metals such as arsenic, cadmium, lead, and mercury are ubiquitous, have no beneficial role in human homeostasis, and contribute to noncommunicable chronic diseases. While novel drug targets for chronic disease are eagerly sought, potentially helpful agents that aid in detoxification of toxic elements, chelators, have largely been restricted to overt acute poisoning. Chelation, that is multiple coordination bonds between organic molecules and metals, is very common in the body and at the heart of enzymes with a metal cofactor such as copper or zinc. Peptides glutathione and metallothionein chelate both essential and toxic elements as they are sequestered, transported, and excreted. Enhancing natural chelation detoxification pathways, as well as use of pharmaceutical chelators against heavy metals are reviewed. Historical adverse outcomes with chelators, lessons learned in the art of using them, and successes using chelation to ameliorate renal, cardiovascular, and neurological conditions highlight the need for renewed attention to simple, safe, inexpensive interventions that offer potential to stem the tide of debilitating, expensive chronic disease. PMID:23690738

  16. 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

  17. Active Insolubilized Antibiotics Based on Cellulose-Metal Chelates1

    PubMed Central

    Kennedy, J. F.; Barker, S. A.; Zamir, A.

    1974-01-01

    Cellulose was converted into a more reactive form by chelation with the transition metals titaniumIII, ironIII, tinIV, vanadiumIII, and zirconiumIV. The remaining unsubstituted ligands of the transition metal ions were found to be amenable to replacement by electron-donating groups of antibiotic molecules. Ampicillin, gentamicin, kanamycin, neomycin, paromomycin, polymyxin B, and streptomycin were used as antibacterial antibiotics, and amphotericin B and natamycin were used as antifungal antibiotics. Antibacterial activity of the products was tested against two gram-positive and two gram-negative bacteria, and antifungal activity was tested against four fungi. That the antibacterial antibiotics had complexed with the cellulose-metal chelates was demonstrated in that the product cellulose-metal-antibiotic chelates exhibited antibiotic activities whereas the metal chelates of cellulose themselves were inactive. Of 140 tests conducted, cellulose-metal-antibiotic chelates were active in 102 cases. Since the antibiotic derivatives were water insoluble and in fact retain some of the antibacterial activities of the parent compounds, the chelation method provides a facile way of rendering cellulose surfaces, etc., resistant to microbial attack over and above that degree of protection afforded by noncovalent adsorption of the antibiotic to cellulose itself. The underlying principles of the chelation reactions involved are discussed in detail. PMID:4451349

  18. Chelation therapy for metal intoxication: comments from a thermodynamic viewpoint.

    PubMed

    Nurchi, Valeria Marina; Alonso, Miriam Crespo; Toso, Leonardo; Lachowicz, Joanna Izabela; Crisponi, Guido

    2013-10-01

    Chelation therapy plays a prominent role in the clinical treatment of metal intoxication. In this paper the principal causes of metal toxicity are exposed, and the chemical and biomedical requisites of a chelating agent are sketched. The chelating agents currently in use for scavenging toxic metal ions from humans belong to few categories: those characterized by coordinating mercapto groups, by oxygen groups, poliaminocarboxylic acids, and dithiocarbamates. Considering that the complex formation equilibria have been studied for less than 50% of chelators in use, some reflections on the utility of stability constants are presented, together with an evaluation of ligands under the stability profile. The competition between endogenous and toxic target metal ions for the same chelating agent is furthermore examined. A thorough examination of stability constant databases has allowed to select, for each toxic metal, the ligands distinguished by the best pMe values. Even though this selection does not consider the biomedical requisites of a chelating agent, it gives a clear picture both of the pMe values that can be attained, and of the most appropriate chelators for each metal ion. PMID:23895193

  19. Nanoparticle and Iron Chelators as a Potential Novel Alzheimer Therapy

    PubMed Central

    Liu, Gang; Men, Ping; Perry, George; Smith, Mark A.

    2010-01-01

    Current therapies for Alzheimer disease (AD) such as the acetylcholinesterase inhibitors and the latest NMDA receptor inhibitor, Namenda, provide moderate symptomatic delay at various stages of the disease, but do not arrest the disease progression or bring in meaningful remission. New approaches to the disease management are urgently needed. Although the etiology of AD is largely unknown, oxidative damage mediated by metals is likely a significant contributor since metals such as iron, aluminum, zinc, and copper are dysregulated and/or increased in AD brain tissue and create a pro-oxidative environment. This role of metal ion-induced free radical formation in AD makes chelation therapy an attractive means of dampening the oxidative stress burden in neurons. The chelator desferrioxamine, FDA approved for iron overload, has shown some benefit in AD, but like many chelators, it has a host of adverse effects and substantial obstacles for tissue-specific targeting. Other chelators are under development and have shown various strengths and weaknesses. Here, we propose a novel system of chelation therapy through the use of nanoparticles. Nanoparticles conjugated to chelators show unique ability to cross the blood–brain barrier (BBB), chelate metals, and exit through the BBB with their corresponding complexed metal ions. This method may provide a safer and more effective means of reducing the metal load in neural tissue, thus attenuating the harmful effects of oxidative damage and its sequelae. Experimental procedures are presented in this chapter. PMID:20013176

  20. Chelating agents and their use in radiopharmaceutical sciences.

    PubMed

    Wängler, B; Schirrmacher, R; Bartenstein, P; Wängler, C

    2011-10-01

    Radiometal nuclides can serve as diagnostic markers in molecular imaging or can be used in therapeutic settings for a rising number of human afflictions. For the targeted delivery of these medically interesting ions, appropriate chelating agents forming stable complexes are of fundamental importance. For different metal ions exhibiting different physical and chemical properties, resulting in different coordination chemistries and therefore differing requirements on the chelator used, a broad variety of chelating agents has been developed over the years. Not only the chemical properties of the metal ion determine the choice of the chelator, but also the desired in vivo behavior of the resulting molecular imaging or therapeutic compound influences the choice of the complexation agent. Furthermore, the conjugation chemistry for the introduction of the chelator into the biologically active compound and the complexation reaction of the metal ion can affect the choice of the appropriate chelator. This review outlines chelating agents used in medicinal chemistry, their radiometal complexation behavior and their potential influence on the properties of the resulting drugs. PMID:21762096

  1. Oxidative Stress, Redox Signaling, and Metal Chelation in Anthracycline Cardiotoxicity and Pharmacological Cardioprotection

    PubMed Central

    Popelová, Olga; Vávrová, Anna; Jirkovský, Eduard; Kovaříková, Petra; Geršl, Vladimír

    2013-01-01

    Abstract Significance: Anthracyclines (doxorubicin, daunorubicin, or epirubicin) rank among the most effective anticancer drugs, but their clinical usefulness is hampered by the risk of cardiotoxicity. The most feared are the chronic forms of cardiotoxicity, characterized by irreversible cardiac damage and congestive heart failure. Although the pathogenesis of anthracycline cardiotoxicity seems to be complex, the pivotal role has been traditionally attributed to the iron-mediated formation of reactive oxygen species (ROS). In clinics, the bisdioxopiperazine agent dexrazoxane (ICRF-187) reduces the risk of anthracycline cardiotoxicity without a significant effect on response to chemotherapy. The prevailing concept describes dexrazoxane as a prodrug undergoing bioactivation to an iron-chelating agent ADR-925, which may inhibit anthracycline-induced ROS formation and oxidative damage to cardiomyocytes. Recent Advances: A considerable body of evidence points to mitochondria as the key targets for anthracycline cardiotoxicity, and therefore it could be also crucial for effective cardioprotection. Numerous antioxidants and several iron chelators have been tested in vitro and in vivo with variable outcomes. None of these compounds have matched or even surpassed the effectiveness of dexrazoxane in chronic anthracycline cardiotoxicity settings, despite being stronger chelators and/or antioxidants. Critical Issues: The interpretation of many findings is complicated by the heterogeneity of experimental models and frequent employment of acute high-dose treatments with limited translatability to clinical practice. Future Directions: Dexrazoxane may be the key to the enigma of anthracycline cardiotoxicity, and therefore it warrants further investigation, including the search for alternative/complementary modes of cardioprotective action beyond simple iron chelation. Antioxid. Redox Signal. 00, 000–000. PMID:22794198

  2. Bifunctional thermoelectric tube made of tilted multilayer material as an alternative to standard heat exchangers

    PubMed Central

    Takahashi, Kouhei; Kanno, Tsutomu; Sakai, Akihiro; Tamaki, Hiromasa; Kusada, Hideo; Yamada, Yuka

    2013-01-01

    Enormously large amount of heat produced by human activities is now mostly wasted into the environment without use. To realize a sustainable society, it is important to develop practical solutions for waste heat recovery. Here, we demonstrate that a tubular thermoelectric device made of tilted multilayer of Bi0.5Sb1.5Te3/Ni provides a promising solution. The Bi0.5Sb1.5Te3/Ni tube allows tightly sealed fluid flow inside itself, and operates in analogy with the standard shell and tube heat exchanger. We show that it achieves perfect balance between efficient heat exchange and high-power generation with a heat transfer coefficient of 4.0 kW/m2K and a volume power density of 10 kW/m3 using low-grade heat sources below 100°C. The Bi0.5Sb1.5Te3/Ni tube thus serves as a power generator and a heat exchanger within a single unit, which is advantageous for developing new cogeneration systems in factories, vessels, and automobiles where cooling of excess heat is routinely carried out. PMID:23511347

  3. Bifunctional thermoelectric tube made of tilted multilayer material as an alternative to standard heat exchangers.

    PubMed

    Takahashi, Kouhei; Kanno, Tsutomu; Sakai, Akihiro; Tamaki, Hiromasa; Kusada, Hideo; Yamada, Yuka

    2013-01-01

    Enormously large amount of heat produced by human activities is now mostly wasted into the environment without use. To realize a sustainable society, it is important to develop practical solutions for waste heat recovery. Here, we demonstrate that a tubular thermoelectric device made of tilted multilayer of Bi(0.5)Sb(1.5)Te3/Ni provides a promising solution. The Bi(0.5)Sb(1.5)Te3/Ni tube allows tightly sealed fluid flow inside itself, and operates in analogy with the standard shell and tube heat exchanger. We show that it achieves perfect balance between efficient heat exchange and high-power generation with a heat transfer coefficient of 4.0 kW/m(2)K and a volume power density of 10 kW/m(3) using low-grade heat sources below 100°C. The Bi(0.5)Sb(1.5)Te3/Ni tube thus serves as a power generator and a heat exchanger within a single unit, which is advantageous for developing new cogeneration systems in factories, vessels, and automobiles where cooling of excess heat is routinely carried out. PMID:23511347

  4. Slow magnetic relaxation in lanthanide complexes with chelating nitronyl nitroxide radical.

    PubMed

    Wang, Xiao-Ling; Li, Li-Cun; Liao, Dai-Zheng

    2010-06-01

    Two rare-earth radical complexes [Ln(hfac)(3)NIT-2Py].0.5C(7)H(16) [Ln = Tb (1), Dy (2)] have been synthesized and characterized structurally as well as magnetically. Both complexes are isomorphous, in which the NIT-2Py radical is coordinated to the Ln(III) ion in a chelating manner. Magnetic studies reveal that complex 1 shows a frequency-dependent, alternating-current magnetic susceptibility typical of a single-molecule magnet, whereas slow magnetic relaxation is observed in 2 under an applied direct-current field. PMID:20438100

  5. Radical initiated polymerization in a bifunctional mixture via computer simulation

    NASA Astrophysics Data System (ADS)

    Diamond, Keri L.; Pandey, Ras B.; Thames, Shelby F.

    2004-06-01

    Computer simulations are performed to study the polymerization behavior in a mixture of bifunctional groups such as olefins (A) and acrylates (B) in an effective solvent (a coarse description for vegetable oil derived macromonomers (VOMMs) in solution) on a cubic lattice. A set of interactions between these units and solvent (S) constituents and their relative concentrations (pA, pB, and pS) are considered. Samples are equilibrated with Metropolis algorithm to model the perceived behavior of VOMMs. The covalent bonding between monomeric units is then implemented via reaction pathways initiated by stochastic motion of free radicals (a very small fraction). The rate of reaction shows decay patterns with the time steps (t) with power laws (i.e., Rabαt-r, r≅0.4-0.8), exponential decays (i.e., Rabαe-0.001t), and their combination. Growth of A-B bonding is studied as a function of polymer concentration p=pA+pB for four different model systems appropriate for VOMMs. The data from the free radical initiated simulations are compared to the original simulations with homopolymerization. While most of the data are consistent with experimental observations, the variations are found to be model dependent.

  6. Bioinspired Bifunctional Membrane for Efficient Clean Water Generation.

    PubMed

    Liu, Yang; Lou, Jinwei; Ni, Mengtian; Song, Chengyi; Wu, Jianbo; Dasgupta, Neil P; Tao, Peng; Shang, Wen; Deng, Tao

    2016-01-13

    Solving the problems of water pollution and water shortage is an urgent need for the sustainable development of modern society. Different approaches, including distillation, filtration, and photocatalytic degradation, have been developed for the purification of contaminated water and the generation of clean water. In this study, we explored a new approach that uses solar light for both water purification and clean water generation. A bifunctional membrane consisting of a top layer of TiO2 nanoparticles (NPs), a middle layer of Au NPs, and a bottom layer of anodized aluminum oxide (AAO) was designed and fabricated through multiple filtration processes. Such a design enables both TiO2 NP-based photocatalytic function and Au NP-based solar-driven plasmonic evaporation. With the integration of these two functions into a single membrane, both the purification of contaminated water through photocatalytic degradation and the generation of clean water through evaporation were demonstrated using simulated solar illumination. Such a demonstration should also help open up a new strategy for maximizing solar energy conversion and utilization. PMID:26646606

  7. Gold(I) catalysts with bifunctional P, N ligands.

    PubMed

    Wetzel, Corinna; Kunz, Peter C; Thiel, Indre; Spingler, Bernhard

    2011-08-15

    A series of phosphanes with imidazolyl substituents were prepared as hemilabile PN ligands. The corresponding gold(I) complexes were tested as bifunctional catalysts in the Markovnikov hydration of 1-octyne, as well as in the synthesis of propargylamines by the three component coupling reaction of piperidine, benzaldehyde, and phenylacetylene. While the activity in the hydration of 1-octyne was low, the complexes are potent catalysts for the three component coupling reaction. In homogeneous solution the conversions to the respective propargylamine were considerably higher than under aqueous biphasic conditions. The connectivity of the imidazolyl substituents to the phosphorus atom, their substitution pattern, as well as the number of heteroaromatic substituents have pronounced effects on the catalytic activity of the corresponding gold(I) complexes. Furthermore, formation of polymetallic species with Au(2), Au(3), and Au(4) units has been observed and the solid-state structures of the compounds [(5)(2)Au(3)Cl(2)]Cl and [(3c)(2)Au(4)Cl(2)]Cl(2) (3c = tris(2-isopropylimidazol-4(5)-yl phosphane, 5 = 2-tert-butylimidazol-4(5)-yldiphenyl phosphane) were determined. The gold(I) complexes of imidazol-2-yl phosphane ligands proved to be a novel source for bis(NHC)gold(I) complexes (NHC = N-heterocyclic carbene). PMID:21761834

  8. Identification of a Bifunctional Maize C- and O-Glucosyltransferase*

    PubMed Central

    Falcone Ferreyra, María Lorena; Rodriguez, Eduardo; Casas, María Isabel; Labadie, Guillermo; Grotewold, Erich; Casati, Paula

    2013-01-01

    Flavonoids accumulate in plant vacuoles usually as O-glycosylated derivatives, but several species can also synthesize flavonoid C-glycosides. Recently, we demonstrated that a flavanone 2-hydroxylase (ZmF2H1, CYP93G5) converts flavanones to the corresponding 2-hydroxy derivatives, which are expected to serve as substrates for C-glycosylation. Here, we isolated a cDNA encoding a UDP-dependent glycosyltransferase (UGT708A6), and its activity was characterized by in vitro and in vivo bioconversion assays. In vitro assays using 2-hydroxyflavanones as substrates and in vivo activity assays in yeast co-expressing ZmF2H1 and UGT708A6 show the formation of the flavones C-glycosides. UGT708A6 can also O-glycosylate flavanones in bioconversion assays in Escherichia coli as well as by in vitro assays with the purified recombinant protein. Thus, UGT708A6 is a bifunctional glycosyltransferase that can produce both C- and O-glycosidated flavonoids, a property not previously described for any other glycosyltransferase. PMID:24045947

  9. Aminothiol multidentate chelators against Chagas disease.

    PubMed

    Deharo, E; Loyevsky, M; John, C; Balanza, E; Ruiz, G; Muñoz, V; Gordeuk, V R

    2000-03-01

    Three compounds of an aminothiol family of iron chelators were examined for activity against trypomastigote (human) and epimastigote (vector) forms of Trypanosoma cruzi: tetraethyl and tetramethyl derivatives of ethane-1,2-bis (N-1-amino-3-ethyl butyl-3-thiol) (BAT-TE and BAT-TM) and N',N',N'-tris-(2-methyl-2-mercaptopriopyl)- 1,4,7-triazacyclonane (TAT). BAT-TE at 270 microM completely arrested the growth of trypomastigote forms in mouse blood stored at 4 degrees C for 24 h (IC(50) 67.7+/-7 microM), while BAT-TM arrested growth at 630 microM (IC(50) 158+/-17 microM) and TAT at concentrations >800 microM (IC(50) 415+/-55 microM). In T. cruzi-infected mice, BAT-TE and BAT-TM had no anti-trypanosomal activity in doses up to 200 mg/kg, whether the route of administration was intraperitoneal or oral, and TAT was not tested due to insufficient quantity. TAT had an IC(50) of 52+/-7 microM against the epimastigote forms while BAT-TM and BAT-TE were inhibitory only at concentrations >250 microM. The trypanocidal activity of BAT derivatives in blood stored at 4 degrees C makes these compounds potential candidates for the purpose of clearing donated blood of trypomastigotes. PMID:10831386

  10. Bifunctional drugs for the treatment of asthma and chronic obstructive pulmonary disease.

    PubMed

    Page, Clive; Cazzola, Mario

    2014-08-01

    Over the last decade, there has been a steady increase in the use of fixed-dose combinations of drugs for the treatment of a range of diseases, including hypertension, cancer, AIDS, tuberculosis and other infectious diseases. It is now evident that patients with asthma or chronic obstructive pulmonary disease (COPD) can also benefit from the use of fixed-dose combinations, including combinations of a long-acting β2-agonist and an inhaled corticosteroid, and combinations of long-acting β2-agonists and long-acting muscarinic receptor antagonists. In fact, there are now a number of "triple-inhaler" fixed-dose combinations under development, with the first such triple combination having been approved in India. This use of combinations containing drugs with complementary pharmacological actions in the treatment of patients with asthma or COPD has also led to the discovery and development of drugs having two different primary pharmacological actions in the same molecule, which we have called "bifunctional drugs". In this review, we discuss the state of the art of these new bifunctional drugs as novel treatments for asthma and COPD that can be categorised as bifunctional bronchodilators, bifunctional bronchodilator/anti-inflammatory drugs and bifunctional anti-inflammatory drugs. PMID:24696121

  11. Perovskite-nitrogen-doped carbon nanotube composite as bifunctional catalysts for rechargeable lithium-air batteries.

    PubMed

    Park, Hey Woong; Lee, Dong Un; Park, Moon Gyu; Ahmed, Raihan; Seo, Min Ho; Nazar, Linda F; Chen, Zhongwei

    2015-03-01

    Developing an effective bifunctional catalyst is a significant issue, as rechargeable metal-air batteries are very attractive for future energy systems. In this study, a facile one-pot process is introduced to prepare an advanced bifunctional catalyst (op-LN) incorporating nitrogen-doped carbon nanotubes (NCNTs) into perovskite La0.5 Sr0.5 Co0.8 Fe0.2 O3 nanoparticles (LSCF-NPs). Confirmed by half-cell testing, op-LN exhibits synergistic effects of LSCF-NP and NCNT with excellent bifunctionality for both the oxygen reduction reaction and the oxygen evolution reaction. Furthermore, op-LN exhibits comparable performances in these reactions to Pt/C and Ir/C, respectively, which highlights its potential for use as a commercially viable bifunctional catalyst. Moreover, the results obtained by testing op-LN in a practical Li-air battery demonstrate improved and complementary charge/discharge performance compared to those of LSCF-NP and NCNT, and this confirms that simply prepared op-LN is a promising candidate as a highly effective bifunctional catalyst for rechargeable metal-air batteries. PMID:25684405

  12. Chelation in metal intoxication XVI. Influence of chelating agents on chromate poisoned rats

    SciTech Connect

    Tandon, S.K.; Srivastava, L.

    1985-01-01

    The ability of selective polyaminocarboxylic acids and common drugs to reduce the body burden of chromium and restore Cr induced biochemical alterations in chromate intoxicated rats was investigated. 1,2 Cychlohexylene dinitrilotetraacetic acid (CDTA) and triethylenetetramine hexacetic acid (TTHA) were more effective than p-aminosalicylic acid (PAS) and isoniazid (INH) in enhancing urinary excretion of Cr, lowering hepatic and blood levels of Cr and restoring inhibited activity of hepatic aldolase. The chromate antidotal property of chelators seem to be related to the combination of nitrogen and oxygen as the electron donating centres.

  13. Characterization and expression of human bifunctional 3'-phosphoadenosine 5'-phosphosulphate synthase isoforms.

    PubMed Central

    Fuda, Hirotoshi; Shimizu, Chikara; Lee, Young C; Akita, Harukuni; Strott, Charles A

    2002-01-01

    Sulphonation, a fundamental process essential for normal growth and development, requires the sulphonate donor molecule 3'-phosphoadenosine 5'-phosphosulphate (PAPS), which is produced from ATP and inorganic sulphate by the bifunctional enzyme PAPS synthase. In humans, two genes encode isoenzymes that are 77% identical at the amino acid level, and alternative splicing creates two subtypes of PAPS synthase 2. The question as to whether distinctions in amino acid composition are reflected in differences in activity has been examined. The specific activity of the PAPS synthase 2 subtypes is 10- to 15-fold higher than that for PAPS synthase 1. The greater catalytic efficiency of the PAPS synthase 2 subtypes is demonstrated further by the 3- to 6-fold higher k(cat)/K(m) ratios for ATP and inorganic sulphate as compared with the ratios for PAPS synthase 1. In humans, PAPS synthase 1 is expressed ubiquitously, and is the dominant isoform in most tissues, whereas expression of the PAPS synthase 2 subtypes is variable and tissue-specific. It is noteworthy that, similar to other human tissues, PAPS synthase 1 also appears to be the dominant isoform expressed in cartilage. The latter finding initially created a conundrum, since there is a specific human dwarfing disorder that is known to be caused by a mutation in the PAPS synthase 2 gene. This apparent enigma would seem to be resolved by examination of cartilage from guinea-pigs as an animal model. Similar to humans, cartilage from mature animals predominantly expresses PAPS synthase 1. In contrast, expression of PAPS synthase 1 is relatively low in the cartilage of immature guinea-pigs, including the growth plate of long bones, whereas PAPS synthase 2 is the highly expressed isoenzyme. PMID:11931637

  14. 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.

  15. An efficient chelator for complexation of thorium-227.

    PubMed

    Ramdahl, Thomas; Bonge-Hansen, Hanne T; Ryan, Olav B; Larsen, Smund; Herstad, Gunnar; Sandberg, Marcel; Bjerke, Roger M; Grant, Derek; Brevik, Ellen M; Cuthbertson, Alan S

    2016-09-01

    We present the synthesis and characterization of a highly efficient thorium chelator, derived from the octadentate hydroxypyridinone class of compounds. The chelator forms extremely stable complexes with fast formation rates in the presence of Th-227 (ambient temperature, 20min). In addition, mouse biodistribution data are provided which indicate rapid hepatobiliary excretion route of the chelator which, together with low bone uptake, supports the stability of the complex in vivo. The carboxylic acid group may be readily activated for conjugation through the ɛ-amino groups of lysine residues in biomolecules such as antibodies. This chelator is a critical component of a new class of Targeted Thorium Conjugates (TTCs) currently under development in the field of oncology. PMID:27476138

  16. 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.

  17. An Evaluation of the Chelating Agent EDDS for Marigold Production

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Aminopolycarboxylic acid (APCA) ligands (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 plants. The offsite runoff and contamina...

  18. Cell assay using a two-photon-excited europium chelate

    PubMed Central

    Xiao, Xudong; Haushalter, Jeanne P.; Kotz, Kenneth T.; Faris, Gregory W.

    2011-01-01

    We report application of two-photon excitation of europium chelates to immunolabeling of epidermal growth factor receptor (EGFR) cell surface proteins on A431 cancer cells. The europium chelates are excited with two photons of infrared light and emit in the visible. Europium chelates are conjugated to antibodies for EGFR. A431 (human epidermoid carcinoma) cells are labeled with this conjugate and imaged using a multiphoton microscope. To minimize signal loss due to the relatively long-lived Eu3+ emission, the multiphoton microscope is used with scanning laser two-photon excitation and non-scanning detection with a CCD. The chelate labels show very little photobleaching (less than 1% during continuous illumination in the microscope for 20 minutes) and low levels of autofluorescence (less than 1% of the signal from labeled cells). The detection limit of the europium label in the cell assay is better than 100 zeptomoles. PMID:21833362

  19. Comparing potential copper chelation mechanisms in Parkinson's disease protein

    NASA Astrophysics Data System (ADS)

    Rose, Frisco; Hodak, Miroslav; Bernholc, Jerry

    2011-03-01

    We have implemented the nudged elastic band (NEB) as a guided dynamics framework for our real-space multigrid method of DFT-based quantum simulations. This highly parallel approach resolves a minimum energy pathway (MEP) on the energy hypersurface by relaxing intermediates in a chain-of-states. As an initial application we present an investigation of chelating agents acting on copper ion bound to α -synuclein, whose misfolding is implicated in Parkinson's disease (PD). Copper ions are known to act as highly effective misfolding agents in a-synuclein and are thus an important target in understanding PD. Furthermore, chelation therapy has shown promise in the treatment of Alzheimer's and other neuro-degenerative diseases with similar metal-correlated pathologies. At present, our candidate chelating agents include nicotine, curcumin and clioquinol. We examine their MEP activation barriers in the context of a PD onset mechanism to assess the viability of various chelators for PD remediation.

  20. 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

  1. Iron chelators ICL670 and 311 inhibit HIV-1 transcription

    SciTech Connect

    Debebe, Zufan; Ammosova, Tatyana; Jerebtsova, Marina; Kurantsin-Mills, Joseph; Niu, Xiaomei; Charles, Sharroya; Richardson, Des R.; Ray, Patricio E.; Gordeuk, Victor R.; Nekhai, Sergei

    2007-10-25

    HIV-1 replication is induced by an excess of iron and iron chelation by desferrioxamine (DFO) inhibits viral replication by reducing proliferation of infected cells. Treatment of cells with DFO and 2-hydroxy-1-naphthylaldehyde isonicotinoyl hydrazone (311) inhibit expression of proteins that regulate cell-cycle progression, including cycle-dependent kinase 2 (CDK2). Our recent studies showed that CDK2 participates in HIV-1 transcription and viral replication suggesting that inhibition of CDK2 by iron chelators might also affect HIV-1 transcription. Here we evaluated the effect of a clinically approved orally effective iron chelator, 4-[3,5-bis-(hydroxyphenyl)-1,2,4-triazol-1-yl]-benzoic acid (ICL670) and 311 on HIV-1 transcription. Both ICL670 and 311 inhibited Tat-induced HIV-1 transcription in CEM-T cells, 293T and HeLa cells. Neither ICL670 nor 311 induced cytotoxicity at concentrations that inhibited HIV-1 transcription. The chelators decreased cellular activity of CDK2 and reduced HIV-1 Tat phosphorylation by CDK2. Neither ICL670A or 311 decreased CDK9 protein level but significantly reduced association of CDK9 with cyclin T1 and reduced phosphorylation of Ser-2 residues of RNA polymerase II C-terminal domain. In conclusion, our findings add to the evidence that iron chelators can inhibit HIV-1 transcription by deregulating CDK2 and CDK9. Further consideration should be given to the development of iron chelators for future anti-retroviral therapeutics.

  2. 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.

  3. 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.

  4. Iron Chelation Adherence to Deferoxamine and Deferasirox in Thalassemia

    PubMed Central

    Trachtenberg, Felicia; Vichinsky, Elliott; Haines, Dru; Pakbaz, Zahra; Mednick, Lauren; Sobota, Amy; Kwiatkowski, Janet; Thompson, Alexis A.; Porter, John; Coates, Thomas; Giardina, Patricia J.; Olivieri, Nancy; Yamashita, Robert; Neufeld, Ellis J.

    2015-01-01

    The Thalassemia Clinical Research Network collected adherence information from 79 patients on deferoxamine and 186 on deferasirox from 2007 to 2009. Chelation adherence was defined as percent of doses administered in the last 4 weeks (patient report) out of those prescribed (chart review). Chelation history since 2002 was available for 97 patients currently on deferoxamine and 217 on deferasirox, with crude estimates of adherence from chart review. Self-reported adherence to both deferoxamine and deferasirox were quite high, with slightly higher adherence to the oral chelator (97 vs. 92%). Ninety percent of patients on deferasirox reported at least 90% adherence, compared with 75% of patients on deferoxamine. Adherence to both chelators was highest in children, followed by adolescents and older adults. Predictors of lower deferoxamine adherence were smoking in the past year, problems sticking themselves (adults only), problems wearing their pump, and fewer transfusions in the past year. Predictors of lower deferasirox adherence were bodily pain and depression. Switching chelators resulted in increased adherence, regardless of the direction of the switch, although switching from deferoxamine to deferasirox was far more common. As adherence to deferoxamine is higher than previously reported, it appears beneficial for patients to have a choice in chelators. PMID:21523808

  5. Polymer-Supported Reagents: The Role of Bifunctionality in the Design of Ion-Selective Complexants

    SciTech Connect

    Alexandratos, S. D.

    2001-06-01

    The importance of multi-functionality in the preparation of ion-selective polymers is evident from the structure of enzymes where specific metal ions are bound through cooperative interactions among different amino acids. In synthetic polymers, ionic selectivity is enhanced when a chemical reaction is superimposed on an ion-exchange process. The concept of reactive ion exchange has been extended through the synthesis of crosslinked polymers whose metal ion selectivity is a function of reduction, coordination or precipitation reactions as determined by various covalently bound ligands. Development of three classes of dual mechanism bifunctional polymers, a new series of bifunctional diphosphonate polymers, and novel bifunctional ion-selective polymers with enhanced ionic accessibility has been accomplished.

  6. Enhanced Bifunctional Oxygen Catalysis in Strained LaNiO3 Perovskites.

    PubMed

    Petrie, Jonathan R; Cooper, Valentino R; Freeland, John W; Meyer, Tricia L; Zhang, Zhiyong; Lutterman, Daniel A; Lee, Ho Nyung

    2016-03-01

    Strain is known to greatly influence low-temperature oxygen electrocatalysis on noble metal films, leading to significant enhancements in bifunctional activity essential for fuel cells and metal-air batteries. However, its catalytic impact on transition-metal oxide thin films, such as perovskites, is not widely understood. Here, we epitaxially strain the conducting perovskite LaNiO3 to systematically determine its influence on both the oxygen reduction and oxygen evolution reaction. Uniquely, we found that compressive strain could significantly enhance both reactions, yielding a bifunctional catalyst that surpasses the performance of noble metals such as Pt. We attribute the improved bifunctionality to strain-induced splitting of the eg orbitals, which can customize orbital asymmetry at the surface. Analogous to strain-induced shifts in the d-band center of noble metals relative to the Fermi level, such splitting can dramatically affect catalytic activity in this perovskite and other potentially more active oxides. PMID:26866808

  7. Electrochemical Investigation of Interaction between a Bifunctional Probe and GG Mismatch Duplex.

    PubMed

    Li, Jiao; He, Hanping; Peng, Xiaoqian; Huang, Min; Zhang, Xiuhua; Wang, Shengfu

    2015-01-01

    A bifunctional probe (FecNC), containing a recognition part and an electrochemical active center, was applied to electrochemical detection of GG mismatch duplexes. The preparation of gold electrodes modified by mismatch and complementatry duplexes was characterized by electrochemical impedance spectroscopy (EIS) and optimized for better detection in terms of self-assembly time, hybridization time, and incubation time. The interaction between FecNC and DNA duplexes modified on the surface of a gold electrode was explored by square wave voltammetry (SWV) and EIS. The results showed that the DNA duplexes with GG mismatch on the surface of a gold electrode was easily detected by the largest electrochemical signal of the bifunctional probe because of its selective binding to GG mismatches. The bifunctional probe could offer a simple, effective electrochemical detection of GG mismatches, and theoretical bases for development of electrochemical biosensors. Further, the method would be favorable for diagnosis of genetic diseases. PMID:26165289

  8. Nickel sulfide microsphere film on Ni foam as an efficient bifunctional electrocatalyst for overall water splitting.

    PubMed

    Zhu, Wenxin; Yue, Xiaoyue; Zhang, Wentao; Yu, Shaoxuan; Zhang, Yuhuan; Wang, Jing; Wang, Jianlong

    2016-01-25

    Developing low-cost, efficient, and bifunctional electrocatalysts for both the hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) is an appealing yet challenging task. Herein, for the first time, a NiS microsphere film was grown in situ on Ni foam (NiS/Ni foam) via a sulfurization reaction as an efficient bifunctional electrocatalyst for overall water splitting with superior activity and good durability. This NiS/Ni foam electrode delivers 20 mA cm(-2) at an overpotential of 158 mV for the HER and 50 mA cm(-2) at an overpotential of 335 mV for the OER in 1.0 M KOH. This bifunctional electrode also enables a high-efficiency alkaline water electrolyzer with 10 mA cm(-2) at a cell voltage of only 1.64 V, which could be promising in water splitting devices for large-scale hydrogen production. PMID:26661579

  9. The magnesium chelation step in chlorophyll biosynthesis

    SciTech Connect

    Weinstein, J.

    1990-11-01

    In photosynthetic organisms, the biogenesis of energy transducing membranes requires the coordinate synthesis of prosthetic groups, proteins, and various lipids. Two of the major prosthetic groups, chlorophyll and heme, share a common biosynthetic pathway that diverges at the point of metal insertion into protoporphyrin IX (Proto). Insertion of iron leads to the formation of hemes, while insertion of magnesium is the first step unique to chlorophyll formation. This project is directed toward identifying the enzyme(s) responsible for magnesium chelation and elucidating the mechanism which regulates the flux of precursors through the branch point enzymes in isolated chloroplasts. Using intact chloroplasts from greening cucumber cotyledons, we have confirmed the ATP requirement for Mg-Proto formation. Use of non-hydrolyzable ATP analogs, uncouplers and ionophores has led to the conclusions that ATP hydrolysis is necessary, but that this hydrolysis is not linked to the requirement for membrane intactness by transmembrane ion gradients or electrical potentials. The enzyme(s) are flexible with respect to the porphyrin substrate specificity, accepting porphyrins with -vinyl, -ethyl, or -H substituents at the 2 and 4 positions. The activity increases approximately four-fold during greening. Possible physiological feedback inhibitors such as heme, protochlorophyllide, and chlorophyllide had no specific effect on the activity. The activity has now been assayed in barely, corn and peas, with the system from peas almost ten-fold more active than the cucumber system. Work is continuing in pea chloroplasts with the development of a continuous assay and investigation of the feasibility of characterizing an active, organelle-free preparation. 6 figs.

  10. Synthesis, characterization and catalytic activity of acid-base bifunctional materials through protection of amino groups

    SciTech Connect

    Shao, Yanqiu; Liu, Heng; Yu, Xiaofang; Guan, Jingqi; Kan, Qiubin

    2012-03-15

    Graphical abstract: Acid-base bifunctional mesoporous material SO{sub 3}H-SBA-15-NH{sub 2} was successfully synthesized under low acidic medium through protection of amino groups. Highlights: Black-Right-Pointing-Pointer The acid-base bifunctional material SO{sub 3}H-SBA-15-NH{sub 2} was successfully synthesized through protection of amino groups. Black-Right-Pointing-Pointer The obtained bifunctional material was tested for aldol condensation. Black-Right-Pointing-Pointer The SO{sub 3}H-SBA-15-NH{sub 2} catalyst containing amine and sulfonic acid groups exhibited excellent acid-basic properties. -- Abstract: Acid-base bifunctional mesoporous material SO{sub 3}H-SBA-15-NH{sub 2} was successfully synthesized under low acidic medium through protection of amino groups. X-ray diffraction (XRD), N{sub 2} adsorption-desorption, transmission electron micrographs (TEM), back titration, {sup 13}C magic-angle spinning (MAS) NMR and {sup 29}Si magic-angle spinning (MAS) NMR were employed to characterize the synthesized materials. The obtained bifunctional material was tested for aldol condensation reaction between acetone and 4-nitrobenzaldehyde. Compared with monofunctional catalysts of SO{sub 3}H-SBA-15 and SBA-15-NH{sub 2}, the bifunctional sample of SO{sub 3}H-SBA-15-NH{sub 2} containing amine and sulfonic acid groups exhibited excellent acid-basic properties, which make it possess high activity for the aldol condensation.

  11. Method for preparing radionuclide-labeled chelating agent-ligand complexes

    DOEpatents

    Meares, Claude F.; Li, Min; DeNardo, Sally J.

    1999-01-01

    Radionuclide-labeled chelating agent-ligand complexes that are useful in medical diagnosis or therapy are prepared by reacting a radionuclide, such as .sup.90 Y or .sup.111 In, with a polyfunctional chelating agent to form a radionuclide chelate that is electrically neutral; purifying the chelate by anion exchange chromatography; and reacting the purified chelate with a targeting molecule, such as a monoclonal antibody, to form the complex.

  12. Reaction Current Phenomenon in Bifunctional Catalytic Metal-Semiconductor Nanostructures

    NASA Astrophysics Data System (ADS)

    Hashemian, Mohammad Amin

    Energy transfer processes accompany every elementary step of catalytic chemical processes on material surface including molecular adsorption and dissociation on atoms, interactions between intermediates, and desorption of reaction products from the catalyst surface. Therefore, detailed understanding of these processes on the molecular level is of great fundamental and practical interest in energy-related applications of nanomaterials. Two main mechanisms of energy transfer from adsorbed particles to a surface are known: (i) adiabatic via excitation of quantized lattice vibrations (phonons) and (ii) non-adiabatic via electronic excitations (electron/hole pairs). Electronic excitations play a key role in nanocatalysis, and it was recently shown that they can be efficiently detected and studied using Schottky-type catalytic nanostructures in the form of measureable electrical currents (chemicurrents) in an external electrical circuit. These nanostructures typically contain an electrically continuous nanocathode layers made of a catalytic metal deposited on a semiconductor substrate. The goal of this research is to study the direct observations of hot electron currents (chemicurrents) in catalytic Schottky structures, using a continuous mesh-like Pt nanofilm grown onto a mesoporous TiO2 substrate. Such devices showed qualitatively different and more diverse signal properties, compared to the earlier devices using smooth substrates, which could only be explained on the basis of bifunctionality. In particular, it was necessary to suggest that different stages of the reaction are occurring on both phases of the catalytic structure. Analysis of the signal behavior also led to discovery of a formerly unknown (very slow) mode of the oxyhydrogen reaction on the Pt/TiO2(por) system occurring at room temperature. This slow mode was producing surprisingly large stationary chemicurrents in the range 10--50 microA/cm2. Results of the chemicurrent measurements for the bifunctional

  13. Bifunctional aldehyde/alcohol dehydrogenase (ADHE) in chlorophyte algal mitochondria.

    PubMed

    Atteia, Ariane; van Lis, Robert; Mendoza-Hernández, Guillermo; Henze, Katrin; Martin, William; Riveros-Rosas, Hector; González-Halphen, Diego

    2003-09-01

    Protein profiles of mitochondria isolated from the heterotrophic chlorophyte Polytomella sp. grown on ethanol at pH 6.0 and pH 3.7 were analyzed by Blue Native and denaturing polyacrylamide gel electrophoresis. Steady-state levels of oxidative phosphorylation complexes were influenced by external pH. Levels of an abundant, soluble, mitochondrial protein of 85 kDa and its corresponding mRNA increased at pH 6.0 relative to pH 3.7. N-terminal and internal sequencing of the 85 kDa mitochondrial protein together with the corresponding cDNA identified it as a bifunctional aldehyde/alcohol dehydrogenase (ADHE) with strong similarity to homologues from eubacteria and amitochondriate protists. A mitochondrial targeting sequence of 27 amino acids precedes the N-terminus of the mature mitochondrial protein. A gene encoding an ADHE homologue was also identified in the genome of Chlamydomonas reinhardtii, a photosynthetic relative of Polytomella. ADHE reveals a complex picture of sequence similarity among homologues. The lack of ADHE from archaebacteria indicates a eubacterial origin for the eukaryotic enzyme. Among eukaryotes, ADHE has hitherto been characteristic of anaerobes since it is essential to cytosolic energy metabolism of amitochondriate protists such as Giardia intestinalis and Entamoeba histolytica. Its abundance and expression pattern suggest an important role for ADHE in mitochondrial metabolism of Polytomella under the conditions studied. The current data are compatible with the view that Polytomella ADHE could be involved either in ethanol production or assimilation, or both, depending upon environmental conditions. Presence of ADHE in an oxygen-respiring algal mitochondrion and co-expression at ambient oxygen levels with respiratory chain components is unexpected with respect to the view that eukaryotes acquired ADHE genes specifically as an adaptation to an anaerobic lifestyle. PMID:14756315

  14. Physical properties of bifunctional BST/LSMO nanocomposites

    SciTech Connect

    Beltran-Huarac, Juan Morell, Gerardo; Martinez, Ricardo

    2014-02-28

    We report the fabrication of bifunctional nanocomposites consisting of ferroelectric Ba{sub 0.7}Sr{sub 0.3}TiO{sub 3} (BST) and ferromagnetic La{sub 0.67}Sr{sub 0.33}MnO{sub 3} (LSMO) at different concentrations via a high-temperature solid state route. The structural, dielectric, electrical, magnetodielectric (MD), magnetoelectric (ME) and magnetic properties of BST/LSMO nanocomposites were systematically investigated over a wide range of temperatures and frequencies. The X-Ray Diffraction analyses reveal the nanocrystalline nature of the heterostructures, wherein both perovskite phases co-exist. No parasitic phases were observed. The study of the dielectric properties shows that the nanocomposites exhibit relaxor ferroelectric character, with ferroelectric-paraelectric phase transition temperatures around 287–292 K that do not follow the Curie-Weiss law. The electrical measurements indicate that ac conductivities of the nanocomposites follow the Jonscher's universal power law, with activation energies of 0.42–0.63 eV based on Arrhenius-type behavior at high temperatures. The nanocomposites exhibit well-defined ferromagnetic hysteresis loops at room temperature (RT). The MD and ME measurements at RT indicate that BST/LSMO exhibits a nonlinear ME effect at low frequencies, with a threshold near 0.5 T. The magnetocapacitance (MC{sub p}) measurements evidence a quadratic dependence on magnetic field, further confirming the multiferroic nature of BST/LSMO. The order of MC{sub p} was found to be ∼7% per Tesla. The analysis of the MC{sub p} measurements indicates that one of the BST/LSMO compositions studied can be considered as a new multiferroic compound.

  15. Bifunctional Ligands Allow Deliberate Extrinsic Reprogramming of the Glucocorticoid Receptor

    PubMed Central

    Højfeldt, Jonas W.; Cruz-Rodríguez, Osvaldo; Imaeda, Yasuhiro; Van Dyke, Aaron R.; Carolan, James P.; Mapp, Anna K.

    2014-01-01

    Therapies based on conventional nuclear receptor ligands are extremely powerful, yet their broad and long-term use is often hindered by undesired side effects that are often part of the receptor's biological function. Selective control of nuclear receptors such as the glucocorticoid receptor (GR) using conventional ligands has proven particularly challenging. Because they act solely in an allosteric manner, conventional ligands are constrained to act via cofactors that can intrinsically partner with the receptor. Furthermore, effective means to rationally encode a bias for specific coregulators are generally lacking. Using the (GR) as a framework, we demonstrate here a versatile approach, based on bifunctional ligands, that extends the regulatory repertoire of GR in a deliberate and controlled manner. By linking the macrolide FK506 to a conventional agonist (dexamethasone) or antagonist (RU-486), we demonstrate that it is possible to bridge the intact receptor to either positively or negatively acting coregulatory proteins bearing an FK506 binding protein domain. Using this strategy, we show that extrinsic recruitment of a strong activation function can enhance the efficacy of the full agonist dexamethasone and reverse the antagonist character of RU-486 at an endogenous locus. Notably, the extrinsic recruitment of histone deacetylase-1 reduces the ability of GR to activate transcription from a canonical GR response element while preserving ligand-mediated repression of nuclear factor-κB. By providing novel ways for the receptor to engage specific coregulators, this unique ligand design approach has the potential to yield both novel tools for GR study and more selective therapeutics. PMID:24422633

  16. Janus nanobelts: fabrication, structure and enhanced magnetic-fluorescent bifunctional performance

    NASA Astrophysics Data System (ADS)

    Ma, Qianli; Yu, Wensheng; Dong, Xiangting; Wang, Jinxian; Liu, Guixia

    2014-02-01

    A new nanostructure of magnetic-fluorescent bifunctional Janus nanobelts with Fe3O4/PMMA as one half and Tb(BA)3phen/PMMA as the other half has been successfully fabricated by a specially designed parallel spinneret electrospinning technology. The morphology and properties of the final products were investigated in detail by X-ray diffractometry (XRD), scanning electron microscopy (SEM), energy dispersive spectrometry (EDS), biological microscopy (BM), vibrating sample magnetometry (VSM) and fluorescence spectroscopy. The results revealed that the [Fe3O4/PMMA]//[Tb(BA)3phen/PMMA] magnetic-fluorescent bifunctional Janus nanobelts possess superior magnetic and fluorescent properties due to their special nanostructure. Compared with Fe3O4/Tb(BA)3phen/PMMA composite nanobelts, the magnetic-fluorescent bifunctional Janus nanobelts provided better performance. The new magnetic-fluorescent bifunctional Janus nanobelts have potential applications in novel nano-bio-label materials, drug target delivery materials and future nanodevices due to their excellent magnetic-fluorescent properties, flexibility and insolubility. Moreover, the construction technique for the Janus nanobelts is of universal significance for the fabrication of other multifunctional Janus nanobelts.A new nanostructure of magnetic-fluorescent bifunctional Janus nanobelts with Fe3O4/PMMA as one half and Tb(BA)3phen/PMMA as the other half has been successfully fabricated by a specially designed parallel spinneret electrospinning technology. The morphology and properties of the final products were investigated in detail by X-ray diffractometry (XRD), scanning electron microscopy (SEM), energy dispersive spectrometry (EDS), biological microscopy (BM), vibrating sample magnetometry (VSM) and fluorescence spectroscopy. The results revealed that the [Fe3O4/PMMA]//[Tb(BA)3phen/PMMA] magnetic-fluorescent bifunctional Janus nanobelts possess superior magnetic and fluorescent properties due to their special

  17. Fabrication and Characterization of Luminescent Magnetic Bifunctional Nanocomposite Based on TbPO4·H2O Nanowires and Fe3O4 Nanoparticles

    NASA Astrophysics Data System (ADS)

    Huong, Nguyen Thanh; Hung, Nguyen Manh; Lien, Pham Thi; Van, Nguyen Duc; Nam, Pham Hong; Binh, Nguyen Thanh; Minh, Le Quoc

    2016-05-01

    The fabrication and properties of luminescent magnetic bifunctional nanocomposites comprised of TbPO4·H2O nanowires as a core and magnetite nanoparticles as a shell are presented. TbPO4·H2O nanowires were synthesized by a microwave-assisted method while the grafting process of freshly-formed superparamagnetic magnetite nanoparticles on the surface of luminescent nanowires was carried out by a co-precipitate method. The effects of the Fe3O4/TbPO4·H2O mass ratio on the luminescent and magnetic properties of the obtained nanocomposite were also investigated. The results showed that, for the optimized bifunctional nanocomposites, green luminescent emissions at 488 nm, 542 nm, 585 nm, 620 nm and superparamagnetic behavior with saturation magnetization M s of 6 emu/g were achieved. With a hyperthermia temperature of ~43.5°C under an alternating current (AC) magnetic field, the obtained TbPO4·H2O/Fe3O4 nanocomposite was expected to be used for both optical probing and hyperthermia cancer treatments in biomedical applications.

  18. Cobalt sulfide/N,S codoped porous carbon core-shell nanocomposites as superior bifunctional electrocatalysts for oxygen reduction and evolution reactions.

    PubMed

    Chen, Binling; Li, Rong; Ma, Guiping; Gou, Xinglong; Zhu, Yanqiu; Xia, Yongde

    2015-12-28

    Exploring highly-efficient and low-cost bifunctional electrocatalysts for both oxygen reduction reaction (ORR) and oxygen evolution reactions (OER) in the renewable energy area has gained momentum but still remains a significant challenge. Here we present a simple but efficient method that utilizes ZIF-67 as the precursor and template for the one-step generation of homogeneous dispersed cobalt sulfide/N,S-codoped porous carbon nanocomposites as high-performance electrocatalysts. Due to the favourable molecular-like structural features and uniform dispersed active sites in the precursor, the resulting nanocomposites, possessing a unique core-shell structure, high porosity, homogeneous dispersion of active components together with N and S-doping effects, not only show excellent electrocatalytic activity towards ORR with the high onset potential (around -0.04 V vs.-0.02 V for the benchmark Pt/C catalyst) and four-electron pathway and OER with a small overpotential of 0.47 V for 10 mA cm(-2) current density, but also exhibit superior stability (92%) to the commercial Pt/C catalyst (74%) in ORR and promising OER stability (80%) with good methanol tolerance. Our findings suggest that the transition metal sulfide-porous carbon nanocomposites derived from the one-step simultaneous sulfurization and carbonization of zeolitic imidazolate frameworks are excellent alternative bifunctional electrocatalysts towards ORR and OER in the next generation of energy storage and conversion technologies. PMID:26599403

  19. Fabrication and Characterization of Luminescent Magnetic Bifunctional Nanocomposite Based on TbPO4·H2O Nanowires and Fe3O4 Nanoparticles

    NASA Astrophysics Data System (ADS)

    Huong, Nguyen Thanh; Hung, Nguyen Manh; Lien, Pham Thi; Van, Nguyen Duc; Nam, Pham Hong; Binh, Nguyen Thanh; Minh, Le Quoc

    2016-07-01

    The fabrication and properties of luminescent magnetic bifunctional nanocomposites comprised of TbPO4·H2O nanowires as a core and magnetite nanoparticles as a shell are presented. TbPO4·H2O nanowires were synthesized by a microwave-assisted method while the grafting process of freshly-formed superparamagnetic magnetite nanoparticles on the surface of luminescent nanowires was carried out by a co-precipitate method. The effects of the Fe3O4/TbPO4·H2O mass ratio on the luminescent and magnetic properties of the obtained nanocomposite were also investigated. The results showed that, for the optimized bifunctional nanocomposites, green luminescent emissions at 488 nm, 542 nm, 585 nm, 620 nm and superparamagnetic behavior with saturation magnetization M s of 6 emu/g were achieved. With a hyperthermia temperature of ~43.5°C under an alternating current (AC) magnetic field, the obtained TbPO4·H2O/Fe3O4 nanocomposite was expected to be used for both optical probing and hyperthermia cancer treatments in biomedical applications.

  20. Sequestration of chelated copper by structural Fe(II): Reductive decomplexation and transformation of Cu(II)-EDTA.

    PubMed

    He, Hongping; Wu, Deli; Zhao, Linghui; Luo, Cong; Dai, Chaomeng; Zhang, Yalei

    2016-05-15

    Chelated coppers, such as Cu(II)-EDTA, are characteristically refractory and difficult to break down because of their high stability and solubility. Cu(II)-EDTA sequestration by structural Fe(II) (Fe(II)) was investigated intensively in this study. Up to 101.21mgCu(II)/gFe(II) was obtained by Fe(II) in chelated copper sequestration under near neutral pH condition (pH 7.70). The mechanism of Cu(II)-EDTA sequestration by Fe(II) was concluded as follows: 3Cu(II)-EDTA+7Fe(II)+9H2O → Cu(0)↓+ Cu2O↓(the major product)+2Fe2O3·H2O↓+3Fe(II)-EDTA +14H(+) Novel results strongly indicate that Cu(II) reductive transformation induced by surface Fe(II) was mainly responsible for chelated copper sequestration. Cu(0) generation was initially facilitated, and subsequent reduction of Cu(II) into Cu(I) was closely combined with the gradual increase of ORP (Oxidation-Reduction Potential). Cu-containing products were inherently stable, but Cu2O would be reoxidized to Cu(II) with extra-aeration, resulting in the release of copper, which was beneficial to Cu reclamation. Concentration diminution of Cu(II)-EDTA within the electric double layer and competitive adsorption were responsible for the negative effects of Ca(2+), Mg(2+). By generating vivianite, PO4(3-) was found to decrease surface Fe(II) content. This study is among the first ones to identify the indispensible role of reductive decomplexation in chelated copper sequestration. Given the high feasibility and reactivity, Fe(II) may provide a potential alternative in chelated metals pollution controlling. PMID:26878707

  1. Highly regioselective hydroformylation with hemispherical chelators.

    PubMed

    Sémeril, David; Matt, Dominique; Toupet, Loïc

    2008-01-01

    The hemispherical diphosphites (R,R)- or (S,S)-5,11,17,23-tetra-tert-butyl-25,27-di(OR)-26,28-bis(1,1'-binaphthyl-2,2'-dioxyphosphanyloxy)calix[4]arene (R=OPr, OCH(2)Ph, OCH(2)-naphtyl, O-fluorenyl; R=H, R'=OPr) (L(R)), all with C(2) symmetry, have been synthesised starting from the appropriate di-O-alkylated calix[4]arene precursor. In the presence of [Rh(acac)(CO)(2)], these ligands straightforwardly provide chelate complexes in which the metal centre sits in a molecular pocket defined by two naphthyl planes related by the C(2) axis and the two apically situated R groups. Hydroformylation of octene with the L(Pr)/Rh system turned out to be highly regioselective, the linear-to-branched (l:b) aldehyde ratio reaching 58:1. The l:b ratio significantly increased when the propyl groups were replaced by -CH(2)Ph (l:b=80) or -CH(2)naphthyl (l:b=100) groups, that is, with substituents able to sterically interact with the apical metal sites, but without inducing an opening of the cleft nesting the catalytic centre. The trend to preferentially form the aldehyde the shape of which fits with the shape of the catalytic pocket was further confirmed in the hydroformylation of styrene, for which, in contrast to catalysis with conventional diphosphanes, the linear aldehyde was the major product (up to ca. 75 % linear aldehyde). In the hydroformylation of trans-2-octene with the L(benzyl)/Rh system, combined isomerisation/hydroformylation led to a remarkably high l:b aldehyde ratios of 25, thus showing that isomerisation is more effective than hydroformylation. Unusually large amounts of linear products were also observed with all the above diphosphites in the tandem hydroformylation/amination of styrene (l:b of ca. 3:1) as well as in the hydroformylation of allyl benzyl ether (l:b ratio up to 20). PMID:18686280

  2. Metal chelates anchored to poly-l-peptides and linear d,l-α-peptides with promising nanotechnological applications

    NASA Astrophysics Data System (ADS)

    Punzi, P.; Giordano, C.; Marino, F.; Morosetti, S.; De Santis, P.; Scipioni, A.

    2012-10-01

    Regular configurationally alternating amino acid sequences generate cyclic and linear helical peptides with a local β-conformation able to self-assemble in nanowires and nanoscaffolds directed and stabilized by hydrogen bonds. The possibility of modulating the chemical profile of the various amino acid residues containing reactive side chains means that peptides could be flexible templates for creating various building blocks. A method for the design of molecules with potential spintronic properties is described. Peptides containing lysine residues, the side chains of which are bridged through the formation of metal chelates via Schiff bases, could provide stable molecular channels. When metal chelates with high electron spin states are used, their coupling could generate materials that are interesting due to their magnetic properties as well as for the patterning of nanometric lattices driven by their orientation under a magnetic field. With this aim, three alternating d- and l-lysine-containing octapeptides are synthesized and the formation of their bis(pyridoxalaldimine) copper(II) chelate derivatives is shown by absorption and circular dichroism spectroscopies.

  3. Oxidation-Induced Degradable Nanogels for Iron Chelation

    PubMed Central

    Liu, Zhi; Wang, Yan; Purro, Max; Xiong, May P.

    2016-01-01

    Iron overload can increase cellular oxidative stress levels due to formation of reactive oxygen species (ROS); untreated, it can be extremely destructive to organs and fatal to patients. Since elevated oxidative stress levels are inherent to the condition in such patients, oxidation-induced degradable nanogels for iron chelation were rationally designed by simultaneously polymerizing oxidation-sensitive host-guest crosslinkers between β-cyclodextrin (β-CD) and ferrocene (Fc) and iron chelating moieties composed of deferoxamine (DFO) into the final gel scaffold in reverse emulsion reaction chambers. UV-Vis absorption and atomic absorption spectroscopy (AAS) was used to verify iron chelating capability of nanogels. These materials can degrade into smaller chelating fragments at rates proportional to the level of oxidative stress present. Conjugating DFO reduces the cytotoxicity of the chelator in the macrophage cells. Importantly, the nanogel can effectively reduce cellular ferritin expression in iron overloaded cells and regulate intracellular iron levels at the same time, which is important for maintaining a homeostatic level of this critical metal in cells. PMID:26868174

  4. Ab Initio Coordination Chemistry for Nickel Chelation Motifs

    PubMed Central

    Jesu Jaya Sudan, R.; Lesitha Jeeva Kumari, J.; Sudandiradoss, C.

    2015-01-01

    Chelation therapy is one of the most appreciated methods in the treatment of metal induced disease predisposition. Coordination chemistry provides a way to understand metal association in biological structures. In this work we have implemented coordination chemistry to study nickel coordination due to its high impact in industrial usage and thereby health consequences. This paper reports the analysis of nickel coordination from a large dataset of nickel bound structures and sequences. Coordination patterns predicted from the structures are reported in terms of donors, chelate length, coordination number, chelate geometry, structural fold and architecture. The analysis revealed histidine as the most favored residue in nickel coordination. The most common chelates identified were histidine based namely HHH, HDH, HEH and HH spaced at specific intervals. Though a maximum coordination number of 8 was observed, the presence of a single protein donor was noted to be mandatory in nickel coordination. The coordination pattern did not reveal any specific fold, nevertheless we report preferable residue spacing for specific structural architecture. In contrast, the analysis of nickel binding proteins from bacterial and archeal species revealed no common coordination patterns. Nickel binding sequence motifs were noted to be organism specific and protein class specific. As a result we identified about 13 signatures derived from 13 classes of nickel binding proteins. The specifications on nickel coordination presented in this paper will prove beneficial for developing better chelation strategies. PMID:25985439

  5. Essential Metalloelement Chelates Facilitate Repair of Radiation Injury

    PubMed Central

    Soderberg, Lee S. F.; Chang, Louis W.; Walker, Richard B.

    2001-01-01

    Treatment with essential metalloelement (Cu, Fe, Mn, and Zn) chelates or combinations of them before and/or after radiation injury is a useful approach to overcoming radiation injury. No other agents are known to increase survival when they are used to treat after irradiation, in a radiorecovery treatment paradigm. These chelates may be useful in facilitating de novo syntheses of essential metalloelement-dependent enzymes required to repair radiation injury. Reports of radioprotection, which involves treatment before irradiation, with calcium-channel blockers, acyl Melatonin homologs, and substituted anilines, which may serve as chelating agents after biochemical modification in vivo, as well as Curcumin, which is a chelating agent, have been included in this review. These inclusions are intended to suggest additional approaches to combination treatments that may be useful in facilitating radiation recovery. These approaches to radioprotection and radiorecovery offer promise in facilitating recovery from radiation-induced injury experienced by patients undergoing radiotherapy for neoplastic disease and by individuals who experience environmental, occupational, or accidental exposure to ultraviolet, x-ray, or γ-ray radiation. Since there are no existing treatments of radiation-injury intended to facilitate tissue repair, studies of essential metalloelement chelates and combinations of them, as well as combinations of them with existing organic radioprotectants, seem worthwhile. PMID:18475999

  6. 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.

  7. 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.

  8. A bifunctional chiral [2]catenane based on 1,1'-binaphthyl-phosphates.

    PubMed

    Mitra, R; Thiele, M; Octa-Smolin, F; Letzel, M C; Niemeyer, J

    2016-05-21

    A novel [2]catenane was synthesised by ring-closing metathesis from a Ca-bisphosphate template. The resulting interlocked structure features two chiral 1,1'-binaphthyl-phosphates, leading to a bifunctional catenane structure. Initial binding studies point at the applicability of such mechanically interlocked bisphosphates as artificial receptors for dicationic guest molecules. PMID:27058367

  9. Porous MoO2 Nanosheets as Non-noble Bifunctional Electrocatalysts for Overall Water Splitting.

    PubMed

    Jin, Yanshuo; Wang, Haotian; Li, Junjie; Yue, Xin; Han, Yujie; Shen, Pei Kang; Cui, Yi

    2016-05-01

    A porous MoO2 nanosheet as an active and stable bifunctional electrocatalyst for overall water splitting, is presented. It needs a cell voltage of only about 1.53 V to achieve a current density of 10 mA cm(-2) and maintains its activity for at least 24 h in a two-electrode configuration. PMID:26996884

  10. Sensitivity and robustness in covalent modification cycles with a bifunctional converter enzyme.

    PubMed

    Straube, Ronny

    2013-10-15

    Regulation by covalent modification is a common mechanism to transmit signals in biological systems. The modifying reactions are catalyzed either by two distinct converter enzymes or by a single bifunctional enzyme (which may employ either one or two catalytic sites for its opposing activities). The reason for this diversification is unclear, but contemporary theoretical models predict that systems with distinct converter enzymes can exhibit enhanced sensitivity to input signals whereas bifunctional enzymes with two catalytic sites are believed to generate robustness against variations in system's components. However, experiments indicate that bifunctional enzymes can also exhibit enhanced sensitivity due to the zero-order effect, raising the question whether both phenomena could be understood within a common mechanistic model. Here, I argue that this is, indeed, the case. Specifically, I show that bifunctional enzymes with two catalytic sites can exhibit both ultrasensitivity and concentration robustness, depending on the kinetic operating regime of the enzyme's opposing activities. The model predictions are discussed in the context of experimental observations of ultrasensitivity and concentration robustness in the uridylylation cycle of the PII protein, and in the phosphorylation cycle of the isocitrate dehydrogenase, respectively. PMID:24138868

  11. Asymmetric α-amination of β-keto esters using a guanidine–bisurea bifunctional organocatalyst

    PubMed Central

    Yamamoto, Yoshiharu

    2016-01-01

    Summary An asymmetric α-amination of β-keto esters with azodicarboxylate in the presence of a guanidine–bisurea bifunctional organocatalyst was investigated. The α-amination products were obtained in up to 99% yield with up to 94% ee. PMID:26977179

  12. Bifunctional N-heterocyclic carbene-catalyzed highly enantioselective synthesis of spirocyclic oxindolo-β-lactams.

    PubMed

    Zhang, Han-Ming; Gao, Zhong-Hua; Ye, Song

    2014-06-01

    The N-heterocyclic carbene-catalyzed Staudinger reaction of ketenes with isatin-derived ketimines was investigated. The bifunctional NHCs with a free hydroxyl group were demonstrated as efficient catalysts for the reaction, giving the corresponding spirocyclic oxindolo-β-lactams in high yields with excellent diastereo- and enantioselectivities. PMID:24856000

  13. Alternative security

    SciTech Connect

    Weston, B.H. )

    1990-01-01

    This book contains the following chapters: The Military and Alternative Security: New Missions for Stable Conventional Security; Technology and Alternative Security: A Cherished Myth Expires; Law and Alternative Security: Toward a Just World Peace; Politics and Alternative Security: Toward a More Democratic, Therefore More Peaceful, World; Economics and Alternative Security: Toward a Peacekeeping International Economy; Psychology and Alternative Security: Needs, Perceptions, and Misperceptions; Religion and Alternative Security: A Prophetic Vision; and Toward Post-Nuclear Global Security: An Overview.

  14. Metal distribution and spectroscopic analysis after soil washing with chelating agents and humic substances.

    PubMed

    Tsang, Daniel C W; Hartley, Neil R

    2014-03-01

    Biodegradable chelating agents ([S,S]-ethylenediamine-N,N-disuccinic acid (EDDS) and glutamic-N,N-diacetic acid (GLDA)) and natural humic substances (lignite-derived, standard, and commercially available humic acids) are potentially useful for enhancing soil remediation of timber treatment sites. This study integrated macroscopic and spectroscopic analyses to assess their influence on the distribution and chemical speciation of the remaining metals as well as their interaction with the soil surface after 48-h washing of a field-contaminated soil. The results demonstrated that EDDS and GLDA were an appealing alternative to non-biodegradable ethylenediamine-tetraacetic acid, but the three humic substances were less effective. As shown by sequential extractions, Cu was primarily extracted from the carbonate fraction while Cr and As extraction resulted from (co-)dissolution of the oxide fraction. As a result, the relative proportion of strongly bound organic matter and residual fractions increased by 7-16 %. However, it was noteworthy that the exchangeable fraction also increased by 5-11 %, signifying that a portion of the remaining metals was destabilized by chelating agents and transformed to be more labile in the treated soil. The X-ray photoelectron spectroscopy spectra confirmed the substantial removal of readily accessible Cu from the soil surface, but Cr maintained its original chemical forms of trivalent chromium oxides and iron-chromium coprecipitates, whereas As remained as arsenic trioxide/pentoxide and copper arsenate precipitates. On the other hand, the absence of characteristic peaks of adsorbed carboxylate groups in the Fourier-transform infrared (FTIR) spectra inferred that the extent of adsorption of chelating agents and humic substances on the bulk soil was insufficient to be characterized by FTIR analysis. These results suggested that attention should be paid to the exchangeable fraction of Cu and oxides/coprecipitates of As prior to possible on

  15. Media composition: antioxidants/chelators and cellular function.

    PubMed

    Combelles, Catherine M H; Hennet, Margo L

    2012-01-01

    Protection of embryos against oxidative insults during culture is necessary to maintain viability. Generation of excessive levels of reactive oxygen species (ROS) is triggered by various components of the in vitro environment, most of which embryos do not normally encounter in vivo. To compensate for these deficiencies in the culture environment, antioxidants and chelators are often used to control or suppress ROS levels as embryos develop. However, there is no consensus regarding dosage, time of exposure, or appropriate combinations of antioxidants and chelators in embryo culture. In order to elucidate this aspect of an embryo's chemical surroundings in vitro, we present the current knowledge on the function and effect of each antioxidant or chelator that is often included in an embryo culture medium. PMID:22829373

  16. Iron chelation inhibits the development of pulmonary vascular remodeling.

    PubMed

    Wong, Chi-Ming; Preston, Ioana R; Hill, Nicholas S; Suzuki, Yuichiro J

    2012-11-01

    Reactive oxygen species (ROS) have been implicated in the pathogenesis of pulmonary hypertension. Because iron is an important regulator of ROS biology, this study examined the effects of iron chelation on the development of pulmonary vascular remodeling. The administration of an iron chelator, deferoxamine, to rats prevented chronic hypoxia-induced pulmonary hypertension and pulmonary vascular remodeling. Various iron chelators inhibited the growth of cultured pulmonary artery smooth muscle cells. Protein carbonylation, an important iron-dependent biological event, was promoted in association with pulmonary vascular remodeling and cell growth. A proteomic approach identified that Rho GDP-dissociation inhibitor (a negative regulator of RhoA) is carbonylated. In human plasma, the protein carbonyl content was significantly higher in patients with idiopathic pulmonary arterial hypertension than in healthy controls. These results suggest that iron plays an important role in the ROS-dependent mechanism underlying the development of pulmonary hypertension. PMID:22974762

  17. The effect of iron overload and chelation on erythroid differentiation.

    PubMed

    Taoka, Kazuki; Kumano, Keiki; Nakamura, Fumihiko; Hosoi, Masataka; Goyama, Susumu; Imai, Yoichi; Hangaishi, Akira; Kurokawa, Mineo

    2012-02-01

    We investigated the mechanisms of hematopoietic disorders caused by iron overload and chelation, in particular, the inhibition of erythroblast differentiation. Murine c-kit(+) progenitor cells or human CD34(+) peripheral blood hematopoietic progenitors were differentiated in vitro to the erythroid lineage with free iron and/or an iron chelator. Under iron overload, formation of erythroid burst-forming unit colonies and differentiation to mature erythroblasts were significantly suppressed; these effects were canceled by iron chelation with deferoxamine (DFO). Moreover, excessive iron burden promoted apoptosis in immature erythroblasts by elevating intracellular reactive oxygen species (ROS). Interestingly, both DFO and a potent anti-oxidant agent reduced intracellular ROS levels and suppressed apoptosis, thus restoring differentiation to mature erythroblasts. Accordingly, intracellular ROS may represent a new therapeutic target in the treatment of iron overload. PMID:22193844

  18. Molecular nanotechnologies of gelatin-immobilization using macrocyclic metal chelates

    PubMed Central

    Mikhailov, Oleg V.

    2014-01-01

    This article is a review of recent developments in the self-assembled nanostructures based on chelate coordination compounds. Molecular nanotechnologies of self-assembly of 3d-element aza- and thiazametalmacrocyclic complexes that happen in nanoreactors on the basis of metal hexacyanoferrate(II) gelatin-immobilized matrix under their contact with water solutions containing various (N,O,S)-donor atomic ligands and organic compounds having one or two carbonyl groups have been considered in this review. It has been noted that the assortment of macrocyclic metal chelates obtained as a result of using molecular nanotechnologies in such specific conditions considerably differs from the assortment of metal chelates formed at the conditions traditional for chemical synthesis. PMID:24516711

  19. Polyvalent metal ion chelating agents for xanthan solutions

    SciTech Connect

    Miller, J.W.; Tate, B.E.

    1984-08-21

    A stable xanthan solution with superior filterability and subterranean injectivity characteristics comprises biopolymer and a chelating agent selected from aliphatic alpha-hydroxy acids having from about 2-7 carbon atoms; aliphatic and aromatic beta-keto compounds having from about 4-9 carbon atoms; or 2- and 4-pyrones having a hydroxyl group alpha to the carbonyl and having 5 or 6 carbon atoms; said chelating agent being present in an amount of at least about 1.0 ppm of the total solution. A method of enhancing oil recovery comprising employing as a mobility control solution in oil-bearing formations a mixture of xanthan biopolymer and a chelating agent is also disclosed.

  20. Dissociation of gadolinium chelates in mice: relationship to chemical characteristics.

    PubMed

    Wedeking, P; Kumar, K; Tweedle, M F

    1992-01-01

    Tissue distributions of seven 153Gd-labeled Gd chelates were determined at five residence intervals (5 min to 14 days) following intravenous administration of 0.4 mmol/kg to mice. Relationships were sought among physicochemical parameters: thermodynamic and conditional (pH 7.4) equilibrium stability constants (log K and log K'), acid dissociation rate constants (k(obs)), lipophilicity (log P), overall charge, and size (molecular weight). Size and lipophilicity did not correlate with tissue distributions. There were possible correlations between anionic charge and rapid, early renal excretion and between stability constants and long-term residual Gd deposition. Strong correlations (r greater than 0.99) were found between acid dissociation rates and long-term deposition of Gd in the whole body, liver, and femur. This is attributed to dissociation of Gd from the chelates in vivo. Acid dissociation rates may be useful in predicting dissociation of Gd from chelates in vivo. PMID:1501535

  1. Clinical monitoring and management of complications related to chelation therapy in patients with β-thalassemia.

    PubMed

    Saliba, Antoine N; El Rassi, Fuad; Taher, Ali T

    2016-01-01

    Iron chelating agents - deferoxamine (DFO), deferiprone (DFP), and deferasirox (DFX) - are used to treat chronic iron overload in patients with β-thalassemia in an attempt to reduce morbidity and mortality related to siderosis. Each of the approved iron chelating agents has its own advantages over the others and also has its own risks, whether related to over-chelation or not. In this review, we briefly discuss the methods to monitor the efficacy of iron chelation therapy (ICT) and the evidence behind the use of each iron chelating agent. We also portray the risks and complications associated with each iron chelating agent and recommend strategies to manage adverse events. PMID:26613264

  2. Lauriston S. Taylor Lecture: the quest for therapeutic actinide chelators.

    PubMed

    Durbin, Patricia W

    2008-11-01

    All of the actinides are radioactive. Taken into the body, they damage and induce cancer in bone and liver, and in the lungs if inhaled, and U(VI) is a chemical kidney poison. Containment of radionuclides is fundamental to radiation protection, but if it is breached accidentally or deliberately, decontamination of exposed persons is needed to reduce the consequences of radionuclide intake. The only known way to reduce the health risks of internally deposited actinides is to accelerate their excretion with chelating agents. Ethylendiaminetetraacetic acid (EDTA) and diethylenetriaminepentaacetic acid (DTPA) were introduced in the 1950's. DTPA is now clinically accepted, but its oral activity is low, it must be injected as a Ca(II) or Zn(II) chelate to avoid toxicity, and it is structurally unsuitable for chelating U(VI) or Np(V). Actinide penetration into the mammalian iron transport and storage systems suggested that actinide ions would form stable complexes with the Fe(III)-binding units found in potent selective natural iron chelators (siderophores). Testing of that biomimetic approach began in the late 1970's with the design, production, and assessment for in vivo Pu(IV) chelation of synthetic multidentate ligands based on the backbone structures and Fe(III)-binding groups of siderophores. New efficacious actinide chelators have emerged from that program, in particular, octadentate 3,4,3-LI(1,2-HOPO) and tetradentate 5-LIO(Me-3,2-HOPO) have potential for clinical acceptance. Both are much more effective than CaNa3-DTPA for decorporation of Pu(IV), Am(III), U(VI), and Np(IV,V), they are orally active, and toxicity is acceptably low at effective dosage. PMID:18849679

  3. 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. PMID:19595699

  4. 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.

  5. Combinational chelation therapy abrogates lead-induced neurodegeneration in rats

    SciTech Connect

    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.

  6. Iron chelators ICL670 and 311 inhibit HIV-1 transcription.

    PubMed

    Debebe, Zufan; Ammosova, Tatyana; Jerebtsova, Marina; Kurantsin-Mills, Joseph; Niu, Xiaomei; Charles, Sharroya; Richardson, Des R; Ray, Patricio E; Gordeuk, Victor R; Nekhai, Sergei

    2007-10-25

    HIV-1 replication is induced by an excess of iron and iron chelation by desferrioxamine (DFO) inhibits viral replication by reducing proliferation of infected cells. Treatment of cells with DFO and 2-hydroxy-1-naphthylaldehyde isonicotinoyl hydrazone (311) inhibit expression of proteins that regulate cell-cycle progression, including cycle-dependent kinase 2 (CDK2). Our recent studies showed that CDK2 participates in HIV-1 transcription and viral replication suggesting that inhibition of CDK2 by iron chelators might also affect HIV-1 transcription. Here we evaluated the effect of a clinically approved orally effective iron chelator, 4-[3,5-bis-(hydroxyphenyl)-1,2,4-triazol-1-yl]-benzoic acid (ICL670) and 311 on HIV-1 transcription. Both ICL670 and 311 inhibited Tat-induced HIV-1 transcription in CEM-T cells, 293T and HeLa cells. Neither ICL670 nor 311 induced cytotoxicity at concentrations that inhibited HIV-1 transcription. The chelators decreased cellular activity of CDK2 and reduced HIV-1 Tat phosphorylation by CDK2. Neither ICL670A or 311 decreased CDK9 protein level but significantly reduced association of CDK9 with cyclin T1 and reduced phosphorylation of Ser-2 residues of RNA polymerase II C-terminal domain. In conclusion, our findings add to the evidence that iron chelators can inhibit HIV-1 transcription by deregulating CDK2 and CDK9. Further consideration should be given to the development of iron chelators for future anti-retroviral therapeutics. PMID:17631934

  7. SEPARATION OF PLUTONIUM FROM LANTHANUM BY CHELATION-EXTRACTION

    DOEpatents

    James, R.A.; Thompson, S.G.

    1958-12-01

    Plutonium can be separated from a mixture of plutonlum and lanthanum in which the lanthanum to plutonium molal ratio ls at least five by adding the ammonium salt of N-nitrosoarylhydroxylamine to an aqueous solution having a pH between about 3 and 0.2 and containing the plutonium in a valence state of at least +3, to form a plutonium chelate compound of N-nitrosoarylhydroxylamine. The plutonium chelate compound may be recovered from the solution by extracting with an immiscible organic solvent such as chloroform.

  8. Bi-functional CD22 ligands use multimeric immunoglobulins as protein scaffolds in assembly of immune complexes on B cells

    PubMed Central

    O'Reilly, Mary K.; Collins, Brian E.; Han, Shoufa; Liao, Liang; Rillahan, Cory; Kitov, Pavel I.; Bundle, David R.; Paulson, James C.

    2008-01-01

    CD22 is a B cell specific sialic-acid-binding immunoglobulin-like lectin (Siglec) whose function as a regulator of B cell signaling is modulated by its interaction with glycan ligands bearing the sequence NeuAcα2-6Gal. To date, only highly multivalent polymeric ligands (n=450) have achieved sufficient avidity to bind to CD22 on native B cells. Here we demonstrate that a synthetic bi-functional molecule comprising a ligand of CD22 linked to an antigen (nitrophenol; NP) can use a monoclonal anti-NP-IgM as a decavalent protein scaffold to efficiently drive assembly of IgM-CD22 complexes on the surface of native B cells. Surprisingly, anti-NP antibodies of lower valency, IgA (n =4) and IgG (n =2), were also found to drive complex formation, though with lower avidity. Ligands bearing alternate linkers of variable length and structure were constructed to establish the importance of a minimal length requirement, and versatility in the structural requirement. We show that the ligand drives assembly of IgM complexes exclusively on the surface of B cells and not other classes of white blood cells that do not express CD22, which lends itself to the possibility of targeting B cells in certain hematopoietic malignancies. PMID:18505252

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

    SciTech Connect

    Bao, Yizhong; Wang, Dan; Li, Zhiming; Hu, Yuxing; Xu, Aihong; Wang, Quanrui; Shao, Chunlin; Chen, Honghong

    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) levels 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.

  10. New developments and controversies in iron metabolism and iron chelation therapy

    PubMed Central

    Kontoghiorghe, Christina N; Kontoghiorghes, George J

    2016-01-01

    haemochromatosis, thalassaemia intermedia and ex-thalassaemia transplanted patients who are safely treated with venesection. Iron chelating drugs can override normal regulatory pathways, correct iron imbalance and minimise iron toxicity. The use of iron chelating drugs as main, alternative or adjuvant therapy is in progress in many conditions, especially those with non established or effective therapies. PMID:27019793

  11. New developments and controversies in iron metabolism and iron chelation therapy.

    PubMed

    Kontoghiorghe, Christina N; Kontoghiorghes, George J

    2016-03-26

    haemochromatosis, thalassaemia intermedia and ex-thalassaemia transplanted patients who are safely treated with venesection. Iron chelating drugs can override normal regulatory pathways, correct iron imbalance and minimise iron toxicity. The use of iron chelating drugs as main, alternative or adjuvant therapy is in progress in many conditions, especially those with non established or effective therapies. PMID:27019793

  12. Rhodium catalyzed chelation-assisted C-H bond functionalization reactions

    PubMed Central

    Colby, Denise A.; Tsai, Andy S.; Bergman, Robert G.; Ellman, Jonathan A.

    2011-01-01

    Conspectus Over the last several decades, researchers have achieved remarkable progress in the field of organometallic chemistry. The development of metal-catalyzed cross-coupling reactions represents a paradigm shift in chemical synthesis, and today synthetic chemists can readily access carbon-carbon and carbon-heteroatom bonds from a vast array of starting compounds. Although we cannot understate the importance of these methods, the required pre-functionalization to carry out these reactions adds cost and reduces the availability of the starting reagents. The use of C-H bond activation in lieu of pre-functionalization has presented a tantalizing alternative to classical cross-coupling reactions. Researchers have met the challenges of selectivity and reactivity associated with the development of C-H bond functionalization reactions with an explosion of creative advances in substrate and catalyst design. Literature reports on selectivity based on steric effects, acidity, and electronic and directing group effects are now numerous. Our group has developed an array of C-H bond functionalization reactions that take advantage of a chelating directing group, and this Account surveys our progress in this area. The use of chelation control in C-H bond functionalization offers several advantages with respect to substrate scope and application to total synthesis. The predictability and decreased dependence on the inherent stereoelectronics of the substrate generally result in selective and high yielding transformations with broad applicability. The nature of the chelating moiety can be chosen to serve as a functional handle in subsequent elaborations. Our work began with the use of Rh(I) catalysts in intramolecular aromatic C-H annulations, which we further developed to include enantioselective transformations. The application of this chemistry to the simple olefinic C-H bonds found in α,β-unsaturated imines allowed access to highly substituted olefins, pyridines, and

  13. Questions and Answers: The NIH Trial of EDTA Chelation Therapy for Coronary Heart Disease

    MedlinePlus

    ... a trained health professional. What did the chelation infusions contain? For TACT, the active, 10-component, chelation ... of normal saline and 1.2% dextrose. The infusions were prepared at a central pharmacy for the ...

  14. Iron chelating active packaging: Influence of competing ions and pH value on effectiveness of soluble and immobilized hydroxamate chelators.

    PubMed

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

    2016-04-01

    Many packaged foods utilize synthetic chelators (e.g. ethylenediaminetetraacetic acid, EDTA) to inhibit iron-promoted oxidation or microbial growth which would result in quality loss. To address consumer demands for all natural products, we have previously developed a non-migratory iron chelating active packaging material by covalent immobilization of polyhydroxamate and demonstrated its efficacy in delaying lipid oxidation. Herein, we demonstrate the ability of this hydroxamate-functionalized iron chelating active packaging to retain iron chelating capacity; even in the presence of competing ions common in food. Both immobilized and soluble hydroxamate chelators retained iron chelating capacity in the presence of calcium, magnesium, and sodium competing ions, although at pH 5.0 the presence of calcium reduced immobilized hydroxamate iron chelation. A strong correlation was found between colorimetric and mass spectral analysis of iron chelation by the chelating packaging material. Such chelating active packaging may support reducing additive use in product formulations, while retaining quality and shelf life. PMID:26593563

  15. Desferrithiocin: A Search for Clinically Effective Iron Chelators

    PubMed Central

    2015-01-01

    The successful search for orally active iron chelators to treat transfusional iron-overload diseases, e.g., thalassemia, is overviewed. The critical role of iron in nature as a redox engine is first described, as well as how primitive life forms and humans manage the metal. The problems that derive when iron homeostasis in humans is disrupted and the mechanism of the ensuing damage, uncontrolled Fenton chemistry, are discussed. The solution to the problem, chelator-mediated iron removal, is clear. Design options for the assembly of ligands that sequester and decorporate iron are reviewed, along with the shortcomings of the currently available therapeutics. The rationale for choosing desferrithiocin, a natural product iron chelator (a siderophore), as a platform for structure–activity relationship studies in the search for an orally active iron chelator is thoroughly developed. The study provides an excellent example of how to systematically reengineer a pharmacophore in order to overcome toxicological problems while maintaining iron clearing efficacy and has led to three ligands being evaluated in human clinical trials. PMID:25207964

  16. Technical Report Summary: Metal Chelate, Eu-QCTME

    SciTech Connect

    Richter, James, A.

    2008-05-08

    A novel fluorescent metal complex, Eu-QCTME has shown promise for the early stage detection of cancer. This material has been shown to bind preferentially to xenographic tumors. The study, using HT29 murine xenographic tumors was performed to determine if the chelate preferentially binds to tumor tissue and the potential for an early stage diagnostic test and treatment for epithelial cell cancers.

  17. Efficacy of reversal of aortic calcification by chelating agents

    PubMed Central

    Lei, Yang; Sinha, Aditi; Vyavahare, Naren

    2013-01-01

    Elastin specific medial vascular calcification, termed Monckeberg’s sclerosis has been recognized as a major risk factor for various cardiovascular events. We hypothesize that chelating agents, such as disodium ethylene diamine tetraacetic acid (EDTA), diethylene triamine pentaacetic acid (DTPA) and sodium thiosulfate (STS) might reverse elastin calcification by directly removing calcium (Ca) from calcified tissues into soluble calcium complexes. We assessed the chelating ability of EDTA, DTPA, and STS on removal of calcium from hydroxyapatite (HA) powder, calcified porcine aortic elastin, and calcified human aorta in vitro. We show that both EDTA and DTPA could effectively remove calcium from HA and calcified tissues, while STS was not effective. The tissue architecture was not altered during chelation. In the animal model of aortic elastin-specific calcification, we further show that local periadventitial delivery of EDTA loaded in to poly (lactic-co-glycolic acid) (PLGA) nanoparticles regressed elastin specific calcification in the aorta. Collectively, the data indicate that elastin-specific medial vascular calcification could be reversed by chelating agents. PMID:23963635

  18. Chelation And Extraction Of Metals For GC-MS Analysis

    NASA Technical Reports Server (NTRS)

    Sinha, Mahadeva P.

    1995-01-01

    Chelation followed by supercritical-fluid extraction enables mass-spectrometric analysis. When fully developed, method implemented in field-portable apparatus for detection and quantification of metals in various matrices without need for elaborate preparation of samples. Used to analyze soil samples for toxic metals.

  19. Scintigraphic monitoring of immunotoxins using radionuclides and heterobifunctional chelators

    SciTech Connect

    Reardan, D.; Bernhard, S.

    1991-10-22

    This patent describes a method for in vivo radioimmunodetection of cytotoxic immunotoxin. It comprises administering internally to a mammal a radio-labeled immunotoxin, wherein a heterobifunctional chelating agent provides a chemical bridge between a radiolabel and a cytotoxic component bound to the antigen-binding component of the immunotoxin, and detecting externally the distribution of the immunotoxin in the mammal.

  20. The antioxidant effect of fermented papaya preparation involves iron chelation.

    PubMed

    Prus, E; Fibach, E

    2012-01-01

    Iron-overload is a major clinical problem in various diseases. Under this condition, serum iron which surpasses the binding capacity of transferrin is present as non-transferrin bound iron and cellular unbound Labile Iron Pool (LIP) is increased. LIP participates in the generation of free radicals, including reactive oxygen species (ROS). Increased ROS, with concomitant decrease in anti-oxidants, results in oxidative stress and toxicity to the liver, heart and other tissues, causing serious morbidity and eventually mortality. Therapeutic iron chelation reduces the LIP and thereby ameliorates oxidative stress-mediated toxicity. Many food-derived antioxidants have the capacities to scavenge ROS and chelate iron. We have reported that fermented papaya preparation (FPP) has ROS scavenging effect on blood cells in vitro or in vivo (in thalassemic patients and experimental animals). We now investigated FPP's iron chelating effect - its ability to prevent (and revert) LIP accumulation. Liver- and heart-derived cells, and RBCs were exposed to non-transferrin bound iron in the form of ferrous ammonium sulfate and the effect of FPP on their LIP content and ROS generation was measured by flow-cytometry. The results indicate that FPP reduces LIP and ROS, and suggests that its antioxidant mechanism is related, at least in part, to iron chelation. PMID:22824747

  1. Evaluation of intakes of transuranics influenced by chelation therapy

    SciTech Connect

    LaBone, T.R.

    1994-02-01

    Once an intake of transuranics occurs, there are only three therapeutic procedures available to the physician for reducing the intake and mitigating the dose: excision of material from wounds, removal of material from the lungs with lavage, and chelation therapy. The only chelation agents approved in the United States for the treatment of occupational intakes of transuranics are the zinc and calcium salts of diethylene-triamine-pentaacetic acid, better known as Zn-DTPA and Ca-DTPA. In the past 35 years, approximately 3000 doses of DTPA have been administrated to over 500 individuals who had intakes of transuranics. The drug is considered to be quiet safe and has few side effects. For the internal dosimetrist, perhaps the most important aspects of chelation therapy is that if enhances the excretion rate of a transuranic and perturbs the shape of the urinary excretion curve. These perturbations last for months and are so great that standard urinary excretion models cannot be used to evaluate the intake. We review here a method for evaluating intakes of transuranics influenced by chelation therapy that has been used with some degree of success at the Savannah River Site for over 20 years.

  2. EDTA Chelation Therapy, Without Added Vitamin C, Decreases Oxidative DNA Damage and Lipid Peroxidation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Chelation therapy is thought to not only remove contaminating metals, but also to decrease free radical production. However, in standard EDTA chelation therapy high doses of vitamin C with potential prooxidant effects are often added to the chelation solution. We demonstrated previously that the in...

  3. Organically modified porous hydroxyapatites: A comparison between alkylphosphonate grafting and citrate chelation

    SciTech Connect

    El-Hammari, L.; Marroun, H.; Laghzizil, A.; Saoiabi, A.; Roux, C.; Livage, J.; Coradin, T.

    2008-04-15

    Two alternative methods to prepare organically modified porous hydroxyapatites following a 'one pot' approach were compared. The partial substitution of inorganic phosphates by alkylphosphonates leads to mesoporous materials with high specific surface area (>200 m{sup 2} g{sup -1}). The incorporation of the organic moieties within the hydroxyapatite structure is confirmed by Infra-red and solid-state NMR spectroscopy and depends on the nature of the alkyl chain. However, it induces a significant loss of the material crystallinity. In contrast, the introduction of citrate, a calcium-chelating agent, to the precursor solution does not improve the material specific surface area but allows a better control of the hydroxyapatite structure, both in terms of crystallinity and pore size distribution. - Graphical abstract: Evolution of pore size distribution of hydroxyapatite (HAp) after alkylphosphonate grafting (20% TPOH) or citrate addition (c-HAp) demonstrates the formation of organically modified mesoporous materials.

  4. Increasing round trip efficiency of hybrid Li-air battery with bifunctional catalysts

    SciTech Connect

    Huang, K; Li, YF; Xing, YC

    2013-07-30

    Previously it was shown that Pt as cathode catalyst ha's a large overpotential during charge in rechargeable hybrid Li-air battery with sulfuric acid catholyte. This article demonstrates that a bifunctional catalyst composed of Pt and IrO2 supported on carbon nanotubes can address this problem. The specially designed and synthesized bifunctional catalyst showed significant overpotential reduction and achieved a round trip energy efficiency of 81% after 10 cycles, higher than many achieved in aprotic Li-O-2 batteries. The hybrid Li-air battery was discharged and recharged for 20 cycles at 0.2 mA/cm(2), showing a fairly stable cell performance. A specific capacity of 306 mAh/g and a specific energy of 1110 Wh/kg were obtained for the hybrid Li-air battery in terms of acid weight. (c) 2013 Elsevier Ltd. All rights reserved.

  5. Synthesis of acid-base bifunctional mesoporous materials by oxidation and thermolysis

    SciTech Connect

    Yu, Xiaofang; Zou, Yongcun; Wu, Shujie; Liu, Heng; Guan, Jingqi; Kan, Qiubin

    2011-06-15

    Graphical abstract: A novel and efficient method has been developed for the synthesis of acid-base bifunctional catalyst. The obtained sample of SO{sub 3}H-MCM-41-NH{sub 2} containing amine and sulfonic acids exhibits excellent catalytic activity in aldol condensation reaction. Research highlights: {yields} Synthesize acid-base bifunctional mesoporous materials SO{sub 3}H-MCM-41-NH{sub 2}. {yields} Oxidation and then thermolysis to generate acidic site and basic site. {yields} Exhibit good catalytic performance in aldol condensation reaction between acetone and various aldehydes. -- Abstract: A novel and efficient method has been developed for the synthesis of acid-base bifunctional catalyst SO{sub 3}H-MCM-41-NH{sub 2}. This method was achieved by co-condensation of tetraethylorthosilicate (TEOS), 3-mercaptopropyltrimethoxysilane (MPTMS) and (3-triethoxysilylpropyl) carbamicacid-1-methylcyclohexylester (3TAME) in the presence of cetyltrimethylammonium bromide (CTAB), followed by oxidation and then thermolysis to generate acidic site and basic site. X-ray diffraction (XRD) and transmission electron micrographs (TEM) show that the resultant materials keep mesoporous structure. Thermogravimetric analysis (TGA), X-ray photoelectron spectra (XPS), back titration, solid-state {sup 13}C CP/MAS NMR and solid-state {sup 29}Si MAS NMR confirm that the organosiloxanes were condensed as a part of the silica framework. The bifunctional sample (SO{sub 3}H-MCM-41-NH{sub 2}) containing amine and sulfonic acids exhibits excellent acid-basic properties, which make it possess high activity in aldol condensation reaction between acetone and various aldehydes.

  6. Porous cobalt-based thin film as a bifunctional catalyst for hydrogen generation and oxygen generation.

    PubMed

    Yang, Yang; Fei, Huilong; Ruan, Gedeng; Tour, James M

    2015-05-27

    A mixed-phased Co-based catalyst composed of Co phosphide and Co phosphate is successfully fabricated for bifunctional water electrolysis. The highly porous morphology in this anodized film enables efficient catalytic activity toward water splitting in an extremely low loading mass. The mixed phases in the porous film afford an ability to generate both H2 and O2 in a single electrolyzer. PMID:25872881

  7. Highly enantioselective conjugate addition of malononitrile to 2-enoylpyridines with bifunctional organocatalyst.

    PubMed

    Molleti, Nagaraju; Rana, Nirmal K; Singh, Vinod K

    2012-09-01

    An efficient enantioselective conjugate addition of malononitrile to a range of β-substituted 2-enoylpyridines catalyzed by cinchona alkaloid-based bifunctional urea catalysts has been developed. Both enantiomers of the products could be achieved with the same level of enantioselectivity by using pseudoenantiomeric catalysts in up to 97% ee and in excellent yields. One of the enantioenriched products has been transformed to a highly functionalized piperidone derivative. PMID:22920458

  8. 3D Ordered Mesoporous Bifunctional Oxygen Catalyst for Electrically Rechargeable Zinc-Air Batteries.

    PubMed

    Park, Moon Gyu; Lee, Dong Un; Seo, Min Ho; Cano, Zachary Paul; Chen, Zhongwei

    2016-05-01

    To enhance energy efficiency and durability, a highly active and durable 3D ordered mesoporous cobalt oxide framework has been developed for rechargeable zinc-air batteries. The bifunctional air electrode consisting of 3DOM Co3 O4 having high active surface area and robust structure, results in superior charge and discharge battery voltages, and durable performance for electrically rechargeable zinc-air batteries. PMID:27043451

  9. L-Proline Derived Bifunctional Organocatalysts: Enantioselective Michael Addition of Dithiomalonates to trans-β-Nitroolefins.

    PubMed

    Jin, Hui; Kim, Seung Tae; Hwang, Geum-Sook; Ryu, Do Hyun

    2016-04-15

    A series of novel L-proline derived tertiary amine bifunctional organocatalysts 9 are reported, which were applied to the asymmetric Michael addition of dithiomalonates 2 to trans-β-nitroolefins 1. The reaction proceeded in high yields (up to 99%) with high enantioselectivities (up to 97% ee). The synthetic utility of this methodology was demonstrated in the short synthesis of (R)-phenibut in high yield. PMID:26989804

  10. Synthesis of New Bis(3-hydroxy-4-pyridinone) Ligands as Chelating Agents for Uranyl Complexation.

    PubMed

    Jin, Bo; Zheng, Rongzong; Peng, Rufang; Chu, Shijin

    2016-01-01

    Five new bis(3-hydroxy-4-pyridinone) tetradentate chelators were synthesized in this study. The structures of these tetradentate chelators were characterized by ¹H-NMR, (13)C-NMR, FT-IR, UV-vis, and mass spectral analyses. The binding abilities of these tetradentate chelators for uranyl ion at pH 7.4 were also determined by UV spectrophotometry in aqueous media. Results showed that the efficiencies of these chelating agents are dependent on the linker length. Ligand 4b is the best chelator and suitable for further studies. PMID:27005598

  11. Alternate Alternates: A Medley of Alternate Assessments.

    ERIC Educational Resources Information Center

    Burdette, Paula J.; Olsen, Ken

    This paper highlights eight states that have implemented alternate assessments for children with disabilities who cannot participate in their state and district-wide assessment programs. The alternate assessment systems in Delaware, Florida, Georgia, Indiana, Minnesota, North Dakota, Utah, and West Virginia are briefly described, along with their…

  12. Evolution of a bifunctional enzyme: 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase.

    PubMed Central

    Bazan, J F; Fletterick, R J; Pilkis, S J

    1989-01-01

    The bifunctional rat liver enzyme 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (ATP:D-fructose-6-phosphate 2-phosphotransferase/D-fructose-2,6-bisphosphate 2-phosphohydrolase, EC 2.7.1.105/EC 3.1.3.46) is constructed of two independent catalytic domains. We present evidence that the kinase and bisphosphatase halves of the bifunctional enzyme are, respectively, structurally similar to the glycolytic enzymes 6-phosphofructo-1-kinase and phosphoglycerate mutase. Computer-assisted modeling of the C-terminal bisphosphatase domain reveals a hydrophobic core and active site residue constellation equivalent to the yeast mutase structure; structural differences map to length-variable, surface-located loops. Sequence patterns derived from the structural alignment of mutases and the bisphosphatase further detect a significant similarity to a family of acid phosphatases. The N-terminal kinase domain, in turn, is predicted to form a nucleotide-binding fold that is analogous to a segment of 6-phosphofructo-1-kinase, suggesting that these unrelated enzymes bind fructose 6-phosphate and ATP substrates in a similar geometry. This analysis indicates that the bifunctional enzyme is the likely product of gene fusion of kinase and mutase/phosphatase catalytic units. Images PMID:2557623

  13. Bifunctional Perovskite Oxide Catalysts for Oxygen Reduction and Evolution in Alkaline Media.

    PubMed

    Gupta, Shiva; Kellogg, William; Xu, Hui; Liu, Xien; Cho, Jaephil; Wu, Gang

    2016-01-01

    Oxygen electrocatalysis, namely of the oxygen reduction reaction (ORR) and the oxygen evolution reaction (OER), governs the performance of numerous electrochemical energy systems such as reversible fuel cells, metal-air batteries, and water electrolyzers. However, the sluggish kinetics of these two reactions and their dependency on expensive noble metal catalysts (e.g, Pt or Ir) prohibit the sustainable commercialization of these highly innovative and in-demand technologies. Bifunctional perovskite oxides have emerged as a new class of highly efficient non-precious metal catalysts (NPMC) for oxygen electrocatalysis in alkaline media. In this review, we discuss the state-of-the-art understanding of bifunctional properties of perovskites with regards to their OER/ORR activity in alkaline media and review the associated reaction mechanisms on the oxides surface and the related activity descriptors developed in the recent literature. We also summarize the present strategies to modify their electronic structure and to further improve their performance for the ORR/OER through highlighting the new concepts relating to the role of surface redox chemistry and oxygen deficiency of perovskite oxides for the ORR/OER activity. In addition, we provide a brief account of recently developed advanced perovskite-nanocarbon hybrid bifunctional catalysts with much improved performances. PMID:26247625

  14. Comparison of Dynamical Behaviors Between Monofunctional and Bifunctional Two-Component Signaling Modules

    NASA Astrophysics Data System (ADS)

    Yang, Xiyan; Wu, Yahao; Yuan, Zhanjiang

    2015-06-01

    Two-component signaling modules exist extensively in bacteria and microbes. These modules can be, based on their distinct network structures, divided into two types: the monofunctional system (denoted by MFS) where the sensor kinase (SK) modulates only phosphorylation of the response regulator (RR), and the bifunctional system (denoted by BFS) where the SK catalyzes both phosphorylation and dephosphorylation of the RR. Here, we analyze dynamical behaviors of these two systems based on stability theory, focusing on differences between them. The analysis of the deterministic behavior indicates that there is no difference between the two modules, that is, each system has the unique stable steady state. However, there are significant differences in stochastic behavior between them. Specifically, if the mean phosphorylated SK level is kept the same for the two modules, then the variance and the Fano factor for the phosphorylated RR in the BFS are always no less than those in the MFS, indicating that bifunctionality always enhances fluctuations. The correlation between the phosphorylated SK and the phosphorylated RR in the BFS is always positive mainly due to competition between system components, but this correlation in the MFS may be positive, almost zero, or negative, depending on the ratio between two rate constants. Our overall analysis indicates that differences between dynamical behaviors of monofunctional and bifunctional signaling modules are mainly in the stochastic rather than deterministic aspect.

  15. Enhanced Bifunctional Oxygen Catalysis in Strained LaNiO3 Perovskites

    DOE PAGESBeta

    Petrie, Jonathan R.; Cooper, Valentino R.; Freeland, John W.; Meyer, Tricia L.; Zhang, Zhiyong; Lutterman, Daniel A.; Lee, Ho Nyung

    2016-02-11

    Strain is known to greatly influence low-temperature oxygen electrocatalysis on noble metal films, leading to significant enhancements in bifunctional activity essential for fuel cells and metal-air batteries. Still, its catalytic impact on transition-metal oxide thin films, such as perovskites, is not widely understood. Here, we epitaxially strain the conducting perovskite LaNiO3 to systematically determine its influence on both the oxygen reduction and oxygen evolution reaction. Uniquely, we found that compressive strain could significantly enhance both reactions, yielding a bifunctional catalyst that surpasses the performance of noble metals such as Pt. We attribute the improved bifunctionality to strain-induced splitting of themore » eg orbitals, which can customize orbital asymmetry at the surface. Lastly, analogous to strain-induced shifts in the d-band center of noble metals relative to the Fermi level, such splitting can dramatically affect catalytic activity in this perovskite and other potentially more active oxides.« less

  16. Mechanical Characterization of a Bi-functional Tetronic Hydrogel Adhesive for Soft Tissues

    PubMed Central

    Sanders, Lindsey; Stone, Roland; Webb, C. Kenneth; Mefford, O. Thompson; Nagatomi, Jiro

    2014-01-01

    Although a number of tissue adhesives and sealants for surgical use are currently available, attaining a useful balance in high strength, high compliance, and low swelling has proven difficult. Recent studies have demonstrated that a 4-arm poly(propylene oxide)-poly(ethylene oxide) (PPO-PEO) block copolymer, Tetronic, can be chemically modified to form a hydrogel tissue adhesive21–23. Building on the success of these studies, the present study explored bi-functionalization of Tetronic with acrylates for chemical crosslinking of the hydrogel and N-hydroxysuccinimide (NHS) for reaction with tissue amines. The adhesive bond strengths of various uni- and bi-functional Tetronic blends (T1107 ACR: T1107 ACR/NHS) determined by lap shear testing ranged between 8 and 74 kPa, with the 75:25 (T1107 ACR: T1107 ACR/NHS) blend displaying the highest value. These results indicated that addition of NHS led to improvement of tissue bond strength over acrylation alone Furthermore, ex vivo pressure tests using the rat bladder demonstrated that the bi-functional Tetronic adhesive exhibited high compliance and maintained pressures under hundreds of filling and emptying cycles. Together, the results of the present study provided evidence that the bi-functional Tetronic adhesive with a proper blend ratio may be used to achieve an accurate balance in bulk and tissue bond strengths, as well as the compliance and durability for soft tissue such as the bladder. PMID:25111445

  17. Modular "Click" Preparation of Bifunctional Polymeric Heterometallic Catalysts.

    PubMed

    Wang, Wenlong; Zhao, Liyuan; Lv, Hui; Zhang, Guodong; Xia, Chungu; Hahn, F Ekkehardt; Li, Fuwei

    2016-06-27

    Heterobimetallic molecular complexes or strictly alternating metallated polymers are obtained by a click reaction between mononuclear metal complexes (secondary building units, SBUs) bearing NHCs functionalized with either p-azidophenyl or p-ethynylphenyl wingtips. With a copper-NHC complex as SBU the formation of molecular or polymeric compounds did not require any additives as the copper complex catalyzes the click reaction. Transmetallation from heterobimetallic Cu/Ag derivatives to Cu/Pd derivatives was achieved. The linker between the SBUs (flexible or rigid) influences the catalytic activity of the heterobimetallic compounds. The polymer with alternating copper-NHC and silver-NHC units and a flexible methylene-triazole bridge between them shows the highest activity in the catalytic alkynylation of trifluoromethyl ketones to give fluorinated propargylic alcohols. PMID:27331787

  18. Cobalt sulfide/N,S codoped porous carbon core-shell nanocomposites as superior bifunctional electrocatalysts for oxygen reduction and evolution reactions

    NASA Astrophysics Data System (ADS)

    Chen, Binling; Li, Rong; Ma, Guiping; Gou, Xinglong; Zhu, Yanqiu; Xia, Yongde

    2015-12-01

    Exploring highly-efficient and low-cost bifunctional electrocatalysts for both oxygen reduction reaction (ORR) and oxygen evolution reactions (OER) in the renewable energy area has gained momentum but still remains a significant challenge. Here we present a simple but efficient method that utilizes ZIF-67 as the precursor and template for the one-step generation of homogeneous dispersed cobalt sulfide/N,S-codoped porous carbon nanocomposites as high-performance electrocatalysts. Due to the favourable molecular-like structural features and uniform dispersed active sites in the precursor, the resulting nanocomposites, possessing a unique core-shell structure, high porosity, homogeneous dispersion of active components together with N and S-doping effects, not only show excellent electrocatalytic activity towards ORR with the high onset potential (around -0.04 V vs. -0.02 V for the benchmark Pt/C catalyst) and four-electron pathway and OER with a small overpotential of 0.47 V for 10 mA cm-2 current density, but also exhibit superior stability (92%) to the commercial Pt/C catalyst (74%) in ORR and promising OER stability (80%) with good methanol tolerance. Our findings suggest that the transition metal sulfide-porous carbon nanocomposites derived from the one-step simultaneous sulfurization and carbonization of zeolitic imidazolate frameworks are excellent alternative bifunctional electrocatalysts towards ORR and OER in the next generation of energy storage and conversion technologies.Exploring highly-efficient and low-cost bifunctional electrocatalysts for both oxygen reduction reaction (ORR) and oxygen evolution reactions (OER) in the renewable energy area has gained momentum but still remains a significant challenge. Here we present a simple but efficient method that utilizes ZIF-67 as the precursor and template for the one-step generation of homogeneous dispersed cobalt sulfide/N,S-codoped porous carbon nanocomposites as high-performance electrocatalysts. Due to the

  19. Alternative Therapies

    MedlinePlus

    ... Late Effects of Poliomyelitis for Physicians and Survivors © Alternative Therapies Alternative therapies, also called complementary, can support ... of motion, pain, and fatigue are often reported. Energy work includes acupuncture and acupressure, traditional Chinese medicine ...

  20. A Novel Antimycobacterial Compound Acts as an Intracellular Iron Chelator

    PubMed Central

    Dragset, Marte S.; Poce, Giovanna; Alfonso, Salvatore; Padilla-Benavides, Teresita; Ioerger, Thomas R.; Kaneko, Takushi; Sacchettini, James C.; Biava, Mariangela; Parish, Tanya; Argüello, José M.

    2015-01-01

    Efficient iron acquisition is crucial for the pathogenesis of Mycobacterium tuberculosis. Mycobacterial iron uptake and metabolism are therefore attractive targets for antitubercular drug development. Resistance mutations against a novel pyrazolopyrimidinone compound (PZP) that is active against M. tuberculosis have been identified within the gene cluster encoding the ESX-3 type VII secretion system. ESX-3 is required for mycobacterial iron acquisition through the mycobactin siderophore pathway, which could indicate that PZP restricts mycobacterial growth by targeting ESX-3 and thus iron uptake. Surprisingly, we show that ESX-3 is not the cellular target of the compound. We demonstrate that PZP indeed targets iron metabolism; however, we found that instead of inhibiting uptake of iron, PZP acts as an iron chelator, and we present evidence that the compound restricts mycobacterial growth by chelating intrabacterial iron. Thus, we have unraveled the unexpected mechanism of a novel antimycobacterial compound. PMID:25645825

  1. Lanthanides caged by the organic chelates; structural properties

    NASA Astrophysics Data System (ADS)

    Smentek, Lidia

    2011-04-01

    The structure, in particular symmetry, geometry and morphology of organic chelates coordinated with the lanthanide ions are analyzed in the present review. This is the first part of a complete presentation of a theoretical description of the properties of systems, which are widely used in technology, but most of all, in molecular biology and medicine. The discussion is focused on the symmetry and geometry of the cages, since these features play a dominant role in the spectroscopic activity of the lanthanides caged by organic chelates. At the same time, the spectroscopic properties require more formal presentation in the language of Racah algebra, and deserve a separate analysis. In addition to the parent systems of DOTA, DOTP, EDTMP and CDTMP presented here, their modifications by various antennas are analyzed. The conclusions that have a strong impact upon the theory of the energy transfer and the sensitized luminescence of these systems are based on the results of numerical density functional theory calculations.

  2. 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.

  3. Nanomagnetic chelators for removal of toxic metal ions

    NASA Astrophysics Data System (ADS)

    Singh, Sarika; Barick, K. C.; Bahadur, D.

    2013-02-01

    Ethylenediamine trtraaceteic acid (EDTA) functionalized Fe3O4 nanomagnetic chelators (NMCs) were synthesized by co-precipitation method followed by in-situ grafting of EDTA. XRD and TEM analyses reveal the formation of highly crystalline single-phase Fe3O4 nanoparticles of size about 10 nm. Surface functionalization of Fe3O4 with EDTA was evident from FTIR spectroscopy, TGA analysis and zeta-potential measurement. These NMCs exhibit superparamagnetic behavior at room temperature with strong field dependent magnetic responsivity. It has been observed that NMCs have strong tendency for adsorption of various toxic metal ions (Ni2+, Cr3+, Cu2+, Cd2+, Co2+ and Pb2+) from waste-water. Furthermore, these magnetic chelators can be used as highly efficient separable and reusable material for removal of toxic metal ions.

  4. Challenges Associated with Metal Chelation Therapy in Alzheimer's Disease

    PubMed Central

    Hegde, Muralidhar L.; Bharathi, P.; Suram, Anitha; Venugopal, Chitra; Jagannathan, Ramya; Poddar, Pankaj; Srinivas, Pullabhatla; Sambamurti, Kumar; Rao, Kosagisharaf Jagannatha; Scancar, Janez; Messori, Luigi; Zecca, Luigi; Zatta, Paolo

    2010-01-01

    A close association between brain metal dishomeostasis and the onset and/or progression of Alzheimer's disease (AD) has been clearly established in a number of studies, although the underlying biochemical mechanisms remain obscure. This observation renders chelation therapy an attractive pharmacological option for the treatment of this disease. However, a number of requirements must be fulfilled in order to adapt chelation therapy to AD so that the term “metal targeted strategies” seems now more appropriate. Indeed, brain metal redistribution rather than brain metal scavenging and removal is the major goal of this type of intervention. The most recent developments in metal targeted strategies for AD will be discussed using, as useful examples, clioquinol, curcumin, and epigallocatechin, and the future perspectives will also be outlined. PMID:19363258

  5. Multidentate terephthalamidate and hydroxypyridonate ligands: towards new orally active chelators.

    PubMed

    Abergel, Rebecca J; Raymond, Kenneth N

    2011-01-01

    The limitations of current therapies for the treatment of iron overload or radioisotope contamination have stimulated efforts to develop new orally bioavailable iron and actinide chelators. Siderophore-inspired tetradentate, hexadentate and octadentate terephthalamidate and hydroxypyridonate ligands were evaluated in vivo as selective and efficacious iron or actinide chelating agents, with several metal loading and ligand assessment procedures, using (59)Fe, (238)Pu, and (241)Am as radioactive tracers. The compounds presented in this study were compared to commercially available therapeutic sequestering agents [deferoxamine (DFO) for iron and diethylenetriaminepentaacetic acid (DPTA) for actinides] and are unrivaled in terms of affinity, selectivity and decorporation efficacy, which attests to the fact that high metal affinity may overcome the low bioavailability properties commonly associated to multidenticity. PMID:21599440

  6. MULTIDENTATE TEREPHTHALAMIDATE AND HYDROXYPYRIDONATE LIGANDS: TOWARDS NEW ORALLY ACTIVE CHELATORS

    SciTech Connect

    Abergel, Rebecca J.; Raymond, Kenneth N.

    2011-07-13

    The limitations of current therapies for the treatment of iron overload or radioisotope contamination have stimulated efforts to develop new orally bioavailable iron and actinide chelators. Siderophore-inspired tetradentate, hexadentate and octadentate terephthalamidate and hydroxypyridonate ligands were evaluated in vivo as selective and efficacious iron or actinide chelating agents, with several metal loading and ligand assessment procedures, using {sup 59}Fe, {sup 238}Pu, and {sup 241}Am as radioactive tracers. The compounds presented in this study were compared to commercially available therapeutic sequestering agents [deferoxamine (DFO) for iron and diethylenetriaminepentaacetic acid (DPTA) for actinides] and are unrivaled in terms of affinity, selectivity and decorporation efficacy, which attests to the fact that high metal affinity may overcome the low bioavailability properties commonly associated to multidenticity.

  7. Design of a bifunctional fusion protein for ovarian cancer drug delivery: single-chain anti-CA125 core-streptavidin fusion protein.

    PubMed

    Wang, Welson Wen-Shang; Das, Dipankar; McQuarrie, Stephen A; Suresh, Mavanur R

    2007-03-01

    We have developed a universal ovarian cancer cell targeting vehicle that can deliver biotinylated therapeutic drugs. A single-chain antibody variable domain (scFv) that recognizes the CA125 antigen of ovarian cancer cells was fused with a core-streptavidin domain (core-streptavidin-VL-VH and VL-VH-core-streptavidin orientations) using recombinant DNA technology and then expressed in Escherichia coli using the T7 expression system. The bifunctional fusion protein (bfFp) was expressed in a shaker flask culture, extracted from the periplasmic soluble protein, and affinity purified using an IMAC column. The two distinct activities (biotin binding and anti-CA125) of the bfFp were demonstrated using ELISA, Western blot and confocal laser-scanning microscopy (CLSM). The ELISA method utilized human NIH OVCAR-3 cells along with biotinylated bovine serum albumin (B-BSA) or biotinylated liposomes, whereas, the Western blot involved probing with B-BSA. The CLSM study has shown specificity in binding to the OVCAR-3 cell-line. ELISA and Western blot studies have confirmed the bifunctional activity and specificity. In the presence of bfFp, there was enhanced binding of biotinylated antigen and liposome to OVCAR-3 cells. In contrast, the control EMT6 cells, which do not express the CA125 antigen, showed minimal binding of the bfFp. Consequently, bfFp based targeting of biotinylated therapeutic drugs, proteins, liposomes, or nanoparticles could be an alternative, convenient method to deliver effective therapy to ovarian cancer patients. Peritoneal infusion of the bfFp-therapeutic complex could also be effective in locally targeting the most common site of metastatic spread. PMID:17257818

  8. Sperm surface protein PH-20 is bifunctional: one activity is a hyaluronidase and a second, distinct activity is required in secondary sperm-zona binding.

    PubMed

    Hunnicutt, G R; Primakoff, P; Myles, D G

    1996-07-01

    In previous studies, we have found that the sperm membrane protein PH-20 acts during two different stages of fertilization. On acrosome-intact sperm, PH-20 has a hyaluronidase activity that is required for sperm penetration through the cumulus cell layer that surrounds the oocyte. On acrosome-reacted sperm, PH-20 has a required function in sperm-zona binding (secondary binding). Because hyaluronic acid (HA) has been detected in the zona pellucida, secondary sperm-zona adhesion could depend on repetitive binding and hydrolysis of HA by PH-20 acting as a hyaluronidase. Alternatively, PH-20 may be bifunctional and have a second, different activity required for secondary binding. To distinguish between these two possibilities, in this study we used reagents that inhibit either PH-20's function in sperm-zona binding or its hyaluronidase activity. We found that an anti-PH-20 monoclonal antibody that inhibited sperm-zona binding (approximately 90%) had no effect on hyaluronidase activity. Conversely, apigenin, a hyaluronidase inhibitor, blocked PH-20 hyaluronidase activity 93% without inhibiting sperm-zona binding. Similarly, another anti-PH-20 monoclonal antibody that inhibited hyaluronidase activity 95% only partially inhibited sperm-zona binding (approximately 45%). We also extensively pretreated oocytes with hyaluronidase to remove all accessible HA on or in the zona pellucida and found little or no effect on secondary sperm-zona binding. Our results suggest that PH-20 is bifunctional and has two activities: a hyaluronidase activity and a second, separate activity required for secondary sperm-zona binding. PMID:8793062

  9. EFFECT OF TEMPERATURE ON THE SORPTION OF CHELATED RADIONUCLIDES.

    USGS Publications Warehouse

    Maest, Ann S.; Crerar, David A.; Dillon, Edward C.; Trehu, Stephen M.; Rountree, Tamara N.

    1985-01-01

    Temperature effects in the near-field radioactive waste disposal environment can result in changes in the adsorptive capacity and character of the substrate and the chemistry of the reacting fluids. This work examines the effect of temperature on 1) the kinetics of radionuclide sorption onto clays from 25 degree -75 degree C and 2) the degradation and metal-binding ability of two organic complexing agents found in chelated radioactive wastes and natural groundwaters.

  10. 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.

  11. Decontamination of process equipment using recyclable chelating solvent

    SciTech Connect

    Jevec, J.; Lenore, C.; Ulbricht, S.

    1995-10-01

    The Department of Energy (DOE) is now faced with the task of meeting decontamination and decommissioning obligations at numerous facilities by the year 2019. Due to the tremendous volume of material involved, innovative decontamination technologies are being sought that can reduce the volumes of contaminated waste materials and secondary wastes requiring disposal. This report describes the results of the performance testing of chelates and solvents for the dissolution of uranium.

  12. 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.

  13. 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.

  14. Targeting Chelatable Iron as a Therapeutic Modality in Parkinson's Disease

    PubMed Central

    Moreau, Caroline; Devedjian, Jean Christophe; Kluza, Jérome; Petrault, Maud; Laloux, Charlotte; Jonneaux, Aurélie; Ryckewaert, Gilles; Garçon, Guillaume; Rouaix, Nathalie; Duhamel, Alain; Jissendi, Patrice; Dujardin, Kathy; Auger, Florent; Ravasi, Laura; Hopes, Lucie; Grolez, Guillaume; Firdaus, Wance; Sablonnière, Bernard; Strubi-Vuillaume, Isabelle; Zahr, Noel; Destée, Alain; Corvol, Jean-Christophe; Pöltl, Dominik; Leist, Marcel; Rose, Christian; Defebvre, Luc; Marchetti, Philippe; Cabantchik, Z. Ioav; Bordet, Régis

    2014-01-01

    Abstract Aims: The pathophysiological role of iron in Parkinson's disease (PD) was assessed by a chelation strategy aimed at reducing oxidative damage associated with regional iron deposition without affecting circulating metals. Translational cell and animal models provided concept proofs and a delayed-start (DS) treatment paradigm, the basis for preliminary clinical assessments. Results: For translational studies, we assessed the effect of oxidative insults in mice systemically prechelated with deferiprone (DFP) by following motor functions, striatal dopamine (HPLC and MRI-PET), and brain iron deposition (relaxation-R2*-MRI) aided by spectroscopic measurements of neuronal labile iron (with fluorescence-sensitive iron sensors) and oxidative damage by markers of protein, lipid, and DNA modification. DFP significantly reduced labile iron and biological damage in oxidation-stressed cells and animals, improving motor functions while raising striatal dopamine. For a pilot, double-blind, placebo-controlled randomized clinical trial, early-stage Parkinson's patients on stabilized dopamine regimens enrolled in a 12-month single-center study with DFP (30 mg/kg/day). Based on a 6-month DS paradigm, early-start patients (n=19) compared to DS patients (n=18) (37/40 completed) responded significantly earlier and sustainably to treatment in both substantia nigra iron deposits (R2* MRI) and Unified Parkinson's Disease Rating Scale motor indicators of disease progression (p<0.03 and p<0.04, respectively). Apart from three rapidly resolved neutropenia cases, safety was maintained throughout the trial. Innovation: A moderate iron chelation regimen that avoids changes in systemic iron levels may constitute a novel therapeutic modality for PD. Conclusions: The therapeutic features of a chelation modality established in translational models and in pilot clinical trials warrant comprehensive evaluation of symptomatic and/or disease-modifying potential of chelation in PD. Antioxid

  15. Examining the fixation kinetics of chelated and non-chelated copper micronutrient and the applications to micronutrient management in semi-arid alkaline soils

    NASA Astrophysics Data System (ADS)

    Udeigwe, T. K.; Eichmann, M. B.; Menkiti, M. C.

    2015-10-01

    The relationship between the deficiency of a nutrient in plants and its total concentration in the soil is complex. This study examined and compared the fixation and fixation kinetics of copper (Cu) in chelated (Ethylene diamine tetraacetic acid, EDTA) and non-chelated mixed systems of micronutrients in the semi-arid soils of the Southern High Plains, US using findings from Cu extraction studies and kinetic models. Approximately, 22 % more Cu was fixed in the non-chelated system within the first 14 days with only 7 % difference between the two systems by day 90. Findings suggest a decrease in the effectiveness of chelated micronutrient over time, highlighting the significance of timing even when chelated micronutrients are applied. The strengths of the relationship of change in available Cu with respect to other micronutrients [iron (Fe), manganese (Mn), and zinc (Zn)] were higher in the non-chelated system (R2: 0.68-0.94), compared to the chelated (R2: 0.42-0.81) with slopes of 0.40 (Cu-Fe), 0.31 (Cu-Mn), and 1.04 (Cu-Zn) in the non-chelated system and 0.26 (Cu-Fe), 0.22 (Cu-Mn), and 0.90 (Cu-Zn) in the chelated. Reduction in the amount of available Cu was best described by the power function model (R2 = 0.91, SE = 0.081) in the non-chelated system and second order model (R2 = 0.95, SE = 0.010) in the chelated system. The applications generated from this study could be used as tools for improved micronutrient management and also provide baseline data for future work in other semi-arid/arid alkaline soils of the world. Findings are also more applicable to field settings, an improvement over related previous studies.

  16. 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.

  17. Copper and Zinc Chelation as a Treatment of Alzheimer's Disease

    NASA Astrophysics Data System (ADS)

    Hodak, Miroslav; Bernholc, Jerry

    2014-03-01

    Alzheimer's disease (AD) is a neurodegenerative disorder affecting millions of people in the U.S. The cause of the disease remains unknown, but amyloid- β (A β), a short peptide, is considered causal its pathogenesis. At cellular level, AD is characterized by deposits mainly composed of A β that also contain elevated levels of transition metals ions. Targeting metals is a promising new strategy for AD treatment, which uses moderately strong metal chelators to sequester them from A β or the environment. PBT2 is a chelating compound that has been the most promising in clinical trials. In our work, we use computer simulations to investigate complexes of a close analog of PBT2 with Cu2+ and Zn2+ ions. The calculations employ KS/FD DFT method, which combines Kohn-Sham DFT with the frozen-density DFT to achieve efficient description of explicit solvent beyond the first solvation shell. Our work is based on recent experiments and examines both 1:1 and 2:1 chelator-metal stochiometries detected experimentally. The results show that copper attaches more strongly than zinc, find that 1:1 complexes involve water in the first coordination shell and determine which one of several possible 2:1 geometries is the most preferable.

  18. Mobility of chelated radionuclides in engineered concrete barriers

    SciTech Connect

    Dicke, C.A.; Smith, R.W.

    1993-12-31

    Concrete is a major component in many low-level radioactive waste (LLW) disposal facilities. The use of concrete is widespread because of its physical and structural properties and because it provides geochemical control on metal and radionuclide releases. Organic compounds are often disposed with radionuclides in LLW disposal facilities. Interactions between radionuclides and chelating agents must be evaluated to estimate mobility of radionuclides in concrete vaults. This paper quantifies the effects of two common organic components [citric acid and ethylenediaminetetraacetic acid (EDTA)] on radionuclide mobility in concrete barriers by using equilibrium geochemical calculations. Equilibrium speciation calculations indicate that some radionuclides are chelated in groundwater (pH 7) but are destabilized in the highly alkaline (pH 13) concrete pore fluids. Radionuclides complexed by by EDTA and citrate are replaced by calcium in the concrete pore fluids. In addition, the citrate nuclide complex reacts to form uncomplexed citrate in concrete pore fluids. The chemical performance of concrete LLW disposal facilities should not be compromised by small amounts of chelating agents disposed with some radionuclides. However, EDTA may form significant nickel and cobalt complexes above the pH important in the long-term service life of concrete barriers.

  19. Effectiveness of chelation therapy with time after acute uranium intoxication

    SciTech Connect

    Domingo, J.L.; Ortega, A.; Llobet, J.M.; Corbella, J. )

    1990-01-01

    The effect of increasing the time interval between acute uranium exposure and chelation therapy was studied in male Swiss mice. Gallic acid, 4,5-dihydroxy-1,3- benzenedisulfonic acid (Tiron), diethylenetriaminepentaacetic acid (DTPA), and 5-aminosalicylic acid (5-AS) were administered ip at 0, 0.25, 1, 4, and 24 hr after sc injection of 10 mg/kg of uranyl acetate dihydrate. Chelating agents were given at doses equal to one-fourth of their respective LD50 values. Daily elimination of uranium into urine and feces was determined for 4 days after which time the mice were killed, and the concentration of uranium was measured in kidney, spleen, and bone. The excretion of uranium was especially rapid in the first 24 hr. Treatment with Tiron or gallic acid at 0, 0.25, or 1 hr after uranium exposure significantly increased the total excretion of the metal. In kidney and bone, only administration of Tiron at 0, 0.25, or 1 hr after uranium injection, or gallic acid at 1 hr after uranium exposure significantly reduced tissue uranium concentrations. Treatment at later times (4 to 24 hr) did not increase the total excretion of the metal and did not decrease the tissue uranium concentrations 4 days after uranyl acetate administration. The results show that the length of time before initiating chelation therapy for acute uranium intoxication greatly influences the effectiveness of this therapy.

  20. Azide-bridged Cu(ii), Mn(ii) and Co(ii) coordination polymers constructed with a bifunctional ligand of 6-(1H-tetrazol-5-yl)-2,2'-bipyridine.

    PubMed

    Tsao, Jung-Yu; Tsai, Jia-Dong; Yang, Chen-I

    2016-02-28

    Three new azide-bridged coordination polymers, [M(N3)(tzbp)]n (M = Cu, 1·Cu; Mn, 2·Mn; Co, 3·Co), were successfully synthesized by the introduction of a bifunctional tetrazolate/2,2′-bipyridine ligand, 6-(1H-tetrazol-5-yl)-2,2′-bipyridine (Htzbp), from the in situ [2 + 3] cycloaddition of 6-cyano-2,2′-bipyridine in the presence of an excess of sodium azide under hydrothermal conditions. Compounds 1·Cu−3·Co were characterized by X-ray crystallography, IR spectroscopy, thermogravimetry, and elemental analysis. With tzbp− ligands acting in the chelating coordination mode, compound 1·Cu was comprised of a single end-on N3− (EO-N3) bridged one-dimensional (1D) zigzag structure. Both compounds 2·Mn and 3·Co adopt two-dimensional (2D) layered structures composed of a double EO-N3 bridged dinuclear motif, [M2(EO-N3)2], which are interlinked by tzbp− ligands in the chelating/bridging mode. The layers of 2·Mn and 3·Co are stacked on each other in ⋯ABAB⋯ and ⋯AAAA⋯ fashions, respectively. Magnetic investigations revealed that intrachain antiferromagnetic interactions were dominant in compound 1·Cu, and both 2·Mn and 3·Co exhibited spin-canted antiferromagnetism with critical temperatures (TN) of 3.0 and 18.4 K, respectively. Furthermore, below TN, the field-induced magnetic transitions of spin-flop and metamagnetism were observed in 2·Mn and 3·Co, respectively. PMID:26790962

  1. Complementary and Alternative Therapies in Amyotrophic Lateral Sclerosis.

    PubMed

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

    2015-11-01

    Given the severity of their illness and lack of effective disease-modifying agents, it is not surprising that most patients with amyotrophic lateral sclerosis (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 article reviews these in detail. The authors also describe 3 models by which physicians may frame discussions about alternative therapies: paternalism, autonomy, and shared decision making. Finally, the authors review a program called ALSUntangled, which uses shared decision making to review alternative therapies for ALS. PMID:26515629

  2. The protection conferred by chelation therapy in post-MI diabetics might be replicated by high-dose zinc supplementation.

    PubMed

    McCarty, Mark F; DiNicolantonio, James J

    2015-05-01

    The recent Trial to Assess Chelation Therapy (TACT) study, enrolling subjects who had previously experienced a myocardial infarction, has provided strong evidence that intravenous chelation therapy can markedly reduce risk for mortality and vascular events in diabetics, whereas no discernible benefit was observed in non-diabetics. It has plausibly been suggested that this reflects a role for transition metal ions--iron or copper--in the genesis of advanced glycation end products, key mediators of diabetic complications that can destabilize plaque. Since phlebotomy therapy fails to prevent vascular events in diabetics, we hypothesize that labile copper may be the chief culprit whose removal by chelation mediated the benefit observed in TACT. If so, strategies less time and labor intensive than chelation therapy might provide comparable benefit. A number of recent studies report that the copper-specific orally-active chelator trientine can reduce risk for range of diabetic complications in rodents; a clinical trial with this agent demonstrated some decrease in left ventricular mass in diabetics with ventricular hypertrophy. However, until this agent becomes less expensive, supplementation with high-dose zinc may represent a more feasible alternative. Zinc opposes the absorption and redox activity of copper via induction of the antioxidant protein metallothionein, which binds copper tightly. A great many studies demonstrate that increased expression of metallothionein decreases risk for tissue damage in diabetic rodents, and in some of these studies metallothionein expression was boosted by supplemental zinc. Zinc supplementation also modestly improves glycemic control in type 2 diabetics, and might reduce risk for diabetes by protecting pancreatic beta cells from oxidative stress. A long term study assessing the impact of supplementing diabetics with high-dose zinc, assessing risk for mortality, vascular events, and diabetic complications, may be warranted. Histidine

  3. 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

  4. Mobilization and redistribution of lead over the course of calcium disodium ethylenediamine tetraacetate chelation therapy

    SciTech Connect

    Cory-Slechta, D.A.; Weiss, B.; Cox, C.

    1987-12-01

    After its successful application to the treatment of acute Pb poisoning, Ca disodium EDTA came into routine clinical use for diagnosis and treatment of subacute and chronic Pb poisoning. Despite widespread use, few definitive conclusions have emerged about the sources of Pb mobilized by Ca disodium EDTA. Furthermore, the possibility that mobilized Pb may be redistributed has been suggested. The current studies indicate that the standard therapeutic protocol for Ca disodium EDTA has little impact on critical organs such as brain and liver and moreover, that diagnostic Ca disodium EDTA chelation may even increase the concentration of Pb in these tissues. After a 3 to 4 month exposure to Pb acetate in drinking water, different groups of rats received daily i.p. injections of saline (control), 75 or 150 mg/kg of Ca disodium EDTA for either 1, 2, 3, 4 or 5 days and were then sacrificed 24 hr after the final injection. Tissue analyses indicated that Pb was mobilized from bone and kidney and redistributed initially to both brain and liver. Levels in both brain and liver declined with subsequent Ca disodium EDTA injections, but no net loss from either tissue occurred over the 5-day treatment period despite a decline in blood Pb levels and a marked enhancement of urinary Pb excretion. These findings stress the need for further investigation of Ca disodium EDTAs effects and for parallel evaluation of alternate chelating agents, and suggest that a re-evaluation of both the diagnostic and therapeutic roles of Ca disodium EDTA may be advisable.

  5. Unusual non-bifunctional mechanism for Co-PNP complex catalyzed transfer hydrogenation governed by the electronic configuration of metal center.

    PubMed

    Hou, Cheng; Jiang, Jingxing; Li, Yinwu; Zhang, Zhihan; Zhao, Cunyuan; Ke, Zhuofeng

    2015-10-01

    The mimic of hydrogenases has unleashed a myriad of bifunctional catalysts, which are widely used in the catalytic hydrogenation of polar multiple bonds. With respect to ancillary ligands, the bifunctional mechanism is generally considered to proceed via the metal-ligand cooperation transition state. Inspired by the interesting study conducted by Hanson et al. (Chem Commun., 2013, 49, 10151), we present a computational study of a distinctive example, where a Co(II)-PNP catalyst with an ancillary ligand exhibits efficient transfer hydrogenation through a non-bifunctional mechanism. Both the bifunctional and non-bifunctional mechanisms are discussed. The calculated results, which are based on a full model of the catalyst, suggest that the inner-sphere non-bifunctional mechanism is more favorable (by ∼11 kcal mol(-1)) than the outer-sphere bifunctional mechanism, which is in agreement with the experimental observations. The origin of this mechanistic preference of the Co(II)-PNP catalyst can be attributed to its preference for the square planar geometry. A traditional bifunctional mechanism is less plausible for Co(II)-PNP due to the high distortion energy caused by the change in electronic configuration with the varied ligand field. Considering previous studies that focus on the development of ligands more often, this computational study indicates that the catalytic hydrogenation mechanism is controlled not only by the structure of the ligand but also by the electronic configuration of the metal center. PMID:26332273

  6. Enantio- and Diastereoselective Additions to Aldehydes Using the Bifunctional Reagent 2-(Chloromethyl)-3-(tributylstannyl)propene: Application to a Synthesis of the C16–C27 Segment of Bryostatin 1

    PubMed Central

    Keck, Gary E.; Yu, Tao; McLaws, Mark D.

    2006-01-01

    Reactions of the bifunctional allylstannane 2-(chloromethyl)-3-(tributylstannyl)propene with aldehydes have been examined. These generally occur in high yields using Lewis acid promoters and the products can be isolated and purified without incident. Good yields and high enantioselectivities are also realized in catalytic asymmetric allylations (CAA reactions) using the previously described BITIP catalyst system. Protection of the free hydroxyl can be accomplished without cyclization to the derived tetrahydrofuran, although this transformation is also facile. The utility of the incorporated allyl chloride functionality allows for the obvious use of such products in reactions with nucleophiles. Use of these products in a less obvious connective strategy is demonstrated in the synthesis of the C12–C27 segment of bryostatin 1 where a connective, or “lynchpin”, double-allylation process was employed. The β-hydroxy allyl chloride obtained from an initial chelation-controlled allylation of aldehyde 16 was converted to allylstannane 19 and applied in a second allylation reaction, thus allowing for a highly convergent synthesis of the bryostatin C ring backbone in a stereoselective fashion. PMID:15787541

  7. Unidirectional Adsorption of Bifunctional 1,4-Phenylene Diisocyanide on the Ge(100)-2 × 1 Surface.

    PubMed

    Shong, Bonggeun; Sandoval, Tania E; Crow, Allison M; Bent, Stacey F

    2015-03-19

    Adsorption of bifunctional organic molecules on semiconductor surfaces is important for surface modification; however, most bifunctional molecules previously studied have yielded mixtures of singly and dually tethered adsorbates. Here we report the adsorption of bifunctional 1,4-phenylene diisocyanide (PDI) on the Ge(100)-2 × 1 surface, in which singly bound adsorbates are selectively produced. As shown by polarized multiple internal reflection infrared spectroscopy experiments and density functional theory calculations, PDI adsorbates form a single C-dative bonding configuration through one of the isocyanide functionalities, retaining one unreacted isocyanide moiety per adsorbate. The angle of the molecular axis is ∼30° from the surface normal. The delocalized π* molecular orbital of the free molecule is also preserved upon adsorption. These results demonstrate the potential usefulness of isocyanide adsorbates as a means toward selective organic functionalization of semiconductor surfaces. PMID:26262866

  8. Integrating NiCo Alloys with Their Oxides as Efficient Bifunctional Cathode Catalysts for Rechargeable Zinc-Air Batteries.

    PubMed

    Liu, Xien; Park, Minjoon; Kim, Min Gyu; Gupta, Shiva; Wu, Gang; Cho, Jaephil

    2015-08-10

    The lack of high-efficient, low-cost, and durable bifunctional electrocatalysts that act simultaneously for the oxygen reduction reaction (ORR) and the oxygen evolution reaction (OER) is currently one of the major obstacles to commercializing the electrical rechargeability of zinc-air batteries. A nanocomposite CoO-NiO-NiCo bifunctional electrocatalyst supported by nitrogen-doped multiwall carbon nanotubes (NCNT/CoO-NiO-NiCo) exhibits excellent activity and stability for the ORR/OER in alkaline media. More importantly, real air cathodes made from the bifunctional NCNT/CoO-NiO-NiCo catalysts further demonstrated superior performance to state-of-the-art Pt/C or Pt/C+IrO2 catalysts in primary and rechargeable zinc-air batteries. PMID:26118973

  9. Nanostructured Perovskite LaCo1-xMnxO3 as Bifunctional Catalysts for Rechargeable Metal-Air Batteries

    NASA Astrophysics Data System (ADS)

    Ge, Xiaoming; Li, Bing; Wuu, Delvin; Sumboja, Afriyanti; An, Tao; Hor, T. S. Andy; Zong, Yun; Liu, Zhaolin

    2015-09-01

    Bifunctional catalyst that is active for both oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) is one of the most important components of rechargeable metal-air batteries. Nanostructured perovskite bifunctional catalysts comprising La, Co and Mn(LaCo1-xMnxO3, LCMO) are synthesized by hydrothermal methods. The morphology, structure and electrochemical activity of the perovskite bifunctional catalysts are characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD) and rotating disk electrode (RDE) techniques. Nanorod, nanodisc and nanoparticle are typical morphologies of LCMO. The electrocatalytic activity of LCMO is significantly improved by the addition of conductive materials such as carbon nanotube. To demonstrate the practical utilization, LCMO in the composition of LaCo0.8Mn0.2O3(LCMO82) is used as air cathode catalysts for rechargeable zinc-air batteries. The battery prototype can sustain 470 h or 40 discharge-charge cycles equivalent.

  10. CCCCC pentadentate chelates with planar Möbius aromaticity and unique properties

    PubMed Central

    Zhu, Congqing; Yang, Caixia; Wang, Yongheng; Lin, Gan; Yang, Yuhui; Wang, Xiaoyong; Zhu, Jun; Chen, Xiaoyuan; Lu, Xin; Liu, Gang; Xia, Haiping

    2016-01-01

    The coordinating atoms in polydentate chelates are primarily heteroatoms. We present the first examples of pentadentate chelates with all binding atoms of the chelating agent being carbon atoms, denoted as CCCCC chelates. Having up to five metal-carbon bonds in the equatorial plane has not been previously observed in transition metal chemistry. Density functional theory calculations showed that the planar metallacycle has extended Craig-Möbius aromaticity arising from 12-center–12-electron dπ-pπ π-conjugation. These planar chelates have broad absorption in the ultraviolet-visible–near-infrared region and, thus, notable photothermal performance upon irradiation by an 808-nm laser, indicating that these chelates have potential applications in photothermal therapy. The combination of facile synthesis, high stability, and broad absorption of these complexes could make the polydentate carbon chain a novel building block in coordination chemistry. PMID:27574707

  11. CCCCC pentadentate chelates with planar Möbius aromaticity and unique properties.

    PubMed

    Zhu, Congqing; Yang, Caixia; Wang, Yongheng; Lin, Gan; Yang, Yuhui; Wang, Xiaoyong; Zhu, Jun; Chen, Xiaoyuan; Lu, Xin; Liu, Gang; Xia, Haiping

    2016-08-01

    The coordinating atoms in polydentate chelates are primarily heteroatoms. We present the first examples of pentadentate chelates with all binding atoms of the chelating agent being carbon atoms, denoted as CCCCC chelates. Having up to five metal-carbon bonds in the equatorial plane has not been previously observed in transition metal chemistry. Density functional theory calculations showed that the planar metallacycle has extended Craig-Möbius aromaticity arising from 12-center-12-electron dπ-pπ π-conjugation. These planar chelates have broad absorption in the ultraviolet-visible-near-infrared region and, thus, notable photothermal performance upon irradiation by an 808-nm laser, indicating that these chelates have potential applications in photothermal therapy. The combination of facile synthesis, high stability, and broad absorption of these complexes could make the polydentate carbon chain a novel building block in coordination chemistry. PMID:27574707

  12. EDTA Chelation Therapy to Reduce Cardiovascular Events in Persons with Diabetes.

    PubMed

    Ouyang, Pamela; Gottlieb, Sheldon H; Culotta, Valerie L; Navas-Acien, Ana

    2015-11-01

    The Trial to Assess Chelation Therapy (TACT) was a randomized double-blind placebo-controlled trial enrolling patients age ≥50 years with prior myocardial infarction. TACT used a 2 × 2 factorial design to study ethylene diamine tetraacetic acid (EDTA) chelation and high-dose vitamin supplementation. Chelation provided a modest but significant reduction in cardiovascular endpoints. The benefit was stronger and significant among participants with diabetes but absent in those without diabetes. Mechanisms by which chelation might reduce cardiovascular risk in persons with diabetes include the effects of EDTA chelation on transition and toxic metals. Transition metals, particularly copper and iron, play important roles in oxidative stress pathways. Toxic metals, in particular cadmium and lead, are toxic for the cardiovascular system. This review discusses the epidemiologic evidence and animal and human studies supporting the role of these metals in the development of diabetes and ischemic heart disease and potential ways by which EDTA chelation could confer cardiovascular benefit. PMID:26364188

  13. Chelation of cadmium without increased renal cadmium deposition.

    PubMed Central

    Cherian, M G

    1984-01-01

    Cadmium (Cd) is mainly accumulated in liver and kidney bound to metallothionein (MT) and excreted very slowly from the body. In chronic exposure, Cd is gradually transported from liver to kidney; the renal toxic effects appear when renal Cd concentration exceeds the critical concentration. In order to prevent the Cd-induced renal disease, it is important to control the movement of Cd to the kidney and its renal deposition. However, the chelation of Cd from liver is difficult because of the high affinity of intracellular MT for Cd. A number of chelating agents containing both carboxyl and thiol groups were able to mobilize and excrete Cd more easily in a short time (1/2 hr) after Cd exposure than longer times (24 hr), after MT synthesis. The renal deposition of Cd increased on BAL (2,3-dimercaptopropanol) treatment a short time (1/2 hr) after Cd exposure. However, it was observed that if BAL was administered 24 hr after Cd exposure, it could mobilize Cd from hepatic MT and increase the biliary excretion of Cd without any increase in renal Cd concentration. Studies using a number of structurally related thiols (mono-, di- and trithiols) showed that the major structural requirement for in vivo chelation of Cd from intracellular MT were the vicinal thiol groups on an aliphatic chain, and lipophilicity. BAL was the most effective of all the compounds studied and it did not mobilize Cd to the kidney, when most of the intracellular Cd was bound to MT. Furthermore, a delayed treatment with BAL or DTPA (diethylenetriamine pentaacetic acid) after synthesis of MT resulted in an increase in fecal or urinary excretion of Cd in rat model experiment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:6734559

  14. Characterization of modular bifunctional processive endoglucanase Cel5 from Hahella chejuensis KCTC 2396.

    PubMed

    Ghatge, Sunil Subhash; Telke, Amar Anandrao; Kang, Seo-Hee; Arulalapperumal, Venkatesh; Lee, Keun-Woo; Govindwar, Sanjay Prabhu; Um, Youngsoon; Oh, Doo-Byoung; Shin, Hyun-Dong; Kim, Seon-Won

    2014-05-01

    Cel5 from marine Hahella chejuensis is composed of glycoside hydrolase family-5 (GH5) catalytic domain (CD) and two carbohydrate binding modules (CBM6-2). The enzyme was expressed in Escherichia coli and purified to homogeneity. The optimum endoglucanase and xylanase activities of recombinant Cel5 were observed at 65 °C, pH 6.5 and 55 °C, pH 5.5, respectively. It exhibited K m of 1.8 and 7.1 mg/ml for carboxymethyl cellulose and birchwood xylan, respectively. The addition of Ca(2+) greatly improved thermostability and endoglucanase activity of Cel5. The Cel5 retained 90 % of its endoglucanase activity after 24 h incubation in presence of 5 M concentration of NaCl. Recombinant Cel5 showed production of cellobiose after hydrolysis of cellulosic substrates (soluble/insoluble) and methylglucuronic acid substituted xylooligosaccharides after hydrolysis of glucuronoxylans by endo-wise cleavage. These results indicated that Cel5 as bifunctional enzyme having both processive endoglucanase and xylanase activities. The multidomain structure of Cel5 is clearly distinguished from the GH5 bifunctional glycoside hydrolases characterized to date, which are single domain enzymes. Sequence analysis and homology modeling suggested presence of two conserved binding sites with different substrate specificities in CBM6-2 and a single catalytic site in CD. Residues Glu132 and Glu219 were identified as key catalytic amino acids by sequence alignment and further verified by using site directed mutagenesis. CBM6-2 plays vital role in catalytic activity and thermostability of Cel5. The bifunctional activities and multiple substrate specificities of Cel5 can be utilized for efficient hydrolysis of cellulose and hemicellulose into soluble sugars. PMID:24343767

  15. Mechanical characterization of a bifunctional Tetronic hydrogel adhesive for soft tissues.

    PubMed

    Sanders, Lindsey; Stone, Roland; Webb, Kenneth; Mefford, Thompson; Nagatomi, Jiro

    2015-03-01

    Although a number of tissue adhesives and sealants for surgical use are currently available, attaining a useful balance in high strength, high compliance, and low swelling has proven difficult. Recent studies have demonstrated that a four-arm poly(propylene oxide)-poly(ethylene oxide) block copolymer, Tetronic, can be chemically modified to form a hydrogel tissue adhesive (Cho et al., Acta Biomater 2012;8:2223-2232; Barrett et al., Adv Health Mater 2012;1-11; Balakrishnan, Evaluating mechanical performance of hydrogel-based adhesives for soft tissue applications. Clemson University, All Theses, Paper 1574: Tiger Prints; 2013). Building on the success of these studies, this study explored bifunctionalization of Tetronic with acrylates for chemical crosslinking of the hydrogel and N-hydroxysuccinimide (NHS) for reaction with tissue amines. The adhesive bond strengths of various uni and bifunctional Tetronic blends (T1107 ACR: T1107 ACR/NHS) determined by lap shear testing ranged between 8 and 74 kPa, with the 75:25 (T1107 ACR: T1107 ACR/NHS) blend displaying the highest value. These results indicated that addition of NHS led to improvement of tissue bond strength over acrylation alone. Furthermore, ex vivo pressure tests using the rat bladder demonstrated that the bifunctional Tetronic adhesive exhibited high compliance and maintained pressures under hundreds of filling and emptying cycles. Together, the results of this study provided evidence that the bifunctional Tetronic adhesive with a proper blend ratio may be used to achieve an accurate balance in bulk and tissue bond strengths, as well as the compliance and durability for soft tissue such as the bladder. PMID:25111445

  16. Alkenes as Chelating Groups in Diastereoselective Additions of Organometallics to Ketones

    PubMed Central

    2015-01-01

    Alkenes have been discovered to be chelating groups to Zn(II), enforcing highly stereoselective additions of organozincs to β,γ-unsaturated ketones. 1H NMR studies and DFT calculations provide support for this surprising chelation mode. The results expand the range of coordinating groups for chelation-controlled carbonyl additions from heteroatom Lewis bases to simple C–C double bonds, broadening the 60 year old paradigm. PMID:25328269

  17. Synergistic intracellular iron chelation combinations: mechanisms and conditions for optimizing iron mobilization.

    PubMed

    Vlachodimitropoulou Koumoutsea, Evangelia; Garbowski, Maciej; Porter, John

    2015-09-01

    Iron chelators are increasingly combined clinically but the optimal conditions for cellular iron mobilization and mechanisms of interaction are unclear. Speciation plots for iron(III) binding of paired combinations of the licensed iron chelators desferrioxamine (DFO), deferiprone (DFP) and deferasirox (DFX) suggest conditions under which chelators can combine as 'shuttle' and 'sink' molecules but this approach does not consider their relative access and interaction with cellular iron pools. To address this issue, a sensitive ferrozine-based detection system for intracellular iron removal from the human hepatocyte cell line (HuH-7) was developed. Antagonism, synergism or additivity with paired chelator combinations was distinguished using mathematical isobologram analysis over clinically relevant chelator concentrations. All combinations showed synergistic iron mobilization at 8 h with clinically achievable concentrations of sink and shuttle chelators. Greatest synergism was achieved by combining DFP with DFX, where about 60% of mobilized iron was attributable to synergistic interaction. These findings predict that the DFX dose required for a half-maximum effect can be reduced by 3·8-fold when only 1 μmol/l DFP is added. Mechanisms for the synergy are suggested by consideration of the iron-chelate speciation plots together with the size, charge and lipid solubilities for each chelator. Hydroxypyridinones with low lipid solubilities but otherwise similar properties to DFP were used to interrogate the mechanistic interactions of chelator pairs. These studies confirm that synergistic cellular iron mobilization requires one chelator to have the physicochemical properties to enter cells, chelate intracellular iron and subsequently donate iron to a second 'sink' chelator. PMID:26033030

  18. Mesoporous organosilica nanotubes containing a chelating ligand in their walls

    NASA Astrophysics Data System (ADS)

    Liu, Xiao; Goto, Yasutomo; Maegawa, Yoshifumi; Ohsuna, Tetsu; Inagaki, Shinji

    2014-11-01

    We report the synthesis of organosilica nanotubes containing 2,2'-bipyridine chelating ligands within their walls, employing a single-micelle-templating method. These nanotubes have an average pore diameter of 7.8 nm and lengths of several hundred nanometers. UV-vis absorption spectra and scanning transmission electron microscopy observations of immobilized nanotubes with an iridium complex on the bipyridine ligands showed that the 2,2'-bipyridine groups were homogeneously distributed in the benzene-silica walls. The iridium complex, thus, immobilized on the nanotubes exhibited efficient catalytic activity for water oxidation using Ce4+, due to the ready access of reactants to the active sites in the nanotubes.

  19. Chelate-modified polymers for atmospheric gas chromatography

    NASA Technical Reports Server (NTRS)

    Christensen, W. W.; Mayer, L. A.; Woeller, F. H. (Inventor)

    1980-01-01

    Chromatographic materials were developed to serve as the stationary phase of columns used in the separation of atmospheric gases. These materials consist of a crosslinked porous polymer matrix, e.g., a divinylbenzene polymer, into which has been embedded an inorganic complexed ion such as N,N'-ethylene-bis-(acetylacetoniminato)-cobalt (2). Organic nitrogenous bases, such as pyridine, may be incorporated into the chelate polymer complexes to increase their chromatographic utility. With such materials, the process of gas chromatography is greatly simplified, especially in terms of time and quantity of material needed for a gas separation.

  20. Supported bifunctional thioureas as recoverable and reusable catalysts for enantioselective nitro-Michael reactions

    PubMed Central

    Ceballos, Miriam; Maestro, Alicia; Sanz, Isabel

    2016-01-01

    Summary The catalytic activity of different supported bifunctional thioureas on sulfonylpolystyrene resins has been studied in the nitro-Michael addition of different nucleophiles to trans-β-nitrostyrene derivatives. The activity of the catalysts depends on the length of the tether linking the chiral thiourea to the polymer. The best results were obtained with the thiourea derived from (L)-valine and 1,6-hexanediamine. The catalysts can be used in only 2 mol % loading, and reused for at least four cycles in neat conditions. The ball milling promoted additions also worked very well. PMID:27340453

  1. Direct transformation of esters into arenes with 1,5-bifunctional organomagnesium reagents.

    PubMed

    Link, Achim; Fischer, Christian; Sparr, Christof

    2015-10-01

    A direct transformation of carboxylic acid esters into arenes with 1,5-bifunctional organomagnesium reagents is described. This efficient and practical method enables the one-step defunctionalization of various carboxylic acid esters to prepare benzene, anthracene, tetracene, and pentacene derivatives. A double nucleophilic addition of the 1,5-organodimagnesium reagent to the ester is followed by an immediate 1,4-elimination reaction that leads to the direct [5+1] formation of a new aromatic ring. PMID:26291060

  2. A novel bifunctional mitochondria-targeted anticancer agent with high selectivity for cancer cells.

    PubMed

    He, Huan; Li, Dong-Wei; Yang, Li-Yun; Fu, Li; Zhu, Xun-Jin; Wong, Wai-Kwok; Jiang, Feng-Lei; Liu, Yi

    2015-01-01

    Mitochondria have recently emerged as novel targets for cancer therapy due to its important roles in fundamental cellular function. Discovery of new chemotherapeutic agents that allow for simultaneous treatment and visualization of cancer is urgent. Herein, we demonstrate a novel bifunctional mitochondria-targeted anticancer agent (FPB), exhibiting both imaging capability and anticancer activity. It can selectively accumulate in mitochondria and induce cell apoptosis. Notably, it results in much higher toxicity toward cancer cells owing to much higher uptake by cancer cells. These features make it highly attractive in cancer imaging and treatment. PMID:26337336

  3. Acid–base bifunctional shell cross-linked micelle nanoreactor for one-pot tandem reaction

    SciTech Connect

    Lee, Li -Chen; Lu, Jie; Weck, Marcus; Jones, Christopher W.

    2015-12-29

    Shell cross-linked micelles (SCMs) containing acid sites in the shell and base sites in the core are prepared from amphiphilic poly(2-oxazoline) triblock copolymers. The materials are utilized as two-chamber nanoreactors for a prototypical acid-base bifunctional tandem deacetalization-nitroaldol reaction. Furthermore, the acid and base sites are localized in different regions of the micelle, allowing the two steps in the reaction sequence to largely proceed in separate compartments, akin to the compartmentalization that occurs in biological systems.

  4. An efficient bifunctional electrocatalyst for water splitting based on cobalt phosphide

    NASA Astrophysics Data System (ADS)

    Yang, Libin; Qi, Honglan; Zhang, Chengxiao; Sun, Xuping

    2016-06-01

    The development of highly efficient electrocatalysts for water splitting is critical for various renewable-energy technologies. In this letter, we demonstrate a cobalt phosphide nanowire array grown on a Ti mesh (CoP/TM) behaving as a bifunctional electrocatalyst for water splitting. The CoP/TM electrode delivers 10 mA cm‑2 at an overpotential of 72 mV for the hydrogen evolution reaction (HER) and 310 mV for the oxygen evolution reaction (OER) in 1.0 M KOH. Furthermore, its corresponding two-electrode alkaline electrolyzer displays 10 mA cm‑2 at 1.64 V.

  5. Bifunctional phase-transfer catalysis in the asymmetric synthesis of biologically active isoindolinones

    PubMed Central

    Di Mola, Antonia; Tiffner, Maximilian; Scorzelli, Francesco; Palombi, Laura; Filosa, Rosanna; De Caprariis, Paolo

    2015-01-01

    Summary New bifunctional chiral ammonium salts were investigated in an asymmetric cascade synthesis of a key building block for a variety of biologically relevant isoindolinones. With this chiral compound in hand, the development of further transformations allowed for the synthesis of diverse derivatives of high pharmaceutical value, such as the Belliotti (S)-PD172938 and arylated analogues with hypnotic sedative activity, obtained in good overall total yield (50%) and high enantiomeric purity (95% ee). The synthetic routes developed herein are particularly convenient in comparison with the current methods available in literature and are particularly promising for large scale applications. PMID:26734105

  6. Au@Cu(II)-MOF: Highly Efficient Bifunctional Heterogeneous Catalyst for Successive Oxidation-Condensation Reactions.

    PubMed

    Wang, Jing-Si; Jin, Fa-Zheng; Ma, Hui-Chao; Li, Xiao-Bo; Liu, Ming-Yang; Kan, Jing-Lan; Chen, Gong-Jun; Dong, Yu-Bin

    2016-07-01

    A new composite Au@Cu(II)-MOF catalyst has been synthesized via solution impregnation and full characterized by HRTEM, SEM-EDS, XRD, gas adsorption-desorption, XPS, and ICP analysis. It has been shown here that the Cu(II)-framework can be a useful platform to stabilize and support gold nanoparticles (Au NPs). The obtained Au@Cu(II)-MOF exhibits a bifunctional catalytic behavior and is able to promote selective aerobic benzyl alcohol oxidation-Knoevenagel condensation in a stepwise way. PMID:27322613

  7. Highly Enantioselective, Intermolecular Hydroamination of Allenyl Esters Catalyzed by Bifunctional Phosphinothioureas

    PubMed Central

    2015-01-01

    Bifunctional phosphinothiourea catalysts have been developed successfully for the highly regio- and enantioselective γ-hydroamination of allenyl and propargyl esters with N-methoxy carbamate nucleophiles to yield α,β-unsaturated γ-amino acid ester products. In the case of propargyl ester substrates, the reaction proceeds through reversible phosphinothiourea-catalyzed isomerization to the corresponding allenyl ester. The high enantioselectivity of the process is attributed to a cooperative conjugate addition of a thiourea-bound carbamate anion to a vinyl phosphonium ion resulting from covalent activation of the allenyl ester substrate. PMID:25496451

  8. Bifunctional Organic Polymeric Catalysts with a Tunable Acid-Base Distance and Framework Flexibility

    NASA Astrophysics Data System (ADS)

    Chen, Huanhui; Wang, Yanan; Wang, Qunlong; Li, Junhui; Yang, Shiqi; Zhu, Zhirong

    2014-09-01

    Acid-base bifunctional organic polymeric catalysts were synthesized with tunable structures. we demonstrated two synthesis approaches for structural fine-tune. In the first case, the framework flexibility was tuned by changing the ratio of rigid blocks to flexible blocks within the polymer framework. In the second case, we precisely adjusted the acid-base distance by distributing basic monomers to be adjacent to acidic monomers, and by changing the chain length of acidic monomers. In a standard test reaction for the aldol condensation of 4-nitrobenzaldehyde with acetone, the catalysts showed good reusability upon recycling and maintained relatively high conversion percentage.

  9. Bifunctional Brønsted Base Catalyzes Direct Asymmetric Aldol Reaction of α-Keto Amides.

    PubMed

    Echave, Haizea; López, Rosa; Palomo, Claudio

    2016-03-01

    The first enantioselective direct cross-aldol reaction of α-keto amides with aldehydes, mediated by a bifunctional ureidopeptide-based Brønsted base catalyst, is described. The appropriate combination of a tertiary amine base and an aminal, and urea hydrogen-bond donor groups in the catalyst structure promoted the exclusive generation of the α-keto amide enolate which reacted with either non-enolizable or enolizable aldehydes to produce highly enantioenriched polyoxygenated aldol adducts without side-products resulting from dehydration, α-keto amide self-condensation, aldehyde enolization, and isotetronic acid formation. PMID:26835655

  10. An efficient bifunctional electrocatalyst for water splitting based on cobalt phosphide.

    PubMed

    Yang, Libin; Qi, Honglan; Zhang, Chengxiao; Sun, Xuping

    2016-06-10

    The development of highly efficient electrocatalysts for water splitting is critical for various renewable-energy technologies. In this letter, we demonstrate a cobalt phosphide nanowire array grown on a Ti mesh (CoP/TM) behaving as a bifunctional electrocatalyst for water splitting. The CoP/TM electrode delivers 10 mA cm(-2) at an overpotential of 72 mV for the hydrogen evolution reaction (HER) and 310 mV for the oxygen evolution reaction (OER) in 1.0 M KOH. Furthermore, its corresponding two-electrode alkaline electrolyzer displays 10 mA cm(-2) at 1.64 V. PMID:27146428

  11. A novel bifunctional mitochondria-targeted anticancer agent with high selectivity for cancer cells

    PubMed Central

    He, Huan; Li, Dong-Wei; Yang, Li-Yun; Fu, Li; Zhu, Xun-Jin; Wong, Wai-Kwok; Jiang, Feng-Lei; Liu, Yi

    2015-01-01

    Mitochondria have recently emerged as novel targets for cancer therapy due to its important roles in fundamental cellular function. Discovery of new chemotherapeutic agents that allow for simultaneous treatment and visualization of cancer is urgent. Herein, we demonstrate a novel bifunctional mitochondria-targeted anticancer agent (FPB), exhibiting both imaging capability and anticancer activity. It can selectively accumulate in mitochondria and induce cell apoptosis. Notably, it results in much higher toxicity toward cancer cells owing to much higher uptake by cancer cells. These features make it highly attractive in cancer imaging and treatment. PMID:26337336

  12. Bifunctional phase-transfer catalysis in the asymmetric synthesis of biologically active isoindolinones.

    PubMed

    Di Mola, Antonia; Tiffner, Maximilian; Scorzelli, Francesco; Palombi, Laura; Filosa, Rosanna; De Caprariis, Paolo; Waser, Mario; Massa, Antonio

    2015-01-01

    New bifunctional chiral ammonium salts were investigated in an asymmetric cascade synthesis of a key building block for a variety of biologically relevant isoindolinones. With this chiral compound in hand, the development of further transformations allowed for the synthesis of diverse derivatives of high pharmaceutical value, such as the Belliotti (S)-PD172938 and arylated analogues with hypnotic sedative activity, obtained in good overall total yield (50%) and high enantiomeric purity (95% ee). The synthetic routes developed herein are particularly convenient in comparison with the current methods available in literature and are particularly promising for large scale applications. PMID:26734105

  13. Tunable catalytic properties of bi-functional mixed oxides in ethanol conversion to high value compounds

    DOE PAGESBeta

    Ramasamy, Karthikeyan K.; Gray, Michel; Job, Heather; Smith, Colin; Wang, Yong

    2016-02-03

    Here, a highly versatile ethanol conversion process to selectively generate high value compounds is presented here. By changing the reaction temperature, ethanol can be selectively converted to >C2 alcohols/oxygenates or phenolic compounds over hydrotalcite derived bi-functional MgO–Al2O3 catalyst via complex cascade mechanism. Reaction temperature plays a role in whether aldol condensation or the acetone formation is the path taken in changing the product composition. This article contains the catalytic activity comparison between the mono-functional and physical mixture counterpart to the hydrotalcite derived mixed oxides and the detailed discussion on the reaction mechanisms.

  14. Recovery of uranium from acid media by macroporous bifunctional phosphinic acid resin

    SciTech Connect

    Sabharwal, K.N.; Srinivasan, T.G.; Rao, P.R.V.; Nandy, K.K.

    1996-11-01

    The extraction of uranium from various acid media such as nitric acid, sulphuric acid, hydrochloric acid, phosphoric acid and perchloric acid by a macroporous bifunctional phosphinic acid resin (MPBPA) has been studied. The distribution coefficients for the extraction of uranium by the MPBPA resin are compared with the corresponding values reported in literature for the conventional sulphonic acid resin. The results clearly indicate the suitability of the MPBPA resin to recover uranium from different types of acid solutions of widely ranging acidities. 17 refs., 6 figs., 5 tabs.

  15. Cobalt nanoparticles embedded in N-doped carbon as an efficient bifunctional electrocatalyst for oxygen reduction and evolution reactions

    NASA Astrophysics Data System (ADS)

    Su, Yunhe; Zhu, Yihua; Jiang, Hongliang; Shen, Jianhua; Yang, Xiaoling; Zou, Wenjian; Chen, Jianding; Li, Chunzhong

    2014-11-01

    Cobalt based catalysts are promising bifunctional electrocatalysts for both oxygen reduction and oxygen evolution reactions (ORR and OER) in unitized regenerative fuel cells (URFCs) operating with alkaline electrolytes. Here we report a hybrid composite of cobalt nanoparticles embedded in nitrogen-doped carbon (Co/N-C) via a solvothermal carbonization strategy. With the synergistic effect arising from the N-doped carbon and cobalt nanoparticles in the composite, the Co/N-C hybrid catalyst exhibits highly efficient bifunctional catalytic activity and excellent stability toward both ORR and OER. The ΔE (oxygen electrode activity parameter for judging the overall electrocatalytic activity of a bifunctional electrocatalyst) value for Co/N-C is 0.859 V, which is smaller than those of Pt/C and most of the non-precious metal catalysts in previous studies. Furthermore, the Co/N-C composite also shows better bifunctional catalytic activity than its oxidative counterparts, which could be attributed to the high specific surface area and the efficient charge transfer ability of the composite, as well as the good synergistic effect between N-doped carbon and the Co nanoparticles in the Co/N-C composite.Cobalt based catalysts are promising bifunctional electrocatalysts for both oxygen reduction and oxygen evolution reactions (ORR and OER) in unitized regenerative fuel cells (URFCs) operating with alkaline electrolytes. Here we report a hybrid composite of cobalt nanoparticles embedded in nitrogen-doped carbon (Co/N-C) via a solvothermal carbonization strategy. With the synergistic effect arising from the N-doped carbon and cobalt nanoparticles in the composite, the Co/N-C hybrid catalyst exhibits highly efficient bifunctional catalytic activity and excellent stability toward both ORR and OER. The ΔE (oxygen electrode activity parameter for judging the overall electrocatalytic activity of a bifunctional electrocatalyst) value for Co/N-C is 0.859 V, which is smaller than those

  16. NiCoMnO4: A Bifunctional Affinity Probe for His-Tagged Protein Purification and Phosphorylation Sites Recognition.

    PubMed

    Qi, Xiaoyue; Chen, Long; Zhang, Chaoqun; Xu, Xinyuan; Zhang, Yiding; Bai, Yu; Liu, Huwei

    2016-07-27

    A bifunctional affinity probe NiCoMnO4 was designed and prepared with controllable morphology and size using facile methods. It was observed that the probe could be applied in His-tagged proteins purification and phosphopeptides enrichment simply through the buffer modulation. NiCoMnO4 particles showed satisfactory cycling performance for His-tagged proteins purification and broad pH-tolerance of loading buffer for phosphopeptides affinity. Therefore, a high-throughput, cost-effective, and efficient protein/peptide purification method was developed within 10 min based on the novel bifunctional affinity probe. PMID:27381638

  17. Branched polymeric media: boron-chelating resins from hyperbranched polyethylenimine.

    PubMed

    Mishra, Himanshu; Yu, Changjun; Chen, Dennis P; Goddard, William A; Dalleska, Nathan F; Hoffmann, Michael R; Diallo, Mamadou S

    2012-08-21

    Extraction of boron from aqueous solutions using selective resins is important in a variety of applications including desalination, ultrapure water production, and nuclear power generation. Today's commercial boron-selective resins are exclusively prepared by functionalization of styrene-divinylbenzene (STY-DVB) beads with N-methylglucamine to produce resins with boron-chelating groups. However, such boron-selective resins have a limited binding capacity with a maximum free base content of 0.7 eq/L, which corresponds to a sorption capacity of 1.16 ± 0.03 mMol/g in aqueous solutions with equilibrium boron concentration of ∼70 mM. In this article, we describe the synthesis and characterization of a new resin that can selectively extract boron from aqueous solutions. We show that branched polyethylenimine (PEI) beads obtained from an inverse suspension process can be reacted with glucono-1,5-D-lactone to afford a resin consisting of spherical beads with high density of boron-chelating groups. This resin has a sorption capacity of 1.93 ± 0.04 mMol/g in aqueous solution with equilibrium boron concentration of ∼70 mM, which is 66% percent larger than that of standard commercial STY-DVB resins. Our new boron-selective resin also shows excellent regeneration efficiency using a standard acid wash with a 1.0 M HCl solution followed by neutralization with a 0.1 M NaOH solution. PMID:22827255

  18. Luminescence of carbazolyl-containing polymers doped with iridium chelates

    NASA Astrophysics Data System (ADS)

    Skryshevskii, Yu. A.

    2008-05-01

    White light emission is shown to be obtainable at room temperature through the mixing of poly-N-vinylcarbazole (PVC) host fluorescence with fac-tris(2-phenylpyridyl)Ir(III) [Ir(ppy)3] and bis[2-(2'-benzothienyl)pyridinato-N,C3'](acetylacetonate)iridium (III) [Btp2Ir(acac)] dopant phosphorescence whereas at very low temperature through the superposition of poly-N-epoxypropyl-3,6-dibromocarbazole (3,6-DBrPEPC) host and Btp2Ir(acac) dopant phosphorescence emissions. The balance between basic colors is adjusted by the variation of triplet-emitter dopant concentrations. Spin-allowed singlet-singlet energy transfer from the host to iridium chelate dopants by the Forster mechanism is the dominant process in PVC. Spin-forbidden triplet-singlet transfer by the Forster mechanism from the host to the dopant occurs at low temperatures in 3,6-DBrPEPC due to strong spin-orbit coupling induced by the heavy bromine atoms. Spin-allowed transfer from the same host’s triplet excited state to the iridium chelate occurs via electron exchange at high temperatures.

  19. Using iron chelating agents to enhance dermatological PDT

    NASA Astrophysics Data System (ADS)

    Curnow, Alison; Dogra, Yuktee; Winyard, Paul; Campbell, Sandra

    2009-06-01

    Topical protoporphyrin IX (PPIX) induced photodynamic therapy (PDT) of basal cell carcinoma (BCC) produces good clinical outcomes with excellent cosmesis as long as the disease remains superficial. Efficacy for nodular BCC however appears inferior to standard treatment unless repeat treatments are performed. Enhancement is therefore required and is possible by employing iron chelating agents to temporarily increase PPIX accumulation above the levels normally obtained using aminolevulinic acid (ALA) or the methyl ester of ALA (MAL) alone. In vitro studies investigated the effect of the novel iron chelator, CP94 on necrotic or apoptotic cell death in cultured human skin fibroblasts and epidermal carcinoma cells incubated with MAL. Furthermore, following a dose escalating safety study conducted with ALA in patients, an additional twelve nodular BCCs were recruited for topical treatment with standard MAL-PDT +/- increasing doses of CP94. Six weeks later following clinical assessment, the whole treatment site was excised for histological analysis. CP94 produced greater cell death in vitro when administered in conjunction with MAL than this porphyrin precursor could produce when administered alone. Clinically, PDT treatment using Metvix + CP94 was a simple and safe modification associated with a trend of reduced tumor thickness with increasing CP94 dose.

  20. Competition among marine phytoplankton for different chelated iron species

    NASA Astrophysics Data System (ADS)

    Hutchins, David A.; Witter, Amy E.; Butler, Alison; Luther, George W.

    1999-08-01

    Dissolved-iron availability plays a critical role in controlling phytoplankton growth in the oceans,. The dissolved iron is overwhelmingly (~99%) bound to organic ligands with a very high affinity for iron, but the origin, chemical identity and biological availability of this organically complexed Fe is largely unknown. The release into sea water of complexes that strongly chelate iron could result from the inducible iron-uptake systems of prokaryotes (siderophore complexes) or by processes such as zooplankton-mediated degradation and release of intracellular material (porphyrin complexes). Here we compare the uptake of siderophore- and porphyrin-complexed 55Fe by phytoplankton, using both cultured organisms and natural assemblages. Eukaryotic phytoplankton efficiently assimilate porphyrin-complexed iron, but this iron source is relatively unavailable to prokaryotic picoplankton (cyanobacteria). In contrast, iron bound to a variety of siderophores is relatively more available to cyanobacteria than to eukaryotes, suggesting that the two plankton groups exhibit fundamentally different iron-uptake strategies. Prokaryotes utilize iron complexed to either endogenous or exogenous siderophores, whereas eukaryotes may rely on a ferrireductase system, that preferentially accesses iron chelated by tetradentate porphyrins, rather than by hexadentate siderophores. Competition between prokaryotes and eukaryotes for organically-bound iron may therefore depend on the chemical nature of available iron complexes, with consequences for ecological niche separation, plankton community size-structure and carbon export in low-iron waters.

  1. Chelating polymeric beads as potential therapeutics for Wilson's disease.

    PubMed

    Mattová, Jana; Poučková, Pavla; Kučka, Jan; Skodová, Michaela; Vetrík, Miroslav; Stěpánek, Petr; Urbánek, Petr; Petřík, Miloš; Nový, Zbyněk; Hrubý, Martin

    2014-10-01

    Wilson's disease is a genetic disorder caused by a malfunction of ATPase 7B that leads to high accumulation of copper in the organism and consequent toxic effects. We propose a gentle therapy to eliminate the excessive copper content with oral administration of insoluble non-resorbable polymer sorbents containing selective chelating groups for copper(II). Polymeric beads with the chelating agents triethylenetetramine, N,N-di(2-pyridylmethyl)amine, and 8-hydroxyquinoline (8HQB) were investigated. In a preliminary copper uptake experiment, we found that 8HQB significantly reduced copper uptake (using copper-64 as a radiotracer) after oral administration in Wistar rats. Furthermore, we measured organ radioactivity in rats to demonstrate that 8HQB radiolabelled with iodine-125 is not absorbed from the gastrointestinal tract after oral administration. Non-resorbability and the blockade of copper uptake were also confirmed with small animal imaging (PET/CT) in mice. In a long-term experiment with Wistar rats fed a diet containing the polymers, we have found that there were no signs of polymer toxicity and the addition of polymers to the diet led to a significant reduction in the copper contents in the kidneys, brains, and livers of the rats. We have shown that polymers containing specific ligands could potentially be novel therapeutics for Wilson's disease. PMID:24815561

  2. Chelation of lysosomal iron protects against ionizing radiation.

    PubMed

    Berndt, Carsten; Kurz, Tino; Selenius, Markus; Fernandes, Aristi P; Edgren, Margareta R; Brunk, Ulf T

    2010-12-01

    Ionizing radiation causes DNA damage and consequent apoptosis, mainly due to the production of hydroxyl radicals (HO•) that follows radiolytic splitting of water. However, superoxide (O2•-) and H2O2 also form and induce oxidative stress with resulting LMP (lysosomal membrane permeabilization) arising from iron-catalysed oxidative events. The latter will contribute significantly to radiation-induced cell death and its degree largely depends on the quantities of lysosomal redox-active iron present as a consequence of autophagy and endocytosis of iron-rich compounds. Therefore radiation sensitivity might be depressed by lysosome-targeted iron chelators. In the present study, we have shown that cells in culture are significantly protected from ionizing radiation damage if initially exposed to the lipophilic iron chelator SIH (salicylaldehyde isonicotinoyl hydrazone), and that this effect is based on SIH-dependent lysosomal stabilization against oxidative stress. According to its dose-response-modifying effect, SIH is a most powerful radioprotector and a promising candidate for clinical application, mainly to reduce the radiation sensitivity of normal tissue. We propose, as an example, that inhalation of SIH before each irradiation session by patients undergoing treatment for lung malignancies would protect normally aerated lung tissue against life-threatening pulmonary fibrosis, whereas the sensitivity of malignant lung tumours, which usually are non-aerated, will not be affected by inhaled SIH. PMID:20846118

  3. In Vivo Iron-Chelating Activity and Phenolic Profiles of the Angel's Wings Mushroom, Pleurotus porrigens (Higher Basidiomycetes).

    PubMed

    Khalili, Masoumeh; Ebrahimzadeh, Mohammad Ali; Kosaryan, Mehrnoush

    2015-01-01

    Pleurotus porrigens is an culinary-medicinal mushroom. It is locally called sadafi and is found in the northern regions of Iran, especially in Mazandaran. This mushroom is used to prepare a variety of local and specialty foods. Because of the phenol and flavonoid contents and the strong iron-chelating activity of this mushroom, it was selected for an assay of in vivo iron-chelating activity. Methanolic extract was administered intraperitoneally to iron-overloaded mice at two dosages (200 and 400 mg/kg/24 hours) for a total of 20 days, with a frequency of 5 times a week for 4 successive weeks. The total iron content was determined by atomic absorption spectroscopy. Plasma Fe3+ content was determined using a kit. Liver sections were stained by hematoxylin and eosin and Perls stain. A significant decrease in the plasma concentration of iron was observed in mice treated with extracts (P < 0.001). The animals showed a dramatic decrease in plasma Fe3+ content when compared with the control group (P < 0.001). Also, Perls stain improved the smaller amount of deposited iron in the liver of iron-overloaded mice treated with the extract. Liver sections revealed a marked reduction in the extent of necrotic hepatocytes, fibrous tissues, and pseudo-lobules. A high-performance liquid chromatography method was developed to simultaneously separate 7 phenolic acids in extract. Rutin (1.784 ± 0.052 mg g(-1) of extract) and p-coumaric acid (1.026 ± 0.043 mg g(-1) of extract) were detected as the main flavonoid and phenolic acids in extract, respectively. The extract exhibited satisfactory potency to chelate excessive iron in mice, potentially offering new natural alternatives to treat patients with iron overload. More studies are needed to determine which compounds are responsible for these biological activities. PMID:26756297

  4. Influence of chelation strength and bacterial uptake of gallium salicylidene acylhydrazide on biofilm formation and virulence of Pseudomonas aeruginosa.

    PubMed

    Hakobyan, Shoghik; Rzhepishevska, Olena; Björn, Erik; Boily, Jean-François; Ramstedt, Madeleine

    2016-07-01

    Development of antibiotic resistance in bacteria causes major challenges for our society and has prompted a great need for new and alternative treatment methods for infection. One promising approach is to target bacterial virulence using for example salicylidene acylhydrazides (hydrazones). Hydrazones coordinate metal ions such as Fe(III) and Ga(III) through a five-membered and a six-membered chelation ring. One suggested mode of action is via restricting bacterial Fe uptake. Thus, it was hypothesized that the chelating strength of these substances could be used to predict their biological activity on bacterial cells. This was investigated by comparing Ga chelation strength of two hydrazone complexes, as well as bacterial Ga uptake, biofilm formation, and virulence in the form of production and secretion of a toxin (ExoS) by Pseudomonas aeruginosa. Equilibrium constants for deprotonation and Ga(III) binding of the hydrazone N'-(5-chloro-2-hydroxy-3-methylbenzylidene)-2,4-dihydroxybenzhydrazide (ME0329), with anti-virulence effect against P. aeruginosa, were determined and compared to bacterial siderophores and the previously described Ga(III) 2-oxo-2-[N-(2,4,6-trihydroxy-benzylidene)-hydrazino]-acetamide (Ga-ME0163) and Ga-citrate complexes. In comparison with these two complexes, it was shown that the uptake of Ga(III) was higher from the Ga-ME0329 complex. The results further show that the Ga-ME0329 complex reduced ExoS expression and secretion to a higher extent than Ga-citrate, Ga-ME0163 or the non-coordinated hydrazone. However, the effect against biofilm formation by P. aeruginosa, by the ME0329 complex, was similar to Ga-citrate and lower than what has been reported for Ga-ME0163. PMID:27118030

  5. Alternative Schools.

    ERIC Educational Resources Information Center

    Pritchett, Stanley; Kimsey, Steve

    2002-01-01

    Describes the design of the DeKalb Alternative School in Atlanta, Georgia, located in a renovated shopping center. Purchasing commercial land and renovating the existing building saved the school system time and money. (EV)

  6. Gold nanoparticles functionalised with fast water exchanging Gd3+ chelates: linker effects on the relaxivity.

    PubMed

    Ferreira, Miguel F; Gonçalves, Janaina; Mousavi, Bibimaryam; Prata, Maria I M; Rodrigues, Sérgio P J; Calle, Daniel; López-Larrubia, Pilar; Cerdan, Sebastian; Rodrigues, Tiago B; Ferreira, Paula M; Helm, Lothar; Martins, José A; Geraldes, Carlos F G C

    2015-03-01

    The relaxivity displayed by Gd(3+) chelates immobilized onto gold nanoparticles is the result of the complex interplay between the nanoparticle size, the water exchange rate and the chelate structure. In this work we study the effect of the length of ω-thioalkyl linkers, anchoring fast water exchanging Gd(3+) chelates onto gold nanoparticles, on the relaxivity of the immobilized chelates. Gold nanoparticles functionalized with Gd(3+) chelates of mercaptoundecanoyl and lipoyl amide conjugates of the DO3A-N-(α-amino)propionate chelator were prepared and studied as potential CA for MRI. High relaxivities per chelate, of the order of magnitude 28-38 mM(-1) s(-1) (30 MHz, 25 °C), were attained thanks to simultaneous optimization of the rotational correlation time and of the water exchange rate. Fast local rotational motions of the immobilized chelates around connecting linkers (internal flexibility) still limit the attainable relaxivity. The degree of internal flexibility of the immobilized chelates seems not to be correlated with the length of the connecting linkers. Biodistribution and MRI studies in mice suggest that the in vivo behavior of the gold nanoparticles was determined mainly by size. Small nanoparticles (HD = 3.9 nm) undergo fast renal clearance and avoidance of the RES organs while larger nanoparticles (HD = 4.8 nm) undergo predominantly hepatobiliary excretion. High relaxivities, allied to chelate and nanoparticle stability and fast renal clearance in vivo suggest that functionalized gold nanoparticles hold great potential for further investigation as MRI contrast agents. This study contributes to a better understanding of the effect of linker length on the relaxivity of gold nanoparticles functionalized with Gd(3+) complexes. It is a relevant contribution towards "design rules" for nanostructures functionalized with Gd(3+) chelates as Contrast Agents for MRI and multimodal imaging. PMID:25611006

  7. Characteristics of bifunctional acidic endoglucanase (Cel5B) from Gloeophyllum trabeum.

    PubMed

    Kim, Ho Myeong; Lee, Yoon Gyo; Patel, Darshan H; Lee, Kwang Ho; Lee, Dae-Seok; Bae, Hyeun-Jong

    2012-07-01

    The endoglucanase (Cel5B) from the filamentous fungus Gloeophyllum trabeum was cloned and expressed without a signal peptide, and alanine residue 22 converted to glutamine in Pichia pastoris GS115. The DNA sequence of Cel5B had an open reading frame of 1,077 bp, encoding a protein of 359 amino acid residues with a molecular weight of 47 kDa. On the basis of sequence similarity, Cel5B displayed active site residues at Glu-175 and Glu-287. Both residues lost full hydrolytic activity when replaced with alanine through point mutation. The purified recombinant Cel5B showed very high specific activity, about 80- to 1,000-fold and 13- to 70-fold in comparison with other endoglucanases and cellobiohydrolase, on carboxymethylcellulose and filter paper, respectively, at pH 3.5 and 55°C. Cel5B displayed bifunctional characteristics under acidic conditions. The kinetic properties of the enzyme determined using a Lineweaver-Burk plot indicated that Cel5B is a catalytically efficient cellulolytic enzyme. These results suggest that Cel5B has high bifunctional endo- and exoglucanase activity under acidic conditions and is a good candidate for bioconversion of lignocellulose. PMID:22395898

  8. A bifunctional spin label reports the structural topology of phospholamban in magnetically-aligned bicelles.

    PubMed

    McCaffrey, Jesse E; James, Zachary M; Svensson, Bengt; Binder, Benjamin P; Thomas, David D

    2016-01-01

    We have applied a bifunctional spin label and EPR spectroscopy to determine membrane protein structural topology in magnetically-aligned bicelles, using monomeric phospholamban (PLB) as a model system. Bicelles are a powerful tool for studying membrane proteins by NMR and EPR spectroscopies, where magnetic alignment yields topological constraints by resolving the anisotropic spectral properties of nuclear and electron spins. However, EPR bicelle studies are often hindered by the rotational mobility of monofunctional Cys-linked spin labels, which obscures their orientation relative to the protein backbone. The rigid and stereospecific TOAC label provides high orientational sensitivity but must be introduced via solid-phase peptide synthesis, precluding its use in large proteins. Here we show that a bifunctional methanethiosulfonate spin label attaches rigidly and stereospecifically to Cys residues at i and i+4 positions along PLB's transmembrane helix, thus providing orientational resolution similar to that of TOAC, while being applicable to larger membrane proteins for which synthesis is impractical. Computational modeling and comparison with NMR data shows that these EPR experiments provide accurate information about helix tilt relative to the membrane normal, thus establishing a robust method for determining structural topology in large membrane proteins with a substantial advantage in sensitivity over NMR. PMID:26720587

  9. Bifunctional Spin Labeling of Muscle Proteins: Accurate Rotational Dynamics, Orientation, and Distance by EPR.

    PubMed

    Thompson, Andrew R; Binder, Benjamin P; McCaffrey, Jesse E; Svensson, Bengt; Thomas, David D

    2015-01-01

    While EPR allows for the characterization of protein structure and function due to its exquisite sensitivity to spin label dynamics, orientation, and distance, these measurements are often limited in sensitivity due to the use of labels that are attached via flexible monofunctional bonds, incurring additional disorder and nanosecond dynamics. In this chapter, we present methods for using a bifunctional spin label (BSL) to measure muscle protein structure and dynamics. We demonstrate that bifunctional attachment eliminates nanosecond internal rotation of the spin label, thereby allowing the accurate measurement of protein backbone rotational dynamics, including microsecond-to-millisecond motions by saturation transfer EPR. BSL also allows for accurate determination of helix orientation and disorder in mechanically and magnetically aligned systems, due to the label's stereospecific attachment. Similarly, labeling with a pair of BSL greatly enhances the resolution and accuracy of distance measurements measured by double electron-electron resonance (DEER). Finally, when BSL is applied to a protein with high helical content in an assembly with high orientational order (e.g., muscle fiber or membrane), two-probe DEER experiments can be combined with single-probe EPR experiments on an oriented sample in a process we call BEER, which has the potential for ab initio high-resolution structure determination. PMID:26477249

  10. Bifunctional catalysis of the dedeuteration of methoxyacetone-1,1,3,3,3-d

    SciTech Connect

    Hine, J.; Sinha, A.

    1984-06-15

    The dedeuteration of methoxyacetone-1,1,3,3,3-d/sub 5/ is subject to bifunctional catalysis by 3-(dimethylamino)-propylamine (3DP) and (1R,2S,3R,4R)-3-((dimethylamino)methyl)-1,7,7-trimethyl-2-norbornamine (DTN). These catalysts act by using their primary amino groups to transform the ketone to an iminium ion and their tertiary amino groups to transfer a deuteron internally, changing the iminium ion to an enamine. Although analogous monofunctional bases favor exchange at the methyl position relative to exchange at the methylene position by factors of up to 4-fold, bifunctional catalysis by the diamines used favors the methyl group by 11- to 15-fold. Exchange at the methylene group in the presence of DTN was strongly stereoselective. The pro-S deuteron was removed 12-20 times as rapidly as the pro-R deuteron. This is the result of the steric effect of the methoxy substituent. 19 references, 2 figures, 2 tables.

  11. Bifunctional Ag/C3N4.5 composite nanobelts for photocatalysis and antibacterium.

    PubMed

    Lei, Renbo; Jian, Jikang; Zhang, Zhihua; Song, Bo; Wu, Rong

    2016-09-30

    Multiple functions can be achieved in carbon nitride-based composite nanomaterials by tuning their components and structures. Here, we report on a large-scale synthesis of novel bifunctional Ag/C3N4.5 composite nanobelts (CNBs) with efficient photocatalytic and antibacterial activity. The Ag/C3N4.5 CNBs were synthesized in high yield by a two-step route including a homogeneous precipitation process and a subsequent calcination treatment. The structural, morphological, compositional, and spectroscopic characterizations revealed that the Ag/C3N4.5 CNBs are composed of N-deficient melem ultrathin nanobelts and crystalline Ag nanoparticles attached to the surface of the nanobelts with good contact. The band gap of the Ag/C3N4.5 CNBs is determined to be about 3.04 eV. The efficient photocatalytic and antibacterial activities of the composite nanomaterials are verified by testing the degradation of Rhodamine B (RhB) and the inhibition zone to bacterium E. coli. The work provides a facile route to bifunctional carbon nitride-based composites with potential applications in the fields of the environment and biology. PMID:27560165

  12. Bifunctional graphene/γ-Fe₂O₃ hybrid aerogels with double nanocrystalline networks for enzyme immobilization.

    PubMed

    Chen, Liang; Wei, Bin; Zhang, Xuetong; Li, Chun

    2013-07-01

    Highly porous hosting materials with conducting (favorable to electron transfer) and magnetic (favorable to product separation) bicontinuous networks should possess great potentials for immobilization of various enzymes in the field of biocatalytic engineering, but the synthesis of such materials is still a great challenge. Herein, bifunctional graphene/γ-Fe2 O3 hybrid aerogels with quite low density (30-65 mg cm(-3) ), large specific surface area (270-414 m(2) g(-1) ), high electrical conductivity (0.5-5 × 10(-2) S m(-1) ), and superior saturation magnetization (23-54 emu g(-1) ) are fabricated. Single networks of either graphene aerogels or γ-Fe2 O3 aerogels are obtained by etching of the hybrid aerogels with acid solution or calcining of the hybrid aerogels in air, indicative of the double networks of the as-synthesized graphene/γ-Fe2 O3 hybrid aerogels for the first time. The resulting bifunctional aerogels are used to immobilize β-glucuronidase for biocatalytic transformation of glycyrrhizin into glycyrrhetinic acid monoglucuronide or glycyrrhetinic acid, with high biocatalytic activity and definite repeatability. PMID:23423944

  13. Binuclear platinum (II)-terpyridine complexes. A new class of bifunctional DNA-intercalating agent.

    PubMed Central

    McFadyen, W D; Wakelin, L P; Roos, I A; Hillcoat, B L

    1986-01-01

    A series of binuclear DNA-binding ligands was prepared by linking two (2,2':6',2"-terpyridine)platinum(II) moieties via alpha omega-dithiols of the type HS-[CH2]n-SH where n = 4-10. A monomeric analogue was also synthesized. Compounds were characterized by elemental analysis and electronic and n.m.r. spectroscopy. Viscometric measurements with sonicated rod-like DNA fragments and covalently closed circular DNA were performed to investigate the mode of binding of these agents. The ligands with n = 5 and 6 function as bis intercalators and form a single 'base-pair sandwich' in violation of neighbour-exclusion binding. Bifunctional reaction occurs for the ligand with n = 7, whereas the ligands with n = 8 and 10 show a preference for mixed monofunctional/bifunctional binding. The data do not permit definitive assignment of the binding mode of the ligands with n = 4 and 9. All compounds are growth-inhibitory against mouse leukaemia L1210 cells in culture with IC50 values in the range 2-14 microM. PMID:3800959

  14. Magnetically labelled gold and epoxy bi-functional microcarriers for suspension based bioassay technologies.

    PubMed

    Vyas, Kunal N; Palfreyman, Justin J; Love, David M; Mitrelias, Thanos; Barnes, Crispin H W

    2012-12-21

    Microarrays and suspension-based assay technologies have attracted significant interest over the past decade with applications ranging from medical diagnostics to high throughput molecular biology. The throughput and sensitivity of a microarray will always be limited by the array density and slow reaction kinetics. Suspension (or bead) based technologies offer a conceptually different approach, improving detection by substituting a fixed plane of operation with many individually distinguishable microcarriers. In addition to all the features of a suspension based assay technology, our technology offers a rewritable label. This has the potential to be truly revolutionary by opening up the possibility of generating, on chip, extensive labelled molecular libraries. We unveil our latest SU-8 microcarrier design with embedded magnetic films that can be utilized for both magnetic and optical labelling. The novel design significantly simplifies fabrication and additionally incorporates a gold cap to provide a dual surface, bi-functional architecture. The microcarriers are fabricated using deep-ultraviolet lithography techniques and metallic thin film growth by evaporation. The bi-functional properties of the microcarriers will allow us to use each microcarrier as its own positive control thereby increasing the reliability of our technology. Here we present details of the design, fabrication, magnetic detection and functionalization of these microcarriers. PMID:23128508

  15. A bifunctional spin label reports the structural topology of phospholamban in magnetically-aligned bicelles

    NASA Astrophysics Data System (ADS)

    McCaffrey, Jesse E.; James, Zachary M.; Svensson, Bengt; Binder, Benjamin P.; Thomas, David D.

    2016-01-01

    We have applied a bifunctional spin label and EPR spectroscopy to determine membrane protein structural topology in magnetically-aligned bicelles, using monomeric phospholamban (PLB) as a model system. Bicelles are a powerful tool for studying membrane proteins by NMR and EPR spectroscopies, where magnetic alignment yields topological constraints by resolving the anisotropic spectral properties of nuclear and electron spins. However, EPR bicelle studies are often hindered by the rotational mobility of monofunctional Cys-linked spin labels, which obscures their orientation relative to the protein backbone. The rigid and stereospecific TOAC label provides high orientational sensitivity but must be introduced via solid-phase peptide synthesis, precluding its use in large proteins. Here we show that a bifunctional methanethiosulfonate spin label attaches rigidly and stereospecifically to Cys residues at i and i + 4 positions along PLB's transmembrane helix, thus providing orientational resolution similar to that of TOAC, while being applicable to larger membrane proteins for which synthesis is impractical. Computational modeling and comparison with NMR data shows that these EPR experiments provide accurate information about helix tilt relative to the membrane normal, thus establishing a robust method for determining structural topology in large membrane proteins with a substantial advantage in sensitivity over NMR.

  16. Pushing the Theoretical Limit of Li-CFx Batteries: A Tale of Bi-functional Electrolyte

    SciTech Connect

    Rangasamy, Ezhiylmurugan; Li, Juchuan; Sahu, Gayatri; Dudney, Nancy J; Liang, Chengdu

    2014-01-01

    In a typical battery, electrodes deliver capacities less or equal the theoretical maxima of the electrode materials.1 The inert electrolyte functions solely as the ionic conductor without contribution to the cell capacity because of its distinct mono-function in the concept of conventional batteries. Here we demonstrate that the most energy-dense Li-CFx battery2 delivers a capacity exceeding the theoretical maximum of CFx with a solid electrolyte of Li3PS4 (LPS) that has dual functions: as the inert electrolyte at the anode and the active component at the cathode. Such a bi-functional electrolyte reconciles both inert and active characteristics through a synergistic discharge mechanism of CFx and LPS. Li3PS4 is known as an inactive solid electrolyte with a broad electrochemical window over 5 V.3 The synergy at the cathode is through LiF, the discharge product of CFx, which activates the electrochemical discharge of LPS at a close electrochemical potential of CFx. Therefore, the solid-state Li-CFx batteries output 126.6% energy beyond their theoretic limits without compromising the stability of the cell voltage. The extra energy comes from the electrochemical discharge of LPS, the inert electrolyte. This bi-functional electrolyte revolutionizes the concept of conventional batteries and opens a new avenue for the design of batteries with an unprecedentedly high energy density.

  17. Determining the Origin of Half-bandgap-voltage Electroluminescence in Bifunctional Rubrene/C60 Devices

    PubMed Central

    Chen, Qiusong; Jia, Weiyao; Chen, Lixiang; Yuan, De; Zou, Yue; Xiong, Zuhong

    2016-01-01

    Lowering the driving voltage of organic light-emitting diodes (OLEDs) is an important approach to reduce their energy consumption. We have fabricated a series of bifunctional devices (OLEDs and photovoltaics) using rubrene and fullerene (C60) as the active layer, in which the electroluminescence threshold voltage(~1.1 V) was half the value of the bandgap of rubrene. Magneto-electroluminescence (MEL) response of planner heterojunction diodes exhibited a small increase in response to a low magnetic field strength (<20 mT); however, a very large decay was observed at a high magnetic field strength (>20 mT). When a hole-transport layer with a low mobility was included in these devices, the MEL response reversed in shape, and simultaneously, the EL threshold voltage became larger than the bandgap voltage. When bulk heterojunction device was examined, the amplitude of MEL curves presented an anomalous voltage-dependence. Following an analysis of the MEL responses of these devices, we proposed that the EL of half-bandgap-voltage device originated from bimolecular triplet-triplet annihilation in the rubrene film, rather than from singlet excitons that formed via an interface auger recombination. This work provides critical insight into the mechanisms of OLED emission and will help advance the applications of bifunctional devices. PMID:27142285

  18. Construction of a bifunctional enzyme fusion for the combined determination of biogenic amines in foods.

    PubMed

    Lee, Jae-Ick; Jang, Jun-Hyuck; Yu, Mi-Ji; Kim, Young-Wan

    2013-09-25

    Biogenic amines (BAs) are a group of low-molecular-mass organic bases derived from free amino acids. Due to the undesirable effects of BAs on human health, amine oxidase-based detection methods for BAs in foods have been developed. Here, we developed a bifunctional enzyme fusion (MAPO) using a Cu(2+)-containing monoamine oxidase (AMAO2) and a flavin adenine dinucleotide-containing putrescine oxidase (APUO) from Arthrobacter aurescens. It was necessary to activate MAPO with supplementary Cu(2+) ions, leading to a 6- to 12-fold improvement in catalytic efficiency (kcat/KM) for monoamines. The optimal temperatures of Cu(2+)-activated MAPO (cMAPO) for both tyramine and putrescine were 50 °C, and the optimal pH values for tyramine and putrescine were pH 7.0 and pH 8.0, respectively, consistent with those of AMAO2 and APUO, respectively. The cMAPO showed relative specific activities of 100, 99, 32, and 32 for 2-phenylethylamine, tyramine, histamine, and putrescine, respectively. The tyramine-equivalent BA contents of fermented soybean pastes by cMAPO were more than 90% of the total BA determined by HPLC. In conclusion, cMAPO is fully bifunctional toward biogenic monoamines and putrescine, allowing the combined determination of multiple BAs in foods. This colorimetric determination method could be useful for point-of-care testing to screen safety-guaranteed products prior to instrumental analyses. PMID:24001036

  19. Conversion of cellulose into isosorbide over bifunctional ruthenium nanoparticles supported on niobium phosphate.

    PubMed

    Sun, Peng; Long, Xiangdong; He, Hao; Xia, Chungu; Li, Fuwei

    2013-11-01

    Considerable effort has been applied to the development of new processes and catalysts for cellulose conversion to valuable platform chemicals. Isosorbide is among the most interesting products as it can be applied as a monomer and building block for the future replacement of fossil resource-based products. A sustainable method of isosorbide production from cellulose is presented in this work. The strategy relies on a bifunctional Ru catalyst supported on mesoporous niobium phosphate in a H2 atmosphere under pressure without further addition of any soluble acid. Over 50 % yield of isosorbide with almost 100 % cellulose conversion can be obtained in 1 h. The large surface area, pore size, and strong acidity of mesoporous niobium phosphate promote the hydrolysis of cellulose and dehydration of sorbitol; additionally, the appropriate size of the supported Ru nanoparticles avoids unnecessary hydrogenolysis of sorbitol. Under a cellulose/catalyst mass ratio of 43.3, the present bifunctional catalyst could be stably used up to six times, with its mesoporous structure well preserved and without detectable Ru leaching into the reaction solution. PMID:24115374

  20. Bifunctional Ligands for Inhibition of Tight-Binding Protein-Protein Interactions.

    PubMed

    Ivan, Taavi; Enkvist, Erki; Viira, Birgit; Manoharan, Ganesh Babu; Raidaru, Gerda; Pflug, Alexander; Alam, Kazi Asraful; Zaccolo, Manuela; Engh, Richard Alan; Uri, Asko

    2016-08-17

    The acknowledged potential of small-molecule therapeutics targeting disease-related protein-protein interactions (PPIs) has promoted active research in this field. The strategy of using small molecule inhibitors (SMIs) to fight strong (tight-binding) PPIs tends to fall short due to the flat and wide interfaces of PPIs. Here we propose a biligand approach for disruption of strong PPIs. The potential of this approach was realized for disruption of the tight-binding (KD = 100 pM) tetrameric holoenzyme of cAMP-dependent protein kinase (PKA). Supported by X-ray analysis of cocrystals, bifunctional inhibitors (ARC-inhibitors) were constructed that simultaneously associated with both the ATP-pocket and the PPI interface area of the catalytic subunit of PKA (PKAc). Bifunctional inhibitor ARC-1411, possessing a KD value of 3 pM toward PKAc, induced the dissociation of the PKA holoenzyme with a low-nanomolar IC50, whereas the ATP-competitive inhibitor H89 bound to the PKA holoenzyme without disruption of the protein tetramer. PMID:27389935

  1. Highly Efficient and Robust Nickel Phosphides as Bifunctional Electrocatalysts for Overall Water-Splitting.

    PubMed

    Li, Jiayuan; Li, Jing; Zhou, Xuemei; Xia, Zhaoming; Gao, Wei; Ma, Yuanyuan; Qu, Yongquan

    2016-05-01

    To search for the efficient non-noble metal based and/or earth-abundant electrocatalysts for overall water-splitting is critical to promote the clean-energy technologies for hydrogen economy. Herein, we report nickel phosphide (NixPy) catalysts with the controllable phases as the efficient bifunctional catalysts for water electrolysis. The phases of NixPy were determined by the temperatures of the solid-phase reaction between the ultrathin Ni(OH)2 plates and NaH2PO2·H2O. The NixPy with the richest Ni5P4 phase synthesized at 325 °C (NixPy-325) delivered efficient and robust catalytic performance for hydrogen evolution reaction (HER) in the electrolytes with a wide pH range. The NixPy-325 catalysts also exhibited a remarkable performance for oxygen evolution reaction (OER) in a strong alkaline electrolyte (1.0 M KOH) due to the formation of surface NiOOH species. Furthermore, the bifunctional NixPy-325 catalysts enabled a highly performed overall water-splitting with ∼100% Faradaic efficiency in 1.0 M KOH electrolyte, in which a low applied external potential of 1.57 V led to a stabilized catalytic current density of 10 mA/cm(2) over 60 h. PMID:27064172

  2. Active-site remodelling in the bifunctional fructose-1,6-bisphosphate aldolase/phosphatase.

    PubMed

    Du, Juan; Say, Rafael F; Lü, Wei; Fuchs, Georg; Einsle, Oliver

    2011-10-27

    Fructose-1,6-bisphosphate (FBP) aldolase/phosphatase is a bifunctional, thermostable enzyme that catalyses two subsequent steps in gluconeogenesis in most archaea and in deeply branching bacterial lineages. It mediates the aldol condensation of heat-labile dihydroxyacetone phosphate (DHAP) and glyceraldehyde-3-phosphate (GAP) to FBP, as well as the subsequent, irreversible hydrolysis of the product to yield the stable fructose-6-phosphate (F6P) and inorganic phosphate; no reaction intermediates are released. Here we present a series of structural snapshots of the reaction that reveal a substantial remodelling of the active site through the movement of loop regions that create different catalytic functionalities at the same location. We have solved the three-dimensional structures of FBP aldolase/phosphatase from thermophilic Thermoproteus neutrophilus in a ligand-free state as well as in complex with the substrates DHAP and FBP and the product F6P to resolutions up to 1.3 Å. In conjunction with mutagenesis data, this pinpoints the residues required for the two reaction steps and shows that the sequential binding of additional Mg(2+) cations reversibly facilitates the reaction. FBP aldolase/phosphatase is an ancestral gluconeogenic enzyme optimized for high ambient temperatures, and our work resolves how consecutive structural rearrangements reorganize the catalytic centre of the protein to carry out two canonical reactions in a very non-canonical type of bifunctionality. PMID:21983965

  3. Structural basis for the bifunctionality of fructose-1,6-bisphosphate aldolase/phosphatase.

    PubMed

    Fushinobu, Shinya; Nishimasu, Hiroshi; Hattori, Daiki; Song, Hyun-Jin; Wakagi, Takayoshi

    2011-10-27

    Enzymes catalyse specific reactions and are essential for maintaining life. Although some are referred to as being bifunctional, they consist of either two distinct catalytic domains or a single domain that displays promiscuous substrate specificity. Thus, one enzyme active site is generally responsible for one biochemical reaction. In contrast to this conventional concept, archaeal fructose-1,6-bisphosphate (FBP) aldolase/phosphatase (FBPA/P) consists of a single catalytic domain, but catalyses two chemically distinct reactions of gluconeogenesis: (1) the reversible aldol condensation of dihydroxyacetone phosphate (DHAP) and glyceraldehyde-3-phosphate (GA3P) to FBP; (2) the dephosphorylation of FBP to fructose-6-phosphate (F6P). Thus, FBPA/P is fundamentally different from ordinary enzymes whose active sites are responsible for a specific reaction. However, the molecular mechanism by which FBPA/P achieves its unusual bifunctionality remains unknown. Here we report the crystal structure of FBPA/P at 1.5-Å resolution in the aldolase form, where a critical lysine residue forms a Schiff base with DHAP. A structural comparison of the aldolase form with a previously determined phosphatase form revealed a dramatic conformational change in the active site, demonstrating that FBPA/P metamorphoses its active-site architecture to exhibit dual activities. Thus, our findings expand the conventional concept that one enzyme catalyses one biochemical reaction. PMID:21983966

  4. Determining the Origin of Half-bandgap-voltage Electroluminescence in Bifunctional Rubrene/C60 Devices

    NASA Astrophysics Data System (ADS)

    Chen, Qiusong; Jia, Weiyao; Chen, Lixiang; Yuan, De; Zou, Yue; Xiong, Zuhong

    2016-05-01

    Lowering the driving voltage of organic light-emitting diodes (OLEDs) is an important approach to reduce their energy consumption. We have fabricated a series of bifunctional devices (OLEDs and photovoltaics) using rubrene and fullerene (C60) as the active layer, in which the electroluminescence threshold voltage(~1.1 V) was half the value of the bandgap of rubrene. Magneto-electroluminescence (MEL) response of planner heterojunction diodes exhibited a small increase in response to a low magnetic field strength (<20 mT) however, a very large decay was observed at a high magnetic field strength (>20 mT). When a hole-transport layer with a low mobility was included in these devices, the MEL response reversed in shape, and simultaneously, the EL threshold voltage became larger than the bandgap voltage. When bulk heterojunction device was examined, the amplitude of MEL curves presented an anomalous voltage-dependence. Following an analysis of the MEL responses of these devices, we proposed that the EL of half-bandgap-voltage device originated from bimolecular triplet-triplet annihilation in the rubrene film, rather than from singlet excitons that formed via an interface auger recombination. This work provides critical insight into the mechanisms of OLED emission and will help advance the applications of bifunctional devices.

  5. Large-scale Generation of Patterned Bubble Arrays on Printed Bi-functional Boiling Surfaces

    NASA Astrophysics Data System (ADS)

    Choi, Chang-Ho; David, Michele; Gao, Zhongwei; Chang, Alvin; Allen, Marshall; Wang, Hailei; Chang, Chih-Hung

    2016-04-01

    Bubble nucleation control, growth and departure dynamics is important in understanding boiling phenomena and enhancing nucleate boiling heat transfer performance. We report a novel bi-functional heterogeneous surface structure that is capable of tuning bubble nucleation, growth and departure dynamics. For the fabrication of the surface, hydrophobic polymer dot arrays are first printed on a substrate, followed by hydrophilic ZnO nanostructure deposition via microreactor-assisted nanomaterial deposition (MAND) processing. Wettability contrast between the hydrophobic polymer dot arrays and aqueous ZnO solution allows for the fabrication of heterogeneous surfaces with distinct wettability regions. Heterogeneous surfaces with various configurations were fabricated and their bubble dynamics were examined at elevated heat flux, revealing various nucleate boiling phenomena. In particular, aligned and patterned bubbles with a tunable departure frequency and diameter were demonstrated in a boiling experiment for the first time. Taking advantage of our fabrication method, a 6 inch wafer size heterogeneous surface was prepared. Pool boiling experiments were also performed to demonstrate a heat flux enhancement up to 3X at the same surface superheat using bi-functional surfaces, compared to a bare stainless steel surface.

  6. Large-scale Generation of Patterned Bubble Arrays on Printed Bi-functional Boiling Surfaces.

    PubMed

    Choi, Chang-Ho; David, Michele; Gao, Zhongwei; Chang, Alvin; Allen, Marshall; Wang, Hailei; Chang, Chih-hung

    2016-01-01

    Bubble nucleation control, growth and departure dynamics is important in understanding boiling phenomena and enhancing nucleate boiling heat transfer performance. We report a novel bi-functional heterogeneous surface structure that is capable of tuning bubble nucleation, growth and departure dynamics. For the fabrication of the surface, hydrophobic polymer dot arrays are first printed on a substrate, followed by hydrophilic ZnO nanostructure deposition via microreactor-assisted nanomaterial deposition (MAND) processing. Wettability contrast between the hydrophobic polymer dot arrays and aqueous ZnO solution allows for the fabrication of heterogeneous surfaces with distinct wettability regions. Heterogeneous surfaces with various configurations were fabricated and their bubble dynamics were examined at elevated heat flux, revealing various nucleate boiling phenomena. In particular, aligned and patterned bubbles with a tunable departure frequency and diameter were demonstrated in a boiling experiment for the first time. Taking advantage of our fabrication method, a 6 inch wafer size heterogeneous surface was prepared. Pool boiling experiments were also performed to demonstrate a heat flux enhancement up to 3X at the same surface superheat using bi-functional surfaces, compared to a bare stainless steel surface. PMID:27034255

  7. MULT1E/mIL-12: a novel bifunctional protein for natural killer cell activation.

    PubMed

    Tietje, A; Li, J; Yu, X; Wei, Y

    2014-05-01

    Natural killer (NK) cells have the potential to be effective killers of tumor cells. They are governed by inhibitory and activating receptors like NKG2D, whose ligands are normally upregulated in cells that are stressed, like cancer cells. Advanced cancer cells, however, have ways to reduce these ligands' expression, leaving them less detectable by NK cells. Along with these receptors, NK cells also require activating cytokines, like interleukin 12 (IL-12). The goal of this study is to develop a novel bi-functional fusion protein for enhanced NK cell activation. The proposed protein combines the extracellular domain of the NKG2D ligand Mouse UL-16-binding protein-like transcript 1 (MULT1E) and mouse IL-12 (mIL-12). It is hypothesized that when expressed by tumor cells, the protein will activate NK and other killer cells using the NKG2D receptor, and deliver mIL-12 to the NK cells where it can interact with the IL-12R and enhance cytotoxicity. The fusion protein, when expressed by engineered tumor cells, indeed activated NK cells in vitro as assayed by increased production of interferon-γ and cytotoxicity and significantly reduced tumor growth in vivo. Although the study is preliminary, the data suggest that the MULT1E/mIL-12 bi-functional fusion protein is an effective activator of NK cells for cancer treatment. PMID:24572784

  8. Subnanometer Cobalt-Hydroxide-Anchored N-Doped Carbon Nanotube Forest for Bifunctional Oxygen Catalyst.

    PubMed

    Kim, Ji Eun; Lim, Joonwon; Lee, Gil Yong; Choi, Sun Hee; Maiti, Uday Narayan; Lee, Won Jun; Lee, Ho Jin; Kim, Sang Ouk

    2016-01-27

    Electrochemical oxygen redox reactions are the crucial elements for energy conversion and storage including fuel cells and metal air batteries. Despite tremendous research efforts, developing high-efficient, low-cost, and durable bifunctional oxygen catalysts remains a major challenge. We report a new class of hybrid material consisting of subnanometer thick amorphous cobalt hydroxide anchored on NCNT as a durable ORR/OER bifunctional catalyst. Although amorphous cobalt species-based catalysts are known as good OER catalysts, hybridizing with NCNT successfully enhanced ORR activity by promoting a 4e reduction pathway. Abundant charge carriers in amorphous cobalt hydroxide are found to trigger the superior OER activity with high current density and low Tafel slope as low as 36 mV/decade. A remarkably high OER turnover frequency (TOF) of 2.3 s(-1) at an overpotential of 300 mV was obtained, one of the highest values reported so far. Moreover, the catalytic activity was maintained over 120 h of cycling. The unique subnanometer scale morphology of amorphous hydroxide cobalt species along with intimate cobalt species-NCNT interaction minimizes the deactivation of catalyst during prolonged repeated cycles. PMID:26766495

  9. Determining the Origin of Half-bandgap-voltage Electroluminescence in Bifunctional Rubrene/C60 Devices.

    PubMed

    Chen, Qiusong; Jia, Weiyao; Chen, Lixiang; Yuan, De; Zou, Yue; Xiong, Zuhong

    2016-01-01

    Lowering the driving voltage of organic light-emitting diodes (OLEDs) is an important approach to reduce their energy consumption. We have fabricated a series of bifunctional devices (OLEDs and photovoltaics) using rubrene and fullerene (C60) as the active layer, in which the electroluminescence threshold voltage(~1.1 V) was half the value of the bandgap of rubrene. Magneto-electroluminescence (MEL) response of planner heterojunction diodes exhibited a small increase in response to a low magnetic field strength (<20 mT); however, a very large decay was observed at a high magnetic field strength (>20 mT). When a hole-transport layer with a low mobility was included in these devices, the MEL response reversed in shape, and simultaneously, the EL threshold voltage became larger than the bandgap voltage. When bulk heterojunction device was examined, the amplitude of MEL curves presented an anomalous voltage-dependence. Following an analysis of the MEL responses of these devices, we proposed that the EL of half-bandgap-voltage device originated from bimolecular triplet-triplet annihilation in the rubrene film, rather than from singlet excitons that formed via an interface auger recombination. This work provides critical insight into the mechanisms of OLED emission and will help advance the applications of bifunctional devices. PMID:27142285

  10. Large-scale Generation of Patterned Bubble Arrays on Printed Bi-functional Boiling Surfaces

    PubMed Central

    Choi, Chang-Ho; David, Michele; Gao, Zhongwei; Chang, Alvin; Allen, Marshall; Wang, Hailei; Chang, Chih-hung

    2016-01-01

    Bubble nucleation control, growth and departure dynamics is important in understanding boiling phenomena and enhancing nucleate boiling heat transfer performance. We report a novel bi-functional heterogeneous surface structure that is capable of tuning bubble nucleation, growth and departure dynamics. For the fabrication of the surface, hydrophobic polymer dot arrays are first printed on a substrate, followed by hydrophilic ZnO nanostructure deposition via microreactor-assisted nanomaterial deposition (MAND) processing. Wettability contrast between the hydrophobic polymer dot arrays and aqueous ZnO solution allows for the fabrication of heterogeneous surfaces with distinct wettability regions. Heterogeneous surfaces with various configurations were fabricated and their bubble dynamics were examined at elevated heat flux, revealing various nucleate boiling phenomena. In particular, aligned and patterned bubbles with a tunable departure frequency and diameter were demonstrated in a boiling experiment for the first time. Taking advantage of our fabrication method, a 6 inch wafer size heterogeneous surface was prepared. Pool boiling experiments were also performed to demonstrate a heat flux enhancement up to 3X at the same surface superheat using bi-functional surfaces, compared to a bare stainless steel surface. PMID:27034255

  11. A Bifunctional Enzyme That Has Both Monoacylglycerol Acyltransferase and Acyl Hydrolase Activities1[W][OA

    PubMed Central

    Vijayaraj, Panneerselvam; Jashal, Charnitkaur B.; Vijayakumar, Anitha; Rani, Sapa Hima; Venkata Rao, D.K.; Rajasekharan, Ram

    2012-01-01

    Monoacylglycerol acyltransferase (MGAT) catalyzes the synthesis of diacylglycerol, the precursor of triacylglycerol biosynthesis and an important signaling molecule. Here, we describe the isolation and characterization of the peanut (Arachis hypogaea) MGAT gene. The soluble enzyme utilizes invariant histidine-62 and aspartate-67 residues of the acyltransferase motif for its MGAT activity. A sequence analysis revealed the presence of a hydrolase (GXSXG) motif, and enzyme assays revealed the presence of monoacylglycerol (MAG) and lysophosphatidylcholine (LPC) hydrolytic activities, indicating the bifunctional nature of the enzyme. The overexpression of the MGAT gene in yeast (Saccharomyces cerevisiae) caused an increase in triacylglycerol accumulation. Similar to the peanut MGAT, the Arabidopsis (Arabidopsis thaliana) homolog (At1g52760) also exhibited both acyltransferase and hydrolase activities. Interestingly, the yeast homolog lacks the conserved HX4D motif, and it is deficient in the acyltransferase function but exhibits MAG and LPC hydrolase activities. This study demonstrates the presence of a soluble MGAT/hydrolase in plants. The predicted three-dimensional homology modeling and substrate docking suggested the presence of two separate substrate (MAG and LPC)-binding sites in a single polypeptide. Our study describes a soluble bifunctional enzyme that has both MGAT and hydrolase functions. PMID:22915575

  12. Carbon Nitrogen Nanotubes as Efficient Bifunctional Electrocatalysts for Oxygen Reduction and Evolution Reactions.

    PubMed

    Yadav, Ram Manohar; Wu, Jingjie; Kochandra, Raji; Ma, Lulu; Tiwary, Chandra Sekhar; Ge, Liehui; Ye, Gonglan; Vajtai, Robert; Lou, Jun; Ajayan, Pulickel M

    2015-06-10

    Oxygen reduction and evolution reactions are essential for broad range of renewable energy technologies such as fuel cells, metal-air batteries and hydrogen production through water splitting, therefore, tremendous effort has been taken to develop excellent catalysts for these reactions. However, the development of cost-effective and efficient bifunctional catalysts for both reactions still remained a grand challenge. Herein, we report the electrocatalytic investigations of bamboo-shaped carbon nitrogen nanotubes (CNNTs) having different diameter distribution synthesized by liquid chemical vapor deposition technique using different nitrogen containing precursors. These CNNTs are found to be efficient bifunctional electrocatalyst for oxygen reduction and evolution reactions. The electrocatalytic activity strongly depends on the nanotube diameter as well as nitrogen functionality type. The higher diameter CNNTs are more favorable for these reactions. The increase in nanotube diameter itself enhances the catalytic activity by lowering the oxygen adsorption energy, better conductivity, and further facilitates the reaction by increasing the percentage of catalytically active nitrogen moieties in CNNTs. PMID:25970133

  13. Long-Term Persistence of Bi-functionality Contributes to the Robustness of Microbial Life through Exaptation

    PubMed Central

    Sterner, Reinhard; Merkl, Rainer

    2016-01-01

    Modern enzymes are highly optimized biocatalysts that process their substrates with extreme efficiency. Many enzymes catalyze more than one reaction; however, the persistence of such ambiguities, their consequences and evolutionary causes are largely unknown. As a paradigmatic case, we study the history of bi-functionality for a time span of approximately two billion years for the sugar isomerase HisA from histidine biosynthesis. To look back in time, we computationally reconstructed and experimentally characterized three HisA predecessors. We show that these ancient enzymes catalyze not only the HisA reaction but also the isomerization of a similar substrate, which is commonly processed by the isomerase TrpF in tryptophan biosynthesis. Moreover, we found that three modern-day HisA enzymes from Proteobacteria and Thermotogae also possess low TrpF activity. We conclude that this bi-functionality was conserved for at least two billion years, most likely without any evolutionary pressure. Although not actively selected for, this trait can become advantageous in the case of a gene loss. Such exaptation is exemplified by the Actinobacteria that have lost the trpF gene but possess the bi-functional HisA homolog PriA, which adopts the roles of both HisA and TrpF. Our findings demonstrate that bi-functionality can perpetuate in the absence of selection for very long time-spans. PMID:26824644

  14. Facile synthesis of 4-vinyl- and 4-fluorovinyl-1,2,3-triazoles via bifunctional “click-olefination” reagents

    PubMed Central

    Kumar, Rakesh; Pradhan, Padmanava; Zajc, Barbara

    2011-01-01

    Modular synthesis of vinyl and fluorovinyl triazoles can be achieved from bifunctional propargyl and fluoropropargyl sulfones by Cu-catalyzed azide-alkyne ligation and Julia-Kocienski olefination. Competitive click reactions of the protio and fluoropropargyl sulfones show higher reactivity of the latter, and a preliminary DFT analysis was performed. PMID:21336351

  15. Scalable Fabrication of Nanoporous Carbon Fiber Films as Bifunctional Catalytic Electrodes for Flexible Zn-Air Batteries.

    PubMed

    Liu, Qin; Wang, Yaobing; Dai, Liming; Yao, Jiannian

    2016-04-01

    A flexible nanoporous carbon-fiber film for wearable electronics is prepared by a facile and scalable method through pyrolysis of electrospun polyimide. It exhibits excellent bifunctional electrocatalytic activities for oxygen reduction and oxygen evolution. Flexible rechargeable zinc-air batteries based on the carbon-fiber film show high round-trip efficiency and mechanical stability. PMID:26914270

  16. Bifunctional-Phosphine-Catalyzed Sequential Annulations of Allenoates and Ketimines: Construction of Functionalized Poly-heterocycle Rings.

    PubMed

    Li, Erqing; Jin, Hongxing; Jia, Penghao; Dong, Xuelin; Huang, You

    2016-09-12

    A highly stereoselective sequential annulation reaction between γ-substituted allenoates and ketimines was reported. By using bifunctional N-acyl aminophosphine catalysts, poly-heterocycle rings were obtained with high stereocontrol in good to excellent yields. The desired products have four contiguous stereogenic centers (one quaternary and three tertiary carbon centers), and only one isomer was obtained in all reactions. PMID:27529614

  17. Removal of heavy metals from a chelated solution with electrolytic foam separation

    SciTech Connect

    Min-Her Leu; Juu-En Chang; Ming-Sheng Ko

    1994-11-01

    An experimental study was conducted on the chelation and electrolytic foam separation of trace amounts of copper, nickel, zinc, and cadmium from a synthetic chelated metal wastewater. Sodium ethylenediaminetetraacetate (EDTA), citrate, sodium diethyldithiocarbamate (NDDTC), and potassium ethyl xanthate (KEtX) were used with sodium dodecylsulfate (NaDS) as a foam-producing agent. Experimental results from an electrolytic foam separation process showed that chelating agents NDDTC and KEtX, due to their higher chelating strength and hydrophobic property, can efficiently separate Cu and Ni from chelated compounds (Cu, Ni/EDTA, and Cu, Ni/citrate). In a Cu-EDTA-NDDTC system with a chelating agent/metal ratio of 4, the residual Cu(II) concentration is 0.7 mg/L. The effects of chelating agent types and different chelating agents concentrations on the removal of metal ions were studied. The effect of NaDS dosage on flotation behavior and the efficiency of metal removal were also investigated.

  18. Effects of chelating agents on protein, oil, fatty acid amd seed mineral concentrations in soybean

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Soybean seed is a major source of protein and oil for human diet. Since not much information is available on the effects of chelating agents on soybean seed composition constituents, the current study aimed to investigate the effects of various chelating agents on soybean [(Glycine max (L.) Merr.)] ...

  19. Inhibitory activity of chelating agent against bacteria associated with poultry processing

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  20. 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... for Use Only as Components of Paper and Paperboard § 176.150 Chelating agents used in the manufacture... the manufacture of paper and paperboard, in accordance with the conditions prescribed in paragraphs...

  1. 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... 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...

  2. 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... 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...

  3. 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... 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...

  4. Covalent attachment of metal chelates to proteins:the stability in vivo and in vitro of the conjugate of albumin with a chelate of 111indium.

    PubMed Central

    Meares, C F; Goodwin, D A; Leung, C S; Girgis, A Y; Silvester, D J; Nunn, A D; Lavender, P J

    1976-01-01

    Human serum albumin has been conjugated to 1-(p-bnezenediazonium)-(ethylenedinitrilo)tetraacetic acid, a powerful chelating agent, and radioactive 111indium ions have been added specifically to the chelating groups. The product, with a specific radioactivity of about 1 mCi/mg of protein, was employed as a radiotracer in scintillation scanning studies with human volunteers. Results show that 48 hr after injection, practically all of the label remains attached to albumin. This is confirmed by electrophoresis of serum proteins; 7 days after injection, 85% of the radioactivity in the serum is still in the albumin fraction. These observations agree with in vitro studies of the labeled albumin in human serum, where loss of the metal ion from the chelating group to the protein transferrin amounts to less than 3% after 1 week and less than 5% after 2 weeks. Measurements of the distribution of label in mice up to 23 days after injection suggest that metabolism of the labeled protein does not lead to binding of indium ions by transferrin. The binding of indium and other metal ions by transferrin has previously posed a major impediment to the use of metal chelates for in vivo diagnostic procedures. Demonstration of the kinetic inertness of the chelate in these experiments suggests the use of related chelates as physical probes of biological systems. Images PMID:825856

  5. Differential response of Arabidopsis leaves and roots to cadmium: glutathione-related chelating capacity vs antioxidant capacity.

    PubMed

    Jozefczak, Marijke; Keunen, Els; Schat, Henk; Bliek, Mattijs; Hernández, Luis E; Carleer, Robert; Remans, Tony; Bohler, Sacha; Vangronsveld, Jaco; Cuypers, Ann

    2014-10-01

    This study aims to uncover the spatiotemporal involvement of glutathione (GSH) in two major mechanisms of cadmium (Cd)-induced detoxification (i.e. chelation and antioxidative defence). A kinetic study was conducted on hydroponically grown Arabidopsis thaliana (L. Heyhn) to gain insight into the early events after exposure to Cd. Cadmium detoxification was investigated at different levels, including gene transcripts, enzyme activities and metabolite content. Data indicate a time-dependent response both within roots and between plant organs. Early on in roots, GSH was preferentially allocated to phytochelatin (PC) synthesis destined for Cd chelation. This led to decreased GSH levels, without alternative pathways activated to complement GSH's antioxidative functions. After one day however, multiple antioxidative pathways increased including superoxide dismutase (SOD), ascorbate (AsA) and catalase (CAT) to ensure efficient neutralization of Cd-induced reactive oxygen species (ROS). As a consequence of Cd retention and detoxification in roots, a delayed response occurred in leaves. Together with high leaf thiol contents and possibly signalling responses from the roots, the leaves were protected, allowing them sufficient time to activate their defence mechanisms. PMID:25049163

  6. Development of a new radiolabel (lead-203) and new chelating agents for labeling monoclonal anntibodies for imaging

    SciTech Connect

    Srivastava, S.C.; Mease, R.C.; Meinken, G.E.; Mausner, L.F.; Steplewski, Z.

    1988-01-01

    High liver uptake and slow body clearance presently limit the usefulness of /sup 111/In labeled antibodies for tumor imaging. We have investigated /sup 203/Pb as an alternate and better antibody label. The DTPA and cyclohexyl EDTA (CDTA) conjugates of an anticolon carcinoma antibody, 17-1A were labeled (bicyclic anhydride method) with /sup 203/Pb and /sup 111/In with 60 and 90% labeling yields, respectively. The biodistribution of /sup 203/Pb-17-1A conjugates was compared with the corresponding /sup 111/In-labeled preparations and with /sup 203/Pb-DTPA, /sup 203/Pb-nitrate and nonrelevant antibody controls in normal and human tumor (SW948) xenografted nude mice at 24, and 96 hr. Lead-203-labeled CDTA and DTPA antibody conjugates gave similar in vivo distributions. Even though the lead bound to these chelate-antibody conjugates was more labile in serum and in vivo, compared to indium, it cleared much faster from the liver and the whole body. A new series of chelating agents based on the incorporation of a trans-1,2- diaminocyclohexane moiety into the carbon backbone of polyaminocarboxylates is being synthesized. These are expected to provide stronger complexing ability for lead and produce greater in vivo stability. These ligands are also expected to be superior to EDTA and DTPA for labeling antibodies with other radiometals, including indium. 32 refs., 3 tabs.

  7. Brazilian Thalassemia Association protocol for iron chelation therapy in patients under regular transfusion

    PubMed Central

    Veríssimo, Monica Pinheiro de Almeida; Loggetto, Sandra Regina; Fabron Junior, Antonio; Baldanzi, Giorgio Roberto; Hamerschlak, Nelson; Fernandes, Juliano Lara; Araujo, Aderson da Silva; Lobo, Clarisse Lopes de Castro; Fertrin, Kleber Yotsumoto; Berdoukas, Vasilios Antonios; Galanello, Renzo

    2013-01-01

    In the absence of an iron chelating agent, patients with beta-thalassemia on regular transfusions present complications of transfusion-related iron overload. Without iron chelation therapy, heart disease is the major cause of death; however, hepatic and endocrine complications also occur. Currently there are three iron chelating agents available for continuous use in patients with thalassemia on regular transfusions (desferrioxamine, deferiprone, and deferasirox) providing good results in reducing cardiac, hepatic and endocrine toxicity. These practice guidelines, prepared by the Scientific Committee of Associação Brasileira de Thalassemia (ABRASTA), presents a review of the literature regarding iron overload assessment (by imaging and laboratory exams) and the role of T2* magnetic resonance imaging (MRI) to control iron overload and iron chelation therapy, with evidence-based recommendations for each clinical situation. Based on this review, the authors propose an iron chelation protocol for patients with thalassemia under regular transfusions. PMID:24478610

  8. The Design and Synthesis of Highly Branched and Spherically Symmetric Fluorinated Macrocyclic Chelators

    PubMed Central

    Jiang, Zhong-Xing; Yu, Y. Bruce

    2010-01-01

    Two novel, highly fluorinated macrocyclic chelators with highly branched and spherically symmetric fluorocarbon moieties have been designed and efficiently synthesized. This is achieved by conjugating a spherically symmetric fluorocarbon moiety to the macrocyclic chelator DOTA, with or without a flexible oligo-oxyethylene linker between these two parts. As a result of the spherical symmetry, all 27 fluorine atoms in each fluorinated chelator give a sharp singlet 19F NMR signal. The hydrophilicity and the 19F relaxation behavior of fluorinated chelators can be modulated by the insertion of a flexible linker between the fluorocarbon moiety and the macrocyclic linker. These chelators serve as prototypes for 1H-19F dual-nuclei magnetic resonance imaging agents. PMID:20585414

  9. Synthesis and characterization of dihexyldithiocarbamate as a chelating agent in extraction of gold(III)

    NASA Astrophysics Data System (ADS)

    Fatimah, Soja Siti; Bahti, Husein H.; Hastiawan, Iwan; Permanasari, Anna

    2016-02-01

    The use of dialkyldithiocarbamates as chelating agents of transition metals have been developing for decades. Many chelating agents have been synthesized and used in the extraction of the metals. Studies on particular aspects of extraction of the metals, such as the effect of increasing hydrophobicity of chelating agents on the effectiveness of the extraction, have been done. However, despite the many studies on the synthesis and applications of this type of chelating agents, interests in the aspect of molecular structure of the synthesized ligands and of their complexes, have been limited. This study aimed at synthesizing and characterizing dihexylthiocarbamate, and using the ligand for the extraction of gold III). Characterization of the ligand and of its metal complex were done by using elemental analysis, DTG, and spectroscopic methods to include NMR, (1H, and 13C), FTIR, and MS-ESI. Data on the synthesis, characterization, and the application of the ligand as a chelating agent are presented.

  10. 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.

  11. Role of pH in metal adsorption from aqueous solutions containing chelating agents on chitosan

    SciTech Connect

    Wu, F.C.; Tseng, R.L.; Juang, R.S.

    1999-01-01

    The role of pH in adsorption of Cu(II) from aqueous solutions containing chelating agents on chitosan was emphasized. Four chelating agents including ethylenediaminetetraacetic acid (EDTA), citric acid, tartaric acid, and sodium gluconate were used. It was shown that the adsorption ability of Cu(II) on chitosan from its chelated solutions varied significantly with pH variations. The competition between coordination of Cu(II) with unprotonated chitosan and electrostatic interaction of the Cu(II) chelates with protonated chitosan took place because of the change in solution pH during adsorption. The maximum adsorption capacity was obtained within each optimal pH range determined from titration curves of the chelated solutions. Coordination of Cu(II) with the unprotonated chitosan was found to dominate at pH below such an optimal pH value.

  12. Bifunctional μ/δ Opioid Peptides: Variation of the Type and Length of the Linker Connecting the Two Components

    PubMed Central

    Ding, Jinguo; Lemieux, Carole; Chung, Nga N.; Schiller, Peter W.

    2011-01-01

    On the basis of evidence that opioid compounds with a mixed μ agonist/δ antagonist profile may produce an antinociceptive effect with low propensity to induce side effects, bifunctional opioid peptides containing the μ agonist [Dmt1]DALDA (H-Dmt-D-Arg-Phe-Lys-NH2; Dmt = 2',6’-dimethyltyrosine) connected tail-to-tail via various α,ω-diaminoalkyl- or diaminocyclohexane linkers to the δ antagonists TICP[Ψ] (H-Tyr-TicΨ[CH2-NH]Cha-Phe-OH; Cha = cyclohexylalanine, Tic = 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid), H-Dmt-Tic-OH or H-Bcp-Tic-OH (Bcp = 4'-[N-((4'-phenyl)phenethyl)carboxamido]phenylalanine) were synthesized and pharmacologically characterized in vitro. Bifunctional [Dmt1]DALDA→NH-(CH2)n-NH←TICP[Ψ] compounds (n = 0–12) showed decreasing μ and δ receptor binding affinities with increasing linker length. As expected, several of the bifunctional peptides were μ agonist/δ antagonists with low nanomolar μ and δ receptor binding affinities. However, compounds with unexpected opioid activity profiles, including a μ partial agonist/δ partial agonist, μ antagonist/δ antagonists and μ agonist/δ agonists, were also identified. These results indicate that the binding affinities and intrinsic efficacies of these bifunctional compounds at both receptors depend on the length and type of the linker connecting the μ and δ components. An important recommendation emerging from this study is that the in vitro activity profiles of bifunctional compounds containing an agonist and an antagonist component connected via a linker need to be determined prior to their pharmacological evaluation in vivo. PMID:22070627

  13. Control of cytoplasmic calcium with photolabile tetracarboxylate 2-nitrobenzhydrol chelators.

    PubMed Central

    Tsien, R Y; Zucker, R S

    1986-01-01

    This paper introduces nitr-2, a new Ca2+ chelator designed to release Ca2+ upon illumination with near UV (300-400 nm) light. Before illumination nitr-2 has Ca2+ dissociation constants of 160 and 630 nM in 0.1 and 0.3 M ionic strength respectively; after photoconversion to a nitrosobenzophenone the values shift to 7 and 18 microM, high enough to liberate substantial amounts of Ca2+ under intracellular conditions. The speed of release is limited by a dark reaction with rate constant 5 s-1. Aplysia central neurons injected with nitr-2 and exposed to UV light exhibit two separate Ca2+-dependent membrane currents: one carried by potassium ions and one a nonspecific cation current. A quantitative estimate of the spatial distribution of intracellular [Ca2+] changes in large cells filled with a high concentration of nitr-2 and exposed to an intense UV flash is offered. PMID:3098316

  14. On hafnium chelation by EDTA and DTPA for TDPAC experiments

    NASA Astrophysics Data System (ADS)

    Chain, Cecilia Y.; Pasquevich, A. F.

    2010-04-01

    Polyaminocarboxilate chelating agents, like ethylenediaminetetraacetic acid (EDTA) and diethylenetriaminepentaacetic acid (DTPA), form stable complexes with many heavy metals ions and are of spread use in the industrial and biomedical field. In this paper, Time Differential Perturbed Angular Correlations (TDPAC) spectroscopy has been used to investigate the formation of Hf-complexes prepared from 181Hf-HfF4 and polyaminocarboxylic acids, by taking into account the possible formation of inorganic compounds. The obtained wet precipitates were measured at room temperature. Different behaviors were observed depending on the ratio fluorine/sodium atoms present in the sample. The obtaining of sodium heptafluorohafnate Na3HfF7 was verified when the ratio F/Na was approximately 1.5 and tridecafluorodihafnate Na5Hf2F13 appeared for relations between 3 and 4. No evidence of hafnium complexation by the polyaminocarboxilic acids was observed.

  15. Chelation-Induced Polymer Structural Hierarchy/Complexity in Water.

    PubMed

    Han, Jie; Zhou, Kaiyi; Zhu, Xuechao; Yu, Qiuping; Ding, Yi; Lu, Xinhua; Cai, Yuanli

    2016-08-01

    Understanding nanoscale structural hierarchy/complexity of hydrophilic flexible polymers is imperative because it can be viewed as an analogue to protein-alike superstructures. However, current understanding is still in infancy. Herein the first demonstration of nanoscale structural hierarchy/complexity via copper chelation-induced self-assembly (CCISA) is presented. Hierarchically-ordered colloidal networks and disks can be achieved by deliberate control of spacer length and solution pH. Dynamic light scattering, transmission electron microscopy, and atomic force microscopy demonstrate that CCISA underwent supramolecular-to-supracolloidal stepwise-growth mechanism, and underline amazing prospects to the hierarchically-ordered superstructures of hydrophilic flexible polymers in water. PMID:27219860

  16. [Chelate-induced phytoextraction of copper contaminated upland red soil].

    PubMed

    Wu, L; Luo, Y; Huang, H

    2001-06-01

    A copper spiked red soil was used in pot experiment to study the effects of EDTA and low molecule weight organic acids on Cu speciation in soil, and Cu uptake by Brassica juncea. The results showed that the mobility of Cu in soil was improved obviously when EDTA was added at the vigorous growth stage. Both water-extractable and exchangeable Cu concentration increased significantly following EDTA addition. Citric acid and malic acid only had an effect on water-extractable Cu, and no effect on Cu uptake by the plant. EDTA significantly increased the concentration of Cu in plant leaves and roots, and the Cu uptake by Brassica juncea. All of these indicated the chelate-induced phytoextraction. PMID:11758431

  17. Mesoporous organosilica nanotubes containing a chelating ligand in their walls

    SciTech Connect

    Liu, Xiao; Goto, Yasutomo; Maegawa, Yoshifumi; Inagaki, Shinji

    2014-11-01

    We report the synthesis of organosilica nanotubes containing 2,2′-bipyridine chelating ligands within their walls, employing a single-micelle-templating method. These nanotubes have an average pore diameter of 7.8 nm and lengths of several hundred nanometers. UV-vis absorption spectra and scanning transmission electron microscopy observations of immobilized nanotubes with an iridium complex on the bipyridine ligands showed that the 2,2′-bipyridine groups were homogeneously distributed in the benzene-silica walls. The iridium complex, thus, immobilized on the nanotubes exhibited efficient catalytic activity for water oxidation using Ce{sup 4+}, due to the ready access of reactants to the active sites in the nanotubes.

  18. Next generation barrier CMP slurry with novel weakly alkaline chelating agent

    NASA Astrophysics Data System (ADS)

    Shiyan, Fan; Yuling, Liu; Ming, Sun; Jiying, Tang; Chenqi, Yan; Hailong, Li; Shengli, Wang

    2015-01-01

    To strengthen the device performance with the pattern wafer by enhancing the Cu polishing rate and improve the surface roughness with the Cu lines, a new weakly alkaline chelating agent with a barrier slurry is developed to meet the process demand of the advanced barrier chemical mechanical planarization (CMP). This new chelating agent has a stronger chelating ability and a lower pH value than the previous generation-FA/O I chelating agent researched before. Without an unstable oxidant agent added in the polishing slurry, it is difficult to enhance the copper polishing rate during the barrier CMP. The stronger chelating ability of the new chelating agent could increase the copper polishing rate along with controlling the Cu/Ta/TEOS removal rate selectivity to meet the requirements of the IC fabrication process. Thus it has solved the problem of excessive roughness due to the lower polishing rate, avoiding reducing the device performance with the pattern wafer. The new chelating agent with its lower pH value could make it possible to protect the low-k dielectric under the barrier layer from structurally breaking. The CMP experiment was performed on the 12 inch MIT 854 pattern wafers with the barrier slurry containing the new weakly alkaline chelating agent. By the DOE optimization, the results indicate that as the new chelating agent concentration in the slurry was up to 2.5 mL/L, the copper polishing rate is about 31.082 nm/min. Meanwhile, the wafer surface has a rather low roughness value of 0.693 nm (10 × 10 μm), the correction ability with the above slurry is adapted to the next generation barrier CMP and the k value of the low-k dielectric seems to have no k-shift. All the results presented show that the new weakly alkaline chelating agent with its superior performance can be used for the advanced barrier CMP.

  19. Clinically Approved Iron Chelators Influence Zebrafish Mortality, Hatching Morphology and Cardiac Function

    PubMed Central

    Hamilton, Jasmine L.; Hatef, Azadeh; Imran ul-haq, Muhammad; Nair, Neelima; Unniappan, Suraj; Kizhakkedathu, Jayachandran N.

    2014-01-01

    Iron chelation therapy using iron (III) specific chelators such as desferrioxamine (DFO, Desferal), deferasirox (Exjade or ICL-670), and deferiprone (Ferriprox or L1) are the current standard of care for the treatment of iron overload. Although each chelator is capable of promoting some degree of iron excretion, these chelators are also associated with a wide range of well documented toxicities. However, there is currently very limited data available on their effects in developing embryos. In this study, we took advantage of the rapid development and transparency of the zebrafish embryo, Danio rerio to assess and compare the toxicity of iron chelators. All three iron chelators described above were delivered to zebrafish embryos by direct soaking and their effects on mortality, hatching and developmental morphology were monitored for 96 hpf. To determine whether toxicity was specific to embryos, we examined the effects of chelator exposure via intra peritoneal injection on the cardiac function and gene expression in adult zebrafish. Chelators varied significantly in their effects on embryo mortality, hatching and morphology. While none of the embryos or adults exposed to DFO were negatively affected, ICL -treated embryos and adults differed significantly from controls, and L1 exerted toxic effects in embryos alone. ICL-670 significantly increased the mortality of embryos treated with doses of 0.25 mM or higher and also affected embryo morphology, causing curvature of larvae treated with concentrations above 0.5 mM. ICL-670 exposure (10 µL of 0.1 mM injection) also significantly increased the heart rate and cardiac output of adult zebrafish. While L1 exposure did not cause toxicity in adults, it did cause morphological defects in embryos at 0.5 mM. This study provides first evidence on iron chelator toxicity in early development and will help to guide our approach on better understanding the mechanism of iron chelator toxicity. PMID:25329065

  20. Cosmic alternatives?

    NASA Astrophysics Data System (ADS)

    Gregory, Ruth

    2009-04-01

    "Cosmologists are often in error but never in doubt." This pithy characterization by the Soviet physicist Lev Landau sums up the raison d'être of Facts and Speculations in Cosmology. Authors Jayant Narlikar and Geoffrey Burbidge are proponents of a "steady state" theory of cosmology, and they argue that the cosmological community has become fixated on a "Big Bang" dogma, suppressing alternative viewpoints. This book very much does what it says on the tin: it sets out what is known in cosmology, and puts forward the authors' point of view on an alternative to the Big Bang.

  1. Stereoelectronic influence of the type of bifunctional ansa-monocyclopentadienyldimethylsilylamido ligand on the molecular structures displayed by zirconium dichloride and 1,4-diphenylbutadiene complexes.

    PubMed

    Braun, Leonie F; Dreier, Thorsten; Christy, Matthew; Petersen, Jeffrey L

    2004-06-28

    A series of organozirconium dichloride and 1,4-diphenylbutadiene complexes featuring a dianionic bifunctional ligand with a cyclopentadienyl-type functionality and an appended amido N donor have been prepared and structurally characterized. [(C(5)H(4))SiMe(2)(N-t-Bu)]ZrCl(2), 1, [(C(9)H(6))SiMe(2)(N-t-Bu)]ZrCl(2), 2, and [(C(5)Me(4))SiMe(2)(N-i-Pr)]ZrCl(2), 3, were prepared in two steps, with ligand chelation accomplished by an amine elimination reaction followed by treatment of the diamido Zr intermediate with an excess of SiMe(3)Cl. X-ray structural analyses reveal that in the solid state 2 is monomeric, whereas 1 and 3 are centrosymmetric dimers linked by a pair of bridging chlorides. The level of asymmetry displayed by the central Zr(2)(micro-Cl)(2) moiety is indicated by the variation in the pair of independent bridging Zr-Cl bond distances, which are 2.618(1) and 2.657(1) A in 1 and 2.542(1) and 2.745(1) A in 3, respectively. The metathetical reactions of [Mg(C(4)H(4)Ph(2))(THF)(3)](n)() with 1, 2, 3, and [(C(5)Me(4))SiMe(2)(N-t-Bu)]ZrCl(2) proceed to afford the corresponding 1,4-diphenylbutadiene derivatives 4, 5, 6, and 7, respectively. Solution NMR data show that 6 is obtained exclusively as the supine isomer, whereas compounds 4, 5, and 7 exist as >20:1, 6:1, and 2:1 mixtures of the supine and prone isomers at ambient temperature. The molecular structures of the supine forms of 4, 5, 6, and 7 are appreciably folded (70-80 degrees ) along the line of intersection between the plane containing the Zr and the two terminal butadiene carbons and the plane of the cis-butadiene fragment. An increase in the folding is accompanied by a decrease in the difference between the average Zr-C(terminal) and Zr-C(internal) bond distances and leads to a more pronounced long-short-long C-C bond sequence within the coordinated butadiene. PMID:15206879

  2. Effects of Zinc Chelators on Aflatoxin Production in Aspergillus parasiticus.

    PubMed

    Wee, Josephine; Day, Devin M; Linz, John E

    2016-01-01

    Zinc concentrations strongly influence aflatoxin accumulation in laboratory media and in food and feed crops. The presence of zinc stimulates aflatoxin production, and the absence of zinc impedes toxin production. Initial studies that suggested a link between zinc and aflatoxin biosynthesis were presented in the 1970s. In the present study, we utilized two zinc chelators, N,N,N',N'-tetrakis (2-pyridylmethyl) ethane-1,2-diamine (TPEN) and 2,3-dimercapto-1-propanesulfonic acid (DMPS) to explore the effect of zinc limitation on aflatoxin synthesis in Aspergillus parasiticus. TPEN but not DMPS decreased aflatoxin biosynthesis up to six-fold depending on whether A. parasiticus was grown on rich or minimal medium. Although we observed significant inhibition of aflatoxin production by TPEN, no detectable changes were observed in expression levels of the aflatoxin pathway gene ver-1 and the zinc binuclear cluster transcription factor, AflR. Treatment of growing A. parasiticus solid culture with a fluorescent zinc probe demonstrated an increase in intracellular zinc levels assessed by increases in fluorescent intensity of cultures treated with TPEN compared to controls. These data suggest that TPEN binds to cytoplasmic zinc therefore limiting fungal access to zinc. To investigate the efficacy of TPEN on food and feed crops, we found that TPEN effectively decreases aflatoxin accumulation on peanut medium but not in a sunflower seeds-derived medium. From an application perspective, these data provide the basis for biological differences that exist in the efficacy of different zinc chelators in various food and feed crops frequently contaminated by aflatoxin. PMID:27271668

  3. Chelating agents and cadmium toxicity: problems and prospects.

    PubMed Central

    Nordberg, G F

    1984-01-01

    Symptoms and signs in humans after excessive exposure to cadmium usually involve the gastrointestinal tract after single oral intake, the lung after acute inhalation, and the kidney after long-term exposure. These organs are usually considered to be the "critical" organs, i.e., the organs most sensitive at a certain type of exposure. The type of Cd-related damage that is most common in humans is probably the renal toxicity after long-term exposure. Most animal experiments, including the most recently published ones, have involved study of gross toxicity and tissue distribution after injection of cadmium in acute experiments. The observations in the older literature that the influence of chelating agents on Cd distribution and excretion is confined to the early period after acute Cd exposure has been confirmed and extended, and the relationship to the time course of metallothionein synthesis has been demonstrated. Although the injection experiments concerning cadmium distribution, particularly those employing repeated exposure, may furnish information that can form a basis for speculation about long-term toxicity to the kidney, there is a lack of direct studies in animals of possible beneficial effects of chelating agents on renal toxicity of cadmium after prolonged exposure. Among the few studies reported, either an increased renal toxicity or a lack of influence on renal toxicity has been observed. The problems in finding a treatment scheme that can be beneficial for the renal toxicity resulting from long-term cadmium exposure thus remain; however, the prospects of finding such schemes in the future seem favorable in view of some of the recent observations. PMID:6428872

  4. Removal of iron by chelation with molecularly imprinted supermacroporous cryogel.

    PubMed

    Çimen, Duygu; Göktürk, Ilgım; Yılmaz, Fatma

    2016-06-01

    Iron chelation therapy can be used for the selective removal of Fe(3+) ions from spiked human plasma by ion imprinting. N-Methacryloyl-(L)-glutamic acid (MAGA) was chosen as the chelating monomer. In the first step, MAGA was complexed with the Fe(3+) ions to prepare the precomplex, and then the ion-imprinted poly(hydroxyethyl methacrylate-N-methacryloyl-(L)-glutamic acid) [PHEMAGA-Fe(3+)] cryogel column was prepared by cryo-polymerization under a semi-frozen temperature of - 12°C for 24 h. Subsequently, the template, of Fe(3+) ions was removed from the matrix by using 0.1 M EDTA solution. The values for the specific surface area of the imprinted PHEMAGA-Fe(3+) and non-imprinted PHEMAGA cryogel were 45.74 and 7.52 m(2)/g respectively, with a pore size in the range of 50-200 μm in diameter. The maximum Fe(3+) adsorption capacity was 19.8 μmol Fe(3+)/g cryogel from aqueous solutions and 12.28 μmol Fe(3+)/g cryogel from spiked human plasma. The relative selectivity coefficients of ion-imprinted cryogel for Fe(3+)/Ni(2+) and Fe(3+)/Cd(2+) were 1.6 and 4.2-fold greater than the non-imprinted matrix, respectively. It means that the PHEMAGA-Fe(3+) cryogel possesses high selectivity to Fe(3+) ions, and could be used many times without significantly decreasing the adsorption capacity. PMID:25727711

  5. Effects of Zinc Chelators on Aflatoxin Production in Aspergillus parasiticus

    PubMed Central

    Wee, Josephine; Day, Devin M.; Linz, John E.

    2016-01-01

    Zinc concentrations strongly influence aflatoxin accumulation in laboratory media and in food and feed crops. The presence of zinc stimulates aflatoxin production, and the absence of zinc impedes toxin production. Initial studies that suggested a link between zinc and aflatoxin biosynthesis were presented in the 1970s. In the present study, we utilized two zinc chelators, N,N,N′,N′-tetrakis (2-pyridylmethyl) ethane-1,2-diamine (TPEN) and 2,3-dimercapto-1-propanesulfonic acid (DMPS) to explore the effect of zinc limitation on aflatoxin synthesis in Aspergillus parasiticus. TPEN but not DMPS decreased aflatoxin biosynthesis up to six-fold depending on whether A. parasiticus was grown on rich or minimal medium. Although we observed significant inhibition of aflatoxin production by TPEN, no detectable changes were observed in expression levels of the aflatoxin pathway gene ver-1 and the zinc binuclear cluster transcription factor, AflR. Treatment of growing A. parasiticus solid culture with a fluorescent zinc probe demonstrated an increase in intracellular zinc levels assessed by increases in fluorescent intensity of cultures treated with TPEN compared to controls. These data suggest that TPEN binds to cytoplasmic zinc therefore limiting fungal access to zinc. To investigate the efficacy of TPEN on food and feed crops, we found that TPEN effectively decreases aflatoxin accumulation on peanut medium but not in a sunflower seeds-derived medium. From an application perspective, these data provide the basis for biological differences that exist in the efficacy of different zinc chelators in various food and feed crops frequently contaminated by aflatoxin. PMID:27271668

  6. Fluorescent chelates for monitoring metal binding with macromolecules.

    PubMed

    Islam, M; Khanin, M; Sadik, O A

    2003-01-01

    Metals and radionuclides are usually coupled with proteins together with suitable ligands for therapeutic, tumor-imaging, pharmaceuticals, and biocompatibility applications. Several ligands that can strongly coordinate a given nuclide in a specific valency are already known. However, the demand for bifunctionality has limited the applications of these ligands. We hereby report the molecular design of a receptor system based on the linkage of protein to monoazo ligands. By use of basic coordination chemistry, 4-(3-quinolinoazo)hydroxybenzoic acid (QABA) and derivatives were successfully conjugated to ovalbumin, bovine serum albumin, and alkaline phosphatase at a site that was distinct from the metal binding site. The presence of carboxylic acid linkage in the QABA served as a convenient bridge for protein conjugation and may allow the generic application of these ligands for bioconjugate synthesis while ensuring a high in vivo stability. The ligand-protein conjugates were characterized using UV-vis spectroscopy, Fourier transform infrared spectroscopy, thin layer chromatography, NMR, and surface-enhanced laser desorption ionization time-of-flight mass spectrometry. The conjugate was tested for the ability to recognize nonradioactive Ga(3+) at a physiological pH, and a binding constant of 1 x 10(20) was recorded. Also, the in vitro testing results indicated that the fluorescent conjugates exhibited significant selectivity for gallium compared to Pb(2+), Hg(2+), Zn(2+), Cu(2+), Fe(3+), and Co(2+) while no responses were obtained for alkaline and alkaline earth metals. These attributes could allow these conjugates to be used as a model for imaging sensors and for metal detection. PMID:12523855

  7. Oxygen electrode bifunctional electrocatalyst NiCo2O4 spinel

    NASA Technical Reports Server (NTRS)

    Fielder, William L.; Singer, Joseph

    1988-01-01

    A significant increase in energy density may be possible if a two-unit alkaline regenerative H2-O2 fuel cell is replaced with a single-unit system that uses passive means for H2O transfer and thermal control. For this single-unit system, new electrocatalysts for the O2 electrode will be required which are not only bifunctionally active but also chemically and electrochemically stable between the voltage range of about 0.7 and 1.5 V. NiCo2O4 spinel is reported to have certain characteristics that make it useful for a study of electrode fabrication techniques. High surface area NiCo2O4 powder was fabricated into unsupported, bifunctional, PTFE-bonded, porous gas fuel cell electrodes by commercial sources using varying PTFE contents and sintering temperatures. The object of this study is to measure the bifunctional activities of these electrodes and to observe what performance differences might result from different commercial electrode fabricators. O2 evolution and O2 reduction data were obtained at 80 C (31 percent KOH). An irreversible reaction (i.e., aging) occurred during O2 evolution at potentials greater than about 1.5 V. Anodic Tafel slopes of 0.06 and 0.12 V/decade were obtained for the aged electrodes. Within the range of 15 to 25 percent, the PTFE content was not a critical parameter for optimizing the electrode for O2 evolution activity. Sintering temperatures between 300 and 340 C may be adequate but heating at 275 C may not be sufficient to properly sinter the PTFE-NiCo2O4 mixture. Electrode disintegration was observed during O2 reduction. Transport of O2 to the NiCo2O4 surface became prohibitive at greater than about -0.02 A/sq cm. Cathodic Tafel slopes of -0.6 and -0.12 V/decade were assumed for the O2 reduction process. A PTFE content of 25 percent (or greater) appears to be preferable for sintering the PTFE-NiCo2O4 mixture.

  8. Unique subunit packing in mycobacterial nanoRNase leads to alternate substrate recognitions in DHH phosphodiesterases

    PubMed Central

    Srivastav, Rajpal; Kumar, Dilip; Grover, Amit; Singh, Ajit; Manjasetty, Babu A.; Sharma, Rakesh; Taneja, Bhupesh

    2014-01-01

    DHH superfamily includes RecJ, nanoRNases (NrnA), cyclic nucleotide phosphodiesterases and pyrophosphatases. In this study, we have carried out in vitro and in vivo investigations on the bifunctional NrnA-homolog from Mycobacterium smegmatis, MSMEG_2630. The crystal structure of MSMEG_2630 was determined to 2.2-Å resolution and reveals a dimer consisting of two identical subunits with each subunit folding into an N-terminal DHH domain and a C-terminal DHHA1 domain. The overall structure and fold of the individual domains is similar to other members of DHH superfamily. However, MSMEG_2630 exhibits a distinct quaternary structure in contrast to other DHH phosphodiesterases. This novel mode of subunit packing and variations in the linker region that enlarge the domain interface are responsible for alternate recognitions of substrates in the bifunctional nanoRNases. MSMEG_2630 exhibits bifunctional 3′-5′ exonuclease [on both deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) substrates] as well as CysQ-like phosphatase activity (on pAp) in vitro with a preference for nanoRNA substrates over single-stranded DNA of equivalent lengths. A transposon disruption of MSMEG_2630 in M. smegmatis causes growth impairment in the presence of various DNA-damaging agents. Further phylogenetic analysis and genome organization reveals clustering of bacterial nanoRNases into two distinct subfamilies with possible role in transcriptional and translational events during stress. PMID:24878921

  9. Alternative Thinking.

    ERIC Educational Resources Information Center

    Herman, Dan

    1999-01-01

    Explains how advances in diesel and alternative fuels has caused schools to reconsider their use for their bus fleets. Reductions in air pollution emissions, cost-savings developments, and the economies experienced from less downtime and maintenance requirements are explored. (GR)

  10. Alternative Conceptualizations.

    ERIC Educational Resources Information Center

    Borman, Kathryn M., Ed.; O'Reilly, Patricia, Ed.

    1992-01-01

    This theme issue of the serial "Educational Foundations" contains five articles devoted to the topic of "Alternative Conceptualizations" of the foundations of education. In "The Concept of Place in the New Sociology of Education," Paul Theobald examines the notion of place in educational theory and practice. Janice Jipson and Nicholas Paley, in…

  11. ALTERNATIVE OXIDANTS

    EPA Science Inventory

    This chapter reports on the efforts of the USEPA to study chloramines, chlorine dioxide and ozone as alternative oxidants/disinfectants to chlorine for the control of disinfection by-rpdocuts (DBPs) in drinking water. It examines the control of DBPs like trihalomethanes and haloa...

  12. A novel bifunctional histone protein in Streptomyces: a candidate for structural coupling between DNA conformation and transcription during development and stress?

    PubMed Central

    Aldridge, Matthew; Facey, Paul; Francis, Lewis; Bayliss, Sion; Del Sol, Ricardo; Dyson, Paul

    2013-01-01

    Antibiotic-producing Streptomyces are complex bacteria that remodel global transcription patterns and their nucleoids during development. Here, we describe a novel developmentally regulated nucleoid-associated protein, DdbA, of the genus that consists of an N-terminal DNA-binding histone H1-like domain and a C-terminal DksA-like domain that can potentially modulate RNA polymerase activity in conjunction with ppGpp. Owing to its N-terminal domain, the protein can efficiently bind and condense DNA in vitro. Loss of function of this DNA-binding protein results in changes in both DNA condensation during development and the ability to adjust DNA supercoiling in response to osmotic stress. Initial analysis of the DksA-like activity of DdbA indicates that overexpression of the protein suppresses a conditional deficiency in antibiotic production of relA mutants that are unable to synthesise ppGpp, just as DksA overexpression in Escherichia coli can suppress ppGpp0 phenotypes. The null mutant is also sensitive to oxidative stress owing to impaired upregulation of transcription of sigR, encoding an alternative sigma factor. Consequently, we propose this bifunctional histone-like protein as a candidate that could structurally couple changes in DNA conformation and transcription during the streptomycete life-cycle and in response to stress. PMID:23525459

  13. Rhodobacter capsulatus OlsA is a bifunctional enzyme active in both ornithine lipid and phosphatidic acid biosynthesis.

    PubMed

    Aygun-Sunar, Semra; Bilaloglu, Rahmi; Goldfine, Howard; Daldal, Fevzi

    2007-12-01

    The Rhodobacter capsulatus genome contains three genes (olsA [plsC138], plsC316, and plsC3498) that are annotated as lysophosphatidic acid (1-acyl-sn-glycerol-3-phosphate) acyltransferase (AGPAT). Of these genes, olsA was previously shown to be an O-acyltransferase in the second step of ornithine lipid biosynthesis, which is important for optimal steady-state levels of c-type cytochromes (S. Aygun-Sunar, S. Mandaci, H.-G. Koch, I. V. J. Murray, H. Goldfine, and F. Daldal. Mol. Microbiol. 61:418-435, 2006). The roles of the remaining plsC316 and plsC3498 genes remained unknown. In this work, these genes were cloned, and chromosomal insertion-deletion mutations inactivating them were obtained to define their function. Characterization of these mutants indicated that, unlike the Escherichia coli plsC, neither plsC316 nor plsC3498 was essential in R. capsulatus. In contrast, no plsC316 olsA double mutant could be isolated, indicating that an intact copy of either olsA or plsC316 was required for R. capsulatus growth under the conditions tested. Compared to OlsA null mutants, PlsC316 null mutants contained ornithine lipid and had no c-type cytochrome-related phenotype. However, they exhibited slight growth impairment and highly altered total fatty acid and phospholipid profiles. Heterologous expression in an E. coli plsC(Ts) mutant of either R. capsulatus plsC316 or olsA gene products supported growth at a nonpermissive temperature, exhibited AGPAT activity in vitro, and restored phosphatidic acid biosynthesis. The more vigorous AGPAT activity displayed by PlsC316 suggested that plsC316 encodes the main AGPAT required for glycerophospholipid synthesis in R. capsulatus, while olsA acts as an alternative AGPAT that is specific for ornithine lipid synthesis. This study therefore revealed for the first time that some OlsA enzymes, like the enzyme of R. capsulatus, are bifunctional and involved in both membrane ornithine lipid and glycerophospholipid biosynthesis. PMID

  14. Rhodobacter capsulatus OlsA Is a Bifunctional Enyzme Active in both Ornithine Lipid and Phosphatidic Acid Biosynthesis▿ †

    PubMed Central

    Aygun-Sunar, Semra; Bilaloglu, Rahmi; Goldfine, Howard; Daldal, Fevzi

    2007-01-01

    The Rhodobacter capsulatus genome contains three genes (olsA [plsC138], plsC316, and plsC3498) that are annotated as lysophosphatidic acid (1-acyl-sn-glycerol-3-phosphate) acyltransferase (AGPAT). Of these genes, olsA was previously shown to be an O-acyltransferase in the second step of ornithine lipid biosynthesis, which is important for optimal steady-state levels of c-type cytochromes (S. Aygun-Sunar, S. Mandaci, H.-G. Koch, I. V. J. Murray, H. Goldfine, and F. Daldal. Mol. Microbiol. 61:418-435, 2006). The roles of the remaining plsC316 and plsC3498 genes remained unknown. In this work, these genes were cloned, and chromosomal insertion-deletion mutations inactivating them were obtained to define their function. Characterization of these mutants indicated that, unlike the Escherichia coli plsC, neither plsC316 nor plsC3498 was essential in R. capsulatus. In contrast, no plsC316 olsA double mutant could be isolated, indicating that an intact copy of either olsA or plsC316 was required for R. capsulatus growth under the conditions tested. Compared to OlsA null mutants, PlsC316 null mutants contained ornithine lipid and had no c-type cytochrome-related phenotype. However, they exhibited slight growth impairment and highly altered total fatty acid and phospholipid profiles. Heterologous expression in an E. coli plsC(Ts) mutant of either R. capsulatus plsC316 or olsA gene products supported growth at a nonpermissive temperature, exhibited AGPAT activity in vitro, and restored phosphatidic acid biosynthesis. The more vigorous AGPAT activity displayed by PlsC316 suggested that plsC316 encodes the main AGPAT required for glycerophospholipid synthesis in R. capsulatus, while olsA acts as an alternative AGPAT that is specific for ornithine lipid synthesis. This study therefore revealed for the first time that some OlsA enzymes, like the enzyme of R. capsulatus, are bifunctional and involved in both membrane ornithine lipid and glycerophospholipid biosynthesis. PMID

  15. Use of deferasirox, an iron chelator, to overcome imatinib resistance of chronic myeloid leukemia cells

    PubMed Central

    Kim, Dae Sik; Na, Yoo Jin; Kang, Myoung Hee; Yoon, Soo-Young; Choi, Chul Won

    2016-01-01

    Background/Aims: The treatment of chronic myeloid leukemia (CML) has achieved impressive success since the development of the Bcr-Abl tyrosine kinase inhibitor, imatinib mesylate. Nevertheless, resistance to imatinib has been observed, and a substantial number of patients need alternative treatment strategies. Methods: We have evaluated the effects of deferasirox, an orally active iron chelator, and imatinib on K562 and KU812 human CML cell lines. Imatinib-resistant CML cell lines were created by exposing cells to gradually increasing concentrations of imatinib. Results: Co-treatment of cells with deferasirox and imatinib induced a synergistic dose-dependent inhibition of proliferation of both CML cell lines. Cell cycle analysis showed an accumulation of cells in the subG1 phase. Western blot analysis of apoptotic proteins showed that co-treatment with deferasirox and imatinib induced an increased expression of apoptotic proteins. These tendencies were clearly identified in imatinib-resistant CML cell lines. The results also showed that co-treatment with deferasirox and imatinib reduced the expression of BcrAbl, phosphorylated Bcr-Abl, nuclear factor-κB (NF-κB) and β-catenin. Conclusions: We observed synergistic effects of deferasirox and imatinib on both imatinib-resistant and imatinib-sensitive cell lines. These effects were due to induction of apoptosis and cell cycle arrest by down-regulated expression of NF-κB and β-catenin levels. Based on these results, we suggest that a combination treatment of deferasirox and imatinib could be considered as an alternative treatment option for imatinib-resistant CML. PMID:26874514

  16. Mono- and bi-functional arenethiols as surfactants for gold nanoparticles: synthesis and characterization

    NASA Astrophysics Data System (ADS)

    Vitale, Floriana; Fratoddi, Ilaria; Battocchio, Chiara; Piscopiello, Emanuela; Tapfer, Leander; Russo, Maria Vittoria; Polzonetti, Giovanni; Giannini, Cinzia

    2011-12-01

    Stable gold nanoparticles stabilized by different mono and bi-functional arenethiols, namely, benzylthiol and 1,4-benzenedimethanethiol, have been prepared by using a modified Brust's two-phase synthesis. The size, shape, and crystalline structure of the gold nanoparticles have been determined by high-resolution electron microscopy and full-pattern X-ray powder diffraction analyses. Nanocrystals diameters have been tuned in the range 2 ÷ 9 nm by a proper variation of Au/S molar ratio. The chemical composition of gold nanoparticles and their interaction with thiols have been investigated by X-ray photoelectron spectroscopy. In particular, the formation of networks has been observed with interconnected gold nanoparticles containing 1,4-benzenedimethanethiol as ligand.

  17. Novel 3-nitrotriazole-based amides and carbinols as bifunctional anti-Chagasic agents

    PubMed Central

    Papadopoulou, Maria V.; Bloomer, William D.; Lepesheva, Galina I.; Rosenzweig, Howard S.; Kaiser, Marcel; Aguilera-Venegas, Benjamín; Wilkinson, Shane R.; Chatelain, Eric; Ioset, Jean-Robert

    2015-01-01

    3-Nitro-1H-1,2,4-triazole-based amides with a linear, rigid core and 3-nitrotriazole-based fluconazole analogs were synthesized as dual functioning antitrypanosomal agents. Such compounds are excellent substrates for type I nitroreductase (NTR) located in the mitochondrion of trypanosomatids and, at the same time, act as inhibitors of the sterol 14α-demethylase (T. cruzi CYP51) enzyme. Because combination treatments against parasites are often superior to monotherapy, we believe that this emerging class of bifunctional compounds may introduce a new generation of antitrypanosomal drugs. In the present work, the synthesis and in vitro and in vivo evaluation of such compounds is discussed. PMID:25580906

  18. Chimeric bifunctional oligonucleotides as a novel tool to invade telomerase assembly

    PubMed Central

    Azhibek, Dulat; Zvereva, Maria; Zatsepin, Timofei; Rubtsova, Maria; Dontsova, Olga

    2014-01-01

    Telomerase is a key participant in the telomere length maintaining system in eukaryotic cells. Telomerase RNA and protein reverse transcriptase subunits are essential for the appearance of active telomerase in vitro. Telomerase is active in many cancer types and is a potential target for anticancer drug development. Here we report a new approach for impairing telomerase function at the stage of human telomerase assembly. The approach is based on the application of chimeric bifunctional oligonucleotides that contain two oligonucleotide parts complementary to the functional domains of telomerase RNA connected with non-nucleotide linkers in different orientations (5′-3′, 5′-5′ or 3′-3′). Such chimeras inhibited telomerase in vitro in the nM range, but were effective in vivo in sub-nM concentrations, predominantly due to their effect on telomerase assembly and dimerization. PMID:25081209

  19. Polarization holograms in a bifunctional amorphous polymer exhibiting equal values of photoinduced linear and circular birefringences.

    PubMed

    Provenzano, Clementina; Pagliusi, Pasquale; Cipparrone, Gabriella; Royes, Jorge; Piñol, Milagros; Oriol, Luis

    2014-10-01

    Light-controlled molecular alignment is a flexible and useful strategy introducing novelty in the fields of mechanics, self-organized structuring, mass transport, optics, and photonics and addressing the development of smart optical devices. Azobenzene-containing polymers are well-known photocontrollable materials with large and reversible photoinduced optical anisotropies. The vectorial holography applied to these materials enables peculiar optical devices whose properties strongly depend on the relative values of the photoinduced birefringences. Here is reported a polarization holographic recording based on the interference of two waves with orthogonal linear polarization on a bifunctional amorphous polymer that, exceptionally, exhibits equal values of linear and circular birefringence. The peculiar photoresponse of the material coupled with the holographic technique demonstrates an optical device capable of decomposing the light into a set of orthogonally polarized linear components. The holographic structures are theoretically described by the Jones matrices method and experimentally investigated. PMID:25187982

  20. Oxychlorination-Dehydrochlorination Chemistry on Bifunctional Ceria Catalysts for Intensified Vinyl Chloride Production.

    PubMed

    Scharfe, Matthias; Lira-Parada, Pedro A; Paunović, Vladimir; Moser, Maximilian; Amrute, Amol P; Pérez-Ramírez, Javier

    2016-02-24

    Ceria catalyzes the one-step production of the vinyl chloride monomer (VCM) from ethylene with a high yield because of its bifunctional character: redox centers oxychlorinate ethylene to ethylene dichloride (EDC), which is subsequently dehydrochlorinated to VCM over strong acid sites generated in situ. Nanocrystalline CeO2 and CeO2-ZrO2 lead to a VCM yield of 25 % in a single pass, outperforming the best reported systems and reaching industrially attractive levels. The use of CeO2 intensifies the current two-step process within PVC production encompassing CuCl2 -catalyzed oxychlorination and thermal cracking. In addition, ceria-based materials offer stability advantages with respect to the archetypical CuCl2 -based catalysts. PMID:26823027

  1. Bifunctional nanoparticles for SERS monitoring and magnetic intervention of assembly and enzyme cutting of DNAs

    SciTech Connect

    Lin, Liqin; Crew, Elizabeth; Yan, Hong; Shan, Shiyao; Skeete, Zakiya; Mott, Derrick; Krentsel, Tatiana; Yin, Jun; Chernova, Natasha A.; Luo, Jin; Engelhard, Mark H.; Wang, Chong M.; Li, Qingbiao; Zhong, Chuan-Jian

    2013-07-27

    The ability to detect and intervene in DNA assembly, disassembly, and enzyme cutting processes in a solution phase requires effective signal transduction and stimulus response. This report demonstrates a novel bifunctional strategy for the creation of this ability using gold- and silver-coated MnZn ferrite nanoparticles (MZF@Au or MZF@Ag) that impart magnetic and surfaceenhanced Raman scattering (SERS) functionalities to these processes. The double-stranded DNA linkage of labeled gold nanoparticles with MZF@Au (or MZF@Ag) produces interparticle "hot-spots" for real-time SERS monitoring of the DNA assembly, disassembly, or enzyme cutting processes, during which the magnetic component provides an effective means for intervention in the solution. The unique combination of the nanoprobes functionalities serves a new paradigm for the design of functional nanoprobes in biomolecular recognition and intervention.

  2. The fabrication of a bifunctional oxygen electrode without carbon components for alkaline secondary batteries

    NASA Astrophysics Data System (ADS)

    Price, Stephen W. T.; Thompson, Stephen J.; Li, Xiaohong; Gorman, Scott F.; Pletcher, Derek; Russell, Andrea E.; Walsh, Frank C.; Wills, Richard G. A.

    2014-08-01

    The fabrication of a gas diffusion electrode (GDE) without carbon components is described. It is therefore suitable for use as a bifunctional oxygen electrode in alkaline secondary batteries. The electrode is fabricated in two stages (a) the formation of a PTFE-bonded nickel powder layer on a nickel foam substrate and (b) the deposition of a NiCo2O4 spinel electrocatalyst layer by dip coating in a nitrate solution and thermal decomposition. The influence of modifications to the procedure on the performance of the GDEs in 8 M NaOH at 333 K is described. The GDEs can support current densities up to 100 mA cm-2 with state-of-the-art overpotentials for both oxygen evolution and oxygen reduction. Stable performance during >50 successive, 1 h oxygen reduction/evolution cycles at a current density of 50 mA cm-2 has been achieved.

  3. A Bifunctional Electrocatalyst for Oxygen Evolution and Oxygen Reduction Reactions in Water

    PubMed Central

    Faschinger, Felix; Chattopadhyay, Samir; Bhakta, Snehadri; Mondal, Biswajit; Elemans, Johannes A. A. W.; Müllegger, Stefan; Tebi, Stefano; Koch, Reinhold; Klappenberger, Florian; Paszkiewicz, Mateusz; Barth, Johannes V.; Rauls, Eva; Aldahhak, Hazem; Schmidt, Wolf Gero

    2016-01-01

    Abstract Oxygen reduction and water oxidation are two key processes in fuel cell applications. The oxidation of water to dioxygen is a 4 H+/4 e− process, while oxygen can be fully reduced to water by a 4 e−/4 H+ process or partially reduced by fewer electrons to reactive oxygen species such as H2O2 and O2 −. We demonstrate that a novel manganese corrole complex behaves as a bifunctional catalyst for both the electrocatalytic generation of dioxygen as well as the reduction of dioxygen in aqueous media. Furthermore, our combined kinetic, spectroscopic, and electrochemical study of manganese corroles adsorbed on different electrode materials (down to a submolecular level) reveals mechanistic details of the oxygen evolution and reduction processes. PMID:27478281

  4. A Bifunctional Electrocatalyst for Oxygen Evolution and Oxygen Reduction Reactions in Water

    PubMed Central

    Faschinger, Felix; Chattopadhyay, Samir; Bhakta, Snehadri; Mondal, Biswajit; Elemans, Johannes A. A. W.; Müllegger, Stefan; Tebi, Stefano; Koch, Reinhold; Klappenberger, Florian; Paszkiewicz, Mateusz; Barth, Johannes V.; Rauls, Eva; Aldahhak, Hazem; Schmidt, Wolf Gero

    2016-01-01

    Abstract Oxygen reduction and water oxidation are two key processes in fuel cell applications. The oxidation of water to dioxygen is a 4 H+/4 e− process, while oxygen can be fully reduced to water by a 4 e−/4 H+ process or partially reduced by fewer electrons to reactive oxygen species such as H2O2 and O2 −. We demonstrate that a novel manganese corrole complex behaves as a bifunctional catalyst for both the electrocatalytic generation of dioxygen as well as the reduction of dioxygen in aqueous media. Furthermore, our combined kinetic, spectroscopic, and electrochemical study of manganese corroles adsorbed on different electrode materials (down to a submolecular level) reveals mechanistic details of the oxygen evolution and reduction processes. PMID:26773287

  5. Bifunctional hairy silica nanoparticles as high-performance additives for lubricant

    PubMed Central

    Sui, Tianyi; Song, Baoyu; Wen, Yu-ho; Zhang, Feng

    2016-01-01

    Bifunctional hairy silica nanoparticles (BHSNs), which are silica nanoparticles covered with alkyl and amino organic chains, were prepared as high-performance additives for lubricants. Compared with hairy silica nanoparticles covered by a single type of organic chain, binary hairy silica nanoparticles exhibit the advantages of both types of organic chains, which exhibit excellent compatibility with lubricants and adsorbability to metal surfaces. Nanoparticles with different ratios of amino and alkyl ligands were investigated. In comparison to an untreated lubricant, BHSNs reduce the friction coefficient and wear scar diameter by 40% and 60%, respectively. The wear mechanism of BHSNs was investigated, and the protective and filling effect of the nanoparticles improved because of collaboration of amino and alkyl ligands. PMID:26936117

  6. A crystal structure of the bifunctional antibiotic simocyclinone D8, bound to DNA gyrase.

    PubMed

    Edwards, Marcus J; Flatman, Ruth H; Mitchenall, Lesley A; Stevenson, Clare E M; Le, Tung B K; Clarke, Thomas A; McKay, Adam R; Fiedler, Hans-Peter; Buttner, Mark J; Lawson, David M; Maxwell, Anthony

    2009-12-01

    Simocyclinones are bifunctional antibiotics that inhibit bacterial DNA gyrase by preventing DNA binding to the enzyme. We report the crystal structure of the complex formed between the N-terminal domain of the Escherichia coli gyrase A subunit and simocyclinone D8, revealing two binding pockets that separately accommodate the aminocoumarin and polyketide moieties of the antibiotic. These are close to, but distinct from, the quinolone-binding site, consistent with our observations that several mutations in this region confer resistance to both agents. Biochemical studies show that the individual moieties of simocyclinone D8 are comparatively weak inhibitors of gyrase relative to the parent compound, but their combination generates a more potent inhibitor. Our results should facilitate the design of drug molecules that target these unexploited binding pockets. PMID:19965760

  7. A Bifunctional Electrocatalyst for Oxygen Evolution and Oxygen Reduction Reactions in Water.

    PubMed

    Schöfberger, Wolfgang; Faschinger, Felix; Chattopadhyay, Samir; Bhakta, Snehadri; Mondal, Biswajit; Elemans, Johannes A A W; Müllegger, Stefan; Tebi, Stefano; Koch, Reinhold; Klappenberger, Florian; Paszkiewicz, Mateusz; Barth, Johannes V; Rauls, Eva; Aldahhak, Hazem; Schmidt, Wolf Gero; Dey, Abhishek

    2016-02-12

    Oxygen reduction and water oxidation are two key processes in fuel cell applications. The oxidation of water to dioxygen is a 4 H(+)/4 e(-) process, while oxygen can be fully reduced to water by a 4 e(-)/4 H(+) process or partially reduced by fewer electrons to reactive oxygen species such as H2O2 and O2(-). We demonstrate that a novel manganese corrole complex behaves as a bifunctional catalyst for both the electrocatalytic generation of dioxygen as well as the reduction of dioxygen in aqueous media. Furthermore, our combined kinetic, spectroscopic, and electrochemical study of manganese corroles adsorbed on different electrode materials (down to a submolecular level) reveals mechanistic details of the oxygen evolution and reduction processes. PMID:26773287

  8. Bifunctional hairy silica nanoparticles as high-performance additives for lubricant.

    PubMed

    Sui, Tianyi; Song, Baoyu; Wen, Yu-Ho; Zhang, Feng

    2016-01-01

    Bifunctional hairy silica nanoparticles (BHSNs), which are silica nanoparticles covered with alkyl and amino organic chains, were prepared as high-performance additives for lubricants. Compared with hairy silica nanoparticles covered by a single type of organic chain, binary hairy silica nanoparticles exhibit the advantages of both types of organic chains, which exhibit excellent compatibility with lubricants and adsorbability to metal surfaces. Nanoparticles with different ratios of amino and alkyl ligands were investigated. In comparison to an untreated lubricant, BHSNs reduce the friction coefficient and wear scar diameter by 40% and 60%, respectively. The wear mechanism of BHSNs was investigated, and the protective and filling effect of the nanoparticles improved because of collaboration of amino and alkyl ligands. PMID:26936117

  9. Development and computational modeling of novel bifunctional organophosphorus extractants for lanthanoid separation

    SciTech Connect

    Goto, Masahiro; Matsumoto, Satoshi; Uezu, Kazuya; Nakashio, Fumiyuki; Yoshizuka, Kazuharu; Inoue, Katsutoshi

    1999-08-01

    Novel organophosphorus extractants, which have two functional groups in the molecular structure, have been developed for the separation of lanthanoids using the liquid-liquid extraction technique. The separation efficiency and extractability of the novel extractants were investigated for nine lanthanoids. These bifunctional extractants have an extremely high extractability to all the lanthanoids compared to those of commercially available organophosphorus extractants. Two isomers having an identical chemical formulation show significantly different behaviors in lanthanoid extraction. This means that the extraction and separation abilities are quite sensitive to the structure of the spacer connecting the two functional groups. The authors also discuss the experimental results with a computational modeling by means of molecular mechanics and semiempirical molecular orbital methods. The novel molecular mechanics (MM) calculation program MOMEC enables them to analyze the stable conformation of a series of lanthanoid complexes. The calculation suggests that the structural effect of the spacer is one of the decisive factors for enhancing selectivity and extractability in lanthanoid extraction.

  10. Bifunctional Nanoparticle-SILP Catalysts (NPs@SILP) for the Selective Deoxygenation of Biomass Substrates

    SciTech Connect

    Luska, Kylie L.; Julis, Jennifer; Stavitski, Eli; Zakharov, Dmitri N.; Adams, Alina; Leitner, Walter

    2014-08-27

    We immobilized ruthenium nanoparticles onto an acidic supported ionic liquid phase (RuNPs@SILP) in the development of bifunctional catalysts for the selective deoxygenation of biomass substrates. RuNPs@SILPs possessed high catalytic activities, selectivities and recyclabilities in the hydrogenolytic deoxygenation and ring opening of C8- and C9-substrates derived from furfural or 5-hydroxymethylfurfural and acetone. When we tailor the acidity of the SILP through the ionic liquid loading provided a molecular parameter by which the catalytic activity and selectivity of the RuNPs@SILPs were controlled to provide a flexible catalyst system toward the formation of different classes of value-added products: cyclic ethers, primary alcohols or aliphatic ethers.

  11. Bi-functional biobased packing of the cassava starch, glycerol, licuri nanocellulose and red propolis.

    PubMed

    Costa, Samantha Serra; Druzian, Janice Izabel; Machado, Bruna Aparecida Souza; de Souza, Carolina Oliveira; Guimarães, Alaíse Gil

    2014-01-01

    The aim of this study was to characterize and determine the bi-functional efficacy of active packaging films produced with starch (4%) and glycerol (1.0%), reinforced with cellulose nanocrystals (0-1%) and activated with alcoholic extracts of red propolis (0.4 to 1.0%). The cellulose nanocrystals used in this study were extracted from licuri leaves. The films were characterized using moisture, water-activity analyses and water vapor-permeability tests and were tested regarding their total phenolic compounds and mechanical properties. The antimicrobial and antioxidant efficacy of the films were evaluated by monitoring the use of the active films for packaging cheese curds and butter, respectively. The cellulose nanocrystals increased the mechanical strength of the films and reduced the water permeability and water activity. The active film had an antimicrobial effect on coagulase-positive staphylococci in cheese curds and reduced the oxidation of butter during storage. PMID:25383783

  12. Improving battery safety by early detection of internal shorting with a bifunctional separator.

    PubMed

    Wu, Hui; Zhuo, Denys; Kong, Desheng; Cui, Yi

    2014-01-01

    Lithium-based rechargeable batteries have been widely used in portable electronics and show great promise for emerging applications in transportation and wind-solar-grid energy storage, although their safety remains a practical concern. Failures in the form of fire and explosion can be initiated by internal short circuits associated with lithium dendrite formation during cycling. Here we report a new strategy for improving safety by designing a smart battery that allows internal battery health to be monitored in situ. Specifically, we achieve early detection of lithium dendrites inside batteries through a bifunctional separator, which offers a third sensing terminal in addition to the cathode and anode. The sensing terminal provides unique signals in the form of a pronounced voltage change, indicating imminent penetration of dendrites through the separator. This detection mechanism is highly sensitive, accurate and activated well in advance of shorting and can be applied to many types of batteries for improved safety. PMID:25308055

  13. Synthesis and evaluation of novel bifunctional oligomer-based composites for dental applications.

    PubMed

    Xie, Dong; Chung, Il-Doo; Wang, Guigui; Mays, Jimmy

    2006-01-01

    Five novel bifunctional oligomers containing both carboxylic acid and methacrylate groups are synthesized, characterized, and used to formulate compomers by mixing with strontium fluoroaluminosilicate glass powder at a filler level of 75% (by weight). Compressive strength (CS) of the cements and viscosity of the resin liquids are used as screening tools to find the optimal formulation. Diametral tensile (DTS) and flexural strengths (FS) are also determined. Results show that the oligomers derivatized with glycerol dimethacrylate exhibit higher CS than those with 2-hydroxyethyl methacrylate. The CS increases with increasing diluent content, filler level, and light-exposure time. During aging, the cement shows an increase of strength over 24 h and then remains unaltered for up to 3 months. The experimental compomer is 45 and 69% higher in CS, 35 and 174% higher in DTS, and 39 and 170% higher in FS, respectively, as compared to Dyract and Fuji II LC. PMID:16364963

  14. A novel copper(II) coordination polymer with carboxylate and isoindol backbones of a bifunctional ligand

    NASA Astrophysics Data System (ADS)

    Patra, Ayan; Sen, Tamal K.; Musie, Ghezai T.; Mandal, Swadhin K.; Bera, Manindranath

    2013-09-01

    The reaction of a bifunctional ligand, 3-(1-oxo-1,3-dihydro-isoindol-2-yl)-propionic acid (Hpda) with Cu(NO3)2ṡ3H2O in methanol-water in the presence of NaOH at room temperature produces a novel dinuclear copper(II) coordination polymer [Cu2(pda)4]n. The complex is fully characterized in the solid state as well as in solution using various analytical techniques including single crystal X-ray diffraction study. The single crystal X-ray structure analysis reveals that the monomeric unit of complex consists of Cu2(O2CR)4 paddlewheel building unit, where the two copper centers acquire a distorted square pyramidal geometry with amide oxygen of the isoindol ring of an adjacent Hpda ligand sitting on the axial positions.

  15. "Click" chemistry mildly stabilizes bifunctional gold nanoparticles for sensing and catalysis.

    PubMed

    Li, Na; Zhao, Pengxiang; Liu, Na; Echeverria, María; Moya, Sergio; Salmon, Lionel; Ruiz, Jaime; Astruc, Didier

    2014-07-01

    A large family of bifunctional 1,2,3-triazole derivatives that contain both a polyethylene glycol (PEG) chain and another functional fragment (e.g., a polymer, dendron, alcohol, carboxylic acid, allyl, fluorescence dye, redox-robust metal complex, or a β-cyclodextrin unit) has been synthesized by facile "click" chemistry and mildly coordinated to nanogold particles, thus providing stable water-soluble gold nanoparticles (AuNPs) in the size range 3.0-11.2 nm with various properties and applications. In particular, the sensing properties of these AuNPs are illustrated through the detection of an analogue of a warfare agent (i.e., sulfur mustard) by means of a fluorescence "turn-on" assay, and the catalytic activity of the smallest triazole-AuNPs (core of 3.0 nm) is excellent for the reduction of 4-nitrophenol in water. PMID:24891131

  16. Dyes as bifunctional markers of DNA hybridization on surfaces and mutation detection.

    PubMed

    García-Mendiola, Tania; Cerro, María Ramos; López-Moreno, José María; Pariente, Félix; Lorenzo, Encarnación

    2016-10-01

    The interaction of small molecules with DNA has found diagnostic and therapeutic applications. In this work, we propose the use of two different dyes, in particular Azure A and Safranine, as bifunctional markers of on-surface DNA hybridization and potent tools for screening of specific gene mutations directly in real DNA PCR amplicons extracted from blood cells. By combining spectroscopic and electrochemical methods we demonstrate that both dyes can interact with single and double stranded DNA to a different extent, allowing reliable hybridization detection. From these data, we have also elucidated the nature of the interaction. We conclude that the binding mode is fundamentally intercalative with an electrostatic component. The dye fluorescence allows their use as nucleic acid stains for the detection of on-surfaces DNA hybridization. Its redox activity is exploited in the development of selective electrochemical DNA biosensors. PMID:27317997

  17. Bifunctional hairy silica nanoparticles as high-performance additives for lubricant

    NASA Astrophysics Data System (ADS)

    Sui, Tianyi; Song, Baoyu; Wen, Yu-Ho; Zhang, Feng

    2016-03-01

    Bifunctional hairy silica nanoparticles (BHSNs), which are silica nanoparticles covered with alkyl and amino organic chains, were prepared as high-performance additives for lubricants. Compared with hairy silica nanoparticles covered by a single type of organic chain, binary hairy silica nanoparticles exhibit the advantages of both types of organic chains, which exhibit excellent compatibility with lubricants and adsorbability to metal surfaces. Nanoparticles with different ratios of amino and alkyl ligands were investigated. In comparison to an untreated lubricant, BHSNs reduce the friction coefficient and wear scar diameter by 40% and 60%, respectively. The wear mechanism of BHSNs was investigated, and the protective and filling effect of the nanoparticles improved because of collaboration of amino and alkyl ligands.

  18. Novel 3-nitrotriazole-based amides and carbinols as bifunctional antichagasic agents.

    PubMed

    Papadopoulou, Maria V; Bloomer, William D; Lepesheva, Galina I; Rosenzweig, Howard S; Kaiser, Marcel; Aguilera-Venegas, Benjamín; Wilkinson, Shane R; Chatelain, Eric; Ioset, Jean-Robert

    2015-02-12

    3-Nitro-1H-1,2,4-triazole-based amides with a linear, rigid core and 3-nitrotriazole-based fluconazole analogues were synthesized as dual functioning antitrypanosomal agents. Such compounds are excellent substrates for type I nitroreductase (NTR) located in the mitochondrion of trypanosomatids and, at the same time, act as inhibitors of the sterol 14α-demethylase (T. cruzi CYP51) enzyme. Because combination treatments against parasites are often superior to monotherapy, we believe that this emerging class of bifunctional compounds may introduce a new generation of antitrypanosomal drugs. In the present work, the synthesis and in vitro and in vivo evaluation of such compounds is discussed. PMID:25580906

  19. Mono- and bi-functional arenethiols as surfactants for gold nanoparticles: synthesis and characterization

    PubMed Central

    2011-01-01

    Stable gold nanoparticles stabilized by different mono and bi-functional arenethiols, namely, benzylthiol and 1,4-benzenedimethanethiol, have been prepared by using a modified Brust's two-phase synthesis. The size, shape, and crystalline structure of the gold nanoparticles have been determined by high-resolution electron microscopy and full-pattern X-ray powder diffraction analyses. Nanocrystals diameters have been tuned in the range 2 ÷ 9 nm by a proper variation of Au/S molar ratio. The chemical composition of gold nanoparticles and their interaction with thiols have been investigated by X-ray photoelectron spectroscopy. In particular, the formation of networks has been observed with interconnected gold nanoparticles containing 1,4-benzenedimethanethiol as ligand. PMID:21711615

  20. Mechanistic Insights into the Mode of Action of Bifunctional Pyrrolidine-Squaramide-Derived Organocatalysts.

    PubMed

    Roca-López, David; Uria, Uxue; Reyes, Efraim; Carrillo, Luisa; Jørgensen, Karl Anker; Vicario, Jose L; Merino, Pedro

    2016-01-18

    The catalytic modes of action of three squaramide-derived bifunctional organocatalysts have been investigated using DFT methods. The [5+2] cycloaddition between oxidopyrylium ylides and enals was used as the model reaction. Two primary modes were possible for the different catalysts studied. The preference for one mode over the other was due to the possibility of additional favorable π-π interactions between the hydrogen-bond activated pyrylium ylide and an electron-deficient aromatic ring bonded to the squaramide NH group. The model can be extended to other reactions catalyzed by the same catalysts, such as formal [2+2] cycloadditions between nitroalkenes and α,β-unsaturated aldehydes. The computational results were in excellent concurrence with the available experimental reports on the observed total enantioselectivity and differences in diastereoselectivity depending on the substrate and the reaction. PMID:26612630

  1. Bi-Functional Biobased Packing of the Cassava Starch, Glycerol, Licuri Nanocellulose and Red Propolis

    PubMed Central

    Costa, Samantha Serra; Druzian, Janice Izabel; Machado, Bruna Aparecida Souza; de Souza, Carolina Oliveira; Guimarães, Alaíse Gil

    2014-01-01

    The aim of this study was to characterize and determine the bi-functional efficacy of active packaging films produced with starch (4%) and glycerol (1.0%), reinforced with cellulose nanocrystals (0–1%) and activated with alcoholic extracts of red propolis (0.4 to 1.0%). The cellulose nanocrystals used in this study were extracted from licuri leaves. The films were characterized using moisture, water-activity analyses and water vapor-permeability tests and were tested regarding their total phenolic compounds and mechanical properties. The antimicrobial and antioxidant efficacy of the films were evaluated by monitoring the use of the active films for packaging cheese curds and butter, respectively. The cellulose nanocrystals increased the mechanical strength of the films and reduced the water permeability and water activity. The active film had an antimicrobial effect on coagulase-positive staphylococci in cheese curds and reduced the oxidation of butter during storage. PMID:25383783

  2. A Cascade-Reaction Nanoreactor Composed of a Bifunctional Molecularly Imprinted Polymer that Contains Pt Nanoparticles.

    PubMed

    Wang, Jiao; Zhu, Maiyong; Shen, Xiaojuan; Li, Songjun

    2015-05-11

    This study was aimed at addressing the present challenge of cascade reactions, namely, how to furnish the catalysts with desired and hierarchical catalytic ability. This issue was addressed by constructing a cascade-reaction nanoreactor made of a bifunctional molecularly imprinted polymer containing acidic catalytic sites and Pt nanoparticles. The acidic catalytic sites within the imprinted polymer allowed one specified reaction, whereas the encapsulated Pt nanoparticles were responsible for another coupled reaction. To that end, the unique imprinted polymer was fabricated by using two well-coupled templates, that is, 4-nitrophenyl acetate and 4-nitrophenol. The catalytic hydrolysis of the former compound at the acidic catalytic sites led to the formation of the latter compound, which was further reduced by the encapsulated Pt nanoparticles to 4-aminophenol. Therefore, this nanoreactor demonstrated a catalytic-cascade ability. This protocol opens up the opportunity to develop functional catalysts for complicated chemical processes. PMID:25846700

  3. Bifunctional mechanism of catalysis in reactions leading to formation of /alpha/-amino ketones

    SciTech Connect

    Popov, A.F.; Anikeev, A.V.

    1988-10-20

    The kinetics of the reaction of /alpha/-bromoacetophenone and benzyl bromide with aniline and pyridine in the presence of additions of acetic acid and phenol in benzene at 30/degree/C were investigated. The catalytic effects due to the activity of the uncombined forms of the catalyst, their dimers, and their 1:1 complexes with the amines were separated quantitatively. The change in the catalytic activity of the respective particles in the solutions with variation in the structure of the reagents is examined, and possible mechanisms for the catalytic reactions are discussed on this basis. It is concluded that there is a bifunctional mechanism of catalysis by acetic acid in the reaction of /alpha/-bromoacetophenone with aniline.

  4. RNA Secondary Structure Modulates FMRP's Bi-Functional Role in the MicroRNA Pathway.

    PubMed

    Kenny, Phillip; Ceman, Stephanie

    2016-01-01

    MicroRNAs act by post-transcriptionally regulating the gene expression of 30%-60% of mammalian genomes. MicroRNAs are key regulators in all cellular processes, though the mechanism by which the cell activates or represses microRNA-mediated translational regulation is poorly understood. In this review, we discuss the RNA binding protein Fragile X Mental Retardation Protein (FMRP) and its role in microRNA-mediated translational regulation. Historically, FMRP is known to function as a translational suppressor. However, emerging data suggests that FMRP has both an agonistic and antagonistic role in regulating microRNA-mediated translational suppression. This bi-functional role is dependent on FMRP's interaction with the RNA helicase Moloney leukemia virus 10 (MOV10), which modifies the structural landscape of bound mRNA, therefore facilitating or inhibiting its association with the RNA-Induced Silencing Complex. PMID:27338369

  5. Eggplant-derived microporous carbon sheets: towards mass production of efficient bifunctional oxygen electrocatalysts at low cost for rechargeable Zn-air batteries.

    PubMed

    Li, Bing; Geng, Dongsheng; Lee, Xinjing Shannon; Ge, Xiaoming; Chai, Jianwei; Wang, Zhijuan; Zhang, Jie; Liu, Zhaolin; Hor, T S Andy; Zong, Yun

    2015-05-25

    We report 2D microporous carbon sheets with high surface area, derived from eggplant via simple carbonization and KOH activation, as low cost yet efficient bifunctional catalysts for high performance rechargeable zinc-air batteries. PMID:25920952

  6. Proteasome inhibitors act as bifunctional antagonists of human immunodeficiency virus type 1 latency and replication

    PubMed Central

    2013-01-01

    Background Existing highly active antiretroviral therapy (HAART) effectively controls viral replication in human immunodeficiency virus type 1 (HIV-1) infected individuals but cannot completely eradicate the infection, at least in part due to the persistence of latently infected cells. One strategy that is being actively pursued to eliminate the latent aspect of HIV-1 infection involves therapies combining latency antagonists with HAART. However, discordant pharmacokinetics between these types of drugs can potentially create sites of active viral replication within certain tissues that might be impervious to HAART. Results A preliminary reverse genetic screen indicated that the proteasome might be involved in the maintenance of the latent state. This prompted testing to determine the effects of proteasome inhibitors (PIs) on latently infected cells. Experiments demonstrated that PIs effectively activated latent HIV-1 in several model systems, including primary T cell models, thereby defining PIs as a new class of HIV-1 latency antagonists. Expanding upon experiments from previous reports, it was also confirmed that PIs inhibit viral replication. Moreover, it was possible to show that PIs act as bifunctional antagonists of HIV-1. The data indicate that PIs activate latent provirus and subsequently decrease viral titers and promote the production of defective virions from activated cells. Conclusions These results represent a proof-of-concept that bifunctional antagonists of HIV-1 can be developed and have the capacity to ensure precise tissue overlap of anti-latency and anti-replication functions, which is of significant importance in the consideration of future drug therapies aimed at viral clearance. PMID:24156270

  7. Cobalt Selenide Nanostructures: An Efficient Bifunctional Catalyst with High Current Density at Low Coverage.

    PubMed

    Masud, Jahangir; Swesi, Abdurazag T; Liyanage, Wipula P R; Nath, Manashi

    2016-07-13

    Electrodeposited Co7Se8 nanostructures exhibiting flake-like morphology show bifunctional catalytic activity for oxygen evolution and hydrogen evolution reaction (OER and HER, respectively) in alkaline medium with long-term durability (>12 h) and high Faradaic efficiency (99.62%). In addition to low Tafel slope (32.6 mV per decade), the Co7Se8 OER electrocatalyst also exhibited very low overpotential to achieve 10 mA cm(-2) (0.26 V) which is lower than other transition metal chalcogenide based OER electrocatalysts reported in the literature and significantly lower than the state-of-the-art precious metal oxides. A low Tafel slope (59.1 mV per decade) was also obtained for the HER catalytic activity in alkaline electrolyte. The OER catalytic activity could be further improved by creating arrays of 3-dimensional rod-like and tubular structures of Co7Se8 through confined electrodeposition on lithographically patterned nanoelectrodes. Such arrays of patterned nanostructures produced exceptionally high mass activity and gravimetric current density (∼68 000 A g(-1)) compared to the planar thin films (∼220 A g(-1)). Such high mass activity of the catalysts underlines reduction in usage of the active material without compromising efficiency and their practical applicability. The catalyst layer could be electrodeposited on different substrates, and an effect of the substrate surface on the catalytic activity was also investigated. The Co7Se8 bifunctional catalyst enabled water electrolysis in alkaline solution at a cell voltage of 1.6 V. The electrodeposition works with exceptional reproducibility on any conducting substrate and shows unprecedented catalytic performance especially with the patterned growth of catalyst rods and tubes. PMID:27309595

  8. Luminomagnetic bifunctionality of Mn2+-bonded graphene oxide/reduced graphene oxide two dimensional nanosheets

    NASA Astrophysics Data System (ADS)

    Amandeep; Kedawat, Garima; Kumar, Pawan; Anshul, Avaneesh; Deshmukh, Abhay D.; Singh, Om Pal; Gupta, R. K.; Amritphale, S. S.; Gupta, Govind; Singh, V. N.; Gupta, Bipin Kumar

    2015-07-01

    Herein, we report the luminomagnetic bifunctional properties of two-dimensional (2D) Mn2+ bonded graphene oxide (GO)/reduced graphene oxide (RGO) nanosheets synthesized using a facile route of oxidation followed by a solvothermal reduction method. Photoluminescence (PL) studies (excited by different wavelengths) revealed that the resonant energy transfer between Mn2+ and sp3/sp2 clusters of GO/RGO is responsible for the enhancement of emissions. Moreover, pH-sensitive PL behaviors have also been investigated in detail. The ferromagnetic behavior is believed to arise due to defects in Mn2+ bonded GO composites. Thus, present reduction method provides a direct route to tune and enhance the optical properties of GO and RGO nanosheets bonded with Mn2+ ions, which creates an opportunity for various technological applications.Herein, we report the luminomagnetic bifunctional properties of two-dimensional (2D) Mn2+ bonded graphene oxide (GO)/reduced graphene oxide (RGO) nanosheets synthesized using a facile route of oxidation followed by a solvothermal reduction method. Photoluminescence (PL) studies (excited by different wavelengths) revealed that the resonant energy transfer between Mn2+ and sp3/sp2 clusters of GO/RGO is responsible for the enhancement of emissions. Moreover, pH-sensitive PL behaviors have also been investigated in detail. The ferromagnetic behavior is believed to arise due to defects in Mn2+ bonded GO composites. Thus, present reduction method provides a direct route to tune and enhance the optical properties of GO and RGO nanosheets bonded with Mn2+ ions, which creates an opportunity for various technological applications. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr01095k

  9. Increased Catalytic Efficiency Following Gene Fusion of Bifunctional Methionine Sulfoxide Reductase Enzymes from Shewanella oneidensis

    SciTech Connect

    Chen, Baowei; Markillie, Lye Meng; Xiong, Yijia; Mayer, M. Uljana; Squier, Thomas C.

    2007-11-11

    Methionine sulfoxide reductase enzymes MsrA and MsrB have complementary stereospecificies that respectively reduce the S- and R-stereoisomers of methionine sulfoxide (MetSO), and together function as critical antioxidant enzymes. In some pathogenic and metal reducing bacteria these genes are fused to form a bifunctional methionine sulfoxide reductase (i.e., MsrBA) enzyme. To investigate the impact of gene fusion on the substrate specificity and catalytic activities of Msr, we have cloned and expressed the MsrBA enzyme from Shewanella oneidensis, a metal reducing bacterium and fish pathogen. For comparison, we also cloned and expressed the wild-type MsrA enzyme and a genetically engineered MsrB protein. We report that MsrBA is able to completely reduce (i.e., repair) MetSO in the calcium regulatory protein calmodulin; in comparison only partial repair is observed using both MsrA and MsrB enzymes together at 25 °C. MsrBA has a twenty-fold enhanced rate of repair for MetSO in proteins in comparison with the individual MsrA or MsrB enzymes alone and respective 14- and 50-fold increases in catalytic efficiency (i.e., kcat/KM). In comparison, MsrBA and MsrA have similar catalytic efficiencies when free MetSO is used as a substrate. These results indicate that the individual domains within bifunctional MsrBA work cooperatively to selectively recognize and reduce MetSO in highly oxidized proteins. The enhanced catalytic activity of MsrBA against oxidized proteins and its common expression in bacterial pathogens is consistent with an important role for this enzyme activity in promoting bacterial survival under highly oxidizing conditions associated with pathogenesis or bioremediation.

  10. Mitigation of nitrogen mustard mediated skin injury by a novel indomethacin bifunctional prodrug.

    PubMed

    Composto, Gabriella M; Laskin, Jeffrey D; Laskin, Debra L; Gerecke, Donald R; Casillas, Robert P; Heindel, Ned D; Joseph, Laurie B; Heck, Diane E

    2016-06-01

    Nitrogen mustard (NM) is a bifunctional alkylating agent that is highly reactive in the skin causing extensive tissue damage and blistering. In the present studies, a modified cutaneous murine patch model was developed to characterize NM-induced injury and to evaluate the efficacy of an indomethacin pro-drug in mitigating toxicity. NM (20μmol) or vehicle control was applied onto 6mm glass microfiber filters affixed to the shaved dorsal skin of CD-1 mice for 6min. This resulted in absorption of approximately 4μmol of NM. NM caused localized skin damage within 1 d, progressing to an eschar within 2-3 d, followed by wound healing after 4-5 d. NM-induced injury was associated with increases in skin thickness, inflammatory cell infiltration, reduced numbers of sebocytes, basal keratinocyte double stranded DNA breaks, as measured by phospho-histone 2A.X expression, mast cell degranulation and increases in inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Wound healing was characterized by epidermal hyperplasia and marked increases in basal cells expressing proliferating cell nuclear antigen. A novel indomethacin-anticholinergic prodrug (4338) designed to target cyclooxygenases and acetylcholinesterase (AChE), was found to markedly suppress NM toxicity, decreasing wound thickness and eschar formation. The prodrug also inhibited mast cell degranulation, suppressed keratinocyte expression of iNOS and COX-2, as well as markers of epidermal proliferation. These findings indicate that a novel bifunctional pro-drug is effective in limiting NM mediated dermal injury. Moreover, our newly developed cutaneous patch model is a sensitive and reproducible method to assess the mechanism of action of countermeasures. PMID:27189522

  11. Dimerization and Bifunctionality Confer Robustness to the Isocitrate Dehydrogenase Regulatory System in Escherichia coli*

    PubMed Central

    Dexter, Joseph P.; Gunawardena, Jeremy

    2013-01-01

    An important goal of systems biology is to develop quantitative models that explain how specific molecular features give rise to systems-level properties. Metabolic and regulatory pathways that contain multifunctional proteins are especially interesting to study from this perspective because they have frequently been observed to exhibit robustness: the ability for a system to perform its proper function even as levels of its components change. In this study, we use extensive biochemical data and algebraic modeling to develop and analyze a model that shows how robust behavior arises in the isocitrate dehydrogenase (IDH) regulatory system of Escherichia coli, which was shown in 1985 to experimentally exhibit robustness. E. coli IDH is regulated by reversible phosphorylation catalyzed by the bifunctional isocitrate dehydrogenase kinase/phosphatase (IDHKP), and the level of IDH activity determines whether carbon flux is directed through the glyoxylate bypass (for growth on two-carbon substrates) or the full tricarboxylic acid cycle. Our model, which incorporates recent structural data on IDHKP, identifies several specific biochemical features of the system (including homodimerization of IDH and bifunctionality of IDHKP) that provide a potential explanation for robustness. Using algebraic techniques, we derive an invariant that summarizes the steady-state relationship between the phospho-forms of IDH. We use the invariant in combination with kinetic data on IDHKP to calculate IDH activity at a range of total IDH levels and find that our model predicts robustness. Our work unifies much of the known biochemistry of the IDH regulatory system into a single quantitative framework and highlights the importance of constructing biochemically realistic models in systems biology. PMID:23192354

  12. Fabrication and characterization of the nano-composite of whey protein hydrolysate chelated with calcium.

    PubMed

    Xixi, Cai; Lina, Zhao; Shaoyun, Wang; Pingfan, Rao

    2015-03-01

    The nano-composites of whey protein hydrolysate (WPH) chelated with calcium were fabricated in aqueous solution at 30 °C for 20 min, with the ratio of hydrolysate to calcium 15 : 1 (w/w). UV scanning spectroscopy, fluorescent spectroscopy, Fourier transform infrared spectroscopy, dynamic light scattering and atomic force microscopy were applied to characterize the structure of the WPH-calcium chelate. The nano-composites showed the successful incorporation of calcium into the WPH, indicating the interaction between calcium and WPH. The chelation of calcium ions to WPH caused molecular folding and aggregation which led to the formation of a WPH-calcium chelate of nanoparticle size, and the principal sites of calcium-binding corresponded to the carboxyl groups and carbonyl groups of WPH. The WPH-calcium chelate demonstrated excellent stability and absorbability under both acidic and basic conditions, which was beneficial for calcium absorption in the gastrointestinal tract of the human body. Moreover, the calcium absorption of the WPH-calcium chelate on Caco-2 cells was significantly higher than those of calcium gluconate and CaCl₂ in vitro, suggesting the possible increase in calcium bioavailability. The findings suggest that the WPH-calcium chelate has the potential in making dietary supplements for improving bone health of the human body. PMID:25588126

  13. Effect of iron chelators on placental uptake and transfer of iron in rat

    SciTech Connect

    Wong, C.T.; McArdle, H.J.; Morgan, E.H.

    1987-05-01

    The uptake of radiolabeled transferrin and iron by the rat placenta has been studied using two approaches. The first involved injection of a ferrous or ferric iron chelator followed by injection of label. Neither chelator decreased the amount of labelled transferrin in the placenta after 2-h incubation and only bipyridine, a ferrous iron chelator, inhibited iron transport to the fetus. Deferoxamine (DFO), a ferric iron chelator, had no effect on iron transport to the fetus but reduced iron uptake by the liver. Both bipyridine and DFO increased iron excretion into the gut and by the urinary tract to the same degree into the gut, but there was a 10-fold greater urinary excretion with bipyridine than with DFO. Injection of iron attached to the chelators showed that neither bipyridine nor DFO could donate iron to the fetus as efficiently as transferrin. The mechanism involved was further investigated by studying the effect of the chelators on uptake of transferrin-bound iron by placental cells in culture. DFO inhibited iron accumulation more effectively than bipyridine in the cultured cells. The effect was not due to a decrease in the cycling time of the receptor. The results can be explained if the iron is released from the transferrin in intracellular vesicles in the ferrous form, where it may be chelated by bipyridine and prevented from passing to the fetus or converted to the ferric form once it is inside the cell matrix.

  14. 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. PMID:12475278

  15. Generation, Fractionation, and Characterization of Iron-Chelating Protein Hydrolysate from Palm Kernel Cake Proteins.

    PubMed

    Zarei, Mohammad; Ghanbari, Rahele; Tajabadi, Naser; Abdul-Hamid, Azizah; Bakar, Fatimah Abu; Saari, Nazamid

    2016-02-01

    Palm kernel cake protein was hydrolyzed with different proteases namely papain, bromelain, subtilisin, flavourzyme, trypsin, chymotrypsin, and pepsin to generate different protein hydrolysates. Peptide content and iron-chelating activity of each hydrolysate were evaluated using O-phthaldialdehyde-based spectrophotometric method and ferrozine-based colorimetric assay, respectively. The results revealed a positive correlation between peptide contents and iron-chelating activities of the protein hydrolysates. Protein hydrolysate generated by papain exhibited the highest peptide content of 10.5 mM and highest iron-chelating activity of 64.8% compared with the other hydrolysates. Profiling of the papain-generated hydrolysate by reverse phase high performance liquid chromatography fractionation indicated a direct association between peptide content and iron-chelating activity in most of the fractions. Further fractionation using isoelectric focusing also revealed that protein hydrolysate with basic and neutral isoelectric point (pI) had the highest iron-chelating activity, although a few fractions in the acidic range also exhibited good metal chelating potential. After identification and synthesis of papain-generated peptides, GGIF and YLLLK showed among the highest iron-chelating activities of 56% and 53%, whereas their IC50 were 1.4 and 0.2 μM, respectively. PMID:26720491

  16. 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.

  17. Absorption of nitric oxide into aqueous solutions of ferrous chelates accompanied by instantaneous reaction

    SciTech Connect

    Demmink, J.F.; Gils, I.C.F. van; Beenackers, A.A.C.M.

    1997-11-01

    The absorption of nitric oxide (NO) into aqueous solutions of ferrous chelates of nitrilotriacetic acid (NTA), ethylenediaminetetraacetic acid (EDTA), hydroxyethylenediaminetriacetic acid (HEDTA), and diethylenetriaminepentaacetic acid (DTPA) was studied in a stirred cell reactor. The absorption leads to stable ferrous NO chelates. Due to the high reaction rate, in combination with the relatively high P{sub NO} applied, the absorption rate is strongly affected by mass transfer limitation only. By applying penetration theory, the ratio of the diffusion coefficients of ferrous chelates and NO was determined. At elevated T, (D{sub Fe(II)chelate}/D{sub NO}){sup 1/2} decreases due to the unusual T-dependency of D{sub NO}. For ferrous NTA, the formation of the ferrous NO chelate is accompanied by pH effects that can be understood from iron chelate chemistry. In the case of ferrous NTA, pH < 5, or an excess of ligand, these effects lead to local pH gradients at the gas-liquid interface, that substantially affect the NO absorption rates. Kinetic data from the literature on the absorption of NO into ferrous chelates were evaluated using the mass transfer parameters determined. These kinetic data are often unreliable.

  18. 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

  19. 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

    2016-01-01

    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

  20. Alternative/Complementary Approaches to Treatment of Children with Autism Spectrum Disorders.

    ERIC Educational Resources Information Center

    Levy, Susan E.; Hyman, Susan L.

    2002-01-01

    This article reviews common complementary or alternative medicine (CAM) treatments used to address symptoms of autistic spectrum disorders, including vitamin supplements, medications, antibiotics, antifungals, diet strategies, chelation/mercury detoxification, and nonbiologic treatments. Strategies that professionals may use in assessing the…

  1. 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+). PMID:19689133

  2. Alternate fuels

    SciTech Connect

    Ryan, T.W.; Worthen, R.P.

    1981-02-01

    The escalating oil prices and shortages of petroleum based fuels for transportation have made research work on various fuel alternatives, especially for transportation engines, a priority of both the private and public sectors. This book contains 18 papers on this subject. The range of options from the development of completely non-petroleum-based fuels and engines to the use of various non-petroleum gasoline and diesel fuel extenders and improvers are discussed.

  3. Alteration of tissue disposition of cadmium by chelating agents. [Mice; rats

    SciTech Connect

    Klaassen, C.D.; Waalkes, M.P.; Cantilena, L.R. Jr.

    1984-03-01

    The effect of several chelating agents (diethyldithiocarbamic acid, DDC; nitrilotriacetic acid, NTA; 2,3-dimercaptopropanol, BAL; d,l-penicillamine, PEN; 2,3-dimercaptosuccinic acid, DMSA; ethylenediaminetetraacetic acid, EDTA; and diethylenetriaminepentaacetic acid, DTPA) on the toxicity, distribution and excretion of cadmium (Cd) was determined in mice. When chelators were administered immediately after Cd, significant increases in survival were noted after treatment with DMSA, EDTA, and DTPA. DTPA, followed by EDTA and then DMSA, were consistently the most effective in decreasing the tissue concentrations of Cd and increasing the excretion of Cd. NTA, BAL, DDC and PEN had no beneficial effects. To determine the role of MT in the acute decrease in chelator efficacy following Cd poisoning, rats were injected IV with Cd followed by DTPA at various times after Cd. Although DTPA reduced Cd content in the various organs when given immediately after Cd, the chelator was ineffective at all later times. Increases in hepatic and renal metallothionein (MT) did not occur until 2 hr after Cd, and did not coincide with the earlier drop in chelator efficacy. Blockade of MT synthesis by actinomycin D failed to eliminate this decreased DTPA effectiveness. Therefore, it appears that MT does not play an important role in the acute decrease in efficacy of chelation therapy for Cd poisoning. The effect of repeated daily administration of chelators on the distribution and excretion of Cd was studied by administering chelators daily for 5 days starting 48 hr after Cd. DTPA, EDTA, DMSA and BAL significantly increased the urinary elimination of Cd. Thus, mobilization of Cd into urine occurs with repeated chelation therapy, which may decrease tissue concentrations of Cd and reduce the toxicity of the metal. 4 references, 15 figures, 2 tables.

  4. 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

  5. Physicochemical properties of skim milk powders prepared with the addition of mineral chelators.

    PubMed

    Sikand, V; Tong, P S; Vink, Sean; Roy, Soma

    2016-06-01

    The objective of this study was to determine the effect of mineral chelator addition during skim milk powder (SMP) manufacture on the solubility, turbidity, soluble protein, and heat stability (HS). Three chelators (sodium citrate dihydrate, sodium polyphosphate, and disodium EDTA) at 3 different concentrations (5, 15, and 25mM) were added to skim milk concentrate (30% total solids), and the pH was adjusted to 6.65 before spray drying to produce SMP. Spray-dried SMP samples were tested for solubility index (SI). Additionally, samples were reconstituted to contain 9% total solids, adjusted to pH 7.0, and tested for turbidity, protein content from supernatants of ultracentrifuged samples, and HS. Lower SI values were observed for samples treated with 5mM disodium EDTA and sodium polyphosphate than control samples or samples with 5mM sodium citrate dihydrate. Furthermore, lower SI values were observed with an increased level of chelating agents regardless of chelator type. A decreased turbidity value was found with increasing levels of mineral chelating salt treatment. Low turbidity with increasing levels of added chelators may be associated with the dissociation of caseins from micelles. Furthermore, higher protein content was observed in supernatants of ultracentrifuged samples treated with increased level of chelators as compared with the control sample. Higher HS was observed in samples treated with 5mM compared with samples treated with 25mM mineral chelator. The results suggest improved solubility and HS upon addition of mineral chelators to SMP during its manufacture. PMID:27040785

  6. Is Iron Chelation Important in Preventing Glycation of Bovine Serum Albumin in Vitro?

    PubMed

    Galiniak, Sabina; Bartosz, Grzegorz; Sadowska-Bartosz, Izabela

    2015-12-01

    The role of metal (especially) iron ions has been postulated to play a prominent role in protein glycation, suggesting antiglycating effectiveness of metal chelators. However, this rule may not apply to all model glycation systems. We found that metal chelators are not effective in prevention of glycation of bovine serum albumin (BSA) in vitro, and there is no correlation between the antiglycating effects of 32 compounds and their iron chelation activity as measured with the ferrozine test. These data indicate that the glycation of BSA in vitro is iron-independent and is not a proper system to study the role of metals in protein glycation. PMID:26146126

  7. 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.

  8. 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.

  9. Evaluation of chelating agents for radioimmunotherapy with scandium-47

    SciTech Connect

    Mausner, L.F.; Joshi, V.; Kolsky, K.L.

    1995-05-01

    Sc-47 has attractive properties [t{1/2} 3.35d, {beta}{sub max}:441 keV (68%), 601 keV (32%); {gamma} 159.4 keV (68%)] for radioimmunotherapy. Sc also displays favorable coordination chemistry for chelation attachment to antibodies. Due to chemical similarities to In and Y we have tested ligands with Sc-47 originally developed for use with In-111 or Y-90. The Scl-47 was produced with a fast neutron reaction Ti-47 (n,p). The radiochemical separation used cation exchange (AG-MP50) loaded with a 2% H{sub 2}O{sub 2} - 1 M H{sub 2}SO{sub 4} solution, followed by elution of Sc-47 with a 1 M NH{sub 4}{sub 2}SO{sub 4}/0.25 M H{sub 2}SO{sub 4} solution. Further separation and conversion of Sc to chloride form is achieved with a Chelex 100 column. No traces of Ti or Fe could be detected by spectrophotometric assay. Anti-CEA F(ab{prime});{sub 2} antibody conjugates of the following chelates were used for labeling studies: 4-isothiocyanato-cyclohexyl EDTA (4-ICE), N-hydroxysuccinimide ester of DOTA {l_angle}DOTA NHS{r_angle}, 2-{l_angle}p-SCN-Bz{r_angle}-6 methyl DTPA {l_angle}1B4MDTPA{r_angle} and conventional DTPA dianhydride. Labeling yields with Sc-47 were, 4-ICE 80%, DOTAQ-NHS 64%, 1B4MDTPA 98% and DTPA 62%. Serum stability of these preparations was essentially 100% out to 48 h except for DTPA (61%). The biodistribution {l_angle}% ID/g{r_angle} of these conjugates in human tumor xenografted nude mice {l_angle}LS-174% cells{r_angle} was compared. 4-ICE, DOTA-NHS and 1B4M-DTPA(15.4, 7.0, 7.0) but liver uptake was somewhat higher for DOTA-NHS than 4-ICE or 1B4M-DTPA (9.4, 5.8, 5.6). Generally faster whole body clearance for 1B4M-DTPA led to somewhat better tumor to organ ratios by 48 h. The poor stability of DTPA conjugate was evident with poor tumor uptake (12.4), high kidney (14.8), liver (17.1) and bone (3.6). We conclude that ligands which perform better with In-111 and Y-90 also give stable Sc-47 conjugates and their biodistributions are favorable for radioimmunotherapy.

  10. River-derived humic substances as iron chelators in seawater

    PubMed Central

    Krachler, Regina; Krachler, Rudolf F.; Wallner, Gabriele; Hann, Stephan; Laux, Monika; Cervantes Recalde, Maria F.; Jirsa, Franz; Neubauer, Elisabeth; von der Kammer, Frank; Hofmann, Thilo; Keppler, Bernhard K.

    2015-01-01

    The speciation of iron(III) in oxic seawater is dominated by its hydrolysis and sedimentation of insoluble iron(III)-oxyhydroxide. As a consequence, many oceanic areas have very low iron levels in surface seawater which leads to iron deficiency since phytoplankton require iron as a micronutrient in order to grow. Fortunately, iron solubility is not truly as low as Fe(III) solubility measurements in inorganic seawater would suggest, since oceanic waters contain organic molecules which tend to bind the iron and keep it in solution. Various iron-binding organic ligands which combine to stabilize dissolved iron have been detected and thoroughly investigated in recent years. However, the role of iron-binding ligands from terrestrial sources remains poorly constrained. Blackwater rivers supply large amounts of natural organic material (NOM) to the ocean. This NOM (which consists mainly of vascular plant-derived humic substances) is able to greatly enhance iron bioavailability in estuaries and coastal regions, however, breakdown processes lead to a rapid decrease of river-derived NOM concentrations with increasing distance from land. It has therefore been argued that the influence of river-derived NOM on iron biogeochemistry in offshore seawater does not seem to be significant. Here we used a standard method based on 59Fe as a radiotracer to study the solubility of Fe(III)-oxyhydroxide in seawater in the presence of riverine NOM. We aimed to address the question how effective is freshwater NOM as an iron chelator under open ocean conditions where the concentration of land-derived organic material is about 3 orders of magnitude smaller than in coastal regions, and does this iron chelating ability vary between NOM from different sources and between different size fractions of the river-borne NOM. Our results show that the investigated NOM fractions were able to substantially enhance Fe(III)-oxyhydroxide solubility in seawater at concentrations of the NOM ≥ 5

  11. Frequency-domain measurement of luminescent lanthanide chelates.

    PubMed

    Hyppänen, Iko; Soukka, Tero; Kankare, Jouko

    2010-08-01

    The sinusoidal modulation of excitation intensity and phase-sensitive detection of emission is ideally suitable for the accurate determination of the lifetime and intensity of lanthanide luminescence. In this work we elaborate on the general mathematical and instrumental techniques of the frequency-domain (FD) measurements in the low-frequency domain below 100 kHz. A modular FD luminometer is constructed by using a UV-LED as the excitation source, proper light filters in the excitation and emission paths, a photomultiplier with a fast preamplifier, and a conventional dual-phase lock-in amplifier. Starting from the set of linear differential equations governing the excited-state processes of the lanthanide chelates, an equation linking the luminescence intensity to the general form of the excitation modulation was derived. Application to the sinusoidal modulation in the Euler's exponential form gives the expression for the in-phase and out-of-phase signals of a dual-phase lock-in amplifier. It is shown that by using a relatively large number of logarithmically equidistant modulation frequencies it is possible to use the Kramers-Kronig relation for checking the compatibility of the out-of-phase and in-phase signals. As an example, the emission from two different europium(III) chelates were measured by using 200 modulation frequencies between 10 Hz and 100 kHz. In addition to the conventional transition between (5)D(0) and (7)F(2) levels emitting at 615 nm, also the emission from the transition between (5)D(1) and (7)F(1) levels at ca. 540 nm was measured. The latter emission was also measured at different temperatures, yielding the energy difference between the (5)D(1) and (5)D(0) levels. The relatively large number of modulation frequencies allows also an accurate determination of lifetimes and corresponding amplitudes by using an appropriate nonlinear regression method. Comparison of the time-domain and frequency-domain methods shows that the weighting of data is

  12. Modifications of boronic ester pro-chelators triggered by hydrogen peroxide tune reactivity to inhibit metal-promoted oxidative stress.

    PubMed

    Charkoudian, Louise K; Pham, David M; Kwon, Ashley M; Vangeloff, Abbey D; Franz, Katherine J

    2007-11-21

    Several new analogs of salicylaldehyde isonicotinoyl hydrazone (SIH) and salicylaldehyde benzoyl hydrazone (SBH) that contain an aryl boronic ester (BSIH, BSBH) or acid (BASIH) in place of an aryl hydroxide have been synthesized and characterized as masked metal ion chelators. These pro-chelators show negligible interaction with iron(III), although the boronic acid versions exhibit some interaction with copper(II), zinc(II) and nickel(II). Hydrogen peroxide oxidizes the aryl boronate to phenol, thus converting the pro-chelators to tridentate ligands with high affinity metal binding properties. An X-ray crystal structure of a bis-ligated iron(III) complex, [Fe(SBH(m-OMe)(3))(2)]NO(3), confirms the meridonal binding mode of these ligands. Modifications of the aroyl ring of the chelators tune their iron affinity, whereas modifications on the boron-containing ring of the pro-chelators attenuate their reaction rates with hydrogen peroxide. Thus, the methoxy derivative pro-chelator (p-OMe)BASIH reacts with hydrogen peroxide nearly 5 times faster than the chloro derivative (m-Cl)BASIH. Both the rate of pro-chelator to chelator conversion as well as the metal binding affinity of the chelator influence the overall ability of these molecules to inhibit hydroxyl radical formation catalyzed by iron or copper in the presence of hydrogen peroxide and ascorbic acid. This pro-chelator strategy has the potential to improve the efficacy of medicinal chelators for inhibiting metal-promoted oxidative stress. PMID:17992288

  13. A Speciation Study on the Perturbing Effects of Iron Chelators on the Homeostasis of Essential Metal Ions

    PubMed Central

    2015-01-01

    A number of reports have appeared in literature calling attention to the depletion of essential metal ions during chelation therapy on β-thalassaemia patients. We present a speciation study to determine how the iron chelators used in therapy interfere with the homeostatic equilibria of essential metal ions. This work includes a thorough analysis of the pharmacokinetic properties of the chelating agents currently in clinical use, of the amounts of iron, copper and zinc available in plasma for chelation, and of all the implied complex formation constants. The results of the study show that a significant amount of essential metal ions is complexed whenever the chelating agent concentration exceeds the amount necessary to coordinate all disposable iron —a frequently occurring situation during chelation therapy. On the contrary, copper and zinc do not interfere with iron chelation, except for a possible influence of copper on iron speciation during deferiprone treatment. PMID:26192307

  14. Alternative fuels

    NASA Technical Reports Server (NTRS)

    Grobman, J. S.; Butze, H. F.; Friedman, R.; Antoine, A. C.; Reynolds, T. W.

    1977-01-01

    Potential problems related to the use of alternative aviation turbine fuels are discussed and both ongoing and required research into these fuels is described. This discussion is limited to aviation turbine fuels composed of liquid hydrocarbons. The advantages and disadvantages of the various solutions to the problems are summarized. The first solution is to continue to develop the necessary technology at the refinery to produce specification jet fuels regardless of the crude source. The second solution is to minimize energy consumption at the refinery and keep fuel costs down by relaxing specifications.

  15. Lead analysis by anti-chelate fluorescence polarization immunoassay.

    PubMed

    Johnson, David K; Combs, Sherry M; Parsen, John D; Jolley, Michael E

    2002-03-01

    Lead concentrations were determined by a fluorescence polarization immunoassay (FPIA) method that uses polyclonal antibodies raised against the lead(II) chelate of ethylenediamine-N,N,N',N'-tetraacetic acid (EDTA). The technique is based on competition for a fixed concentration of antibody binding sites between Pb-EDTA, formed by treating the sample with excess EDTA, and a fixed concentration of a fluorescent analogue of the Pb-EDTA complex. The objective was to correlate results obtained by FPIA with those produced by conventional atomic spectroscopy analysis of soils, solid waste leachates (produced by the Toxicity Characteristic Leachate Procedure; TCLP), airborne dust, and drinking water. Linear regression analysis of FPIA results for 138 soil samples containing 0-3094 ppm Pb(II) by flame atomic absorption spectroscopy and 40 TCLP extracts containing 0-668 ppm Pb(II) by inductively coupled plasma atomic emission spectroscopy produced correlation coefficients (r2) of 0.96 and 0.93, respectively. Pilot studies of mineral acid extracts of airborne dust trapped on fiberglass filters and of two sources of drinking water demonstrated the feasibility of also measuring lead in these matrixes by FPIA. The limit of detection under conditions that minimized sample dilution was approximately 1 ppb, and cross reactivity with 15 nontarget metals was below 0.5% in all cases. The methods are simple to perform and are amenable to field testing and mobile laboratory use, allowing timely and cost-effective characterization of suspected sources of lead contamination. PMID:11917989

  16. Shape control of magnesium oxysulfate granules using an ethanolamine chelate.

    PubMed

    Kang, Kuk-Hyoun; Lee, Dong-Kyu; Ruh, Hyun; Ahn, Seonghee; Yu, Hyunung

    2014-11-01

    Shape control of inorganic nanomaterials during hydrothermal syntheses is crucial for fine-tuning the function of these materials, which are widely utilized in semiconductors, ceramics, and optical devices. In particular, magnesium compounds possess many desirable physical properties such as high thermal stability, wide band gap and high secondary electron emission yield, which allow their application as polymeric resins, cements, reinforcements, and fillers. However, conventional synthetic methods often require extreme reaction conditions such as high temperatures, high pressures, or prolonged reaction times. Additionally, various shape control methods are typically quite complicated and time consuming under conventional parameters. In this work, magnesium oxysulfate (5Mg(OH)2 x MgSO4 x 3H2O) granules of various shapes were fabricated by introducing ethanolamine chelate during hydrothermal reaction at a relatively low temperature and pressure. The strong interaction between ethanolamine and Mg2+ produced 5Mg(OH)2 x MgSO4 x 3H2O granules in the form of flakes, flowers, or whiskers through self-assembly this formation is dependent on concentration, reaction time, and temperature. The physicochemical properties of the samples were investigated using X-ray diffraction, field emission scanning electron microscopy, transmission electron microscopy, Fourier transform infrared spectroscopy, and thermogravimetric analysis. PMID:25958602

  17. Multifunctional iron-chelators with protective roles against neurodegenerative diseases.

    PubMed

    Nunes, Andreia; Marques, Sérgio M; Quintanova, Catarina; Silva, Diana F; Cardoso, Sandra M; Chaves, Sílvia; Santos, M Amélia

    2013-05-01

    The multifactorial nature of Alzheimer's disease (AD), and the absence of a disease modifying drug, makes the development of new multifunctional drugs an attractive therapeutic strategy. Taking into account the hallmarks of AD patient brains, such as low levels of acetylcholine, misfolding of proteins and associated beta-amyloid (Aβ) aggregation, oxidative stress and metal dyshomeostasis, we have developed a series of compounds that merge three different approaches: metal attenuation, anti-Aβ aggregation and anti-acetylcholinesterase activity. Therefore, 3-hydroxy-4-pyridinone (3,4-HP) and benzothiazole molecular moieties were selected as starting frameworks due to their well known affinity for iron and Aβ peptides, respectively. The linkers between these two main functional groups were selected on the basis of virtual screening, so that the final molecule could further inhibit the acetylcholinesterase, responsible for the cholinergic losses. We describe herein the design and synthesis of the new hybrid compounds, followed by the assessment of solution properties, namely iron chelation and anti-oxidant capacity. The compounds were bioassayed for their capacity to inhibit AChE, as well as self- and Zn mediated-Aβ(1-42) aggregation. Finally, we assessed their effects on the viability of neuronal cells stressed with Aβ(42). PMID:23487286

  18. Chelating water-soluble polymers for waste minimization

    SciTech Connect

    Smith, B.; Cournoyer, M.; Duran, B.; Ford, D.; Gibson, R.; Lin, M.; Meck, A.; Robinson, P.; Robison, T.

    1996-11-01

    Within the DOE complex and in industry there is a tremendous need for advanced metal ion recovery and waste minimization techniques. This project sought to employ capabilities for ligand-design and separations chemistry in which one can develop and evaluate water- soluble chelating polymers for recovering actinides and toxic metals from various process streams. Focus of this work was (1) to develop and select a set of water-soluble polymers suitable for a selected waste stream and (2) demonstrate this technology in 2 areas: removal of (a) actinides and toxic RCRA metals from waste water and (b) recovery of Cu and other precious metals from industrial process streams including from solid catalysts and aqueous waste streams. The R&D was done in 4 phases for each of the 2 target areas: polymer synthesis for scaleup, equipment assembly, process demonstration at a DOE or industrial site, and advanced ligand/polymer synthesis. The TA- 50 site at Los Alamos was thought to be appropriate due to logistics and to its being representative of similar problems throughout the DOE complex.

  19. Chelating ability and biological activity of hesperetin Schiff base.

    PubMed

    Lodyga-Chruscinska, Elzbieta; Symonowicz, Marzena; Sykula, Anna; Bujacz, Anna; Garribba, Eugenio; Rowinska-Zyrek, Magdalena; Oldziej, Stanislaw; Klewicka, Elzbieta; Janicka, Magdalena; Krolewska, Karolina; Cieslak, Marcin; Brodowska, Katarzyna; Chruscinski, Longin

    2015-02-01

    Hydrazone hesperetin Schiff base (HHSB) - N-[(±)-[5,7-dihydroxy-2-(3-hydroxy-4-methoxy-phenyl)chroman-4-ylidene]amino]benzamide has been synthesized and its crystal structure was determined. This compound was used for the formation of Cu(II) complexes in solid state and in solution which were characterized using different spectroscopic methods. The analyses of potentiometric titration curves revealed that monomeric and dimeric complexes of Cu(II) are formed above pH7. The ESI-MS (electrospray ionization-mass spectrometry) spectra confirmed their formation. The EPR and UV-visible spectra evidenced the involvement of oxygen and nitrogen atoms in Cu(II) coordination. Hydrazone hesperetin Schiff base can show keto-enol tautomerism and coordinate Cu(II) in the keto (O(-), N, Oket) and in the enolate form (O(-), N, O(-)enol). The semi-empirical molecular orbital method PM6 and DFT (density functional theory) calculations have revealed that the more stable form of the dimeric complex is that one in which the ligand is present in the enol form. The CuHHSB complex has shown high efficiency in the cleavage of plasmid DNA in aqueous solution, indicating its potential as chemical nuclease. Studies on DNA interactions, antimicrobial and cytotoxic activities have been undertaken to gain more information on the biological significance of HHSB and copper(II)-HHSB chelate species. PMID:25486205

  20. mer and fac isomerism in tris chelate diimine metal complexes.

    PubMed

    Dabb, Serin L; Fletcher, Nicholas C

    2015-03-14

    In this perspective, we highlight the issue of meridional (mer) and facial (fac) orientation of asymmetrical diimines in tris-chelate transition metal complexes. Diimine ligands have long been the workhorse of coordination chemistry, and whilst there are now good strategies to isolate materials where the inherent metal centered chirality is under almost complete control, and systematic methodologies to isolate heteroleptic complexes, the conceptually simple geometrical isomerism has not been widely investigated. In systems where the two donor atoms are significantly different in terms of the σ-donor and π-accepting ability, the fac isomer is likely to be the thermodynamic product. For the diimine complexes with two trigonal planar nitrogen atoms there is much more subtlety to the system, and external factors such as the solvent, lattice packing and the various steric considerations play a delicate role in determining the observed and isolable product. In this article we discuss the possibilities to control the isomeric ratio in labile systems, consider the opportunities to separate inert complexes and discuss the observed differences in their spectroscopic properties. Finally we report on the ligand orientation in supramolecular systems where facial coordination leads to simple regular structures such as helicates and tetrahedra, but the ability of the ligand system to adopt a mer orientation enables self-assembled structures of considerable beauty and complexity. PMID:25600485

  1. Purification, crystallization and preliminary X-ray crystallographic analysis of rice bifunctional α-amylase/subtilisin inhibitor from Oryza sativa

    SciTech Connect

    Lin, Yi-Hung; Peng, Wen-Yan; Huang, Yen-Chieh; Guan, Hong-Hsiang; Hsieh, Ying-Cheng; Liu, Ming-Yih; Chang, Tschining; Chen, Chun-Jung

    2006-08-01

    The crystallization of rice α-amylase/subtilisin bifunctional inhibitor is reported. Rice bifunctional α-amylase/subtilisin inhibitor (RASI) can inhibit both α-amylase from larvae of the red flour beetle (Tribolium castaneum) and subtilisin from Bacillus subtilis. The synthesis of RASI is up-regulated during the late milky stage in developing seeds. The 8.9 kDa molecular-weight RASI from rice has been crystallized using the hanging-drop vapour-diffusion method. According to 1.81 Å resolution X-ray diffraction data from rice RASI crystals, the crystal belongs to space group P2{sub 1}2{sub 1}2, with unit-cell parameters a = 79.99, b = 62.95, c = 66.70 Å. Preliminary analysis indicates two RASI molecules in an asymmetric unit with a solvent content of 44%.

  2. Spinel Mn-Co oxide in N-doped carbon nanotubes as a bifunctional electrocatalyst synthesized by oxidative cutting.

    PubMed

    Zhao, Anqi; Masa, Justus; Xia, Wei; Maljusch, Artjom; Willinger, Marc-Georg; Clavel, Guylhaine; Xie, Kunpeng; Schlögl, Robert; Schuhmann, Wolfgang; Muhler, Martin

    2014-05-28

    The notorious instability of non-precious-metal catalysts for oxygen reduction and evolution is by far the single unresolved impediment for their practical applications. We have designed highly stable and active bifunctional catalysts for reversible oxygen electrodes by oxidative thermal scission, where we concurrently rupture nitrogen-doped carbon nanotubes and oxidize Co and Mn nanoparticles buried inside them to form spinel Mn-Co oxide nanoparticles partially embedded in the nanotubes. Impressively high dual activity for oxygen reduction and evolution is achieved using these catalysts, surpassing those of Pt/C, RuO2, and IrO2 and thus raising the prospect of functional low-cost, non-precious-metal bifunctional catalysts in metal-air batteries and reversible fuel cells, among others, for a sustainable and green energy future. PMID:24815686

  3. N,P-Codoped Carbon Networks as Efficient Metal-free Bifunctional Catalysts for Oxygen Reduction and Hydrogen Evolution Reactions.

    PubMed

    Zhang, Jintao; Qu, Liangti; Shi, Gaoquan; Liu, Jiangyong; Chen, Jianfeng; Dai, Liming

    2016-02-01

    The high cost and scarcity of noble metal catalysts, such as Pt, have hindered the hydrogen production from electrochemical water splitting, the oxygen reduction in fuel cells and batteries. Herein, we developed a simple template-free approach to three-dimensional porous carbon networks codoped with nitrogen and phosphorus by pyrolysis of a supermolecular aggregate of self-assembled melamine, phytic acid, and graphene oxide (MPSA/GO). The pyrolyzed MPSA/GO acted as the first metal-free bifunctional catalyst with high activities for both oxygen reduction and hydrogen evolution. Zn-air batteries with the pyrolyzed MPSA/GO air electrode showed a high peak power density (310 W g(-1) ) and an excellent durability. Thus, the pyrolyzed MPSA/GO is a promising bifunctional catalyst for renewable energy technologies, particularly regenerative fuel cells. PMID:26709954

  4. Vanadium nanobelts coated nickel foam 3D bifunctional electrode with excellent catalytic activity and stability for water electrolysis.

    PubMed

    Yu, Yu; Li, Pei; Wang, Xiaofang; Gao, Wenyu; Shen, Zongxu; Zhu, Yanan; Yang, Shuliang; Song, Weiguo; Ding, Kejian

    2016-05-19

    Pursuit of highly active, stable and low-cost electrocatalysts for hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) is the key point for large-scale water splitting. A vanadium nanobelts coating on a nickel foam (V/NF) is proposed as an excellent 3D bifunctional electrode for water electrolysis here, which exhibits high activities with overpotentials of 292 and 176 mV at 10 mA cm(-2) for OER and HER, respectively. When employed as a bifunctional electrocatalyst in an alkaline water electrolyzer, a cell voltage of 1.80 V was required to achieve 20 mA cm(-2) with a slight increase during a 24 h durability test. The existence of the appropriate amount of nitrogen and oxygen elements in the surface region of vanadium nanobelts is regarded to be responsible for the electrocatalytic activity. PMID:27152646

  5. MOFs as multifunctional catalysts: one-pot synthesis of menthol from citronellal over a bifunctional MIL-101 catalyst.

    PubMed

    Cirujano, F G; Llabrés i Xamena, F X; Corma, A

    2012-04-14

    A bifunctional MOF catalyst containing coordinatively unsaturated Cr(3+) sites and palladium nanoparticles (Pd@MIL-101) has been used for the cyclization of citronellal to isopulegol and for the one-pot tandem isomerization/hydrogenation of citronellal to menthol. The MOF was found to be stable under the reaction conditions used, and the results obtained indicate that the performance of this bifunctional solid catalyst is comparable with other state-of-the-art materials for the tandem reaction: Full citronellal conversion was attained over Pd@MIL-101 in 18 h, with 86% selectivity to menthols and a diastereoselectivity of 81% to the desired (-)-menthol, while up to 30 h were necessary for attaining similar values over Ir/H-beta under analogous reaction conditions. PMID:22382815

  6. Vertically integrated translational studies of PDX1 as a therapeutic target for pancreatic cancer via a novel bifunctional RNAi platform.

    PubMed

    Wu, J; Liu, S; Yu, J; Zhou, G; Rao, D; Jay, C M; Kumar, P; Sanchez, R; Templeton, N; Senzer, N; Maples, P; Nemunaitis, J; Brunicardi, F C

    2014-02-01

    RNA interference (RNAi) represents a powerful, new tool for scientific investigation as well as a promising new form of targeted gene therapy, with applications currently in clinical trials. Bifunctional short hairpin RNA (shRNA) are synthetic RNAi molecules, engineered to utilize multiple endogenous RNAi pathways to specifically silence target genes. Pancreatic and duodenal homeobox 1 (PDX1) is a key regulator of pancreatic development, β-cell differentiation, normal β-cell function and pancreatic cancer. Our aim is to review the process of identifying PDX1 as a specific, potential RNAi target in pancreatic cancer, as well as the underlying mechanisms and various forms of RNAi, with subsequent testing and development of PDX1-targeted bifunctional shRNA therapy. PMID:24457987

  7. Dual-Doped Molybdenum Trioxide Nanowires: A Bifunctional Anode for Fiber-Shaped Asymmetric Supercapacitors and Microbial Fuel Cells.

    PubMed

    Yu, Minghao; Cheng, Xinyu; Zeng, Yinxiang; Wang, Zilong; Tong, Yexiang; Lu, Xihong; Yang, Shihe

    2016-06-01

    A novel in situ N and low-valence-state Mo dual doping strategy was employed to significantly improve the conductivity, active-site accessibility, and electrochemical stability of MoO3 , drastically boosting its electrochemical properties. Consequently, our optimized N-MoO3-x nanowires exhibited exceptional performances as a bifunctional anode material for both fiber-shaped asymmetric supercapacitors (ASCs) and microbial fuel cells (MFCs). The flexible fiber-shaped ASC and MFC device based on the N-MoO3-x anode could deliver an unprecedentedly high energy density of 2.29 mWh cm(-3) and a remarkable power density of 0.76 μW cm(-1) , respectively. Such a bifunctional fiber-shaped N-MoO3-x electrode opens the way to integrate the electricity generation and storage for self-powered sources. PMID:27097987

  8. Chelating stability of an amphoteric chelating polymer flocculant with Cu(II), Pb(II), Cd(II), and Ni(II)

    NASA Astrophysics Data System (ADS)

    Liu, Lihua; Li, Yanhong; Liu, Xing; Zhou, Zhihua; Ling, Yulin

    2014-01-01

    The absorption spectra of Cu2+, Pb2+, Cd2+, and Ni2+ chelates of an amphoteric chelating polymer flocculant (ACPF) were measured by ultraviolet spectrophotometry, and their compositions and stability constants (β) were calculated. ACPF exhibited three apparent absorption peaks at 204, 251, and 285 nm. The sbnd CSS- group of ACPF reacted with Cu2+, Ni2+, Pb2+, and Cd2+ to form ACPF-Cu2+, ACPF-Ni2+, ACPF-Pb2+, and ACPF-Cd2+ chelates, respectively, according to a molar ratio of 2:1. The maximum absorption peaks of ACPF-Cu2+, ACPF-Ni2+, ACPF-Pb2+, and ACPF-Cd2+ appeared at 319, 326, 310, and 313.5 nm, respectively. The maximum absorption peaks of the chelates showed significant red shifting compared with the absorption peaks of ACPF. The β values of the ACPF-Cu2+, ACPF-Pb2+, ACPF-Cd2+, and ACPF-Ni2+ chelates were (1.37 ± 0.35) × 1012, (3.26 ± 0.39) × 1011, (2.05 ± 0.27) × 1011, and (3.04 ± 0.45) × 1010, respectively. The leaching rate of heavy metal ions from the chelating precipitates decreased with increasing pH. ACPF-Cu2+, ACPF-Ni2+, ACPF-Pb2+, and ACPF-Cd2+ were very stable at pH ⩾ 5.6. Cu2+, Ni2+, Pb2+, and Cd2+ concentrations in the leaching liquors were lower than the corresponding limits specified by the Integrated Wastewater Discharge Standard of China.

  9. Steps toward high specific activity labeling of biomolecules for therapeutic application: preparation of precursor [(188)Re(H(2)O)(3)(CO)(3)](+) and synthesis of tailor-made bifunctional ligand systems.

    PubMed

    Schibli, Roger; Schwarzbach, Rolf; Alberto, Roger; Ortner, Kirstin; Schmalle, Helmut; Dumas, Cécile; Egli, André; Schubiger, P August

    2002-01-01

    Two kit preparations of the organometallic precursor [(188)Re(H(2)O)(3)(CO)(3)](+) in aqueous media are presented. Method A uses gaseous carbon monoxide and amine borane (BH(3).NH(3)) as the reducing agent. In method B CO(g) is replaced by K(2)[H(3)BCO(2)] that releases carbon monoxide during hydrolysis. Both procedures afford the desired precursor in yields >85% after 10 min at 60 degrees C. HPLC and TLC analyses revealed 7 +/- 3% of unreacted (188)ReO(4)(-) and <5% of colloidal (188)ReO(2). Solutions of up to 14 GBq/mL Re-188 have been successfully carbonylated with these two methods. The syntheses of two tailor-made bifunctional ligand systems for the precursor [(188)Re(H(2)O)(3)(CO)(3)](+) are presented. The tridentate chelates consist of a bis[imidazol-2-yl]methylamine or an iminodiacetic acid moiety, respectively. Both types of ligand systems have been prepared with alkyl spacers of different length and a pendent primary amino or carboxylic acid functionality, enabling the amidic linkage to biomolecules. The tridentate coordination of the ligands to the rhenium-tricarbonyl core could be elucidated on the macroscopic level by X-ray structure analyses and 1D and 2D NMR experiments of two representative model complexes. On the nca level, the ligands allow labeling yields >95% with [(188)Re(H(2)O)(3)(CO)(3)](+) under mild reaction conditions (PBS buffer, 60 degrees C, 60 min) at ligand concentrations between 5 x 10(-4) M and 5 x 10(-5) M. Thus, specific activities of 22-220 GBq pe micromol of ligand could be achieved. Incubation of the corresponding Re-188 complexes in human serum at 37 degrees C revealed stabilities between 80 +/- 4% and 45 +/- 10% at 24 h, respectively, and 63 +/- 3% and 34 +/- 3% at 48 h postincubation in human serum depending on the chelating system. Decomposition product was mainly (188)ReO(4)(-). The routine kit-preparation of the precursor [(188)Re(H(2)O)(3)(CO)(3)](+) in combination with tailor-made ligand systems enables the

  10. BENCH-SCALE RECOVERY OF LEAD USING AND ELECTRO- MEMBRANE/CHELATION PROCESS

    EPA Science Inventory

    This report presents the results of a bench-scale treatability test to investigate key process parameters influencing an innovative chelation electrodeposition process for recovery of lead from contaminated sons. thylenediamine tetraacetic acid (EDTA) and diethylenetriamine penta...

  11. Highly Diastereoselective Chelation-controlled Additions to α-Silyloxy Ketones

    PubMed Central

    Stanton, Gretchen R.; Koz, Gamze

    2011-01-01

    The polar Felkin-Anh, Cornforth, and Cram-chelation models predict that the addition of organometallic reagents to silyl–protected α–hydroxy ketones proceeds via a non-chelation pathway to give anti-diol addition products. This prediction has held true for the vast majority of additions reported in the literature and few methods for chelation-controlled additions of organometallic reagents to silyl–protected α–hydroxy ketones have been introduced. Herein, we present a general and highly diastereoselective method for the addition of dialkylzincs and (E)-di-, (E)-tri- and (Z)-disubstituted vinylzinc reagents to α-silyloxy ketones using alkyl zinc halide Lewis acids, RZnX, to give chelation-controlled products (dr ≥18:1). The compatibility of organozinc reagents with other functional groups makes this method potentially very useful in complex molecule synthesis. PMID:21534530

  12. Simultaneous measurement of NK cell cytotoxicity against two target cell lines labelled with fluorescent lanthanide chelates.

    PubMed

    Lövgren, J; Blomberg, K

    1994-07-12

    We describe a cytotoxicity assay which permits the simultaneous measurement of natural killer cell activity against two different cell lines. The target cell lines are labelled either with a fluorescent europium chelate or with a fluorescent terbium chelate and cell death is quantified by measuring the chelate release. K-562, Molt4 and Daudi cell lines have been used as targets. The release of the two chelates from the target cells can be detected with the help of time resolved fluorometry. As the measurements are made after background fluorescence has decayed no additional steps are needed to correct for the background from the medium. The assay procedure used for measurement of cytotoxicity against two target cell lines is very similar to the widely used 51Cr release assay. PMID:8034979

  13. 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...

  14. Highly bright avidin-based affinity probes carrying multiple lanthanide chelates.

    PubMed

    Wirpsza, Laura; Pillai, Shyamala; Batish, Mona; Marras, Salvatore; Krasnoperov, Lev; Mustaev, Arkady

    2012-11-01

    Lanthanide ion luminescence has a long lifetime enabling highly sensitive detection in time-gated mode. The sensitivity can be further increased by using multiple luminescent labels attached to a carrier molecule, which can be conjugated to an object of interest. We found that up to 30 lanthanide chelates can be attached to avidin creating highly bright constructs. These constructs with Eu(3+) chelates display synergistic effect that enhance the brightness of heavily modified samples, while the opposite effect was observed for Tb(3+) chelates thereby significantly reducing their light emission. This undesirable quenching of Tb(3+) luminophores was completely suppressed by the introduction of an aromatic spacer between the chelate and the protein attachment site. The estimated detection limit for the conjugates is in the 10(-14)-10(-15) M range. We demonstrated a high sensitivity for the new probes by using them to label living cells of bacterial and mammalian origin. PMID:23018156

  15. Synergistic bifunctional catalyst design based on perovskite oxide nanoparticles and intertwined carbon nanotubes for rechargeable zinc-air battery applications.

    PubMed

    Lee, Dong Un; Park, Hey Woong; Park, Moon Gyu; Ismayilov, Vugar; Chen, Zhongwei

    2015-01-14

    Advanced morphology of intertwined core-corona structured bifunctional catalyst (IT-CCBC) is introduced where perovskite lanthanum nickel oxide nanoparticles (LaNiO3 NP) are encapsulated by high surface area network of nitrogen-doped carbon nanotubes (NCNT) to produce highly active and durable bifunctional catalyst for rechargeable metal-air battery applications. The unique composite morphology of IT-CCBC not only enhances the charge transport property by providing rapid electron-conduction pathway but also facilitates in diffusion of hydroxyl and oxygen reactants through the highly porous framework. Confirmed by electrochemical half-cell testing, IT-CCBC in fact exhibits very strong synergy between LaNiO3 NP and NCNT demonstrating bifunctionality with significantly improved catalytic activities of oxygen reduction reaction (ORR) and oxygen evolution reaction (OER). Furthermore, when compared to the state-of-art catalysts, IT-CCBC outperforms Pt/C and Ir/C in terms of ORR and OER, respectively, and shows improved electrochemical stability compared to them after cycle degradation testing. The practicality of the catalyst is corroborated by testing in a realistic rechargeable zinc-air battery utilizing atmospheric air in ambient conditions, where IT-CCBC demonstrates superior charge and discharge voltages and long-term cycle stability with virtually no battery voltage fading. These improved electrochemical properties of the catalyst are attributed to the nanosized dimensions of LaNiO3 NP controlled by simple hydrothermal technique, which enables prolific growth of and encapsulation by highly porous NCNT network. The excellent electrochemical results presented in this study highlight IT-CCBC as highly efficient and commercially viable bifunctional catalyst for rechargeable metal-air battery applications. PMID:25494945

  16. Highly active and durable core-corona structured bifunctional catalyst for rechargeable metal-air battery application.

    PubMed

    Chen, Zhu; Yu, Aiping; Higgins, Drew; Li, Hui; Wang, Haijiang; Chen, Zhongwei

    2012-04-11

    A new class of core-corona structured bifunctional catalyst (CCBC) consisting of lanthanum nickelate centers supporting nitrogen-doped carbon nanotubes (NCNT) has been developed for rechargeable metal-air battery application. The nanostructured design of the catalyst allows the core and corona to catalyze the oxygen evolution reaction (OER) and oxygen reduction reaction (ORR), respectively. These materials displayed exemplary OER and ORR activity through half-cell testing, comparable to state of the art commercial lanthanum nickelate (LaNiO(3)) and carbon-supported platinum (Pt/C), with added bifunctional capabilities allowing metal-air battery rechargeability. LaNiO(3) and Pt/C are currently the most accepted benchmark electrocatalyst materials for the OER and ORR, respectively; thus with comparable activity toward both of these reactions, CCBC are presented as a novel, inexpensive catalyst component for the cathode of rechargeable metal-air batteries. Moreover, after full-range degradation testing (FDT) CCBC retained excellent activity, retaining 3 and 13 times greater ORR and OER current upon comparison to state of the art Pt/C. Zinc-air battery performances of CCBC is in good agreement with the half-cell experiments with this bifunctional electrocatalyst displaying high activity and stability during battery discharge, charge, and cycling processes. Owing to its outstanding performance toward both the OER and ORR, comparable with the highest performing commercial catalysts to date for each of the respective reaction, coupled with high stability and rechargeability, CCBC is presented as a novel class of bifunctional catalyst material that is very applicable to future generation rechargeable metal-air batteries. PMID:22372510

  17. Dynamic Kinetic Resolution of Biaryl Lactones via a Chiral Bifunctional Amine Thiourea-Catalyzed Highly Atropo-enantioselective Transesterification.

    PubMed

    Yu, Chenguang; Huang, He; Li, Xiangmin; Zhang, Yueteng; Wang, Wei

    2016-06-01

    A solution to the unmet synthetic challenge of achieving highly atropo-enantioselective transesterification of Bringmann's lactones has been realized, employing a chiral bifunctional amine thiourea as promoter. The synergistic activation of the lactones and alcohols/phenols by the respective thiourea and amine groups is crucial for achieving the highly enantioselective, high-yielding dynamic kinetic resolution process. This protocol gives highly optically pure, axially chiral biaryl compounds with a broad substrate scope under mild reaction conditions. PMID:27218264

  18. Vanadium nanobelts coated nickel foam 3D bifunctional electrode with excellent catalytic activity and stability for water electrolysis

    NASA Astrophysics Data System (ADS)

    Yu, Yu; Li, Pei; Wang, Xiaofang; Gao, Wenyu; Shen, Zongxu; Zhu, Yanan; Yang, Shuliang; Song, Weiguo; Ding, Kejian

    2016-05-01

    Pursuit of highly active, stable and low-cost electrocatalysts for hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) is the key point for large-scale water splitting. A vanadium nanobelts coating on a nickel foam (V/NF) is proposed as an excellent 3D bifunctional electrode for water electrolysis here, which exhibits high activities with overpotentials of 292 and 176 mV at 10 mA cm-2 for OER and HER, respectively. When employed as a bifunctional electrocatalyst in an alkaline water electrolyzer, a cell voltage of 1.80 V was required to achieve 20 mA cm-2 with a slight increase during a 24 h durability test. The existence of the appropriate amount of nitrogen and oxygen elements in the surface region of vanadium nanobelts is regarded to be responsible for the electrocatalytic activity.Pursuit of highly active, stable and low-cost electrocatalysts for hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) is the key point for large-scale water splitting. A vanadium nanobelts coating on a nickel foam (V/NF) is proposed as an excellent 3D bifunctional electrode for water electrolysis here, which exhibits high activities with overpotentials of 292 and 176 mV at 10 mA cm-2 for OER and HER, respectively. When employed as a bifunctional electrocatalyst in an alkaline water electrolyzer, a cell voltage of 1.80 V was required to achieve 20 mA cm-2 with a slight increase during a 24 h durability test. The existence of the appropriate amount of nitrogen and oxygen elements in the surface region of vanadium nanobelts is regarded to be responsible for the electrocatalytic activity. Electronic supplementary information (ESI) available: More SEM, TEM images, XRD patterns, LSV curves, XPS spectra. See DOI: 10.1039/c6nr02395a

  19. Iterative Coupling of Two Different Enones by Nitromethane Using Bifunctional Thiourea Organocatalysts. Stereocontrolled Assembly of Cyclic and Acyclic Structures.

    PubMed

    Varga, Szilárd; Jakab, Gergely; Csámpai, Antal; Soós, Tibor

    2015-09-18

    An organocatalytic iterative assembly line has been developed in which nitromethane was sequentially coupled with two different enones using a combination of pseudoenantiomeric cinchona-based thiourea catalysts. Application of unsaturated aldehydes and ketones in the second step of the iterative sequence allows the construction of cyclic syn-ketols and acyclic compounds with multiple contiguous stereocenters. The combination of the multifunctional substrates and ambident electrophiles rendered some organocatalytic transformations possible that have not yet been realized in bifunctional noncovalent organocatalysis. PMID:26301563

  20. Pros and cons of bifunctional platinum(IV) antitumor prodrugs: two are (not always) better than one.

    PubMed

    Gabano, Elisabetta; Ravera, Mauro; Osella, Domenico

    2014-07-14

    This article evaluates the efficacy and applicability of bifunctional prodrugs consisting of a six-coordinate Pt(iv) octahedral core and one or more bioactive molecules. The platinum(iv) complexes release upon reduction the corresponding cytotoxic Pt(ii) agents and the bioactive molecules, able to inhibit some biochemical mechanisms of cancer growth and/or prevent the deactivation of the Pt(ii) metabolites. PMID:24874896