Science.gov

Sample records for chelating bisguanidine ligands

  1. 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.

  2. 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.

  3. 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.

  4. Rare-Earth Metal Postmetallocene Catalysts with Chelating Amido Ligands

    NASA Astrophysics Data System (ADS)

    Li, Tianshu; Jenter, Jelena; Roesky, Peter W.

    This review deals with the synthesis and the catalytic application of noncyclopentadienyl complexes of the rare-earth elements. The main topics of the review are amido metal complexes with chelating bidentate ligands, which show the most similarities to cyclopentadienyl ligands. Benzamidinates and guanidinates will be reviewed in a separate contribution within this book. Beside the synthesis of the complexes, the broad potential of these compounds in homogeneous catalysis is demonstrated. Most of the reviewed catalytic transformations are either C-C multiple bond transformation such as the hydroamination and hydrosilylation or polymerization reaction of polar and nonpolar monomers. In this area, butadiene and isoprene, ethylene, as well as lactides and lactones were mostly used as monomers.

  5. 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.

  6. Di-macrocyclic terephthalamide ligands as chelators for the PET radionuclide zirconium-89

    DOE PAGES

    Pandya, Darpan N.; Pailloux, Sylvie; Tatum, David; ...

    2014-12-18

    The development of bifunctional chelators (BFCs) which can stably chelate zirconium-89 ((89)Zr) while being conjugated to targeting molecules is an area of active research. Herein we report the first octadentate terephthalamide ligands, which are easily radiolabeled with (89)Zr and are highly stable in vitro. Lastly, they represent a novel class of chelators, which are worthy of further development as BFCs for (89)Zr.

  7. 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.

  8. Luminescent solutions and films of new europium complexes with chelating ligands

    NASA Astrophysics Data System (ADS)

    Kharcheva, Anastasia V.; Ivanov, Alexey V.; Borisova, Nataliya E.; Kaminskaya, Tatiana P.; Patsaeva, Svetlana V.; Popov, Vladimir V.; Yuzhakov, Viktor I.

    2015-03-01

    The development of new complexes of rare earth elements (REE) with chelating organic ligands opens up the possibility of purposeful alteration in the composition and structure of the complexes, and therefore tuning their optical properties. New ligands possessing two pyridine rings in their structure were synthesized to improve coordination properties and photophysical characteristics of REE compounds. Complexes of trivalent europium with novel chelating ligands were investigated using luminescence and absorption spectroscopy, as well as atomic force microscopy. Luminescence properties of new compounds were studied both for solutions and films deposited on the solid support. All complexes exhibit the characteristic red luminescence of Eu (III) ion with the absolute lumenescence quantum yield in polar acetonitrile solution varying from 0.21 to 1.45 % and emission lifetime ranged from 0.1 to 1 ms. Excitation spectra of Eu coordination complexes correspond with absorption bands of chelating ligand. The energy levels of the triplet state of the new ligands were determined from the phosphorescence at 77 K of the corresponding Gd (III) complexes. The morphology of films of europium complexes with different substituents in the organic ligands was investigated by atomic force microscopy (AFM). It strongly depends both on the type of substituent in the organic ligand, and the rotation speed of the spin-coater. New europium complexes with chelating ligands containing additional pyridine fragments represent outstanding candidates for phosphors with improved luminescence properties.

  9. Chelate effects in sulfate binding by amide/urea-based ligands.

    PubMed

    Jia, Chuandong; Wang, Qi-Qiang; Begum, Rowshan Ara; Day, Victor W; Bowman-James, Kristin

    2015-07-07

    The influence of chelate and mini-chelate effects on sulfate binding was explored for six amide-, amide/amine-, urea-, and urea/amine-based ligands. Two of the urea-based hosts were selective for SO4(2-) in water-mixed DMSO-d6 systems. Results indicated that the mini-chelate effect provided by a single urea group with two NH binding sites appears to provide enhanced binding over two amide groups. Furthermore, additional urea binding sites incorporated into the host framework appeared to overcome to some extent competing hydration effects with increasing water content.

  10. Drawing Mononuclear Octahedral Coordination Compounds Containing Tridentate Chelating Ligands

    ERIC Educational Resources Information Center

    Mohamadou, Aminou; Ple, Karen; Haudrechy, Arnaud

    2011-01-01

    Complexes with tridentate ligands of the type [M(A-B-C)2], where A [not equal to] B [not equal to] C and with an imposed bonding sequence A-B-C, require special attention to draw all possible stereoisomers. Depending on the nature of the central donor atom B of the tridentate ligand, an easy drawing method is presented that shows seven chiral…

  11. Luminescent solutions and powders of new samarium complexes with N,N',O,O'-chelating ligands

    NASA Astrophysics Data System (ADS)

    Kharcheva, Anastasia V.; Nikolskiy, Kirill S.; Borisova, Nataliya E.; Ivanov, Alexey V.; Reshetova, Marina D.; Yuzhakov, Viktor I.; Patsaeva, Svetlana V.

    2016-04-01

    Imaging techniques in biology and medicine are crucial tools to obtain information on structural and functional properties of living cells and organisms. To fulfill the requirements associated with application of these techniques it appears necessary to design markers with specific characteristics. Luminescent complexes of trivalent lanthanide ions with chelating ligands are of increasing importance in biomedical applications because of their millisecond luminescence lifetime, narrow emission band, high signal-to-noise ratio and minimal photodamage to biological samples. In order to extend the available emission wavelength range the luminescent samarium chelates are highly desirable. In this study the ligands with diamides of 2,2'-bipyridin-6,6'-dicarboxylic acid were used to improve photophysical characteristics of samarium complexes. We report the luminescence characteristics of samarium complexes with novel ligands. All complexes exhibited the characteristic emission of Sm (III) ion with the lines at 565, 597, 605, 645 and 654 nm, the intensity strongly depended on the ligand. Absorption and luminescence excitation spectra of Sm (III) complexes showed main peaks in the UV range demonstrating lanthanide coordination to the ligand. The absolute lumenescence quantum yield was measured for solutions in acetonitrile with excitation at 350 nm. The largest luminescence quantum yield was found for the samarium complex Bipy 6MePy Sm (3%) being much higher that for samarium complexes reported in the literature earlier. These results prove as well that samarium chelates are potential markers for multiparametric imaging techniques.

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

    PubMed

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

    2014-01-01

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

  13. {sup 237}Np: Oxidation state in vivo and chelation by multidentate catecholat and hydroxypyridinonate ligands

    SciTech Connect

    Durbin, P.W.; Kullgren, B.; Allen, P.G.; Bucher, J.J.; Edelstein, N.M.; Shuh, D.K.; Xu, J.; Raymond, K.N. |

    1998-07-01

    Chemically, {sup 237}Np(V) is as toxic as U(VI), and radiologically, about as toxic as {sup 239}Pu. Depending on redox conditions in vivo, {sup 237}Np exists as weakly complexing Np(V) (NpO{sub 2}{sup +}) or as Np(IV), which forms complexes as stable as those of Pu(IV). Ten multidentate catecholate (CAM) and hydroxypyridinonate (HOPO) ligands with great affinity for Pu(IV) were compared with CaNa{sub 3}-DTPA for in vivo chelation of {sup 237}Np. Mice were injected intravenously with {sup 237}NpO{sub 2}Cl: those in a kinetic study were killed 1 to 2,880 min; in ligand studies, fed mice were injected intraperitoneally with a ligand 5, 60, or 1,440 min after {sup 237}Np(V), mice fasted for 16 h were gastrically intubated with a ligand 3 min after {sup 237}Np(V), and all were killed 24 h after ligand administration; tissues and excreta were radioanalyzed. Rapid plasma clearance and urinary excretion of {sup 237}Np(V) resemble U(VI); deposition and early retention in skeleton and liver resemble Pu(IV). The x-ray absorption near edge structure spectroscopy (XANES) spectra of femora of {sup 237}Np(V)-injected mice, compared with spectra of Np(V) and Np(IV) from reference solids, showed predominantly Np(IV). Significant in vivo {sup 237}Np chelation was obtained with all of the HOPO and CAM ligands injected at molar ratio 22; the HOPO ligands reduced {sup 237}Np in skeleton, liver, and other soft tissue, on average, to 72, 25, and 25% of control, respectively, while CaNa{sub 3}-DTPA was ineffective.

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

    DOE PAGES

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

    2015-05-01

    The use of α-emitting isotopes for radionuclide therapy is a promising treatment strategy for small micro-metastatic disease. The radioisotope ²¹³Bi is a nuclide that has found substantial use for targeted α-therapy (TAT). The relatively unexplored aqueous chemistry of Bi³⁺, however, hinders the development of bifunctional chelating agents that can successfully deliver these Bi radioisotopes to the tumor cells. Here, a novel series of nitrogen-rich macrocyclic ligands is explored for their potential use as Bi-selective chelating agents. The ligands, 1,4,7,10-tetrakis(pyridin-2-ylmethyl)-1,4,7,10-tetraazacyclododecane (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

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

    PubMed

    Wang, Jianxu; Xia, Jicheng; Feng, Xinbin

    2017-01-15

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

  16. Reactivity and molecular modeling of new solvatochromic mixed-ligand copper(II) chelates of 2-acetylbutyrolactone and dinitrogen bases

    NASA Astrophysics Data System (ADS)

    Taha, A.; Adly, Omima M. I.; Shebl, Magdy

    2015-04-01

    A new series of solvatochromic mononuclear mixed ligand chelates with the general formula: Cu(AcBL)(L)X; where AcBL = 2-acetylbutyrolactonate, L = N,N,N‧,N‧-tetramethylethylenediamine (Me4en), N,N,N‧,N‧-tetramethylpropylene diamine (Me4pn), 1,10-phenanthroline (Phen) or 2,2‧-bipyridyl (Bipy) and X = ClO4-, NO3- or Br- have been synthesized and characterized by the analytical and spectral methods, as well as magnetic and molar conductance measurements. The d-d absorption bands of Me4en-chelates as Nujol mulls or weak donor solvents solutions revealed square-planar, distorted octahedral and/or distorted trigonal bipyramid geometries for the perchlorate, nitrate and bromide chelates, respectively. However, an octahedral structure is identified for chelates in strong donor solvents. Perchlorate chelates show a remarkable color change from violet to green as the Lewis basicity of the donor solvent increases, whereas bromide chelates are mainly affected by the Lewis acidity of solvent. Specific and non-specific interactions of solvent molecules with the chelates were investigated on the basis of unified solvation model. Structural parameters of the free ligands and their Cu(II)-chelates have been calculated on the basis of semiempirical PM3 level and correlated with the experimental data.

  17. "Straining" to Separate the Rare Earths: How the Lanthanide Contraction Impacts Chelation by Diglycolamide Ligands.

    PubMed

    Ellis, Ross J; Brigham, Derek M; Delmau, Laetitia; Ivanov, Alexander S; Williams, Neil J; Vo, Minh Nguyen; Reinhart, Benjamin; Moyer, Bruce A; Bryantsev, Vyacheslav S

    2017-02-06

    The subtle energetic differences underpinning adjacent lanthanide discrimination are explored with diglycolamide ligands. Our approach converges liquid-liquid extraction experiments with solution-phase X-ray absorption spectroscopy (XAS) and density functional theory (DFT) simulations, spanning the lanthanide series. The homoleptic [(DGA)3Ln](3+) complex was confirmed in the organic extractive solution by XAS, and this was modeled using DFT. An interplay between steric strain and coordination energies apparently gives rise to a nonlinear trend in discriminatory lanthanide ion complexation across the series. Our results highlight the importance of optimizing chelate molecular geometry to account for both coordination interactions and strain energies when designing new ligands for efficient adjacent lanthanide separation for rare-earth refining.

  18. 2-Acylpyrroles as mono-anionic O,N-chelating ligands in silicon coordination chemistry.

    PubMed

    Kämpfe, Alexander; Brendler, Erica; Kroke, Edwin; Wagler, Jörg

    2014-07-21

    Kryptopyrrole (2,4-dimethyl-3-ethylpyrrole) was acylated with, for example, benzoyl chloride to afford 2-benzoyl-3,5-dimethyl-4-ethylpyrrole (L(1)H). With SiCl4 this ligand reacts under liberation of HCl and formation of the complex L(1)2SiCl2. In related reactions with HSiCl3 or H2SiCl2, the same chlorosilicon complex is formed under liberation of HCl and H2 or liberation of H2, respectively. The chlorine atoms of L(1)2SiCl2 can be replaced by fluoride and triflate using ZnF2 and Me3Si-OTf, respectively. The use of a supporting base (triethylamine) is required for the complexation of phenyltrichlorosilane and diphenyldichlorosilane. The complexes L(1)2SiCl2, L(1)2SiF2, L(1)2Si(OTf)2, L(1)2SiPhCl, and L(1)2SiPh2 exhibit various configurations of the octahedral silicon coordination spheres (i.e. cis or trans configuration of the monodentate substituents, different orientations of the bidentate chelating ligands relative to each other). Furthermore, cationic silicon complexes L(1)3Si(+) and L(1) SiPh(+) were synthesized by chloride abstraction with GaCl3. In contrast, reaction of L(1)2SiCl2 with a third equivalent of L(1)H in the presence of excess triethylamine produced a charge-neutral hexacoordinate Si complex with a new tetradentate chelating ligand which formed by Si-templated C-C coupling of two ligands L(1).

  19. Mechanism of cellular accumulation of an iridium(III) pentamethylcyclopentadienyl anticancer complex containing a C,N-chelating ligand.

    PubMed

    Novohradsky, Vojtech; Liu, Zhe; Vojtiskova, Marie; Sadler, Peter J; Brabec, Viktor; Kasparkova, Jana

    2014-03-01

    The effect of replacement of the N,N-chelating ligand 1,10-phenanthroline (phen) in the Ir(III) pentamethylcyclopentadienyl (Cp*) complex [(η(5)-Cp*)(Ir)(phen)Cl](+) (2) with the C,N-chelating ligand 7,8-benzoquinoline (bq) to give [(η(5)-Cp*)(Ir)(bq)Cl] (1) on the cytotoxicity of these Cp*Ir(III) complexes toward cancer cell lines was investigated. Complex 2 is inactive, similar to other Cp*Ir(III) complexes containing the N,N-chelating ligands. In contrast, a single atom change (C(-) for N) in the chelating N,N ligand resulted in potency in human ovarian carcinoma cisplatin-sensitive A2780 cells, and, strikingly, 1 is active in the cisplatin-resistant human breast cancer MCF-7 and A2780/cisR cells. Replacement of the N,N-chelating ligand with the C,N-chelating ligand gives rise to increased hydrophobicity, leading to higher cellular accumulation, higher DNA-bound iridium in cells and higher cytotoxicity. The pathways involved in cellular accumulation of 1 have been further explored and compared with conventional cisplatin. The results show that both energy-independent passive diffusion and energy-dependent transport play a role in accumulation of 1. Further results were consistent with involvement of p-glycoprotein, multidrug resistance-associated protein 1 and glutathione metabolism in the efflux of 1. In contrast, the internalization of 1 mediated by the endocytotic uptake pathway(s) seems less likely. Understanding the factors which contribute to the mechanism of cellular accumulation of this Ir(III) complex can now lead to the design of structurally similar metal complexes for antitumor chemotherapy.

  20. Conversion of a monodentate amidinate-germylene ligand into chelating imine-germanate ligands (on mononuclear manganese complexes).

    PubMed

    Cabeza, Javier A; García-Álvarez, Pablo; Pérez-Carreño, Enrique; Polo, Diego

    2014-08-18

    The unprecedented transformation of a terminal two-electron-donor amidinate-germylene ligand into a chelating three-electron-donor κ(2)-N,Ge-imine-germanate ligand has been achieved by treating the manganese amidinate-germylene complex [MnBr{Ge((i)Pr2bzam)(t)Bu}(CO)4] (1; (i)Pr2bzam = N,N'-bis(isopropyl)benzamidinate) with LiMe or Ag[BF4]. In these reactions, which afford [Mn{κ(2)Ge,N-GeMe((i)Pr2bzam)(t)Bu}(CO)4] (2) and [Mn{κ(2)Ge,N-GeF((i)Pr2bzam)(t)Bu}(CO)4] (3), respectively, the anionic nucleophile, Me(-) or F(-), ends on the Ge atom while an arm of the amidinate fragment migrates from the Ge atom to the Mn atom. In contrast, the reaction of 1 with AgOTf (OTf = triflate) leads to [Mn(OTf){Ge((i)Pr2bzam)(t)Bu}(CO)4] (4), which maintains intact the amidinate-germylene ligand. Complex 4 is very moisture-sensitive, leading to [Mn2{μ-κ(4)Ge2,O2-Ge2(t)Bu2(OH)2O}(CO)8] (5) and [(i)Pr2bzamH2]OTf (6) in wet solvents. In 5, a novel digermanate(II) ligand, [(t)Bu(OH)GeOGe(OH)(t)Bu](2-), doubly bridges two Mn(CO)4 units. The structures of 1-6 have been characterized by spectroscopic (IR, NMR) and single-crystal X-ray diffraction methods.

  1. 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

  2. Synthesis, Characterization, and in Vitro Evaluation of a New TSPO-Selective Bifunctional Chelate Ligand

    PubMed Central

    2014-01-01

    The 18-kDa translocator protein (TSPO) is overexpressed in many types of cancers and is also abundant in activated microglial cells occurring in inflammatory neurodegenerative diseases. Thus, TSPO has become an extremely attractive subcellular target not only for imaging disease states overexpressing this protein, but also for a selective mitochondrial drug delivery. In this work we report the synthesis, the characterization, and the in vitro evaluation of a new TSPO-selective ligand, 2-(8-(2-(bis(pyridin-2-yl)methyl)amino)acetamido)-2-(4-chlorophenyl)H-imidazo[1,2-a]pyridin-3-yl)-N,N-dipropylacetamide (CB256), which fulfils the requirements for a bifunctional chelate approach. The goal was to provide a new TSPO ligand that could be used further to prepare coordination complexes of a metallo drug to be used in diagnosis and therapy. However, the ligand itself proved to be a potent tumor cell growth inhibitor and DNA double-strand breaker. PMID:24944744

  3. Hydroxyiminodisuccinic acid (HIDS): A novel biodegradable chelating ligand for the increase of iron bioavailability and arsenic phytoextraction.

    PubMed

    Rahman, M Azizur; Hasegawa, H; Kadohashi, K; Maki, T; Ueda, K

    2009-09-01

    The influence of biodegradable chelating ligands on arsenic and iron uptake by hydroponically grown rice seedlings (Oryza sativa L.) was investigated. Even though the growth solution contained sufficient Fe, the growth of rice seedlings gradually decreased up to 76% with the increase of pH of the solution from 7 to 11. Iron forms insoluble ferric hydroxide complexes at neutral or alkaline pH in oxic condition. Chelating ligands produce soluble 'Fe-ligand complex' which assist Fe uptake in plants. The biodegradable chelating ligand hydroxyiminodisuccinic acid (HIDS) was more efficient then those of ethylenediaminetetraacetic acid (EDTA), ethylenediaminedisuccinic acid (EDDS), and iminodisuccinic acid (IDS) in the increase of Fe uptake and growth of rice seedling. A total of 79+/-20, 87+/-6, 116+/-15, and 63+/-18mg dry biomass of rice seedlings were produced with the addition of 0.5mM of EDDS, EDTA, HIDS, and IDS in the nutrient solution, respectively. The Fe concentrations in rice tissues were 117+/-15, 82+/-8, 167+/-25, and 118+/-22micromolg(-1) dry weights when 0.25mM of EDDS, EDTA, HIDS, and IDS were added to the nutrient solution, respectively. Most of the Fe accumulated in rice tissues was stored in roots after the addition of chelating ligands in the solution. The results indicate that the HIDS would be a potential alternative to environmentally persistent EDTA for the increase of Fe uptake and plant growth. The HIDS also increased As uptake in rice root though its translocation from root to shoot was not augmented. This study reports HIDS for the first time as a promising chelating ligand for the enhancement of Fe bioavailability and As phytoextraction.

  4. A square-planar tellurium(II) complex with Te,Te'-chelating ligands.

    PubMed

    Chivers, Tristram; Ritch, Jamie S

    2015-05-01

    While exploring the chemistry of tellurium-containing dichalcogenidoimidodiphosphinate ligands, the first all-tellurium member of a series of related square-planar E(II)(E')4 complexes (E and E' are group 16 elements), namely bis(P,P,P',P'-tetraphenylditelluridoimidodiphosphinato-κ(2)Te,Te')tellurium(II) (systematic name: 2,2,4,4,8,8,10,10-octaphenyl-1λ(3),5,6λ(4),7λ(3),11-pentatellura-3,9-diaza-2λ(5),4λ(5),8λ(5),10λ(5)-tetraphosphaspiro[5.5]undeca-1,3,7,9-tetraene), C48H40N2P4Te5, was obtained unexpectedly. The formally Te(II) centre is situated on a crystallographic inversion centre and is Te,Te'-chelated to two anionic [(TePPh2)2N](-) ligands in an anti conformation. The central Te(II)(Te)4 unit is approximately square planar [Te-Te-Te = 93.51 (3) and 86.49 (3)°], with Te-Te bond lengths of 2.9806 (6) and 2.9978 (9) Å.

  5. A chelating dendritic ligand capped quantum dot: preparation, surface passivation, bioconjugation and specific DNA detection

    NASA Astrophysics Data System (ADS)

    Zhou, Dejian; Li, Yang; Hall, Elizabeth A. H.; Abell, Chris; Klenerman, David

    2011-01-01

    Herein we report the synthesis of a new chelating dendritic ligand (CDL) and its use in the preparation a compact, stable and water-soluble quantum dot (QD), and further development of specific DNA sensor. The CDL, which contains a chelative dihydrolipoic acid moiety for strong QD surface anchoring and four dendritic carboxylic acidgroups, provides a stable, compact and entangled hydrophilic coating around the QD that significantly increases the stability of the resulting water-soluble QD. A CDL-capped CdSe/ZnS core/shell QD (CDL-QD) has stronger fluorescence than that capped by a monodendate single-chain thiol, 3-mercapto-propionic acid (MPA-QD). In addition, the fluorescence of the CDL-QD can be enhanced by 2.5-fold by treatments with Zn2+ or S2- ions, presumably due to effective passivation of the surface defects. This level of fluorescence enhancement obtained for the CDL-QD is much greater than that for the MPA-QD. Further, by coupling a short single-stranded DNA target to the QD via the CDL carboxylic acidgroup, a functional QD-DNA conjugate that can resist non-specific adsorption and hybridize quickly to its complementary DNAprobe has been obtained. This functional QD-DNA conjugate is suitable for specific quantification of short, labelled complementary probes at the low DNAprobe:QD copy numbers via a QD-sensitised dyefluorescence resonance energy transfer (FRET) response with 500 pM sensitivity on a conventional fluorimeter.Herein we report the synthesis of a new chelating dendritic ligand (CDL) and its use in the preparation a compact, stable and water-soluble quantum dot (QD), and further development of specific DNA sensor. The CDL, which contains a chelative dihydrolipoic acid moiety for strong QD surface anchoring and four dendritic carboxylic acidgroups, provides a stable, compact and entangled hydrophilic coating around the QD that significantly increases the stability of the resulting water-soluble QD. A CDL-capped CdSe/ZnS core/shell QD (CDL-QD) has

  6. New Synthetic Approach for the Incorporation of 3,2-Hydroxypyridinone (HOPO) Ligands: Synthesis of Structurally Diverse Poly HOPO Chelators

    PubMed Central

    Arumugam, Jayanthi; Brown, Hayley A.; Jacobs, Hollie K.; Gopalan, Aravamudan S.

    2011-01-01

    The HOPO sulfonamide reagent, 3, was prepared from commercial 2,3-dihydroxypyridine in four steps in good yields. Sulfonamide 3 readily underwent selective alkylation with dibromides in the presence of base or could be coupled to alcohols using Mitsunobu conditions. The utility of this nucleophilic HOPO reagent was demonstrated by the synthesis some tris and tetraHOPO chelators. This approach for tethering HOPO ligands is unique and flexible as shown by the preparation of HOPO/iminocarboxylic acid chelator 17. PMID:21709749

  7. Influence of nitrogen-containing chelating ligands on the structures of zinc(II) 4,4'-ethylenedibenzoates.

    PubMed

    Wang, Xiu-Yan; Wang, Jia-Jun; Ng, Seik Weng

    2008-12-01

    The Zn(II) compounds, micro-4,4'-ethylenedibenzoato-bis[acetatoaqua(dipyrido[3,2-a:2',3'-c]phenazine)zinc(II)] dihydrate, [Zn(2)(C(2)H(3)O(2))(2)(C(16)H(10)O(4))(C(18)H(10)N(4))(2)(H(2)O)(2)] x 2H(2)O, (I), and catena-poly[[[aqua(pyrazino[2,3-f][1,10]phenanthroline)zinc(II)]-micro-4,4'-ethylenedibenzoato] N,N-dimethylformamide hemisolvate], {[Zn(C(16)H(10)O(4))(C(14)H(8)N(4))(H(2)O)] x 0.5C(3)H(7)NO}(n), (II), display very different structures because of the influence of the N-donor chelating ligands. In (I), the coordination geometry of each Zn(II) centre is distorted octahedral, involving two N atoms from one dipyrido[3,2-a:2',3'-c]phenazine (L1) ligand, and four O atoms from one bis-chelating acetate anion, one bridging 4,4'-ethylenedibenzoate (bpea) ligand and one water molecule. Adjacent Zn(II) atoms are bridged by one bpea ligand to form a dinuclear complex, and the dinuclear species is centrosymmetric. Two types of pi-pi interactions between neighbouring dinuclear species have been found: one is between the L1 ligands, and the second is between the L1 and bpea ligands. In this way, an interesting two-dimensional supramolecular layer is formed. The layers are further linked by O-H...O and O-H...N hydrogen bonds, generating a three-dimensional supramolecular network. In (II), each Zn(II) atom is square-pyramidally coordinated by two N atoms from one pyrazino[2,3-f][1,10]phenanthroline ligand, three O atoms from two different bpea ligands and one water molecule. The two bpea dianions are situated across inversion centres. The bpea dianions bridge neighbouring Zn(II) centres, giving a one-dimensional chain structure in the ab plane. As in (I), two types of pi-pi interactions between neighbouring chains complete a three-dimensional supramolecular structure. The results indicate that the structures of the N-donor chelating ligands are the dominant factors determining the final supramolecular structures of the two compounds.

  8. A Pyridine Alkoxide Chelate Ligand That Promotes Both Unusually High Oxidation States and Water-Oxidation Catalysis.

    PubMed

    Michaelos, Thoe K; Shopov, Dimitar Y; Sinha, Shashi Bhushan; Sharninghausen, Liam S; Fisher, Katherine J; Lant, Hannah M C; Crabtree, Robert H; Brudvig, Gary W

    2017-03-08

    Water-oxidation catalysis is a critical bottleneck in the direct generation of solar fuels by artificial photosynthesis. Catalytic oxidation of difficult substrates such as water requires harsh conditions, so the ligand must be designed both to stabilize high oxidation states of the metal center and to strenuously resist ligand degradation. Typical ligand choices either lack sufficient electron donor power or fail to stand up to the oxidizing conditions. Our research on Ir-based water-oxidation catalysts (WOCs) has led us to identify a ligand, 2-(2'-pyridyl)-2-propanoate or "pyalk", that fulfills these requirements. Work with a family of Cp*Ir(chelate)Cl complexes had indicated that the pyalk-containing precursor gave the most robust WOC, which was still molecular in nature but lost the Cp* fragment by oxidative degradation. In trying to characterize the resulting active "blue solution" WOC, we were able to identify a diiridium(IV)-mono-μ-oxo core but were stymied by the extensive geometrical isomerism and coordinative variability. By moving to a family of monomeric complexes [Ir(III/IV)(pyalk)3] and [Ir(III/IV)(pyalk)2Cl2], we were able to better understand the original WOC and identify the special properties of the ligand. In this Account, we cover some results using the pyalk ligand and indicate the main features that make it particularly suitable as a ligand for oxidation catalysis. The alkoxide group of pyalk allows for proton-coupled electron transfer (PCET) and its strong σ- and π-donor power strongly favors attainment of exceptionally high oxidation states. The aromatic pyridine ring with its methyl-protected benzylic position provides strong binding and degradation resistance during catalytic turnover. Furthermore, the ligand has two additional benefits: broad solubility in aqueous and nonaqueous solvents and an anisotropic ligand field that enhances the geometry-dependent redox properties of its complexes. After discussion of the general properties, we

  9. New two-dimensional metal-organic networks constructed from 1,2,4,5-benzenetetracarboxylate and chelate ligands.

    PubMed

    Li, Yangguang; Hao, Na; Lu, Ying; Wang, Enbo; Kang, Zhenhui; Hu, Changwen

    2003-05-05

    Two novel nickel coordination polymers [Ni(2)(2,2'-bipy)(2)(OH)(2)(H(2)btec)](3)(n)(1) and [Ni(2)(1,10'-phen)(2)(H(2)O)(2)(btec)](n)(2) (btec = 1,2,4,5-benzenetetracarboxylate) have been hydrothermally synthesized and characterized by elemental analyses, IR and XPS spectra, TG analysis, X-ray powder diffraction, and single crystal X-ray diffraction. Crystal data for 1: C(90)H(66)N(12)O(30)Ni(6), monoclinic P2(1)/c, a = 10.905(2) A, b = 18.006(4) A, c = 20.551(4) A, beta = 94.91(3) degrees, Z = 2. Crystal data for 2: C(34)H(22)N(4)O(10)Ni(2), monoclinic P2(1)/n, a = 10.122(2) A, b = 9.3106(19) A, c = 15.690(3) A, beta = 92.03(3) degrees, Z = 2. Compound 1 exhibits a novel one-dimensional chainlike structure, in which the dinuclear Ni centers are linked by the btec ligands. Furthermore, the adjacent chains are linked into a 2-D wavelike layer via the strong OH.O hydrogen bonding interactions. Compound 2 possesses an unusual two-dimensional steplike network with interesting rhombic grids. Both compounds exhibit unprecedented metal-organic ligand construction modes in [M/btec/L] (M = transition metal; L = chelate ligands) systems. The magnetic behaviors of compounds 1 and 2 have been studied.

  10. Synthesis and characterization of cerium and yttrium alkoxide complexes supported by ferrocene-based chelating ligands.

    PubMed

    Broderick, Erin M; Thuy-Boun, Peter S; Guo, Neng; Vogel, Carola S; Sutter, Jörg; Miller, Jeffrey T; Meyer, Karsten; Diaconescu, Paula L

    2011-04-04

    Two series of Schiff base metal complexes were investigated, where each series was supported by an ancillary ligand incorporating a ferrocene backbone and different N=X functionalities. One ligand is based on an imine, while the other is based on an iminophosphorane group. Cerium(IV), cerium(III), and yttrium(III) alkoxide complexes supported by the two ligands were synthesized. All metal complexes were characterized by cyclic voltammetry. Additionally, NMR, Mössbauer, X-ray absorption near-edge structure (XANES), and absorption spectroscopies were used. The experimental data indicate that iron remains in the +2 oxidation state and that cerium(IV) does not engage in a redox behavior with the ancillary ligand.

  11. Excitation energy transfer in europium chelate with doxycycline in the presence of a second ligand in micellar solutions of nonionic surfactants

    NASA Astrophysics Data System (ADS)

    Smirnova, T. D.; Shtykov, S. N.; Kochubei, V. I.; Khryachkova, E. S.

    2011-01-01

    The complexation of Eu3+ with doxycycline (DC) antibiotic in the presence of several second ligands and surfactant micelles of different types is studied by the spectrophotometric and luminescence methods. It is found that the efficiency of excitation energy transfer in Eu3+-DC chelate depends on the nature of the second ligand and surfactant micelles. Using thenoyltrifluoroacetone (TTA) as an example, it is shown that the second ligand additionally sensitizes the europium fluorescence, and the possibility of intermediate sensitization of DC and then of europium is shown by the example of 1,10-phenanthroline. In all cases, the excitation energy transfer efficiency was increased due to the so-called antenna effect. The decay kinetics of the sensitized fluorescence of the binary and mixed-ligand chelates in aqueous and micellar solutions of nonionic surfactants is studied and the relative quantum yields and lifetimes of fluorescence are determined.

  12. Synthesis of palladium(0) and -(II) complexes with chelating bis(N-heterocyclic carbene) ligands and their application in semihydrogenation.

    PubMed

    Sluijter, Soraya N; Warsink, Stefan; Lutz, Martin; Elsevier, Cornelis J

    2013-05-28

    A transmetallation route, using silver(I) precursors, to several zero- and di-valent palladium complexes with chelating bis(N-heterocyclic carbene) ligands bearing various N-substituents has been established. The resulting complexes have been characterized by NMR and mass spectroscopy. In addition, the structure of a representative compound, [Pd(0)(bis-(Mes)NHC)(η(2)-ma)] (3a), was confirmed by X-ray crystal structure determination. In contrast to the transfer semihydrogenation, in which only low activity was observed, complex 3a showed activity (TOF = 49 mol(sub) mol(cat)(-1) h(-1)) and selectivity comparable to its monodentate counterparts in the semihydrogenation of 1-phenyl-1-propyne with molecular hydrogen.

  13. Hydrogen chemistry of ruthenium complexes containing one chelating (P-P) or (P-N) ligand per Ru atom

    SciTech Connect

    James, B.

    1995-12-01

    Hydrogenation catalysts are of interest to a variety of fields such as fuels preparation. This report describes a hydrogenation catalysts concerning ruthenium. The most versatile hydrogenation catalysts appear to be based on Ru(P-P) species containing one chelating ditertiaryphosphine(P-P) ligand per metal, particularly for asymmetric hydrogenation when (P-P) is chiral. We have studied the interaction of H{sub 2} with, and catalytic hydrogenation activity (toward olefins ketones, nitrites and imines) of, systems containing the {open_quote}RuCl{sub 2}(P-P){close_quote} moiety or corresponding chelating (P-N) ligands where N is a tertiary amine. Variation in conditions leads to detection or isolation of, for example, ({eta}{sup 2}-H{sub 2})(P-P)Ru({mu}-Cl){sub 3}RuCl(P-P) (1), ({eta}{sup 2}-H{sub 2})(P-P)Ru({mu}-Cl){sub 2}({mu}-H)Ru(H)(P-P) (2), and [Ru(H)Cl(P-P)]{sub 3} (3), as well as analogous species where the {eta}{sup 2}-H{sub 2} of 1 or 2 is replaced by olefin, ketone, nitrile, or imine. The connectivity between 1-3, and kinetic and mechanistic details of selected catalytic hydrogenations will be discussed. Within (P-N) systems, the mononuclear species ({eta}{sup 2}-H{sub 2})RuCl{sub 2}(P-N)(PR{sub 3}) and Ru(H)Cl(P-N)(PR{sub 3}) are formed (R = Ph or p-tolyl), as well as species analogous to 2.

  14. Blue-emitting platinum(II) complexes bearing both pyridylpyrazolate chelate and bridging pyrazolate ligands: synthesis, structures, and photophysical properties.

    PubMed

    Chang, Sheng-Yuan; Chen, Jing-Lin; Chi, Yun; Cheng, Yi-Ming; Lee, Gene-Hsiang; Jiang, Chang-Ming; Chou, Pi-Tai

    2007-12-24

    A new Pt(II) dichloride complex [Pt(fppzH)Cl2] (1), in which fppzH = 3-(trifluoromethyl)-5-(2-pyridyl)pyrazole, was prepared by the treatment of a pyridylpyrazole chelate fppzH with K2PtCl4 in aqueous HCl solution. Complex 1 could further react with its parent pyrazole (pzH), 3,5-dimethylpyrazole (dmpzH), or 3,5-di-tert-butylpyrazole (dbpzH) to afford the monometallic [Pt(fppz)(pzH)Cl] (2), [Pt(fppz)(dmpzH)Cl] (3), [Pt(fppz)(dmpzH)2]Cl (4), or two structural isomers with formula [Pt(fppz)(dbpzH)Cl] (5a,b). Single-crystal X-ray diffraction studies of 2, 4, and 5a,b revealed a square planar Pt(II) framework, among which a strong interligand hydrogen bonding occurred between fppz and pzH ligands in 2. This interligand H-bonding is replaced by dual N-H...Cl interaction in 4 and both intermolecular N-H...O (with THF solvate) and N-H...Cl interaction in 5a,b, respectively; the latter are attributed to the bulky tert-butyl substituents that force the dbpzH ligand to adopt the perpendicular arrangement. Furthermore, complex 2 underwent rapid deprotonation in basic media to afford two isomeric complexes with formula [Pt(fppz)(mu-pz)]2 (6a,b), which are related to each other according to the spatial orientation of the fppz chelates, i.e., trans- and cis-isomerism. Similar reaction exerted on 3 afforded isomers 7a,b. Both 6a,b (7a,b) are essentially nonemissive in room-temperature fluid state but afford strong blue phosphorescence in solid state prepared via either vacuum-deposited thin film or 77 K CH2Cl2 matrix. As also supported by the computational approaches, the nature of emission has been assigned to be ligand-centered triplet pipi* mixed with certain metal-to-ligand charge-transfer character.

  15. Ruthenium Bis-diimine Complexes with a Chelating Thioether Ligand: Delineating 1,10-Phenanthrolinyl and 2,2'-Bipyridyl Ligand Substituent Effects

    SciTech Connect

    Al-Rawashdeh, Nathir A. F.; Chatterjee, Sayandev; Krause, Jeanette A.; Connick, William B.

    2014-01-06

    A new series of ruthenium(II) bis-diimine complexes with a chelating thioether donor ligand has been prepared: Ru(diimine)2(dpte)2+ (diimine=1,10-phenanthroline (phen) (1); 5-CH3-phen (2), 5-Cl-phen (3); 5-Br-phen (4); 5-NO2-phen (5); 3,4,7,8-tetramethyl-phen (6); 4,7-diphenyl-phen (7); 5,5'-dimethyl-2,2'-bipyridine (8); 4,4'-di-tert-butyl-2,2'-bipyridine (9)). Crystal structures of 2, 5, 7 and 9 show that the complexes form 2 of the 12 possible conformational/configurational isomers, adopting compact C2-symmetric structures with short intramolecular transannular interactions between the diimine ligands and dpte phenyl groups; crystals of 2 and 5 contain non-statistical distributions of geometric isomers. In keeping with the π-acidity of the dpte, the Ru(III/II) couple, E°'(Ru3+/2+), occurs at relatively high potentials (1.4-1.7 V vs Ag/AgCl), and the lowest spin-allowed MLCT absorption band occurs near 400 nm. Surprisingly, the complexes also exhibit fluid-solution luminescence originating from a lowest MLCT excited state with lifetimes in the 140-750 ns time range; in acetonitrile, compound 8 undergoes photo-induced solvolysis. Variations in the MLCT energies and redox potentials are quantitatively described using a summative Hammett parameter (σT), as well as using Lever's electrochemical parameters (EL). Recommended parameterizations for 2,2'-bipyridyl and 1,10-phenanthrolinyl ligands were derived from analysis of correlations based on 199 measurements of E°'(Ru3+/2+) for 99 homo- and heteroleptic ruthenium(II) tris-diimine complexes. Variations in E°'(Ru3+/2+) due to substituents at the 4- and 4'-positions of bipyridyl ligands and 4- and 7-positions of phenanthrolinyl ligands are significantly more strongly correlated with σp+ than either σm or σp. Substituents at the 5- and 6-positions of phenanthrolinyl ligands are best described by σm and have effects comparable to those of substituents at the 3- and 8-positions. Correlations of EL with σT for 20

  16. Synthesis and luminescence properties of iridium complexes chelated with coumarin ligands.

    PubMed

    Park, Hye Rim; Kim, Bo Young; Kim, Young Kwan; Ha, Yunkyoung

    2013-05-01

    According to a recent report, the organic light-emitting diodes (OLEDs) using the iridium complexes of coumarin derivatives as emissive dopants are highly efficient and stable. Unlike the other Ir(III) phopsphorescent dopants, these coumarin-based Ir(III) complexes can effectively trap and transport electrons in the emissive layer. We have prepared a series of phosphorescent cyclometalated Ir(III) complexes containing 3-(2-pyridinyl)coumarin (pc) as an ancillary ligand. The new heteroleptic iridium complexes, Ir(C--N)2(pc) (CAN = 2-(2,4-difluorophenyl)pyridine (F2-ppy), 2-phenylpyridine (ppy) and 2-phenylquinoline (pq)) were characterized by 1H NMR and mass spectrometer. As main ligands, F2-ppy, ppy and pq were employed, which should have the drastically different ligand molecular orbital energy levels. The iridium complexes showed various emission ranges from 560 to 610 nm, depending upon the relative energy levels of their main and ancillary ligands. The photoabsorption, photoluminescence and electroluminescence of the complexes were studied. We also investigated the electrochemical properties of the iridium complexes to compare the HOMO and LUMO energy levels of these phosphorescent materials.

  17. Chelating tris(amidate) ligands: versatile scaffolds for nickel(II).

    PubMed

    Jones, Matthew B; Newell, Brian S; Hoffert, Wesley A; Hardcastle, Kenneth I; Shores, Matthew P; MacBeth, Cora E

    2010-01-14

    The synthesis and characterization of nickel complexes supported by a family of open-chain, tetradentate, tris(amidate) ligands, [N(o-PhNC(O)R)(3)](3-) ([L(R)](3-) where R = (i)Pr, (t)Bu, and Ph) is described. The complexes [Ni(L(iPr))](-), [Ni(L(tBu))](-), and [Ni(L(Ph))(CH(3)CN)](-) have been characterized by solution-state spectroscopic methods and single crystal X-ray diffraction. Each ligand gives rise to a different primary coordination sphere about the nickel centre. These studies indicate that the ligands' acyl substituents can be used to regulate the coordination mode of the amidate donors to nickel and the coordination number of the nickel centres. In addition, the ability of these complexes to bind cyanide has been explored. These experiments demonstrate that only one of these complexes, [Ni(L(iPr))](-), is able to irreversibly bind cyanide and can be used to assemble [Et(4)N](3)[Ni(L(iPr))(mu(2)-CN)Co(L(iPr))], a cyanide bridged, heterobimetallic complex. The synthesis and characterization of the cyanide containing complexes, including magnetic susceptibility studies, are described.

  18. Synthesis, crystal structure and cytotoxic activity of ruthenium(II) piano-stool complex with N,N-chelating ligand

    NASA Astrophysics Data System (ADS)

    Rogala, Patrycja; Jabłońska-Wawrzycka, Agnieszka; Kazimierczuk, Katarzyna; Borek, Agnieszka; Błażejczyk, Agnieszka; Wietrzyk, Joanna; Barszcz, Barbara

    2016-12-01

    A mononuclear compound of the general formula [(η6-p-cymene)RuIICl(2,2‧-PyBIm)]PF6 has been synthesized from a bidentate N,N-donor ligand, viz. 2,-(2‧-pyridyl)benzimidazole (2,2‧-PyBIm) and the corresponding chloro-complex [(η6-p-cymene)Ru(μ-Cl)Cl]2 (precursor). The isolated coordination compound was characterized by IR, UV-vis and 1H, 13C NMR spectroscopies. The single crystal X-ray analysis of the complex reveals that the asymmetric part of the unit cell consists of two symmetrically independent, [(η6-p-cymene)RuCl(2,2‧-PyBIm)]+ cationic complexes. Each cation exhibits a pseudo-octahedral three-legged piano-stool geometry, in which three "legs" are occupied by one chloride ion and two nitrogen donor atoms of the chelating ligand 2,2‧-PyBIm. The Hirshfeld surface analysis of obtained complex was determined, too. The ionic nature of the compound is identified by a strong band at around 830 cm-1 due to the νP-F stretching mode of the PF6- counter ion. The electronic spectrum of this monomeric complex displays high intensity bands in the ultraviolet region assignable to π→π*/n→π* transitions, as well as a band attributable to the metal-to-ligand charge transfer (MLCT) dπ(Ru)→π*(L) transition. Additionally, the complex has been screened for its cytotoxicity against three human cancer lines: non-small cell lung carcinoma (A549), colon adenocarcinoma (HT29) and breast adenocarcinoma (MCF-7) as well as normal mice fibroblast cells (BALB/3T3). The complex demonstrated a moderate antiproliferative activity against the cell lines tested.

  19. Pore-free matrix with cooperative chelating of hyperbranched ligands for high-performance separation of uranium.

    PubMed

    Li, Yang; Wang, Lei; Li, Bo; Zhang, Meicheng; Wen, Rui; Guo, Xinghua; Li, Xing; Zhang, Ji; Li, Shoujian; Ma, Lijian

    2016-10-04

    A new strategy combining pore-free matrix and cooperative-chelating was proposed in the present paper in order to effectively avoid undesired non-selective physical adsorption and intra-particle diffusion caused by pores and voids in porous sorbents, and to greatly enhance uranium-chelating capability based on hyperbranched amidoxime ligands on the surface of nanodiamond particles. Thus a pore-free, amidoxime-terminated hyperbranched nanodiamond (ND-AO) was designed and synthesized. The experimental results demonstrate that the strategy endows the as-synthesized ND-AO with following expected features: (1) distinctively high uranium selectivity (SU = qe-U /qe-tol ×100 %) from over 80% to nearly 100 % over the whole weak acidity range (pH < 4.5), especially, the SU can reach up to unprecedented > 91 % at pH 4.5, more than 20 percent of selectivity increment over any analogous sorbent materials reported so far, with a uranium sorption capacity of 121mg/g in simulated nuclear industry effluent samples containing 12 coexistent nuclide ions, (2) super-fast equilibrium sorption time of < 30s, (3) one of the highest distribution coefficient ( Kd ) of ~ 3×106 ml/g for U(VI) as well as fairly high sorption capacity of 212 mg/g at pH 4.5 in pure-uranium solution. The strategy could also provide an optional approach for the design and fabrication of other new high-performance sorbing materials with prospective applications in selective separation of other interested metal ions.

  20. Lanthanide mixed ligand chelates for DNA profiling and latent fingerprint detection

    NASA Astrophysics Data System (ADS)

    Menzel, E. R.; Allred, Clay

    1997-02-01

    It is our aim to develop a universally applicable latent fingerprint detection method using lanthanide (rare-earth) complexes as a source of luminescence. Use of these lanthanide complexes offers advantages on several fronts, including benefits from large Stokes shifts, long luminescence lifetimes, narrow emissions, ability of sequential assembly of complexes, and chemical variability of the ligands. Proper exploitation of these advantages would lead to a latent fingerprint detection method superior to any currently available. These same characteristics also lend themselves to many of the problems associated with DNA processing in the forensic science context.

  1. A Pyridine-Based Ligand with Two Hydrazine Functions for Lanthanide Chelation: Remarkable Kinetic Inertness for a Linear, Bishydrated Complex.

    PubMed

    Bonnet, Célia S; Laine, Sophie; Buron, Frédéric; Tircsó, Gyula; Pallier, Agnès; Helm, Lothar; Suzenet, Franck; Tóth, Éva

    2015-06-15

    To study the influence of hydrazine functions in the ligand skeleton, we designed the heptadentate HYD ligand (2,2',2″,2‴-(2,2'-(pyridine-2,6-diyl)bis(2-methylhydrazine-2,1,1-triyl)) tetraacetic acid) and compared the thermodynamic, kinetic, and relaxation properties of its Ln(3+) complexes to those of the parent pyridine (Py) analogues without hydrazine (Py = 2,6-pyridinebis(methanamine)-N,N,N',N'-tetraacetic acid). The protonation constants of HYD were determined by pH-potentiometric measurements, and assigned by a combination of UV-visible and NMR spectroscopies. The protonation sequence is rather unusual and illustrates that small structural changes can strongly influence ligand basicity. The first protonation step occurs on the pyridine nitrogen in the basic region, followed by two hydrazine nitrogens and the carboxylate groups at acidic pH. Contrary to Py, HYD self-aggregates through a pH-dependent process (from pH ca. 4). Thermodynamic stability constants have been obtained by pH-potentiometry and UV-visible spectrophotometry for various Ln(3+) and physiological cations (Zn(2+), Ca(2+), Cu(2+)). LnHYD stability constants show the same trend as those of LnDTPA complexes along the Ln(3+) series, with log K = 18.33 for Gd(3+), comparable to the Py analogue. CuHYD has a particularly high stability (log K > 19) preventing its determination from pH-potentiometric measurements. The stability constant of CuPy was also revisited and found to be underestimated in previous studies, highlighting that UV-visible spectrophotometry is often indispensable to obtain reliable stability constants for Cu(2+) chelates. The dissociation of GdL, assessed by studying the Cu(2+)-exchange reaction, occurs mainly via an acid-catalyzed process, with limited contribution from direct Cu(2+) attack. The kinetic inertness of GdHYD is remarkable for a linear bishydrated chelate; the 25-fold increase in the dissociation half-life with respect to the monohydrated commercial contrast agent

  2. Chelation Motifs Affecting Metal-dependent Viral Enzymes: N′-acylhydrazone Ligands as Dual Target Inhibitors of HIV-1 Integrase and Reverse Transcriptase Ribonuclease H Domain

    PubMed Central

    Carcelli, Mauro; Rogolino, Dominga; Gatti, Anna; Pala, Nicolino; Corona, Angela; Caredda, Alessia; Tramontano, Enzo; Pannecouque, Christophe; Naesens, Lieve; Esposito, Francesca

    2017-01-01

    Human immunodeficiency virus type 1 (HIV-1) infection, still represent a serious global health emergency. The chronic toxicity derived from the current anti-retroviral therapy limits the prolonged use of several antiretroviral agents, continuously requiring the discovery of new antiviral agents with innovative strategies of action. In particular, the development of single molecules targeting two proteins (dual inhibitors) is one of the current main goals in drug discovery. In this contest, metal-chelating molecules have been extensively explored as potential inhibitors of viral metal-dependent enzymes, resulting in some important classes of antiviral agents. Inhibition of HIV Integrase (IN) is, in this sense, paradigmatic. HIV-1 IN and Reverse Transcriptase-associated Ribonuclease H (RNase H) active sites show structural homologies, with the presence of two Mg(II) cofactors, hence it seems possible to inhibit both enzymes by means of chelating ligands with analogous structural features. Here we present a series of N′-acylhydrazone ligands with groups able to chelate the Mg(II) hard Lewis acid ions in the active sites of both the enzymes, resulting in dual inhibitors with micromolar and even nanomolar activities. The most interesting identified N′-acylhydrazone analog, compound 18, shows dual RNase H-IN inhibition and it is also able to inhibit viral replication in cell-based antiviral assays in the low micromolar range. Computational modeling studies were also conducted to explore the binding attitudes of some model ligands within the active site of both the enzymes. PMID:28373864

  3. Protonation of metal-bound ?-hydroxycarboxylate ligand and implication for the role of homocitrate in nitrogenase: Computational study of the oxy-bidentate chelate ring opening

    NASA Astrophysics Data System (ADS)

    Cao, Zexing; Jin, Xi; Zhou, Zhaohui; Zhang, Qianer

    Protonation of the metal-bound oxy-bidentate ligand in the model complexes of [(HS)3(NH3)M(OCH2COO)]q (M = Mo, Fe, V, Co; q = -2, -1) in the gas phase and in solutions of water and acetonitrile has been explored by the density functional approach. Calculations show that protonation of the carboxyl oxygen can open the ?-hydroxycarboxylate chelate ring ligated to a transition-metal center under specific oxidation and spin states. The feasibility of the chelate ring opening by protonation depends on the electronic nature of the metal site in tune with conversion of a six-coordinate with a five-coordinate metal atom. Such selective dissociation of the metal-bound chelate ligand manipulates the availability of an empty site at the metal center and significantly affects reactivity of the metal-mediated chemical processes. Protonation changes the stability of species with different spin multiplicities and impels spin transition at the metal center in dissociation of the oxy-bidentate ligand. Solvent environments of water and acetonitrile play an important role in stabilizing the negatively charged species.

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

    PubMed

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

    2003-08-25

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

  5. Site-specific and covalent attachment of his-tagged proteins by chelation assisted photoimmobilization: a strategy for microarraying of protein ligands.

    PubMed

    Ericsson, Emma M; Enander, Karin; Bui, Lan; Lundström, Ingemar; Konradsson, Peter; Liedberg, Bo

    2013-09-17

    A novel strategy for site-specific and covalent attachment of proteins has been developed, intended for robust and controllable immobilization of histidine (His)-tagged ligands in protein microarrays. The method is termed chelation assisted photoimmobilization (CAP) and was demonstrated using human IgG-Fc modified with C-terminal hexahistidines (His-IgGFc) as the ligand and protein A as the analyte. Alkanethiols terminated with either nitrilotriacetic acid (NTA), benzophenone (BP), or oligo(ethylene glycol) were synthesized and mixed self-assembled monolayers (SAMs) were prepared on gold and thoroughly characterized by infrared reflection absorption spectroscopy (IRAS), ellipsometry, and contact angle goniometry. In the process of CAP, NTA chelates Ni(2+) and the complex coordinates the His-tagged ligand in an oriented assembly. The ligand is then photoimmobilized via BP, which forms covalent bonds upon UV light activation. In the development of affinity biosensors and protein microarrays, site-specific attachment of ligands in a fashion where analyte binding sites are available is often preferred to random coupling. Analyte binding performance of ligands immobilized either by CAP or by standard amine coupling was characterized by surface plasmon resonance in combination with IRAS. The relative analyte response with randomly coupled ligand was 2.5 times higher than when site-specific attachment was used. This is a reminder that also when immobilizing ligands via residues far from the binding site, there are many other factors influencing availability and activity. Still, CAP provides a valuable expansion of protein immobilization techniques since it offers attractive microarraying possibilities amenable to applications within proteomics.

  6. Mixed tridentate π -donor and monodentate π -acceptor ligands as chelating systems for rhenium-188 and technetium-99m nitrido radiopharmaceuticals.

    PubMed

    Boschi, Alessandra; Uccelli, Licia; Pasquali, Micol; Pasqualini, Roberto; Guerrini, Remo; Duatti, Adriano

    2013-09-01

    A new molecular metallic fragment for labeling biologically active molecules with 99mTc and 188Re is described. This system is composed of a combination of tridentate π-donor and monodentate π-acceptor ligands bound to a [M Ξ N]2+ group (M = (99m)Tc, 188Re) in a pseudo square-pyramidal geometry. A simple structural model of the new metallic fragment was obtained by reacting the ligand 2, 2'-iminodiethanethiol [H2NS2 = NH(CH2CH2SH)2] and monodentate tertiary phosphines with the [M Ξ N]2+ group (M = (99m)Tc, (188)Re). In the resulting complexes (dubbed3+1complexes), the tridentate ligand binds the [M Ξ N]2+ core through the two deprotonated, negatively charged, thiol sulfur atoms and the neutral, protonated, amine nitrogen atom. The residual fourth position of the five-coordinated arrangement is occupied by a phosphine ligand. The chemical identity of these model (99m)Tc and (188)Re compounds was established by comparison with the chromatographic properties of the corresponding complexes obtained at the macroscopic level with the long-lived (99)Tc and natural Re isotopes. The investigation was further extended to comprise a series of ligands formed by simple combinations of two basic amino acids or pseudo-amino acids to yield potential tridentate chelating systems having [S, N, S] and [N, N, S] as sets of π-donor atoms. Labeling yields and in vitro stability were investigated using different ancillary ligands. Results showed that SNS-type ligands afforded the highest labeling yields and the most robust 3+1 nitrido complexes with both (99m)Tc and (188)Re. Thus, the new chelating system can be conveniently employed for labeling peptides and other biomolecules with the [M Ξ N]2+ group.

  7. Mixed ligand chelate therapy for plutonium and toxic metals from energy power production. Final report, April 15, 1977-October 14, 1980. [Mice

    SciTech Connect

    Schubert, J.

    1980-10-14

    The results of experiments are summarized on the ability of combinations of chelating agents to modify the genotoxicity or tissue distributions. The mutagenicities of Cr and of chelating agents were determined. The metals described in the report are Pu(IV), Cd(II), Cr(III), and Cr(VI). Accurate measurements were made of the ability of CaNa/sub 2/EDTA, CaNa/sub 3/DTPA, and DMPS to reduce mortality in mice given doses (i.p.) of CdCl/sub 2/ well above the 100% lethal level. The efficacy in terms of the mmoles/kg needed to reduce the mortality was: DTPA > EDTA > DMPS. The combination of DTPA + DMPS proved most promising though little evidence for mixed complex formation was noted. Potentiometric titration studies the case of Pu(IV) a few combinations proved effective, but only when given shortly after Pu administration and then only in the liver but not the skeleton. It is recommended that metabolically stable chelating agents be used in combinations, especially for those combinations which may form very stable mixed ligand chelates.

  8. Chelating fibers prepared with a wet spinning technique using a mixture of a viscose solution and a polymer ligand for the separation of metal ions in an aqueous solution.

    PubMed

    Kagaya, Shigehiro; Miyazaki, Hiroyuki; Inoue, Yoshinori; Kato, Toshifumi; Yanai, Hideyuki; Kamichatani, Waka; Kajiwara, Takehiro; Saito, Mitsuru; Tohda, Koji

    2012-02-15

    Chelating fibers containing polymer ligands such as carboxymethylated polyallylamine, carboxymethylated polyethyleneimine, and a copolymer of diallylamine hydrochloride/maleic acid were prepared with a wet spinning technique using mixtures of a viscose solution and the polymer ligands. The chelating fibers obtained effectively adsorbed various metal ions, including Cd(II), Co(II), Cr(III), Cu(II), Fe(III), Mn(II), Ni(II), Pb(II), Ti(IV), and Zn(II). The metal ions adsorbed could be readily desorbed using 0.1 or 0.5 mol L(-1) HNO(3). The chelating fiber containing carboxymethylated polyallylamine was available for the separation of some metal ions in synthetic wastewater containing a large amount of Na(2)SO(4). The wet spinning technique using a solution containing a base polymer and a polymer ligand was quite simple and effective and would be applicable for preparing various chelating fibers.

  9. Synthesis and coordination chemistry of two N2-donor chelating di(indazolyl)methane ligands: structural characterization and comparison of their metal chelation aptitudes.

    PubMed

    Pettinari, Claudio; Marinelli, Alessandro; Marchetti, Fabio; Ngoune, Jean; Galindo, Agustín; Álvarez, Eleuterio; Gómez, Margarita

    2010-11-15

    The N(2)-donor bidentate ligands di(1H-indazol-1-yl)methane (L(1)) and di(2H-indazol-2-yl)methane (L(2)) (L in general) have been synthesized, and their coordination behavior toward Zn(II), Cd(II), and Hg(II) salts has been studied. Reaction of L(1) and L(2) with ZnX(2) (X = Cl, Br, or I) yields [ZnX(2)L] species (1-6), that, in the solid state, show a tetrahedral structure with dihapto ligand coordination via the pyrazolyl arms. The reaction of L(1) and L(2) with Zn(NO(3))(2)·6H(2)O is strongly dependent on the reaction conditions and on the ligand employed. Reaction of L(1) with equimolar quantities of Zn(NO(3))(2)·6H(2)O yields the neutral six-coordinate species [Zn(NO(3))(2)(L(1))], 7. On the other hand the use of L(1) excess gives the 2:1 adduct [Zn(NO(3))(2)(L(1))(2)], 8 where both nitrates act as a unidentate coordinating ligand. Analogous stoichiometry is found in the compound obtained from the reaction of L(2) with Zn(NO(3))(2)·6H(2)O which gives the ionic [Zn(NO(3))(L(2))(2)](NO(3)), 10. Complete displacement of both nitrates from the zinc coordination sphere is observed when the reaction between L(1) excess and the zinc salt was carried out in hydrothermal conditions. The metal ion type is also determining structure and stoichiometry: the reaction of L(2) with CdCl(2) gave the 2:1 adduct [CdCl(2)(L(2))(2)] 11 where both chlorides complete the coordination sphere of the six-coordinate cadmium center; on the other hand from the reaction of L(1) with CdBr(2) the polynuclear [CdBr(2)(L(1))](n) 12 is obtained, the Br(-) anion acting as bridging ligands in a six-coordinate cadmium coordination environment. The reaction of L(1) and L(2) with HgX(2) (X = Cl, I, SCN) is also dependent on the reaction conditions and the nature of X, two different types of adducts being formed [HgX(L)] (14: L = L(1), 16, 17: L = L(1) or L(2), X = I, 19: L = L(2), X = SCN) and [HgX(L)(2)] (15: L = L(2), X = Cl, 18: L = L(1), X = SCN). The X-ray diffraction analyses of compounds 1

  10. Spectroscopic and structural investigation on intermediates species structurally associated to the tricyclic bisguanidine compound and to the toxic agent, saxitoxin

    NASA Astrophysics Data System (ADS)

    Romani, Davide; Tsuchiya, Shigeki; Yotsu-Yamashita, Mari; Brandán, Silvia Antonia

    2016-09-01

    In the present work, we have studied the structural, topological and spectroscopic properties of five cyclic and of open chain species derived from tricyclic bisguanidine compound in gas and aqueous phases combining the DFT calculations with the experimental infrared and 1H NMR, 13C NMR and UV-visible spectra. These species are members of the saxitoxin family and they were recently synthesized by Tsuchiya et al. (Chemistry. A European Journal, 21 (2015) 7835-7840). Here, the self consistent reaction force (SCRF) calculations were employed in aqueous medium to study the solvation energies by using the polarized continuum (PCM) and solvation (SM) models. All the calculations were performed with the 6-31G* and 6-311++G** basis sets. The atomic charges, electrostatic potentials, bond order, stabilization energy, topological properties suggest the structural connection between the cyclic cationic and saxitoxin species while the electrophilicity and nucleophilicity indexes could be one of the explanations for the Nav blocking activities of these species. The complete vibrational assignments for all the species are reported. The predicted spectra present a reasonable concordance with the corresponding experimental ones.

  11. Binuclear complexes of bis-chelating ligands based on [1,4]dioxocino[6,5-b:7,8-b']dipyridine moieties.

    PubMed

    Casalino, Marcello; De Felice, Vincenzo; Fraldi, Natascia; Panunzi, Achille; Ruffo, Francesco

    2009-07-06

    Ligands based on a [1,4]dioxocino[6,5-b:7,8-b']dipyridine (doxpy) core were prepared and characterized. They all present two equal chelating moieties each one including one N, O, or S donor in addition to a pyridinic nitrogen. These ligands displayed high selectivity for the formation of binuclear complexes. At least one d(8) ion (Pd(II) or Pt(II)) complex was prepared for each type of ligand. The stereochemical behavior of the ligands is discussed on the basis of NMR spectra. Stable atropoisomers were obtained in the case of N-oxides or in case chiral centers were introduced in the ethereal bridge. As for the complexes, stable enantiomers appear to be in principle attainable for all the new compounds. A test on the cooperative ability of two Pd(II) centers has been grounded on the microstructure of the styrene/CO copolymer catalytically produced by a binuclear pyridine-imino complex. In fact, comparison with the microstructure of the copolymers produced by related single-site mono- and (open-chain) binuclear catalysts reveals significant difference, thus giving indication of possible synergic metal activity.

  12. A pyridine alkoxide chelate ligand that promotes both unusually high oxidation states and water-oxidation catalysis

    DOE PAGES

    Michaelos, Thoe K.; Shopov, Dimitar Y.; Sinha, Shashi Bhushan; ...

    2017-03-08

    Here, water-oxidation catalysis is a critical bottleneck in the direct generation of solar fuels by artificial photosynthesis. Catalytic oxidation of difficult substrates such as water requires harsh conditions, so that the ligand must be designed both to stabilize high oxidation states of the metal center and to strenuously resist ligand degradation. Typical ligand choices either lack sufficient electron donor power or fail to stand up to the oxidizing conditions. Our research on Ir-based water-oxidation catalysts (WOCs) has led us to identify a ligand, 2-(2'-pyridyl)-2-propanoate or “pyalk” that fulfills these requirements.

  13. Synthesis and chelation properties of a new polymeric ligand derived from 1-amino-2-naphthol-4-sulfonic Acid.

    PubMed

    Manivannan, Dhanasekaran; Biju, Valsala Madhavan Nair

    2015-01-01

    A novel chelating resin for preconcentration of heavy metals from various seawater samples has been developed by condensing 1-amino-2-hydroxy-7-[(4-hydroxyphenyl)diazenyl] naphthalene-4-sulfonic acid (AHDNS) with formaldehyde (1:2 mole ratio) in the presence of oxalic acid as the catalyst. The resin thus obtained was used as a solid sorbent for the separation of divalent metal ions present at trace levels in seawater. The functionalized phenol (AHDNS) was characterized by spectral studies. The polymeric resin AHDNS-formaldehyde (AHDNS-F) obtained by condensing the functionalized phenol and formaldehyde was characterized by IR and NMR spectral studies. The chelating property of the AHDNS-F resin towards divalent metal ions was studied as a function of pH and in the presence of electrolyte. The metal uptake properties of the resin were determined by using an atomic absorption spectrophotometer. This procedure was validated for recovery of divalent metal ions from seawater samples. The recoveries of cadmium, cobalt, copper, manganese, lead, and zinc were above 92% under the optimum preconcentration conditions. The LOD was <0.73 μg/L and the RSDs were <2%. Thus, the AHDNS-F resin can be widely used as a solid sorbent for the preconcentration of trace metals at ppm levels in seawater samples.

  14. Synthesis, characterization, and antipathogenic studies of some transition metal complexes with N,O-chelating Schiff's base ligand incorporating azo and sulfonamide Moieties

    NASA Astrophysics Data System (ADS)

    Alaghaz, Abdel-Nasser M. A.; Bayoumi, Hoda A.; Ammar, Yousry A.; Aldhlmani, Sharah A.

    2013-03-01

    Chromium(III), Manganese(II), Cobalt(II), nickel(II), copper(II) and cadmium(II) complexes of 4-[4-hydroxy-3-(phenyliminomethyl)-phenylazo]benzenesulfonamide, were prepared and characterized on the basis of elemental analyses, spectral, magnetic, molar conductance and thermal analysis. Square planar, tetrahedral and octahedral geometries have been assigned to the prepared complexes. Dimeric complexes are obtained with 2:2 molar ratio except chromium(III) complex is monomeric which is obtained with 1:1 molar ratios. The IR spectra of the prepared complexes were suggested that the Schiff base ligand(HL) behaves as a bi-dentate ligand through the azomethine nitrogen atom and phenolic oxygen atom. The crystal field splitting, Racah repulsion and nepheloauxetic parameters and determined from the electronic spectra of the complexes. Thermal studies suggest a mechanism for degradation of HL and its metal complexes as function of temperature supporting the chelation modes. Also, the activation thermodynamic parameters, such as ΔE*, ΔH*, ΔS* and ΔG* for the different thermal decomposition steps of HL and its metal complexes were calculated. The pathogenic activities of the synthesized compounds were tested in vitro against the sensitive organisms Staphylococcus aureus (RCMB010027), Staphylococcus epidermidis (RCMB010024) as Gram positive bacteria, Klebsiella pneumonia (RCMB 010093), Shigella flexneri (RCMB 0100542), as Gram negative bacteria and Aspergillus fumigates (RCMB 02564), Aspergillus clavatus (RCMB 02593) and Candida albicans (RCMB05035) as fungus strain, and the results are discussed.

  15. cis-Dioxomolybdenum(VI) complexes of a new ONN chelating thiosemicarbazidato ligand; Synthesis, characterization, crystal, molecular structures and antioxidant activities

    NASA Astrophysics Data System (ADS)

    İlhan Ceylan, Berat; Deniz, Nahide Gulsah; Kahraman, Sibel; Ulkuseven, Bahri

    2015-04-01

    5-Chloro-4-methyl-2-hydroxybenzophenone S-propyl-4-phenyl-thiosemicarbazone (H2L) and its cis-dioxomolybdenum(VI) complexes, in the general formula [MoO2(L)R-OH)] (R: methyl, 1; ethyl, 2; n-propyl, 3; n-butyl, 4; n-pentyl, 5), were synthesized and characterized by micro analysis, electronic, infrared and 1H and 13C NMR spectra. The crystal structures of complexes, 1 and 3, have been solved by direct methods (SIR92) and refined to the residual indexes R1 = 0.098 and R1 = 0.052 respectively. Complexes 1 and 3 are crystallized in the triclinic space group P-1 with Z = 2. The crystal study of complex 1 showed the first example of intermolecular hydrogen bond for this type of molybdenum-thiosemicarbazone complexes. The hydrogen bond is between the hydroxyl proton of attached alcohol and an oxo oxygen (in MoO22+ unit) of another complex molecule, and its bond distance (1.767(1) Å) is shorter than from the σ-coordination bonds in complex 1. Antioxidant activities of the compounds were determined by using 1,1-diphenyl-2-picrylhydrazyl (DPPH) method. Ligand showed 23.61% DPPH radical scavenging activity at 250 mg/L concentration. Cupric Reducing Antioxidant Capacity (CUPRAC) was also evaluated and trolox-equivalent antioxidant capacity (TEAC) values were found for ligand, 1 and 3 as 0.51, 0.33 and 0.30 respectively.

  16. Development of a quinazoline-based chelating ligand for zinc ion and its application to validation of a zinc-ion-coordinated compound.

    PubMed

    Yamada, Hiroshi; Shirai, Akina; Kato, Keisuke; Kimura, Junko; Ichiba, Hideaki; Yajima, Takehiko; Fukushima, Takeshi

    2010-06-01

    A novel fluorescent chelating ligand, 2,4-[bis-(2-hydroxy-3-methoxybenzylidene)]-dihydrazinoquinazoline (HBQZ), was synthesized, and the fluorescence characteristics of its complex with metal ions were investigated. Among the 36 different metal ions tested in this study, it was found that HBQZ emits intense fluorescence at 506 nm with an excitation wavelength of 414 nm in the presence of Zn2+. The fluorescence intensity was almost constant in the pH range 3.5-10.5. Complexes of other metal ions with HBQZ did not show fluorescence, and the detection limit of Zn2+ was approximately 250 nM (16 ppb). The proposed method was applied to the validation test of a bioactive compound containing Zn2+ in its structure--an antibacterial and antifungal reagent, zinc pyrithione (ZnPT). In order to effectively release Zn2+ from ZnPT, a pretreatment procedure involving heating with H3PO4 at 100 degrees C for 60 min was adopted. Under these conditions, a linear calibration curve was obtained in the ZnPT concentration range of 0.79-15.7 microM (0.25-5.0 ppm); the correlation coefficient and the relative standard deviation were 0.996 and within 3.1% (n=5), respectively.

  17. Lanthanide(III) di- and tetra-nuclear complexes supported by a chelating tripodal tris(amidate) ligand

    DOE PAGES

    Brown, Jessie L.; Jones, Matthew B.; Gaunt, Andrew J.; ...

    2015-04-06

    Syntheses, structural, and spectroscopic characterization of multinuclear tris(amidate) lanthanide complexes is described. Addition of K3[N(o-PhNC(O)tBu)3] to LnX3 (LnX3 = LaBr3, CeI3, and NdCl3) in N,N-dimethylformamide (DMF) results in the generation of dinuclear complexes, [Ln(N(o-PhNC(O)tBu)3)(DMF)]2(μ-DMF) (Ln = La (1), Ce (2), Nd(3)), in good yields. Syntheses of tetranuclear complexes, [Ln(N(o-PhNC(O)tBu)3)]4 (Ln = Ce (4), Nd(5)), resulted from protonolysis of Ln[N(SiMe3)2]3 (Ln = Ce, Nd) with N(o-PhNCH(O)tBu)3. As a result, in the solid-state, complexes 1–5 exhibit coordination modes of the tripodal tris(amidate) ligand that are unique to the 4f elements and have not been previously observed in transition metal systems.

  18. Lanthanide(III) di- and tetra-nuclear complexes supported by a chelating tripodal tris(amidate) ligand

    SciTech Connect

    Brown, Jessie L.; Jones, Matthew B.; Gaunt, Andrew J.; Scott, Brian L.; MacBeth, Cora E.; Gordon, John C.

    2015-04-06

    Syntheses, structural, and spectroscopic characterization of multinuclear tris(amidate) lanthanide complexes is described. Addition of K3[N(o-PhNC(O)tBu)3] to LnX3 (LnX3 = LaBr3, CeI3, and NdCl3) in N,N-dimethylformamide (DMF) results in the generation of dinuclear complexes, [Ln(N(o-PhNC(O)tBu)3)(DMF)]2(μ-DMF) (Ln = La (1), Ce (2), Nd(3)), in good yields. Syntheses of tetranuclear complexes, [Ln(N(o-PhNC(O)tBu)3)]4 (Ln = Ce (4), Nd(5)), resulted from protonolysis of Ln[N(SiMe3)2]3 (Ln = Ce, Nd) with N(o-PhNCH(O)tBu)3. As a result, in the solid-state, complexes 1–5 exhibit coordination modes of the tripodal tris(amidate) ligand that are unique to the 4f elements and have not been previously observed in transition metal systems.

  19. Negatively charged Ir(iii) cyclometalated complexes containing a chelating bis-tetrazolato ligand: synthesis, photophysics and the study of reactivity with electrophiles.

    PubMed

    Fiorini, Valentina; Zacchini, Stefano; Raiteri, Paolo; Mazzoni, Rita; Zanotti, Valerio; Massi, Massimiliano; Stagni, Stefano

    2016-08-09

    The bis-tetrazolate dianion [1,2 BTB](2-), which is the deprotonated form of 1,2 bis-(1H-tetrazol-5-yl)benzene [1,2-H2BTB], is for the first time exploited as an ancillary N^N ligand for negatively charged [Ir(C^N)2(N^N)](-)-type complexes, where C^N is represented by cyclometalated 2-phenylpyridine (ppy) or 2-(2,4-difluorophenyl)pyridine (F2ppy). The new Ir(iii) complexes [Ir(ppy)2(1,2 BTB)]- and [Ir(F2ppy)2(1,2 BTB)]- have been fully characterised and the analysis of the X-ray structure of [Ir(ppy)2(1,2 BTB)]- confirmed the coordination of the [1,2 BTB](2-) dianion in a bis chelated fashion through the N-atoms adjacent to each of the tetrazolic carbons. Both of the new anionic Ir(iii) complexes displayed phosphorescence in the visible region, with intense sky-blue (λmax = 460-490 nm) or aqua (λmax = 490-520 nm) emissions originating from [Ir(F2ppy)2(1,2 BTB)]- and [Ir(ppy)2(1,2 BTB)]-, respectively. In comparison with our very recent examples of anionic Ir(iii)tetrazolate cyclometalates, the new Ir(iii) tris chelate complexes [Ir(F2ppy)2(1,2 BTB)]- and [Ir(ppy)2(1,2 BTB)]-, display an improved robustness, allowing the study of their reactivity toward the addition of electrophiles such as H(+) and CH3(+). In all cases, the electrophilic attacks occurred at the coordinated tetrazolate rings, involving the reversible - by a protonation deprotonation mechanism - or permanent - upon addition of a methyl moiety - switching of their global net charge from negative to positive and, in particular, the concomitant variation of their photoluminescence output. The combination of the anionic complexes [Ir(F2ppy)2(1,2 BTB)]- or [Ir(ppy)2(1,2 BTB)]- with a deep red emitting (λmax = 686 nm) cationic Ir(iii) tetrazole complex such as [IrTPYZ-Me]+, where TPYZ-Me is 2-(2-methyl-2H-tetrazol-5-yl)pyrazine, gave rise to two fully Ir(iii)-based soft salts capable of displaying additive and O2-sensitive emission colours, with an almost pure white light obtained by the appropriate

  20. Octanuclear zinc(II) and cobalt(II) clusters produced by cooperative tetrameric assembling of oxime chelate ligands.

    PubMed

    Akine, Shigehisa; Dong, Wenkui; Nabeshima, Tatsuya

    2006-06-12

    We have synthesized an octanuclear zinc(II) cluster [L4Zn8(H2O)3] by the complexation of 3-hydroxysalamo (H4L) with zinc(II) acetate. The complex crystallizes in the triclinic system, space group P, with unit cell parameters a = 18.233(10) A, b = 20.518(11) A, c = 21.366(11) A, alpha = 98.7557(2) degrees, beta = 99.191(11) degrees, gamma = 108.309(10) degrees, and Z = 4. The crystallographic analysis revealed the S4 symmetrical assembling of four ligands and that the tetrameric complex has three water molecules in an unsymmetrical fashion. Spectroscopic analysis of the complex strongly suggests that the octanuclear cluster also exists in solution and maintains a conformation similar to that in the crystal structure, although exchange of the coordinating water molecules presumably takes place. In addition, the formation process of the octanuclear complex is highly cooperative. A high coordinating ability of the [(salamo)Zn] unit as well as the catecholato2- moieties probably stabilizes the octanuclear assembly and makes the complexation process cooperative. The corresponding octanuclear cobalt(II) cluster [L4Co8(EtOH)3] was prepared in a similar manner. Complex [L4Co8(H2O)2X] (X = H2O or EtOH) was obtained by the recrystallization from chloroform/hexane. The complex crystallizes in the triclinic system, space group P, with unit cell parameters a = 15.2359(10) A, b = 16.9625(12) A, c = 18.9325(13) A, alpha = 101.9710(10) degrees, beta = 105.5410(10) degrees, gamma = 97.1290(10) degrees, and Z = 2. Temperature dependence of magnetic susceptibility showed a continuous decrease in the chi(M)T value with decreasing temperature, suggesting antiferromagnetic interaction among cobalt(II) ions. The magnetic susceptibility above 40 K obeys the Curie-Weiss law with a Weiss constant theta of -39 K and a Curie constant C of 19.7 cm(3) K mol(-1).

  1. New tetradentate N,N,N,N-chelating α-diimine ligands and their corresponding zinc and nickel complexes: synthesis, characterisation and testing as olefin polymerisation catalysts.

    PubMed

    Li, Lidong; Gomes, Clara S B; Gomes, Pedro T; Duarte, M Teresa; Fan, Zhiqiang

    2011-04-07

    A series of zinc complexes of the general formula {[ZnCl(ArN=C(An)-C(An)=NAr)](+)}(2)[Zn(2)Cl(6)](2-) (where Ar = 2-(1-benzyl-1H-1,2,3-triazol-4-yl)phenyl 2a, 2-(1-(1-phenylethyl)-1H-1,2,3-triazol-4-yl)phenyl 2b, 2-(1-phenyl-1H-1,2,3-triazol-4-yl)phenyl 2c; An = acenaphthene backbone) were prepared by the condensation of acenaphthenequinone with the corresponding o-triazolyl-substituted anilines (2-(1-benzyl-1H-1,2,3-triazol-4-yl)aniline 1a, 2-(1-(1-phenylethyl)-1H-1,2,3-triazol-4-yl)aniline 1b, 2-(1-phenyl-1H-1,2,3-triazol-4-yl)aniline 1c) which were formed by the copper(I)-catalyzed Huisgen[3+2] dipolar cycloaddition between 2-ethynylaniline and the corresponding azides in high yields, using anhydrous ZnCl(2) as the metal template, in boiling glacial acetic acid. Zinc complexes of the type [ZnCl(ArN=C(An)-C(An)=NAr)](+)[ZnCl(3)(NCCH(3))](-) (4a-c) were synthesized by crystallisation of the corresponding complexes 2a-c in acetonitrile, at -20 °C. After removal of zinc dichloride from complexes 2a-c by the addition of potassium oxalate, in dichloromethane, the tetradentate N,N,N,N-chelating α-diimine ligands of the type ArN=C(An)-C(An)=NAr (5a-c) were obtained. The new ligand precursors and zinc complexes were characterised by elemental analysis, (1)H and (13)C{(1)H} NMR spectroscopy, two-dimensional NMR spectroscopy, and X-ray diffraction. Reaction of the ligand precursors 5a-c with [NiBr(2)(DME)], in dichloromethane, gave nickel complexes of the type [NiBr(2)(ArN=C(An)-C(An)=NAr)] (6a-c). The results of single crystal X-ray diffraction characterisation and magnetic susceptibility measurements demonstrated that nickel complexes 6a-c possess octahedral geometries around the nickel atoms with variable configurations, the Br atoms of which can be ionized when dissolved in methanol. In preliminary catalytic tests, complexes 6a-c revealed to be active as catalysts for the polymerisation of norbornene and styrene, when activated by cocatalyst MAO. The characterisation

  2. Theoretical studies of molecular structure, electronic structure, spectroscopic properties and the ancillary ligand effect: A comparison of tris-chelate ML 3-type and ML 2X-type species for gallium(III) complexes with N, O-donor phenolic ligand, 2-(2-hydroxyphenyl)benzothiazole

    NASA Astrophysics Data System (ADS)

    Tong, Yi-Ping; Lin, Yan-Wen

    2011-02-01

    Two Ga(III) complexes with main ligand, 2-(2-hydroxyphenyl)benzothiazole (HL'), namely mixed-ligand ML 2X-type [GaL' 2X'] ( 1) (HX' = acetic acid, as ancillary ligand) and the meridianal tris-chelate [GaL' 3] ( 2) have been investigated by the density functional theory (DFT/TDDFT) level calculations. Both 1 and 2 can be presented as a similar "mixed-ligand ML 2X-type" species. The molecular geometries, electronic structures, metal-ligand bonding property of Ga-O (N) (main ligand), Ga-O (N) (ancillary ligand) interactions, and the ancillary ligand effect on their HOMO-LUMO gap, their absorption/emission property, and their absorption/emission wavelengths/colors for them have been discussed in detail based on the orbital interactions, the partial density of states (PDOS), and so on. The current investigation also indicates that it is quite probable that by introduction of different ancillary ligands, a series of new mixed-ligand ML 2X-type complexes for group 13 metals can be designed with their absorption/emission property and the absorption/emission wavelengths and colors being tuned.

  3. Theoretical studies of molecular structure, electronic structure, spectroscopic properties and the ancillary ligand effect: a comparison of tris-chelate ML3-type and ML2X-type species for gallium(III) complexes with N,O-donor phenolic ligand, 2-(2-hydroxyphenyl)benzothiazole.

    PubMed

    Tong, Yi-Ping; Lin, Yan-Wen

    2011-02-01

    Two Ga(III) complexes with main ligand, 2-(2-hydroxyphenyl)benzothiazole (HL'), namely mixed-ligand ML2X-type [GaL'2X'] (1) (HX'=acetic acid, as ancillary ligand) and the meridianal tris-chelate [GaL'3] (2) have been investigated by the density functional theory (DFT/TDDFT) level calculations. Both 1 and 2 can be presented as a similar "mixed-ligand ML2X-type" species. The molecular geometries, electronic structures, metal-ligand bonding property of Ga-O (N) (main ligand), Ga-O (N) (ancillary ligand) interactions, and the ancillary ligand effect on their HOMO-LUMO gap, their absorption/emission property, and their absorption/emission wavelengths/colors for them have been discussed in detail based on the orbital interactions, the partial density of states (PDOS), and so on. The current investigation also indicates that it is quite probable that by introduction of different ancillary ligands, a series of new mixed-ligand ML2X-type complexes for group 13 metals can be designed with their absorption/emission property and the absorption/emission wavelengths and colors being tuned.

  4. 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 ...

  5. Cytotoxicity of Ru(II) piano-stool complexes with chloroquine and chelating ligands against breast and lung tumor cells: Interactions with DNA and BSA.

    PubMed

    Colina-Vegas, Legna; Villarreal, Wilmer; Navarro, Maribel; de Oliveira, Clayton Rodrigues; Graminha, Angélica E; Maia, Pedro Ivo da S; Deflon, Victor M; Ferreira, Antonio G; Cominetti, Marcia Regina; Batista, Alzir A

    2015-12-01

    The synthesis and spectroscopic characterization of nine π-arene piano-stool ruthenium (II) complexes with aromatic dinitrogen chelating ligands or containing chloroquine (CQ), are described in this study: [Ru(η(6)-C10H14)(phen)Cl]PF6 (1), [Ru(η(6)-C10H14)(dphphen)Cl]PF6 (2), [Ru(η(6)-C10H14)(bipy)Cl]PF6 (3), [Ru(η(6)-C10H14)(dmebipy)Cl]PF6 (4) and [Ru(η(6)-C10H14)(bdutbipy)Cl]PF6 (5), [Ru(η(6)-C10H14)(phen)CQ](PF6)2 (6), [Ru(η(6)-C10H14)(dphphen)CQ](PF6)2 (7), [Ru(η(6)-C10H14)(bipy)CQ](PF6)2 (8), [Ru(η(6)-C10H14)(dmebipy)CQ](PF6)2 (9): [1,10-phenanthroline (phen), 4,7-diphenyl-1,10-phenanthroline (dphphen), 2,2'-bipyridine (bipy), 5,5'-dimethyl-2,2'-bipyridine (dmebipy), and 4,4'-di-t-butyl-2,2'-bipyridine (dbutbipy)]. The solid state structures of five ruthenium complexes (1-5) were determined by X-ray crystallography. Electrochemical experiments were performed by cyclic voltammetry to estimate the redox potential of the Ru(II)/Ru(III) couple in each case. Their interactions with DNA and BSA, and activity against four cell lines (L929, A549, MDA-MB-231 and MCF-7) were evaluated. Compounds 2, 6 through 9, interact with DNA which was comparable to the one observed for free chloroquine. The results of fluorescence titration revealed that these complexes strongly quenched the intrinsic fluorescence of BSA following a static quenching procedure. Binding constants (Kb) and the number of binding sites (n~1) were calculated using modified Stern-Volmer equations. The thermodynamic parameters ΔG at different temperatures were calculated and subsequently the values of ΔH and ΔS were also calculated, which revealed that hydrophobic and electrostatic interactions play a major role in the BSA-complex association. The MTT assay results indicated that complexes 2, 5 and 7 showed cytostatic effects at appreciably lower concentrations than those needed for cisplatin, chloroquine and doxorubicin.

  6. Tautomerization of 2-nitroso-N-arylanilines by coordination as N,N'-chelate ligands to rhenium(I) complexes and the anticancer activity of newly synthesized oximine rhenium(I) complexes against human melanoma and leukemia cells in vitro.

    PubMed

    Wirth, Stefan; Wallek, Andreas U; Zernickel, Anna; Feil, Florian; Sztiller-Sikorska, M; Lesiak-Mieczkowska, K; Bräuchle, Christoph; Lorenz, Ingo-Peter; Czyz, M

    2010-07-01

    The synthesis, structural characterization and biological activity of eight ortho-quinone(N-aryl)-oximine rhenium(I) complexes are described. The reaction of the halogenido complexes (CO)(5)ReX (X = Cl (4), Br (5)) with 2-nitroso-N-arylanilines {(C(6)H(3)ClNO)NH(C(6)H(4)R)} (R = p-Cl, p-Me, o-Cl, H) (3a-d) in tetrahydrofurane (THF) yields the complexes fac-(CO)(3)XRe{(C(6)H(3)ClNO)NH(C(6)H(4)R)} (6a-d, 7a-d) with the tautomerized ligand acting as a N,N'-chelate. The substitution of two carbonyl ligands leads to the formation of a nearly planar 5-membered metallacycle. During coordination the amino-proton is shifted to the oxygen of the nitroso group which can be observed in solution for 6 and 7 by (1)H NMR spectroscopy and in solid state by crystal structure analysis. After purification, all compounds have been fully characterized by their (1)H and (13)C NMR, IR, UV/visible (UV/Vis) and mass spectra. The X-ray structure analyses revealed a distorted octahedral coordination of the CO, X and N,N'-chelating ligands for all Re(I) complexes. Biological activity of four oximine rhenium(I) complexes was assessed in vitro in two highly aggressive cancer cell lines: human metastatic melanoma A375 and human chronic myelogenous leukemia K562. Chlorido complexes (6a and 6c) were more efficient than bromido compounds (7d and 7b) in inducing apoptotic cell death of both types of cancer cells. Melanoma cells were more susceptible to tested rhenium(I) complexes than leukemia cells. None of the ligands (3a-d) showed any significant anticancer activity.

  7. Chelation of cadmium.

    PubMed Central

    Andersen, O

    1984-01-01

    The toxicity of cadmium is determined by chelation reactions: in vivo, Cd2+ exists exclusively in coordination complexes with biological ligands, or with administered chelating agents. The Cd2+ ion has some soft character, but it is not a typical soft ion. It has a high degree of polarizability, and its complexes with soft ligands have predominantly covalent bond characteristics. Cd2+ forms the most stable complexes with soft donor atoms (S much greater than N greater than 0). The coordination stereochemistry of Cd2+ is unusually varied, including coordination numbers from 2 to 8. Even though the Cd2+ ion is a d10 ion, disturbed coordination geometries are often seen. Generally, the stability of complexes increases with the number of coordination groups contributed by the ligand; consequently, complexes of Cd2+ with polydentate ligands containing SH groups are very stable. Cd2+ in metallothionein (MT) is coordinated with 4 thiolate groups, and the log stability constant is estimated to 25.5. Complexes between Cd2+ and low molecular weight monodentate or bidentate ligands, e.g., free amino acids (LMW-Cd), seem to exist very briefly, and Cd2+ is rapidly bound to high molecular weight proteins, mainly serum albumin. These complexes (HMW-Cd) are rapidly scavenged from blood, mainly by the liver, and Cd2+ is redistributed to MT. After about 1 day the Cd-MT complex (MT-Cd) almost exclusively accounts for the total retained dose of Cd2+, independent of the route of exposure. MT-Cd is slowly transferred to and accumulated in kidney cortex. The acute toxicity and interorgan distribution of parenterally administered Cd2+ are strongly influenced by preceding MT induction, or decreased capacity for MT synthesis; however, the gastrointestinal (GI) uptake of Cd2+ seems unaffected by preceding MT induction resulting in considerable capacity for Cd2+ chelation in intestinal mucosa, and this finding indicates that endogenous MT is not involved in Cd2+ absorption. The toxicity of

  8. Correlation of the structural information obtained for europium-chelate ensembles from gas-phase photoluminescence and ion-mobility spectroscopy with density-functional computations and ligand-field theory.

    PubMed

    Greisch, Jean-François; Chmela, Jiří; Harding, Michael E; Wunderlich, Dirk; Schäfer, Bernhard; Ruben, Mario; Klopper, Wim; Schooss, Detlef; Kappes, Manfred M

    2017-02-22

    We report a combined investigation of europium(iii)9-oxo-phenalen-1-one (PLN) coordination complexes, [Eu(PLN)4AE](+) with AE = Mg, Ca, and Sr, using gas-phase photoluminescence, trapped ion-mobility spectrometry and density-functional computations. In order to sort out the structural impact of the alkali earth dications on the photoluminescence spectra, the experimental data are compared to the predicted ligand-field splittings as well as to the collision cross-sections for different isomers of [Eu(PLN)4AE](+). The best fitting interpretation is that one isomer family predominantly contributes to the recorded luminescence. The present work demonstrates the complexity of the coordination patterns of multicenter lanthanoid chelates involved in dynamical equilibria and the pertinence of using isolation techniques to elucidate their photophysical properties.

  9. Configuration Control in the Synthesis of Homo- and Heteroleptic Bis(oxazolinylphenolato/thiazolinylphenolato) Chelate Ligand Complexes of Oxorhenium(V): Isomer Effect on Ancillary Ligand Exchange Dynamics and Implications for Perchlorate Reduction Catalysis.

    PubMed

    Liu, Jinyong; Wu, Dimao; Su, Xiaoge; Han, Mengwei; Kimura, Susana Y; Gray, Danielle L; Shapley, John R; Abu-Omar, Mahdi M; Werth, Charles J; Strathmann, Timothy J

    2016-03-07

    This study develops synthetic strategies for N,N-trans and N,N-cis Re(O)(LO-N)2Cl complexes and investigates the effects of the coordination spheres and ligand structures on ancillary ligand exchange dynamics and catalytic perchlorate reduction activities of the corresponding [Re(O)(LO-N)2](+) cations. The 2-(2'-hydroxyphenyl)-2-oxazoline (Hhoz) and 2-(2'-hydroxyphenyl)-2-thiazoline (Hhtz) ligands are used to prepare homoleptic N,N-trans and N,N-cis isomers of both Re(O)(hoz)2Cl and Re(O)(htz)2Cl and one heteroleptic N,N-trans Re(O)(hoz)(htz)Cl. Selection of hoz/htz ligands determines the preferred isomeric coordination sphere, and the use of substituted pyridine bases with varying degrees of steric hindrance during complex synthesis controls the rate of isomer interconversion. The five corresponding [Re(O)(LO-N)2](+) cations exhibit a wide range of solvent exchange rates (1.4 to 24,000 s(-1) at 25 °C) and different LO-N movement patterns, as influenced by the coordination sphere of Re (trans/cis), the noncoordinating heteroatom on LO-N ligands (O/S), and the combination of the two LO-N ligands (homoleptic/heteroleptic). Ligand exchange dynamics also correlate with the activity of catalytic reduction of aqueous ClO4(-) by H2 when the Re(O)(LO-N)2Cl complexes are immobilized onto Pd/C. Findings from this study provide novel synthetic strategies and mechanistic insights for innovations in catalytic, environmental, and biomedical research.

  10. Multispectroscopic DNA-binding studies of a tris-chelate nickel(II) complex containing 4,7-diphenyl 1,10-phenanthroline ligands

    NASA Astrophysics Data System (ADS)

    Shahabadi, Nahid; Fatahi, Azadeh

    2010-04-01

    A tris-chelate nickel(II) complex, [Ni(DIP) 3](NO 3) 2 · 3H 2O in which DIP = 4,7-diphenyl 1,10 phenanthroline, was synthesized and characterized by spectroscopic ( 1H NMR and UV-vis) and elemental analysis techniques. Binding interaction of this complex with calf thymus-DNA (CT-DNA) was investigated using emission, absorption, circular dichroism (CD), viscosity and DNA thermal denaturation studies. In absorption spectrum of the complex, as the concentration of DNA increased, appearance of an isobestic point proved the new [Ni(DIP) 3] 2+-DNA complex formation. The intrinsic binding constant ( Kb = 4.34 × 10 4 M -1) is comparable to groove binding complexes. In fluorimetric studies, the dynamic enhancement constants ( kD) and bimolecular enhancement constant ( kB) were calculated and showed that the fluorescence enhancement was initiated by a static process in the ground state. Furthermore, the thermodynamic studies showed that the reaction is exothermic and enthalpy favored (Δ H = -58.41 kJ/mol). A strong CD spectrum in the UV and visible region develops upon addition of CT-DNA into the racemate solution of Ni(II) complex (Pfeiffer effect). This has revealed that a shift in diastereomeric inversion equilibrium takes place in the solution to yield an excess of one of the DNA complex diastereomers. Finally, all of the experimental results prove that the minor groove binding must be predominant.

  11. 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.

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

    PubMed Central

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

    2013-01-01

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

  13. Phosphonated chelates for nuclear imaging.

    PubMed

    Abada, Sabah; Lecointre, Alexandre; Christine, Câline; Ehret-Sabatier, Laurence; Saupe, Falk; Orend, Gertraud; Brasse, David; Ouadi, Ali; Hussenet, Thomas; Laquerrière, Patrice; Elhabiri, Mourad; Charbonnière, Loïc J

    2014-12-21

    A series of bis-, tris- and tetra-phosphonated pyridine ligands is presented. In view of their potential use as chelates for radiopharmaceutical applications, the physico-chemical properties of the ligands and of their Co(II), Ni(II), Cu(II), and Zn(II) complexes were studied by means of potentiometry and UV-Vis absorption spectroscopy. The pKa values of the ligands and of the complexes, as well as the stability constants for the formation of the complexes, are presented. The kinetic aspects of the formation of Cu(II) complexes and of their dissociation in acidic media were studied by means of stopped flow experiments, and the stability of the Cu(II) complex toward reduction to Cu(I) was investigated by cyclic voltammetry and by titration with different reducing agents. The different thermodynamic and kinetic aspects of the polyphosphonated ligands were compared with regard to the impact of the number of phosphonic acid functions. Considering the very promising properties for complexation, preliminary SPECT/CT imaging experiments were carried out on mice with (99m)Tc using the bis- and tetra-phosphonated ligands L(2) and L(1). Finally, a bifunctional version of chelate L(1), L*, was used to label MTn12, a rat monoclonal antibody with both specificity and relatively high affinity for murine tenascin-C. The labeling was monitored by MALDI/MS spectrometry and the affinity of the labeled antibody was checked by immunostaining experiments. After chelation with (99m)Tc, the (99m)Tc-L*-MTn12 antibody was injected into a transgenic mouse with breast cancer and the biodistribution of the labeled antibody was followed by SPECT/CT imaging.

  14. Ruthenium(II) and osmium(II) mixed chelates based on pyrenyl-pyridylimidazole and 2,2'-bipyridine ligands as efficient DNA intercalators and anion sensors.

    PubMed

    Mardanya, Sourav; Karmakar, Srikanta; Maity, Dinesh; Baitalik, Sujoy

    2015-01-20

    We report herein the synthesis and characterization of two monometallic ruthenium(II) and osmium(II) complexes of composition [(bpy)2M(HImzPPy)] (ClO4)2 derived from pyrenylimidazole-10-pyridin-2-yl-9H-9,11-diazacyclopenta[e]pyrene (HImzPPy) and 2,2'-bipyridine (bpy) ligands. X-ray crystallographic study shows that both crystals belong to the triclinic system having space group P1̅. The photophysical properties of 1 and 2 in acetonitrile indicate that the metal-to-ligand charge-transfer excited state is mainly centered in the [M(bpy)2](2+) moiety of the complexes and slightly affected by the extended conjugation of the pyrenylimidazole moiety. Both complexes display one-electron reversible metal-centered oxidative processes and a number of quasi-reversible reductive processes. The binding affinities of the complexes toward calf-thymus DNA (CT-DNA) were thoroughly studied through different methods such as absorption, emission, excited-state lifetime, circular dichroism, and thermal denaturation of DNA and a relative DNA binding study using ethidium bromide. All of these experiments account for the intercalative nature of both 1 and 2 toward CT-DNA as well as their light-switch behavior. The anion recognition study through different spectroscopic techniques reveals that both complexes act as "turn-on" luminescence sensors for H2PO4(-) and "turn-off" sensors toward F(-) and AcO(-). The imidazole N-H proton of the receptors gets deprotonated with the excessive addition of F(-) and AcO(-), while it interacts with H2PO4(-) through hydrogen-bonding interaction. Theoretical calculations (DFT and TD-DFT) were also performed to understand the photophysical properties of the metalloreceptors.

  15. Mixed ligand complexes of cobalt(III) and iron(III) containing N2O2-chelating Schiff base: Synthesis, characterisation, antimicrobial activity, antioxidant and DFT study

    NASA Astrophysics Data System (ADS)

    Pramanik, Harun A. R.; Paul, Pradip C.; Mondal, Paritosh; Bhattacharjee, Chira R.

    2015-11-01

    Six mixed ligand complexes, namely, [Co(acac)L1] (1), [Fe(acac)L1] (2), [Co(acac)L2] (3), [Fe(acac)L2] (4), [Co(acac)L3] (5), and [Fe(acac)L3] (6) (H2L1 = NN/-bis(salicylidene)-trans 1,2 diaminocyclohexane, H2L2 = NN/-bis(salicylidene)-1,2 phenylenediamine, H2L3 = NN/-bis(salicylidene)-4-methyl-1,2-phenylenediamine) were synthesised and characterized using elemental analysis, IR spectra, UV-Vis spectra, mass spectra, magnetic susceptibility measurements, 1H and 13C NMR spectroscopy, thermogravimetric analysis. The molar conductance measurement confirmed the non-electrolytic nature of the complexes in DMF solution. Antioxidant activity of the complexes was studied using the 2, 2-diphenyl-1-picrylhydrazyl (DPPH) scavenging method. Biological studies of the complexes have been carried out in vitro for antimicrobial activity against some selected gram-positive and gram-negative bacteria. DFT calculations were performed using GAUSSIAN 09 program to ascertain the stable electronic structure, HOMO-LUMO energy gap, chemical hardness and dipole moment of the complexes.

  16. Ring opening metathesis polymerization-derived block copolymers bearing chelating ligands: synthesis, metal immobilization and use in hydroformylation under micellar conditions

    PubMed Central

    Pawar, Gajanan M; Weckesser, Jochen

    2010-01-01

    Summary Norborn-5-ene-(N,N-dipyrid-2-yl)carbamide (M1) was copolymerized with exo,exo-[2-(3-ethoxycarbonyl-7-oxabicyclo[2.2.1]hept-5-en-2-carbonyloxy)ethyl]trimethylammonium iodide (M2) using the Schrock catalyst Mo(N-2,6-Me2-C6H3)(CHCMe2Ph)(OCMe(CF3)2)2 [Mo] to yield poly(M1-b-M2). In water, poly(M1-b-M2) forms micelles with a critical micelle-forming concentration (cmc) of 2.8 × 10−6 mol L−1; Reaction of poly(M1-b-M2) with [Rh(COD)Cl]2 (COD = cycloocta-1,5-diene) yields the Rh(I)-loaded block copolymer poly(M1-b-M2)-Rh containing 18 mg of Rh(I)/g of block copolymer with a cmc of 2.2 × 10−6 mol L−1. The Rh-loaded polymer was used for the hydroformylation of 1-octene under micellar conditions. The data obtained were compared to those obtained with a monomeric analogue, i.e. CH3CON(Py)2RhCl(COD) (C1, Py = 2-pyridyl). Using the polymer-supported catalyst under micellar conditions, a significant increase in selectivity, i.e. an increase in the n:iso ratio was accomplished, which could be further enhanced by the addition of excess ligand, e.g., triphenylphosphite. Special features of the micellar catalytic set up are discussed. PMID:20502652

  17. Cu-free 1,3-dipolar cycloaddition click reactions to form isoxazole linkers in chelating ligands for fac-[M(I)(CO)3]+ centers (M = Re, 99mTc).

    PubMed

    Bottorff, Shalina C; Kasten, Benjamin B; Stojakovic, Jelena; Moore, Adam L; MacGillivray, Leonard R; Benny, Paul D

    2014-02-17

    Isoxazole ring formation was examined as a potential Cu-free alternative click reaction to Cu(I)-catalyzed alkyne/azide cycloaddition. The isoxazole reaction was explored at macroscopic and radiotracer concentrations with the fac-[M(I)(CO)3](+) (M = Re, (99m)Tc) 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-[M(I)(CO)3](+) complexes with a model nitrile oxide generator. Macroscale experiments, alkyne-functionalized chelates, or Re complexes indicate facile formation of the isoxazole ring. (99m)Tc 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.

  18. 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...

  19. Development of a reliable analytical method for extraction spectrophotometric determination of ruthenium(III) from catalyst and fissium alloy using o-methylphenyl thiourea as a chromogenic chelating ligand

    NASA Astrophysics Data System (ADS)

    Kuchekar, Shashikant R.; Shelar, Yogesh S.; Aher, Haribhau R.; Han, Sung H.

    2013-04-01

    A simple and selective method is developed for the extraction spectrophotometric determination of ruthenium(III) using o-methylphenyl thiourea (OMPT) as a chromogenic chelating ligand. The basis of the proposed method is ruthenium(III)-OMPT complex formation in aqueous hydrochloric acid media (3.0 mol L-1) after 5.0 min heating on a boiling water bath and the complex formed is extracted into chloroform. The absorbance of green colored ruthenium(III)-OMPT complex is measured at 590 nm against the reagent blank. Beer's law was obeyed up to 42.5 μg mL-1 of ruthenium(III) and the optimum concentration range is 7.56-39.81 μg mL-1 of ruthenium(III) as evaluated by Ringbom's plot. Molar absorptivity and Sandell's sensitivity of ruthenium(III)-OMPT complex in chloroform are 2.34 × 103 L mol-1 cm-1 and 0.043 μg cm-2 respectively. The composition of ruthenium(III):OMPT complex (1:2) was established from slope ratio method, mole ratio method and Job's continuous variation method. Complex was stable for more than 48 h. The interfering effect of various foreign ions was studied and suitable masking agents are used wherever necessary to enhance the selectivity of the method. Proposed method is successfully applied for determination of ruthenium(III) from binary and ternary synthetic mixtures, synthetic mixtures corresponding to fissium alloy and ruthenium catalyst. Repetition of the method was checked by finding relative standard deviation (R.S.D) for 10 determinations which was 0.23%. A scheme for sequential separation of palladium(II), ruthenium(III), rhodium(III) and platinum(IV) has been developed.

  20. Development of a reliable analytical method for extraction spectrophotometric determination of ruthenium(III) from catalyst and fissium alloy using o-methylphenyl thiourea as a chromogenic chelating ligand.

    PubMed

    Kuchekar, Shashikant R; Shelar, Yogesh S; Aher, Haribhau R; Han, Sung H

    2013-04-01

    A simple and selective method is developed for the extraction spectrophotometric determination of ruthenium(III) using o-methylphenyl thiourea (OMPT) as a chromogenic chelating ligand. The basis of the proposed method is ruthenium(III)-OMPT complex formation in aqueous hydrochloric acid media (3.0molL(-1)) after 5.0min heating on a boiling water bath and the complex formed is extracted into chloroform. The absorbance of green colored ruthenium(III)-OMPT complex is measured at 590nm against the reagent blank. Beer's law was obeyed up to 42.5μgmL(-1) of ruthenium(III) and the optimum concentration range is 7.56-39.81μgmL(-1) of ruthenium(III) as evaluated by Ringbom's plot. Molar absorptivity and Sandell's sensitivity of ruthenium(III)-OMPT complex in chloroform are 2.34×10(3)Lmol(-1) cm(-1) and 0.043μgcm(-2) respectively. The composition of ruthenium(III):OMPT complex (1:2) was established from slope ratio method, mole ratio method and Job's continuous variation method. Complex was stable for more than 48h. The interfering effect of various foreign ions was studied and suitable masking agents are used wherever necessary to enhance the selectivity of the method. Proposed method is successfully applied for determination of ruthenium(III) from binary and ternary synthetic mixtures, synthetic mixtures corresponding to fissium alloy and ruthenium catalyst. Repetition of the method was checked by finding relative standard deviation (R.S.D) for 10 determinations which was 0.23%. A scheme for sequential separation of palladium(II), ruthenium(III), rhodium(III) and platinum(IV) has been developed.

  1. 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

  2. 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.

  3. 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.

  4. 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.

  5. Synthesis and characterization of dihexyldithiocarbamate as a chelating agent in extraction of gold(III)

    SciTech Connect

    Fatimah, Soja Siti; Bahti, Husein H.; Hastiawan, Iwan; Permanasari, Anna

    2016-02-08

    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, ({sup 1}H, and {sup 13}C), FTIR, and MS-ESI. Data on the synthesis, characterization, and the application of the ligand as a chelating agent are presented.

  6. Bis-tridentate Chelates of an Asymmetric Ligand: X-ray Structures and Solution NMR Characterization of Divalent Zinc Triad Metal Ion Complexes of N-(2-pyridylmethyl)-N-(2-(methylthio)ethyl)amine.

    PubMed

    Bebout, Deborah C; Lai, Wei; Stamps, Sarah M; Berry, Steven M; Butcher, Raymond J

    2008-04-25

    Divalent zinc triad metal ion complexes of type M(L)(2)(ClO(4))(2) (L = N-(2-pyridylmethyl)-N-(2-(methylthio)ethyl)amine) with N(4)S(2) metal coordination spheres were isolated and characterized by X-ray crystallography and variable temperature proton NMR. Although bis-tridentate chelates have nine geometric isomers, the crystallographically characterized complexes of all three metal ions had trans facial octahedral coordination geometry with C(i) symmetry. Despite the low coordination number and geometric preferences of d(10) metal ions, which facilitate inter- and intramolecular exchange processes, dilute solutions of these bis-tridentate chelates exhibited slow geometric isomerization. Symmetry, sterics and shielding arguments supported specific isomeric assignments for the major and minor chemical shift environments observed at low temperature. At elevated temperature, rapid intramolecular exchange occurred for all three complexes but slow intermolecular exchange on the coupling constant time scale was evidenced through detection of J(HgH) interactions for Hg(L)(2) (2+). These unusual observations are discussed in the context of the zinc triad metal ion coordination chemistry of related bis-tridentate chelates.

  7. 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.

  8. 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.

  9. 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.

  10. Matching chelators to radiometals for radiopharmaceuticals.

    PubMed

    Price, Eric W; Orvig, Chris

    2014-01-07

    Radiometals comprise many useful radioactive isotopes of various metallic elements. When properly harnessed, these have valuable emission properties that can be used for diagnostic imaging techniques, such as single photon emission computed tomography (SPECT, e.g.(67)Ga, (99m)Tc, (111)In, (177)Lu) and positron emission tomography (PET, e.g.(68)Ga, (64)Cu, (44)Sc, (86)Y, (89)Zr), as well as therapeutic applications (e.g.(47)Sc, (114m)In, (177)Lu, (90)Y, (212/213)Bi, (212)Pb, (225)Ac, (186/188)Re). A fundamental critical component of a radiometal-based radiopharmaceutical is the chelator, the ligand system that binds the radiometal ion in a tight stable coordination complex so that it can be properly directed to a desirable molecular target in vivo. This article is a guide for selecting the optimal match between chelator and radiometal for use in these systems. The article briefly introduces a selection of relevant and high impact radiometals, and their potential utility to the fields of radiochemistry, nuclear medicine, and molecular imaging. A description of radiometal-based radiopharmaceuticals is provided, and several key design considerations are discussed. The experimental methods by which chelators are assessed for their suitability with a variety of radiometal ions is explained, and a large selection of the most common and most promising chelators are evaluated and discussed for their potential use with a variety of radiometals. Comprehensive tables have been assembled to provide a convenient and accessible overview of the field of radiometal chelating agents.

  11. Development of a dipodal Schiff base ligand with N-imine and O-naphtholate donors: A potential chelator towards Cu(II) metal ion established through potentiometric and spectrophotometric studies

    NASA Astrophysics Data System (ADS)

    Baral, Minati; Gupta, Amit; Kanungo, B. K.

    2015-08-01

    A novel hydroxynaphthaldehyde derived Schiff base ligand N,N'-bis-[2-[(2-hydroxy-1-naphthyl)methyleneamino]ethyl]propanediamide (DOTA2HNAP) containing nitrogen and oxygen donor atoms has been developed. The lowest energy molecular structure of DOTA2HNAP and its complexes with Cu (II) metal ion were examined by molecular mechanics using MM+ force which later was re-optimized by semi-empirical method. The theoretical IR and UV spectra of the ligand were obtained using semi empirical/ZINDO/PM3 and were compared with the experimental ones. The coordinating ability of DOTA2HNAP with H+ and Cu(II) ions was investigated in 1:99 (DMSO: water) binary solvent mixture at 25±1°C by potentiometric and spectrophotometric method. The electronic spectra of the ligand show three distinct peaks (253nm, 320nm and 360nm) implicating existence of the Schiff base in quinone form that was well supported by theoretical spectral studies. Out of various complex species forming in solution, all the metal ions show higher stability of complexes when in 1:1 metal-ligand stoichiometry, binding through two N-imine and two O-naphtholate groups.

  12. Development of a dipodal Schiff base ligand with N-imine and O-naphtholate donors: A potential chelator towards Cu(II) metal ion established through potentiometric and spectrophotometric studies

    SciTech Connect

    Baral, Minati Gupta, Amit; Kanungo, B. K.

    2015-08-28

    A novel hydroxynaphthaldehyde derived Schiff base ligand N,N’-bis-[2-[(2-hydroxy-1-naphthyl)methyleneamino]ethyl]propanediamide (DOTA2HNAP) containing nitrogen and oxygen donor atoms has been developed. The lowest energy molecular structure of DOTA2HNAP and its complexes with Cu (II) metal ion were examined by molecular mechanics using MM+ force which later was re-optimized by semi-empirical method. The theoretical IR and UV spectra of the ligand were obtained using semi empirical/ZINDO/PM3 and were compared with the experimental ones. The coordinating ability of DOTA2HNAP with H{sup +} and Cu(II) ions was investigated in 1:99 (DMSO: water) binary solvent mixture at 25±1°C by potentiometric and spectrophotometric method. The electronic spectra of the ligand show three distinct peaks (253nm, 320nm and 360nm) implicating existence of the Schiff base in quinone form that was well supported by theoretical spectral studies. Out of various complex species forming in solution, all the metal ions show higher stability of complexes when in 1:1 metal-ligand stoichiometry, binding through two N-imine and two O-naphtholate groups.

  13. 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.

  14. 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.

  15. 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.

  16. (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).

  17. [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).

  18. Synthesis, XAFS and X-ray structural studies of mono- and binuclear metal-chelates of N,O,O(N,O,S) tridentate Schiff base pyrazole derived ligands

    NASA Astrophysics Data System (ADS)

    Burlov, Anatolii S.; Uraev, Ali I.; Garnovskii, Dmitrii A.; Lyssenko, Konstantin A.; Vlasenko, Valery G.; Zubavichus, Yan V.; Murzin, Vadim Yu.; Korshunova, Eugenie V.; Borodkin, Gennadii S.; Levchenkov, Sergey I.; Vasilchenko, Igor S.; Minkin, Vladimir I.

    2014-05-01

    The syntheses of a series of novel N,O,O and N,O,S donor tridentate Schiff base ligands H2L1 and H2L2via the condensation of 1-phenyl-3-methyl-4-formylpyrazol-5-ol(thiol) with 2-hydroxymethylaniline and their Co(II), Ni(II), Cu(II), Fe(III), and Mn(II) complexes are reported. The compounds are characterized by the C, H, N, S, metal elemental analysis, IR spectroscopy; 1H NMR data for ligands, low-temperature magnetic measurements, X-ray absorption spectroscopy. The crystal structures for Ni(II) and Cu(II) coordination compounds with the compositions NiL21 and Cu2L21 are established by X-ray crystallography.

  19. 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.

  20. 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

  1. [Arteriosclerosis and chelate therapy].

    PubMed

    Nissel, H

    1986-11-30

    Based on a case history the therapeutic value of an iv-chelate therapy in arteriosclerosis is discussed. Ethylenediaminetetraacetate (EDTA) is used as a standard regime in the treatment of poisoning with heavy metals. The usefulness of EDTA in arteriosclerosis is doubtful: some authors suppose, that Ca-deposits are removed from arteriosclerotic lesions. This concept has not yet been proven by in-vivo experiments. Severe side effects such as hypocalcemia may cause the death of a patient under treatment. Therefore no real indications exist for treatment of arteriosclerosis with EDTA.

  2. 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.

  3. Perfluorinated nitrosopyrazolone-based erbium chelates: a new efficient solution processable NIR emitter.

    PubMed

    Beverina, Luca; Crippa, Maurizio; Sassi, Mauro; Monguzzi, Angelo; Meinardi, Francesco; Tubino, Riccardo; Pagani, Giorgio A

    2009-09-14

    We show the design and synthesis of new perfluorinated nitrosopyrazolone-based ligands and the original method employed for their complexation of erbium ions in the presence of the co-ligand perfluorotriphenylphosphine oxide; the resulting chelate is non-hygroscopic, solution processable and possesses a NIR emission with lifetimes as long as 16 micros.

  4. Macroreticular chelating ion-exchangers.

    PubMed

    Hirsch, R F; E Gancher, R; Russo, F R

    1970-06-01

    Two macroreticular chelating ion-exchangers have been prepared and characterized. One contains the iminodiacetate group and the second contains the arsonate group as the ion-exchanging site. The macroreticular resins show selectivities among metal ions similar to those of the commercially available naicroreticular chelating resins. Chromatographie separations on the new resins are rapid and sharp.

  5. 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

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

    PubMed

    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.

  7. A new copper(II) chelate complex with tridentate ligand: Synthesis, crystal and molecular electronic structure of aqua-(diethylenetriamine-N, N‧, N‧‧)-copper(II) sulfate monohydrate and its fire retardant properties

    NASA Astrophysics Data System (ADS)

    Lavrenyuk, H.; Mykhalichko, O.; Zarychta, B.; Olijnyk, V.; Mykhalichko, B.

    2015-09-01

    The crystals of a new aqua-(diethylenetriamine-N, N‧, N‧‧)-copper(II) sulfate monohydrate have been synthesized by direct interaction of solid copper(II) sulfate pentahydrate with diethylenetriamine (deta). The crystal structure of [Cu(deta)H2O]SO4ṡH2O (1) has been determined by X-ray diffraction methods at 100 K and characterized using X-ray powder diffraction pattern: space group P 1 bar, a = 7.2819(4), b = 8.4669(4), c = 8.7020(3) Å, α = 83.590(3), β = 89.620(4), γ = 84.946(4)°, Z = 2. The environment of the Cu(II) atom is a distorted, elongated square pyramid which consists of three nitrogen atoms of the deta molecule and oxygen atom of the water molecule in the basal plane of the square pyramid (the average lengths of the in-plane Cu-N and Cu-O bonds are 2.00 Å). The apical position of the coordination polyhedron is occupied by complementary oxygen atom of the sulfate anion (the length of the axial Cu-O bond is 2.421(1) Å). The crystal packing is governed by strong hydrogen bonds of O-H⋯O and N-H⋯O types. The ab initio quantum-chemical calculations have been performed by the restricted Hartree-Fock method with a basis set 6-31∗G using the structural data of [Cu(deta)H2O]SO4ṡH2O. It has been ascertained that the degenerate d-orbitals of the Cu2+ ion split under the co-action of both the square-pyramidal coordination and the chelation. It is significant that visually observed crystals color (blue-violet) of the [Cu(deta)H2O]SO4ṡH2O complex is in good agreement with the calculated value of wavelength of visible light (λ = 5735 Å) which is closely related to the energy of the absorbed photon (Δ = 2.161 eV). Furthermore, the stereo-chemical aspect of influence of the CuSO4 upon combustibility of modified epoxy-amine polymers has been scrutinized.

  8. 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.

  9. 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

  10. 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.

  11. Novel enterobactin analogues as potential therapeutic chelating agents: Synthesis, thermodynamic and antioxidant studies

    PubMed Central

    Zhang, Qingchun; Jin, Bo; Shi, Zhaotao; Wang, Xiaofang; Liu, Qiangqiang; Lei, Shan; Peng, Rufang

    2016-01-01

    A series of novel hexadentate enterobactin analogues, which contain three catechol chelating moieties attached to different molecular scaffolds with flexible alkyl chain lengths, were prepared. The solution thermodynamic stabilities of the complexes with uranyl, ferric(III), and zinc(II) ions were then investigated. The hexadentate ligands demonstrate effective binding ability to uranyl ion, and the average uranyl affinities are two orders of magnitude higher than 2,3-dihydroxy-N1,N4-bis[(1,2-hydroxypyridinone-6-carboxamide)ethyl]terephthalamide [TMA(2Li-1,2-HOPO)2] ligand with similar denticity. The high affinity of hexadentate ligands could be due to the presence of the flexible scaffold, which favors the geometric agreement between the ligand and the uranyl coordination preference. The hexadentate ligands also exhibit higher antiradical efficiency than butylated hydroxyanisole (BHA). These results provide a basis for further studies on the potential applications of hexadentate ligands as therapeutic chelating agents. PMID:27671769

  12. Novel enterobactin analogues as potential therapeutic chelating agents: Synthesis, thermodynamic and antioxidant studies

    NASA Astrophysics Data System (ADS)

    Zhang, Qingchun; Jin, Bo; Shi, Zhaotao; Wang, Xiaofang; Liu, Qiangqiang; Lei, Shan; Peng, Rufang

    2016-09-01

    A series of novel hexadentate enterobactin analogues, which contain three catechol chelating moieties attached to different molecular scaffolds with flexible alkyl chain lengths, were prepared. The solution thermodynamic stabilities of the complexes with uranyl, ferric(III), and zinc(II) ions were then investigated. The hexadentate ligands demonstrate effective binding ability to uranyl ion, and the average uranyl affinities are two orders of magnitude higher than 2,3-dihydroxy-N1,N4-bis[(1,2-hydroxypyridinone-6-carboxamide)ethyl]terephthalamide [TMA(2Li-1,2-HOPO)2] ligand with similar denticity. The high affinity of hexadentate ligands could be due to the presence of the flexible scaffold, which favors the geometric agreement between the ligand and the uranyl coordination preference. The hexadentate ligands also exhibit higher antiradical efficiency than butylated hydroxyanisole (BHA). These results provide a basis for further studies on the potential applications of hexadentate ligands as therapeutic chelating agents.

  13. 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

  14. Chelation in metal intoxication--Principles and paradigms.

    PubMed

    Aaseth, Jan; Skaug, Marit Aralt; Cao, Yang; Andersen, Ole

    2015-01-01

    The present review provides an update of the general principles for the investigation and use of chelating agents in the treatment of intoxications by metals. The clinical use of the old chelators EDTA (ethylenediamine tetraacetate) and BAL (2,3-dimercaptopropanol) is now limited due to the inconvenience of parenteral administration, their own toxicity and tendency to increase the neurotoxicity of several metals. The hydrophilic dithiol chelators DMSA (meso-2,3-dimercaptosuccinic acid) and DMPS (2,3-dimercapto-propanesulphonate) are less toxic and more efficient than BAL in the clinical treatment of heavy metal poisoning, and available as capsules for oral use. In copper overload, DMSA appears to be a potent antidote, although d-penicillamine is still widely used. In the chelation of iron, the thiols are inefficient, since iron has higher affinity for ligands with nitrogen and oxygen, but the new oral iron antidotes deferiprone and desferasirox have entered into the clinical arena. Comparisons of these agents and deferoxamine infusions are in progress. General principles for research and development of new chelators are briefly outlined in this review.

  15. Supercritical Fluid Extraction of Metal Chelate: A Review.

    PubMed

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

    2017-03-04

    Supercritical fluid extraction (SFE), as a new green extraction technology, has been used in extracting various metal species. The solubilities of chelating agents and corresponding metal chelates are the key factors which influence the efficiency of SFE. Other main properties of them such as stability and selectivity are also reviewed. The extraction mechanisms of mainly used chelating agents are explained by typical examples in this paper. This is the important aspect of SFE of metal ions. Moreover, the extraction efficiencies of metal species also depend on other factors such as temperature, pressure, extraction time and matrix effect. The two main complexation methods namely in-situ and on-line chelating SFE are described in detail. As an efficient chelating agent, tributyl phosphate-nitric acid (TBP-HNO3) complex attracts much attention. The SFE of metal ions, lanthanides and actinides as well as organometallic compounds are also summarized. With the proper selection of ligands, high efficient extraction of metal species can be obtained. As an efficient sample analysis method, supercritical fluid chromatography (SFC) is introduced in this paper. Recently, the extraction method combining ionic liquids (ILs) with supercritical fluid has been becoming a novel technology for treating metal ions. The kinetics related to SFE of metal species is discussed with some specific examples.

  16. Competitive coordination between lead and oligoelements with respect to some therapeutic heavy-metal chelators

    NASA Astrophysics Data System (ADS)

    Gourlaouen, C.; Parisel, O.

    The competitive complexation of Ca2+, Fe2+, Cu2+, Zn2+, and Pb2+ toward ethylene diamine tetraacetate (EDTA), dimercaprol and D-penicillamine, three liganding agents commonly used in chelation therapy against heavy metal, especially lead, poisonings is examined by means of B3LYP calculations, natural population analyses, and the topological analysis of the electron localization function. It is shown that Pb2+ can displace any of Ca2+, Fe2+, Cu2+, or Zn2+ chelated by any of dimercaprol or D-penicillamine, but can only displace Ca2+ if EDTA is concerned. The first two chelators thus appear as better entities than EDTA to be used in chelation therapy, where in vivo selective complexation is essential. Moreover, the comparison of the bonding characteristics of Pb2+ with those of the other cations allows deriving three features to be taken into account in designing new chelators expecting to have an increased selectivity toward this cation.

  17. 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.

  18. 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.

  19. Ligand Identification Scoring Algorithm (LISA)

    PubMed Central

    Zheng, Zheng; Merz, Kenneth M.

    2011-01-01

    A central problem in de novo drug design is determining the binding affinity of a ligand with a receptor. A new scoring algorithm is presented that estimates the binding affinity of a protein-ligand complex given a three-dimensional structure. The method, LISA (Ligand Identification Scoring Algorithm), uses an empirical scoring function to describe the binding free energy. Interaction terms have been designed to account for van der Waals (VDW) contacts, hydrogen bonding, desolvation effects and metal chelation to model the dissociation equilibrium constants using a linear model. Atom types have been introduced to differentiate the parameters for VDW, H-bonding interactions and metal chelation between different atom pairs. A training set of 492 protein-ligand complexes was selected for the fitting process. Different test sets have been examined to evaluate its ability to predict experimentally measured binding affinities. By comparing with other well known scoring functions, the results show that LISA has advantages over many existing scoring functions in simulating protein-ligand binding affinity, especially metalloprotein-ligand binding affinity. Artificial Neural Network (ANN) was also used in order to demonstrate that the energy terms in LISA are well designed and do not require extra cross terms. PMID:21561101

  20. Ligand Identification Scoring Algorithm (LISA).

    PubMed

    Zheng, Zheng; Merz, Kenneth M

    2011-06-27

    A central problem in de novo drug design is determining the binding affinity of a ligand with a receptor. A new scoring algorithm is presented that estimates the binding affinity of a protein-ligand complex given a three-dimensional structure. The method, LISA (Ligand Identification Scoring Algorithm), uses an empirical scoring function to describe the binding free energy. Interaction terms have been designed to account for van der Waals (VDW) contacts, hydrogen bonding, desolvation effects, and metal chelation to model the dissociation equilibrium constants using a linear model. Atom types have been introduced to differentiate the parameters for VDW, H-bonding interactions, and metal chelation between different atom pairs. A training set of 492 protein-ligand complexes was selected for the fitting process. Different test sets have been examined to evaluate its ability to predict experimentally measured binding affinities. By comparing with other well-known scoring functions, the results show that LISA has advantages over many existing scoring functions in simulating protein-ligand binding affinity, especially metalloprotein-ligand binding affinity. Artificial Neural Network (ANN) was also used in order to demonstrate that the energy terms in LISA are well designed and do not require extra cross terms.

  1. Interaction of chelating agents with cadmium in mice and rats.

    PubMed Central

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

    1984-01-01

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

  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.

  3. Interaction of chelating agents with cadmium in mice and rats

    SciTech Connect

    Eybl, V.; Sykora, J.; Koutensky, J.; Caisova, D.; Schwartz, A.; Mertl, F.

    1984-03-01

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

  4. Spectroscopic properties and Judd-Ofelt theory analysis of erbium chelates

    NASA Astrophysics Data System (ADS)

    Wang, Huaishan; Qian, Guodong; Wang, Zhiyu; Wang, Minquan

    2005-11-01

    Erbium chelates including tris(acetylacetonato) erbium(III) monohydrate, tris(acetylacetonato)(1,10-phenanthroline) erbium(III) and tris(trifluoroacetylacetonato)(1,10-phenanthroline) erbium(III) are synthesized. Judd-Ofelt theory is employed on basis of the UV-Vis-NIR absorption spectra of erbium chelates dissolved in methanol. Judd-Ofelt parameters of erbium chelates are determined by a least square fitting and dealt with the chemical structure of erbium chelates. Photoluminescence characteristics of erbium chelates are investigated upon excitation at 488 nm by an Ar + laser. The qualitative correlation of Judd-Ofelt parameters with photoluminescence properties for erbium chelates is also discussed. It is found that larger Ω6 value for erbium chelate is and larger photoluminescence intensity at 1.54 μm is, and Ω2 value should contribute to the photoluminescence full width at half maximum (FWHM) at 1.54 μm. The changes of Judd-Ofelt parameters result from the introduction of the second ligand phenathroline or the substitution of electron-drawing group CF 3 in β-diketone for erbium chelates.

  5. Spectroscopic properties and Judd-Ofelt theory analysis of erbium chelates.

    PubMed

    Wang, Huaishan; Qian, Guodong; Wang, Zhiyu; Wang, Minquan

    2005-11-01

    Erbium chelates including tris(acetylacetonato) erbium(III) monohydrate, tris(acetylacetonato)(1,10-phenanthroline) erbium(III) and tris(trifluoroacetylacetonato)(1,10-phenanthroline) erbium(III) are synthesized. Judd-Ofelt theory is employed on basis of the UV-Vis-NIR absorption spectra of erbium chelates dissolved in methanol. Judd-Ofelt parameters of erbium chelates are determined by a least square fitting and dealt with the chemical structure of erbium chelates. Photoluminescence characteristics of erbium chelates are investigated upon excitation at 488 nm by an Ar(+) laser. The qualitative correlation of Judd-Ofelt parameters with photoluminescence properties for erbium chelates is also discussed. It is found that larger Omega(6) value for erbium chelate is and larger photoluminescence intensity at 1.54 microm is, and Omega(2) value should contribute to the photoluminescence full width at half maximum (FWHM) at 1.54 microm. The changes of Judd-Ofelt parameters result from the introduction of the second ligand phenathroline or the substitution of electron-drawing group CF(3) in beta-diketone for erbium chelates.

  6. Uranyl binary and ternary chelates of tenoxicam Synthesis, spectroscopic and thermal characterization of ternary chelates of tenoxicam and alanine with transition metals.

    PubMed

    El-Gamel, Nadia E A

    2007-11-01

    Ternary Fe(III), Co(II), Ni(II), Cu(II), Zn(II) and UO(2)(II) chelates with tenoxicam (Ten) drug (H(2)L(1)) and dl-alanine (Ala) (HL(2)) and also the binary UO(2)(II) chelate with Ten were studied. The structures of the chelates were elucidated using elemental, molar conductance, magnetic moment, IR, diffused reflectance and thermal analyses. UO(2)(II) binary chelate was isolated in 1:2 ratio with the formula [UO(2)(H(2)L)(2)](NO(3))(2). The ternary chelates were isolated in 1:1:1 (M:H(2)L(1):L(2)) ratios and have the general formulae [M(H(2)L(1))(L(2))(Cl)(n)(H(2)O)(m)].yH(2)O (M=Fe(III) (n=2, m=0, y=2), Co(II) (n=1, m=1, y=2) and Ni(II) (n=1, m=1, y=3)); [M(H(2)L(1))(L(2))](X)(z).yH(2)O (M=Cu(II) (X=AcO, z=1, y=0), Zn(II) (X=AcO, z=1, y=3) and UO(2)(II) (X=NO(3), z=1, y=2)). IR spectra reveal that Ten behaves as a neutral bidentate ligand coordinated to the metal ions via the pyridine-N and carbonyl-O groups, while Ala behaves as a uninegatively bidentate ligand coordinated to the metal ions via the deprotonated carboxylate-O and amino-N. The magnetic and reflectance spectral data confirm that all the chelates have octahedral geometry except Cu(II) and Zn(II) chelates have tetrahedral structures. Thermal decomposition of the chelates was discussed in relation to structure and different thermodynamic parameters of the decomposition stages were evaluated.

  7. Uranyl binary and ternary chelates of tenoxicam. Synthesis, spectroscopic and thermal characterization of ternary chelates of tenoxicam and alanine with transition metals

    NASA Astrophysics Data System (ADS)

    El-Gamel, Nadia E. A.

    2007-11-01

    Ternary Fe(III), Co(II), Ni(II), Cu(II), Zn(II) and UO 2(II) chelates with tenoxicam (Ten) drug (H 2L 1) and dl-alanine (Ala) (HL 2) and also the binary UO 2(II) chelate with Ten were studied. The structures of the chelates were elucidated using elemental, molar conductance, magnetic moment, IR, diffused reflectance and thermal analyses. UO 2(II) binary chelate was isolated in 1:2 ratio with the formula [UO 2(H 2L) 2](NO 3) 2. The ternary chelates were isolated in 1:1:1 (M:H 2L 1:L 2) ratios and have the general formulae [M(H 2L 1)(L 2)(Cl) n(H 2O) m]· yH 2O (M = Fe(III) ( n = 2, m = 0, y = 2), Co(II) ( n = 1, m = 1, y = 2) and Ni(II) ( n = 1, m = 1, y = 3)); [M(H 2L 1)(L 2)](X) z· yH 2O (M = Cu(II) (X = AcO, z = 1, y = 0), Zn(II) (X = AcO, z = 1, y = 3) and UO 2(II) (X = NO 3, z = 1, y = 2)). IR spectra reveal that Ten behaves as a neutral bidentate ligand coordinated to the metal ions via the pyridine-N and carbonyl-O groups, while Ala behaves as a uninegatively bidentate ligand coordinated to the metal ions via the deprotonated carboxylate-O and amino-N. The magnetic and reflectance spectral data confirm that all the chelates have octahedral geometry except Cu(II) and Zn(II) chelates have tetrahedral structures. Thermal decomposition of the chelates was discussed in relation to structure and different thermodynamic parameters of the decomposition stages were evaluated.

  8. Synthesis and evaluation of analogues of HYNIC as bifunctional chelators for technetium.

    PubMed

    Meszaros, Levente K; Dose, Anica; Biagini, Stefano C G; Blower, Philip J

    2011-06-21

    6-Hydrazinonicotinic acid (HYNIC, 1) is a well-established bifunctional technetium-binding ligand often used to synthesise bioconjugates for radiolabelling with Tc-99m. It is capable of efficient capture of technetium at extremely low concentrations, but the structure of the labelled complexes is heterogeneous and incompletely understood. In particular, it is of interest to determine whether, at the no-carrier-added level, it acts in a chelating or non-chelating mode. Here we report two new isomers of HYNIC: 2-hydrazinonicotinic acid (2-HYNIC, 2), which (like 1) is capable of chelation through the mutually ortho hydrazine and pyridine nitrogens and 4-hydrazinonicotinic acid (4-HYNIC, 3), which is not (due to the para-relationship of the hydrazine and pyridine nitrogens). LC-MS shows that the coordination chemistry of 2 with technetium closely parallels that of conventional 1, and no advantages of one over the other in terms of potential labelling efficiency or isomerism were discernable. Both 1 and 2 formed complexes with the loss of 5 protons from the ligand set, whether the co-ligand was tricine or EDDA. Ligand 3, however, failed to complex technetium except at very high ligand concentration: the marked contrast with 1 and 2 suggests that chelation, rather than nonchelating coordination, is a key feature of technetium coordination by HYNIC. Two further new HYNIC analogues, 2-chloro-6-hydrazinonicotinic acid (2-chloro-HYNIC, 4a) and 2,6-dihydrazinonicotinic acid (diHYNIC, 5) were also synthesised. The coordination chemistry of 4a with technetium was broadly parallel to that of 1 and 2 although it was a less efficient chelator, while 5 also behaved as an efficient chelator of technetium, but its coordination chemistry remains poorly defined and requires further investigation before it can sensibly be adopted for (99m)Tc-labelling. The new analogues 4a and 5 present an opportunity to develop trifunctional HYNIC analogues for more complex bioconjugate synthesis.

  9. Hydroxypyridonate and hydroxypyrimidinone chelating agents

    DOEpatents

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

    2005-01-25

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

  10. Characterization of the Structural and Chemical Properties of Copper Chelators in Seawater

    DTIC Science & Technology

    2000-09-30

    are pink). All of the strains that don’t make the ligand contain phycocyanin (the cultures are green). So far we have no explanation for this...thiol that does not co-elute with any of her thiol standards. IMPACT/ APPLICATIONS Successful characterization of this material could lead to new...insight into the sources and chemistry of Cu ligands in seawater. Potential applications could arise if we identify a new class of chelators selective

  11. 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 ...

  12. Iron chelation and multiple sclerosis

    PubMed Central

    Weigel, Kelsey J.; Lynch, Sharon G.; LeVine, Steven M.

    2014-01-01

    Histochemical and MRI studies have demonstrated that MS (multiple sclerosis) patients have abnormal deposition of iron in both gray and white matter structures. Data is emerging indicating that this iron could partake in pathogenesis by various mechanisms, e.g., promoting the production of reactive oxygen species and enhancing the production of proinflammatory cytokines. Iron chelation therapy could be a viable strategy to block iron-related pathological events or it can confer cellular protection by stabilizing hypoxia inducible factor 1α, a transcription factor that normally responds to hypoxic conditions. Iron chelation has been shown to protect against disease progression and/or limit iron accumulation in some neurological disorders or their experimental models. Data from studies that administered a chelator to animals with experimental autoimmune encephalomyelitis, a model of MS, support the rationale for examining this treatment approach in MS. Preliminary clinical studies have been performed in MS patients using deferoxamine. Although some side effects were observed, the large majority of patients were able to tolerate the arduous administration regimen, i.e., 6–8 h of subcutaneous infusion, and all side effects resolved upon discontinuation of treatment. Importantly, these preliminary studies did not identify a disqualifying event for this experimental approach. More recently developed chelators, deferasirox and deferiprone, are more desirable for possible use in MS given their oral administration, and importantly, deferiprone can cross the blood–brain barrier. However, experiences from other conditions indicate that the potential for adverse events during chelation therapy necessitates close patient monitoring and a carefully considered administration regimen. PMID:24397846

  13. 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.

  14. Click-to-Chelate: development of technetium and rhenium-tricarbonyl labeled radiopharmaceuticals.

    PubMed

    Kluba, Christiane A; Mindt, Thomas L

    2013-03-12

    The Click-to-Chelate approach is a highly efficient strategy for the radiolabeling of molecules of medicinal interest with technetium and rhenium-tricarbonyl cores. Reaction of azide-functionalized molecules with alkyne prochelators by the Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC; click reaction) enables the simultaneous synthesis and conjugation of tridentate chelating systems for the stable complexation of the radiometals. In many cases, the functionalization of (bio)molecules with the ligand system and radiolabeling can be achieved by convenient one-pot procedures. Since its first report in 2006, Click-to-Chelate has been applied to the development of numerous novel radiotracers with promising potential for translation into the clinic. This review summarizes the use of the Click-to-Chelate approach in radiopharmaceutical sciences and provides a perspective for future applications.

  15. Synthesis, conjugation, and radiolabeling of a novel bifunctional chelating agent for (225)Ac radioimmunotherapy applications.

    PubMed

    Chappell, L L; Deal, K A; Dadachova, E; Brechbiel, M W

    2000-01-01

    225Ac (t(1/2) = 10 days) is an alternative alpha-emitter that has been proposed for radioimmunotherapy (RIT) due to its many favorable properties, such as half-life and mode of decay. The factor limiting use of (225)Ac in RIT is the lack of an acceptably stable chelate for in vivo applications. Herein is described the first reported bifunctional chelate for (225)Ac that has been evaluated for stability for in vivo applications. The detailed synthesis of a bifunctional chelating agent 2-(4-isothiocyanatobenzyl)-1,4,7,10,13, 16-hexaazacyclohexadecane- 1,4,7,10,13,16-hexaacetic acid (HEHA-NCS) is reported. This ligand was conjugated to three monoclonal antibodies, CC49, T101, and BL-3 with chelate-to-protein ratios between 1.4 and 2. The three conjugates were radiolabeled with (225)Ac, and serum stability study of the [(225)Ac]BL-3-HEHA conjugate was performed.

  16. Copper chelators: chemical properties and bio-medical applications.

    PubMed

    Tegoni, M; Valensin, D; Toso, L; Remelli, M

    2014-01-01

    Copper is present in different concentrations and chemical forms throughout the earth crust, surface and deep water and even, in trace amounts, in the atmosphere itself. Copper is one of the first metals used by humans, the first artifacts dating back 10,000 years ago. Currently, the world production of refined copper exceeds 16,000 tons/year. Copper is a micro-element essential to life, principally for its red-ox properties that make it a necessary cofactor for many enzymes, like cytochrome-c oxidase and superoxide dismutase. In some animal species (e.g. octopus, snails, spiders, oysters) copper-hemocyanins also act as carriers of oxygen instead of hemoglobin. However, these red-ox properties also make the pair Cu(+)/Cu(2+) a formidable catalyst for the formation of reactive oxygen species, when copper is present in excess in the body or in tissues. The treatment of choice in cases of copper overloading or intoxication is the chelation therapy. Different molecules are already in clinical use as chelators or under study or clinical trial. It is worth noting that chelation therapy has also been suggested to treat some neurodegenerative diseases or cardiovascular disorders. In this review, after a brief description of the homeostasis and some cases of dyshomeostasis of copper, the main (used or potential) chelators are described; their properties in solution, even in relation to the presence of metal or ligand competitors, under physiological conditions, are discussed. The legislation of the most important Western countries, regarding both the use of chelating agents and the limits of copper in foods, drugs and cosmetics, is also outlined.

  17. Organic acids rather than histidine predominate in Ni chelation in Alyssum hyperaccumulator xylem exudate

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A better understanding of Ni uptake mechanisms by hyperaccumulator plants is necessary to improve Ni uptake efficiency for phytoremediation technologies i.e. phytomining. It is known that an important aspect of Ni translocation involves Ni chelation with organic ligands. However, it is still not cle...

  18. An Evaluation of the Chelating Agent EDDS for Floriculture Crop 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. When complexed with Fe, EDTA and...

  19. Evaluation of the efficiency of DTPA and other new chelating agents for removing neptunium from target organs.

    PubMed

    Paquet, F; Metivier, H; Poncy, J L; Burgada, R; Bailly, T

    1997-05-01

    Diethylenetriamine pentaacetic acid (DTPA) has been tested with 8 other new chelators for neptunium decorporation after systemic contamination in the rat. The ligands were injected intravenously at a dosage of 30 mumol kg-1 and the animals killed 24 h later. The results show that none of the chelators tested was efficient in removing significant amounts of the radionuclide from the body. In order to understand why these chelators were ineffective, in vitro approaches have since been developed in which high concentrations of DTPA were added to Np-bearing ligands in the blood, liver and skeleton. The main conclusions were that under our experimental conditions neptunium was not chelatable after its organ deposition.

  20. Chemistry and bifunctional chelating agents for binding (177)Lu.

    PubMed

    Parus, Józef L; Pawlak, Dariusz; Mikolajczak, Renata; Duatti, Adriano

    2015-01-01

    A short overview of fundamental chemistry of lutetium and of structural characteristics of lutetium coordination complexes, as relevant for understanding the properties of lutetium-177 radiopharmaceuticals, is presented. This includes basic concepts on lutetium electronic structure, lanthanide contraction, coordination geometries, behavior in aqueous solution and thermodynamic stability. An illustration of the structure and binding properties of the most important chelating agents for the Lu(3+) ion in aqueous solution is also reported with specific focus on coordination complexes formed with linear and macrocyclic polydentate amino-carboxylate donor ligands.

  1. Luminescent lanthanide chelates and methods of use

    SciTech Connect

    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.

  2. Isomerism in benzyl-DOTA derived bifunctional chelators: implications for molecular imaging.

    PubMed

    Payne, Katherine M; Woods, Mark

    2015-02-18

    The bifunctional chelator IB-DOTA has found use in a range of biomedical applications given its ability to chelate many metal ions, but in particular the lanthanide(III) ions. Gd(3+) in particular is of interest in the development of new molecular imaging agents for MRI and is highly suitable for chelation by IB-DOTA. Given the long-term instability of the aryl isothiocyanate functional group we have used the more stable nitro derivative (NB-DOTA) to conduct a follow-up study of some of our previous work on the coordination chemistry of chelates of these BFCs. Using a combination of NMR and HPLC to study the Eu(3+) and Yb(3+) chelates of NB-DOTA, we have demonstrated that this ligand will produce two discrete regioisomeric chelates at the point at which the metal ion is introduced into the BFC. These regioisomers are defined by the position of the benzylic substituent on the macrocyclic ring: adopting an equatorial position either at the corner or the side of the [3333] ring conformation. These regioisomers are incapable of interconversion and are distinct, separate structures with different SAP/TSAP ratios. The side isomer exhibits an increased population of the TSAP isomer, pointing to more rapid water exchange kinetics in this regioisomer. This has potential ramifications for the use of these two regioisomers of Gd(3+)-BFC chelates in MRI applications. We have also found that, remarkably, there is little or no freedom of rotation about the first single bond extending from the macrocyclic ring to the benzylic substituent. Since this is the linkage through which the chelate is conjugated to the remainder of the molecular imaging probe, this result implies that there may be reduced local rotation of the Gd(3+) chelate within a molecular imaging probe. This implies that this type of BFC could exhibit higher relaxivities than other types of BFC.

  3. Design of a Hole Trapping Ligand

    DOE PAGES

    La Croix, Andrew D.; O’Hara, Andrew; Reid, Kemar R.; ...

    2017-01-18

    A new ligand that covalently attaches to the surface of colloidal CdSe/ CdS nanorods and can simultaneously chelate a molecular metal center is described. The dithiocarbamate$-$bipyridine ligand system facilitates hole transfer through energetic overlap at the inorganic$-$organic interface and conjugation through the organic ligand to a chelated metal center. Density functional theory calculations show that the coordination of the free ligand to a CdS surface causes the formation of two hybridized molecular states that lie in the band gap of CdS. The further chelation of Fe(II) to the bipyridine moiety causes the presence of seven midgap states. Hole transfer frommore » the CdS valence band to the midgap states is dipole allowed and occurs at a faster rate than what is experimentally known for the CdSe/CdS band-edge radiative recombination. In the case of the ligand bound with iron, a two-step process emerges that places the hole on the iron, again at rates much faster than band gap recombination. The system was experimentally assembled and characterized via UV$-$vis absorbance spectroscopy, fluorescence spectroscopy, time-resolved photoluminescence spectroscopy, and energy dispersive X-ray spectroscopy. Lastly, theoretically predicted red shifts in absorbance were observed experimentally, as well as the expected quench in photoluminescence and lifetimes in time-resolved photoluminescence« less

  4. Synthesis of Two New Group 13 Benzoato-Chloro Complexes: A Structural Study of Gallium and Indium Chelating Carboxylates

    NASA Technical Reports Server (NTRS)

    Duraj, Stan A.; Hepp, Aloysius F.; Woloszynek, Robert; Protasiewicz, John D.; Dequeant, Michael; Ren, Tong

    2010-01-01

    Two new heteroleptic chelated-benzoato gallium (III) and indium (III) complexes have been prepared and structurally characterized. The molecular structures of [GaCl2(4-Mepy)2(O2CPh)]4-Mepy (1) and [InCl(4-Mepy)2(O2CPh)2]4-Mepy (2) have been determined by single-crystal x-ray diffraction. The gallium compound (1) is a distorted octahedron with cis-chloride ligands co-planar with the chelating benzoate and the 4-methylpyridines trans to each other. This is the first example of a Ga(III) structure with a chelating benzoate. The indium compound (2) is a distorted pentagonal bipyramid with two chelating benzoates, one 4-methylpyridine in the plane and a chloride trans to the other 4-methylpyridine. The indium bis-benzoate is an unusual example of a seven-coordinate structure with classical ligands. Both complexes, which due to the chelates, could also be described as pseudo-trigonal bipyramidal, include a three-bladed motif with three roughly parallel aromatic rings that along with a solvent of crystallization and electron-withdrawing chloride ligand(s) stabilize the solid-state structures.

  5. Iron release and uptake by plant ferritin: effects of pH, reduction and chelation.

    PubMed Central

    Laulhere, J P; Briat, J F

    1993-01-01

    Ferritins are iron-storage proteins that accumulate in plastids during seed formation, and also in leaves during senescence or iron overload. Iron release from ferritins occurs during growth of seedlings and greening of plastids. Depending on the concentration of the reducing agent ascorbate, either an overall iron release or uptake by ferritins from iron(III) citrate may occur. We have designed methods to measure these simultaneous and independent uptake and release fluxes. Each individual step of the exchange was studied using different iron chelates and an excess of ligand. It is shown that: (i) the chelated form of iron, and not ionic Fe3+, is the substrate for iron reduction, which controls the subsequent uptake by ferritin; (ii) iron uptake by ferritins is faster at pH 8.4 than at pH 7 or 6 and is inhibited by an excess of strongly binding free ligands; and (iii) strongly binding free ligands are inhibitory during iron release by ascorbate. When reactions are allowed to proceed simultaneously, the iron chelating power is shown to be a key factor in the overall exchange. The interactions of iron chelating power, reducing capacity and pH are discussed with regard to their influence on the biochemical mobilization of iron. Images Figure 1 Figure 6 Figure 7 PMID:8457196

  6. Mathematical modeling of the effects of aerobic and anaerobic chelate bioegradation on actinide speciation.

    SciTech Connect

    Banaszak, J.E.; VanBriesen, J.; Rittmann, B.E.; Reed, D.T.

    1998-03-19

    Biodegradation of natural and anthropogenic chelating agents directly and indirectly affects the speciation, and, hence, the mobility of actinides in subsurface environments. We combined mathematical modeling with laboratory experimentation to investigate the effects of aerobic and anaerobic chelate biodegradation on actinide [Np(IV/V), Pu(IV)] speciation. Under aerobic conditions, nitrilotriacetic acid (NTA) biodegradation rates were strongly influenced by the actinide concentration. Actinide-chelate complexation reduced the relative abundance of available growth substrate in solution and actinide species present or released during chelate degradation were toxic to the organisms. Aerobic bio-utilization of the chelates as electron-donor substrates directly affected actinide speciation by releasing the radionuclides from complexed form into solution, where their fate was controlled by inorganic ligands in the system. Actinide speciation was also indirectly affected by pH changes caused by organic biodegradation. The two concurrent processes of organic biodegradation and actinide aqueous chemistry were accurately linked and described using CCBATCH, a computer model developed at Northwestern University to investigate the dynamics of coupled biological and chemical reactions in mixed waste subsurface environments. CCBATCH was then used to simulate the fate of Np during anaerobic citrate biodegradation. The modeling studies suggested that, under some conditions, chelate degradation can increase Np(IV) solubility due to carbonate complexation in closed aqueous systems.

  7. Chelation technology: a promising green approach for resource management and waste minimization.

    PubMed

    Chauhan, Garima; Pant, K K; Nigam, K D P

    2015-01-01

    Green chemical engineering recognises the concept of developing innovative environmentally benign technologies to protect human health and ecosystems. In order to explore this concept for minimizing industrial waste and for reducing the environmental impact of hazardous chemicals, new greener approaches need to be adopted for the extraction of heavy metals from industrial waste. In this review, a range of conventional processes and new green approaches employed for metal extraction are discussed in brief. Chelation technology, a modern research trend, has shown its potential to develop sustainable technology for metal extraction from various metal-contaminated sites. However, the interaction mechanism of ligands with metals and the ecotoxicological risk associated with the increased bioavailability of heavy metals due to the formation of metal-chelant complexes is still not sufficiently explicated in the literature. Therefore, a need was felt to provide a comprehensive state-of-the-art review of all aspects associated with chelation technology to promote this process as a green chemical engineering approach. This article elucidates the mechanism and thermodynamics associated with metal-ligand complexation in order to have a better understanding of the metal extraction process. The effects of various process parameters on the formation and stability of complexes have been elaborately discussed with respect to optimizing the chelation efficiency. The non-biodegradable attribute of ligands is another important aspect which is currently of concern. Therefore, biotechnological approaches and computational tools have been assessed in this review to illustrate the possibility of ligand degradation, which will help the readers to look for new environmentally safe mobilizing agents. In addition, emerging trends and opportunities in the field of chelation technology have been summarized and the diverse applicability of chelation technology in metal extraction from

  8. Chelation behavior of various flavonols and transfer of flavonol-chelated zinc(II) to alanylaspartic dipeptide: A PCM/DFT investigation

    NASA Astrophysics Data System (ADS)

    Yasarawan, Nuttawisit; Thipyapong, Khajadpai; Ruangpornvisuti, Vithaya

    2016-03-01

    Alanylaspartic dipeptide (AlaAsp) and zinc(II)-flavonol complex could represent a metal-binding site in proteins and a metal-ion releasing agent, respectively. Chelation of zinc(II) by either AlaAsp or flavonol ligands in aqueous solution has been examined using DFT methods with polarizable continuum model (PCM/DFT). Coordination geometry, complexation stoichiometry, coordination bond strength, preferable metal-binding site on ligands and effect of water coordination on the stability of complexes have been addressed. In several cases, the long-range corrected density functional CAM-B3LYP allows the most accurate prediction of both structural and spectroscopic data. The preferential transfer of flavonol-chelated zinc(II) to AlaAsp under solvation is attainable through the ligand-exchange reaction. The energy barrier of such reaction is significantly dependent on the degree of hydrogen bonding within the transition state. In summary, either hydroxylation or methoxylation at particular positions on the 3-hydroxyflavone backbone significantly affects the reactivity of flavonol chelates in the metal-ion transfer.

  9. 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

  10. Sulfur containing platinum(II) complexes with N-heterocyclic carbene ligands obtained by reactions of a hydrosulfido complex.

    PubMed

    Maeda, Yuri; Hashimoto, Hideki; Nishioka, Takanori

    2012-10-21

    A hydrosulfido platinum(ii) complex with a chelated N-heterocyclic carbene (NHC) ligand was oxidised with O(2) in the presence of excess hydrogen sulfide, to give a linear tetrasulfido complex, and without hydrogen sulfide, to give a thiosulfato-bridged dinuclear complex. The hydrosulfido complex also reacted with an acetato complex containing the chelating NHC platinum unit to afford a trinuclear platinum complex with two triply bridging sulfido ligands showing an equilibrium in solution between two isomers based on the arrangement of the chelating NHC ligands.

  11. Exploring copper chelation in Alzheimer's disease protein

    NASA Astrophysics Data System (ADS)

    Rose, Frisco; Hodak, Miroslav; Bernholc, Jerry

    2012-02-01

    Alzheimer's disease (AD) is a neurodegenerative disorder affecting millions of aging people in the U.S. alone. Clinical studies have indicated that metal chelation is a promising new approach in alleviating the symptoms of AD. Our study explores the as yet undetermined mechanism of copper chelation in amyloid-β, a protein implicated in AD. The structure of amyloid-β is derived from experimental results and incorporates a planar copper-ion-binding structure in a semi-solvated state. We investigate the chelation process using the nudged elastic band method implemented in our ab initio real-space multigrid code. We find that an optimal sequence of unbonding and rebonding events as well as proton transfers are required for a viable chelation process. These findings provide fundamental insight into the process of chelation that may lead to more effective AD therapies.

  12. Chelate electronic properties control the redox behaviour and superoxide reactivity of seven-coordinate manganese(II) complexes.

    PubMed

    Liu, Gao-Feng; Dürr, Katharina; Puchta, Ralph; Heinemann, Frank W; van Eldik, Rudi; Ivanović-Burmazović, Ivana

    2009-08-28

    We have synthesized and characterized two Mn(II) seven-coordinate complexes with N5 pentadentate ligands, which contain hydrazone and hydrazide groups respectively. We have shown that insertion of hydrazido (amido) groups into the ligand sphere increases the negative charge of the chelate, without changing a donor atom set and coordination geometry, and radically modulate a redox activity of seven-coordinate manganese complexes, which is important for the function of manganese as a superoxide dismutase catalytic center.

  13. Stereoselective coordination: a six-membered P,N-chelate tailored for asymmetric allylic alkylation.

    PubMed

    Császár, Z; Farkas, G; Bényei, A; Lendvay, G; Tóth, I; Bakos, J

    2015-10-07

    Six-membered chelate complexes [Pd(1a-b)Cl2], (2a-b) and [Pd(1a-b)(η(3)-PhCHCHCHPh)]BF4, (3a-b) of P,N-type ligands 1a, ((2S,4S)-2-diphenyl-phosphino-4-isopropylamino-pentane) and 1b, ((2S,4S)-2-diphenyl-phosphino-4-methylamino-pentane) have been prepared. The Pd-complexes have been characterized in solution by 1D and 2D NMR spectroscopy. The observed structures were confirmed by DFT calculations and in the case of 2a also by X-ray crystallography. Unexpectedly, the coordination of the all-carbon-backbone aminophosphine 1a resulted in not only a stereospecific locking of the donor nitrogen atom into one of the two possible configurations but also the conformation of the six-membered chelate rings containing three alkyl substituents was forced into the same single chair structure showing the axially placed isopropyl group on the coordinated N-atom. The stereodiscriminative complexation of 1a led to the formation of a palladium catalyst with a conformationally rigid chelate having a configurationally fixed nitrogen and electronically different coordination sites due to the presence of P and N donors. The stereochemically fixed catalyst provided excellent ee's (up to 96%) and activities in asymmetric allylic alkylation reactions. In contrast, the chelate rings formed by 1b exist in two different chair conformations, both containing axial methyl groups, but with the opposite configurations of the coordinated N-atom. Pd-complexes of 1b provided low enantioselectivities in similar alkylations, therefore emphasizing the importance of the stereoselective coordination of N-atoms in analogous P-N chelates. The factors determining the coordination of the ligands were also studied with respect to the chelate ring conformation and the nitrogen configuration.

  14. Structural and Antioxidant Properties of Compounds Obtained from Fe2+ Chelation by Juglone and Two of Its Derivatives: DFT, QTAIM, and NBO Studies

    PubMed Central

    Tamafo Fouegue, Aymard Didier; Bikélé Mama, Désiré; Nkungli, Nyiang Kennet; Younang, Elie

    2016-01-01

    The chelating ability of juglone and two of its derivatives towards Fe2+ion and the antioxidant activity (AOA) of the resulting chelates and complexes (in the presence of H2O and CH3OH as ligands) in gas phase is reported via bond dissociation enthalpy, ionization potential, proton dissociation enthalpy, proton affinity, and electron transfer enthalpy. The DFT/B3LYP level of theory associated with the 6-31+G(d,p) and 6-31G(d) Pople-style basis sets on the atoms of the ligands and the central Fe(II), respectively, was used. Negative chelation free energies obtained revealed that juglone derivatives possessing the O-H substituent (L2) have the greatest ability to chelate Fe2+ ion. Apart from 1B, thermodynamic descriptors of the AOA showed that the direct hydrogen atom transfer is the preferred mechanism of the studied molecules. NBO analysis showed that the Fe-ligand bonds are all formed through metal to ligand charge transfer. QTAIM studies revealed that among all the Fe-ligand bonds, the O1-Fe bond of 1A is purely covalent. The aforementioned results show that the ligands can be used to fight against Fe(II) toxicity, thus preserving human health, and fight against the deterioration of industrial products. In addition, most of the complexes studied have shown a better AOA than their corresponding ligands. PMID:27774044

  15. Comprehensive radiolabeling, stability, and tissue distribution studies of technetium-99m single amino acid chelates (SAAC).

    PubMed

    Maresca, Kevin P; Hillier, Shawn M; Femia, Frank J; Zimmerman, Craig N; Levadala, Murali K; Banerjee, Sangeeta R; Hicks, Justin; Sundararajan, Chitra; Valliant, John; Zubieta, Jon; Eckelman, William C; Joyal, John L; Babich, John W

    2009-08-19

    Technetium tricarbonyl chemistry has been a subject of interest in radiopharmaceutical development over the past decade. Despite the extensive work done on developing chelates for Tc(I), a rigorous investigation of the impact of changing donor groups and labeling conditions on radiochemical yields and/or distribution has been lacking. This information is crucially important if these platforms are going to be used to develop molecular imaging probes. Previous studies on the coordination chemistry of the {M(CO)(3)}(+) core have established alkylamine, aromatic nitrogen heterocycles, and carboxylate donors as effective chelating ligands. These observations led to the design of tridentate ligands derived from the amino acid lysine. Such amino acid analogues provide a tridentate donor set for chelation to the metal and an amino acid functionality for conjugation to biomolecules. We recently developed a family of single amino acid chelates (SAAC) that serve this function and can be readily incorporated into peptides via solid-phase synthesis techniques. As part of these continuing studies, we report here on the radiolabeling with technetium-99m ((99m)Tc) and stability of a series of SAAC analogues of lysine. The complexes studied include cationic, neutral, and anionic complexes. The results of tissue distribution studies with these novel complexes in normal rats demonstrate a range of distribution in kidney, liver, and intestines.

  16. Effect of trace iron levels and iron withdrawal by chelation on the growth of Candida albicans and Candida vini.

    PubMed

    Holbein, Bruce E; Mira de Orduña, Ramón

    2010-06-01

    The iron requirements of the opportunistic pathogenic yeast, Candida albicans, and the related nonpathogenic spoilage yeast Candida vini were investigated along with their responses to various exogenous iron chelators. The influence of iron as well as the exogenous chelating agents lactoferrin, EDTA, deferiprone, desferrioxamine, bathophenanthroline sulphonate and a novel carried chelator with a hydroxypyridinone-like Fe-ligand functionality, DIBI, on fungal growth was studied in a chemically defined medium deferrated to trace iron levels (<1.2 microg L(-1) or 0.02 microM of Fe). Candida albicans competed better at low iron levels compared with C. vini, which was also more susceptible to most added chelators. Candida albicans was resistant to lactoferrin at physiologically relevant concentrations, but was inhibited by low concentrations of DIBI. Candida vini was sensitive to lactoferrin as well as to DIBI, whose inhibitory activity was shown to be Fe reversible. The pathogenic potential of C. albicans and the nonpathogenic nature of C. vini were consistent with their differing abilities to grow under iron-limiting conditions and in the presence of exogenous iron chelators. Both yeasts could be controlled by appropriately strong chelators. This work provides the first evidence of the iron requirements of the spoilage organism C. vini and its response to exogenous chelators. Efficient iron withdrawal has the potential to provide the basis for new fungal growth control strategies.

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

    ERIC Educational Resources Information Center

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

    2011-01-01

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

  18. 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.

  19. 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.

  20. Characterization of the Structural and Chemical Properties of Copper Chelators in Seawater

    DTIC Science & Technology

    2001-09-30

    is also readily oxidized to a disulfide. Interestingly, we only detect this compound when we de-metallate the ligand (by acidification to pH 2...by ANSI Std Z39-18 APPROACH Molecular-level studies focus on chelators produced by ubiquitous marine phytoplankton and bacteria, rather than...prior to derivatization, suggesting that it is strongly bound to copper at pH 8, blocking derivatization. Further work is ongoing to establish the

  1. Development of a Tetrathioether (S4) Bifunctional Chelate System for Rh-105

    DTIC Science & Technology

    2012-07-01

    bombesin (BBN) targeting vector. Bombesin targets gastrin releasing peptide (GRP) receptors, which have been shown to be over-expressed on the surface of...prostate cancer cells. Here we report the successful synthesis and characterization of a bombesin agonist coupled tetrathioether (S4) bifunctional...1: Synthesis of bombesin (7-14) coupled tetrathioether bifunctional chelate 1a: Synthesize dicarboxylic acid functionalized ligand 3,3,3-S4-(COOH)2

  2. Shape-controlled Synthesis of Gold Nanoparticles from Gold(III)-chelates of β-diketones

    NASA Astrophysics Data System (ADS)

    Kundu, Subrata; Pal, Anjali; Ghosh, Sujit Kumar; Nath, Sudip; Panigrahi, Sudipa; Praharaj, Snigdhamayee; Basu, Soumen; Pal, Tarasankar

    2005-12-01

    Chelating ligands with β-diketone skeleton have been employed for the first time as reductant to produce ligand stabilized gold nanoparticles of different shapes out of aqueous HAuCl4 solutions. Evolution of stable gold nanoparticles happens to be first order with respect to gold particles having rate constants ˜ ˜10-2 min-1 and subsequent chlorine insertion in the β-diketone skeleton is reported as a general feature. Spherical or triangular or hexagonal particle evolution goes selectively under the influence of different β-diketones in terms of capping and reducing capabilities of the reductants.

  3. Conjugates of Actinide Chelator-Magnetic Nanoparticles for Used Fuel Separation Technology

    SciTech Connect

    Qiang, You; Paszczynski, Andrzej; Rao, Linfeng

    2011-10-30

    The actinide separation method using magnetic nanoparticles (MNPs) functionalized with actinide specific chelators utilizes the separation capability of ligand and the ease of magnetic separation. This separation method eliminated the need of large quantity organic solutions used in the liquid-liquid extraction process. The MNPs could also be recycled for repeated separation, thus this separation method greatly reduces the generation of secondary waste compared to traditional liquid extraction technology. The high diffusivity of MNPs and the large surface area also facilitate high efficiency of actinide sorption by the ligands. This method could help in solving the nuclear waste remediation problem.

  4. Microsolvated and chelated butylzinc cations: formation, relative stability, and unimolecular gas-phase chemistry.

    PubMed

    Fleckenstein, Julia E; Koszinowski, Konrad

    2009-11-23

    Solutions of butylzinc iodide in tetrahydrofuran, acetonitrile, and N,N-dimethylformamide were analyzed by electrospray ionization mass spectrometry. In all cases, microsolvated butylzinc cations [ZnBu(solvent)(n)](+), n=1-3, were detected. The parallel observation of the butylzincate anion [ZnBuI(2)](-) suggests that these ions result from disproportionation of neutral butylzinc iodide in solution. In the presence of simple bidentate ligands (1,2-dimethoxyethane, N,N-dimethyl-2-methoxyethylamine, and N,N,N',N'-tetramethylethylenediamine), chelate complexes of the type [ZnBu(ligand)](+) form quite readily. The relative stabilities of these complexes were probed by competition experiments and analysis of their unimolecular gas-phase reactivity. Fragmentation of mass-selected [ZnBu(ligand)](+) leads to the elimination of butene and formation of [ZnH(ligand)](+). In marked contrast, the microsolvated cations [ZnBu(solvent)(n)](+) lose the attached solvent molecules upon gas-phase fragmentation to produce bare [ZnBu](+), which subsequently dissociates into [C(4)H(9)](+) and Zn. This difference in reactivity resembles the situation in organozinc solution chemistry, in which chelating ligands are needed to activate dialkylzinc compounds for the nucleophilic addition to aldehydes.

  5. Chelation in root canal therapy reconsidered.

    PubMed

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

    2005-11-01

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

  6. Analysis of the Conformational Behavior and Stability of the SAP and TSAP Isomers of Lanthanide(III) NB-DOTA-Type Chelates

    PubMed Central

    Tircso, Gyula; Webber, Benjamin C.; Kucera, Benjamin E.; Young, Victor G.; Woods, Mark

    2011-01-01

    Controlling the water exchange kinetics of macrocyclic Gd3+ chelates, a key parameter in the design of improved magnetic resonance imaging (MRI) contrast media, may be facilitated by selecting the coordination geometry of the chelate. The water exchange kinetics of the mono- capped twisted square antiprism (TSAP) being much closer to optimal than those of the mono capped square antiprism (SAP) render the TSAP isomer more desirable for high relaxivity applications. Two systems have been developed that allow for selection of the TSAP coordination geometry in 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-type Gd3+ chelates, both based upon the macrocycle nitrobenzyl cyclen. In this paper we report investigations into the stability and formation of these chelates. Particular focus is given to the production of two regioisomeric chelates during the chelation reaction. These regioisomers are distinguished by having the nitrobenzyl substituent either on a corner or on the side of the macrocyclic ring. The origin of these two regioisomers appears to stem from a conformation of the ligand in solution in which it is hypothesized that pendant arms lie both above and below the plane of the macrocycle. The conformational changes that then result during the formation of the intermediate H2GdL+ chelate give rise to differing positions of the nitrobenzyl substituent depending upon from which face of the macrocycle the Ln3+ approaches the ligand. PMID:21819053

  7. Unusual dicationic trimetallic aluminum chelates

    NASA Astrophysics Data System (ADS)

    Liu, S.; Munoz-Hernandez, M.-A.; Wei, P.; Atwood, D. A.

    2000-09-01

    The bimetallic compounds, L(AlMeCl) 2 with L=Salpen(tBu) ( N, N'-1,3-propylenenebis(3,5-di- tert-butylsalicylideneimine), Salben(tBu) ( N, N'-1,4-butylenebis(3,5-di- tert-butylsalicylideneimine)) and Salhen(tBu) ( N, N'-1,6 hexylenebis(3,5-di- tert-butylsalicylideneimine)) form the unusual trimetallic dicationic complexes, {[Salpen( tBu) ∗] 2(AlCl) 3]} 2+[GaCl 4] -[GaMe 2Cl 2] - ( 1), {[Salben( tBu) ∗] 2(AlCl) 3]} 2+[GaCl 4] -[GaMe 2Cl 2] - ( 2) and {[Salhen( tBu) ∗] 2(AlCl) 3]} 2+[GaCl 4] -[GaMe 2Cl 2] - ( 3) when combined with GaCl 3 in toluene. In their formation, the ligands of the compounds undergo a unique dealkylation reaction to lose one tBu group from each ligand (marked with an asterisk). These compounds are a new and unique class of aluminum cations. The compounds were characterized by Mp, analyses, IR, 1H NMR, and in the case of 1 and 2, by single-crystal X-ray diffractometry.

  8. Preparation and study of new poly-8-hydroxyquinoline chelators for an anti-Alzheimer strategy.

    PubMed

    Deraeve, Céline; Boldron, Christophe; Maraval, Alexandrine; Mazarguil, Honoré; Gornitzka, Heinz; Vendier, Laure; Pitié, Marguerite; Meunier, Bernard

    2008-01-01

    Fourteen different ligands have been synthesized with two covalently linked 8-hydroxyquinoline motifs that favor metal complexation. These bis-chelators include different bridges at the C2 positions and different substituents to modulate their physicochemical properties. They can form metal complexes in a ratio of one ligand per metal ion with Cu II and Zn II, two metal ions involved in the formation of amyloid aggregates of the toxic Abeta-peptides in the Alzheimer disease. The apparent affinity of all bis-8-hydroxyquinoline ligands for Cu II and Zn II are similar with logK Cu II approximately 16 and logK Zn II approximately 13 and are 10,000 times more efficient than for the corresponding 8-hydroxyquinoline monomers. Their strong chelating capacities allow them to inhibit more efficiently than the corresponding monomers the precipitation of Abeta-peptides induced by Cu II and Zn II and also to inhibit the toxic formation of H2O2 due to copper complexes of Abeta. The best results were obtained with a one-atom linker between the two quinoline units. X-ray analyses of single-crystals of Cu II, Zn II or Ni II complexes of 2,2'-(2,2-propanediyl)-bis(8-hydroxyquinoline), including a one-atom linker, showed that all heteroatoms of the bis-8-hydroxyquinoline ligand chelate the same metal ion in a distorted square-planar geometry. The Cu II and Zn II complexes include a fifth axial ligand and are pentacoordinated.

  9. 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.

  10. 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.

  11. Combined chelation based on glycosyl-mono- and bis-hydroxypyridinones for aluminium mobilization: solution and biodistribution studies.

    PubMed

    Chaves, Sílvia; Dron, Paul I; Danalache, Florina A; Sacoto, Diana; Gano, Lurdes; Santos, M Amélia

    2009-11-01

    Taking into account the recognized interest of a poly-pharmacological strategy in chelation therapy, a study of aluminium combined chelation based on 3-hydroxy-4-pyridinone (3,4-HP) compounds with complementary properties, associated to different denticity, size and extrafunctionality, is presented herein. In particular, Al-chelation has been explored, using a tetradentate IDA bis-(3,4-HP) ligand, L, and two N-glycosyl mono-(3,4-HP) derivatives (A or B). Combined complexation studies with the tetradentate and the most promising bidentate ligand (A) evidenced the formation of ternary complexes with high thermodynamic stability (Al-L-A) being the predominant species at physiological pH. In vivo studies on the ability for radiotracer ((67)Ga) removal from loaded mice, as a model of aluminium accumulation in body, have shown that the simultaneous administration to (67)Ga-loaded mice of a mono- and a bis-(3,4-HP) chelator (e.g. A and L) leads to a rapid metal elimination from main organs and whole animal model. This may be rationalized by coadjuvation and eventual synergistic effects, due to complementary accessibility of the chelators to different cellular compartments.

  12. Anticancer Activity and Modes of Action of (arene) ruthenium(II) Complexes Coordinated to C-, N-, and O-ligands.

    PubMed

    Biersack, Bernhard

    2016-01-01

    An overview of anticancer active (arene)ruthenium(II) complexes coordinated to period 2 element-based ligand systems, i.e., carbon-, nitrogen-, and oxygen-coordinated ligands, is provided in this mini-review. A bridge is forged from the large group of anticancer active ruthenium compounds with monodentate and chelating nitrogen ligands via complexes of O,O-chelating ligands to organometallic ruthenium derivatives coordinated to carbon. (Arene)ruthenium(II) complexes with reduced side-effects and enhanced efficacy against cancer are highlighted. Pertinent literature is covered up to 2014.

  13. Catalytic oxygenation of sp3 "C-H" bonds with Ir(III) complexes of chelating triazoles and mesoionic carbenes.

    PubMed

    Hohloch, Stephan; Kaiser, Selina; Duecker, Fenja Leena; Bolje, Aljoša; Maity, Ramananda; Košmrlj, Janez; Sarkar, Biprajit

    2015-01-14

    Cp*-Ir(III) complexes with additional chelating ligands are known active pre-catalysts for the oxygenation of C-H bonds. We present here eight examples of such complexes where the denticity of the chelating ligands has been varied from the well-known 2,2'-bpy through pyridyl-triazole, bi-triazole to ligands containing pyridyl-triazolylidene, triazolyl-triazolylidene and bi-triazolylidenes. Additionally, we also compare the catalytic results to complexes containing chelating cyclometallated ligands with additional triazole or triazolylidene donors. Single crystal X-ray structural data are presented for all the new complexes that contain one or more triazolylidene donors of the mesoionic carbene type. We present the first example of a metal complex containing a chelating triazole-triazolylidene ligand. The results of the catalytic screening show that complexes containing unsymmetrical donors of the pyridyl-triazole or pyridyl-triazolylidene types are the most potent pre-catalysts for the C-H oxygenation of cyclooctane in the presence of either m-CPBA or NaIO4 as a sacrificial oxidant. These pre-catalysts can also be used to oxygenate C-H bonds in other substrates such as fluorene and ethyl benzene. The most potent pre-catalysts presented here work with a lower catalyst loading and under milder conditions while delivering better product yields in comparison with related literature known Ir(III) pre-catalysts. These results thus point to the potential of ligands with unsymmetrical donors obtained through the click reaction in oxidation catalysis.

  14. Potentiometric, spectroscopic and thermal studies on the metal chelates of 1-(2-thiazolylazo)-2-naphthalenol

    NASA Astrophysics Data System (ADS)

    Omar, M. M.; Mohamed, Gehad G.

    2005-03-01

    The synthesis and characterization of Mn(II), Fe(III), Co(II), Ni(II), Cu(II), Zn(II), Cd(II), Pd(II) and UO 2(II) chelates of 1-(2-thiazolylazo)-2-naphthalenol (TAN) were reported. The dissociation constants of the ligand and the stability constants of the metal complexes were calculated pH-metrically at 25 °C and 0.1 M ionic strength. The solid complexes were characterized by elemental and thermal analyses, molar conductance, IR, magnetic and diffuse reflectance spectra. The complexes were found to have the formulae [M(L) 2] for M = Mn(II), Co(II), Ni(II), Zn(II) and Cd(II); [M(L)X]· nH 2O for M = Cu(II) (X = AcO, n = 3), Pd(II) (X = Cl, n = 0) and UO 2(II) (X = NO 3, n = 0), and [Fe(L)Cl 2(H 2O)]·2H 2O. The molar conductance data reveal that the chelates are non-electrolytes. IR spectra show that the ligand is coordinated to the metal ions in a terdentate manner with ONN donor sites of the naphthyl OH, azo N and thiazole N. An octahedral structure is proposed for Mn(II), Fe(III), Co(II), Ni(II), Zn(II), Cd(II) and UO 2(II) complexes and a square planar structure for Cu(II) and Pd(II) complexes. The thermal behaviour of these chelates shows that water molecules (coordinated and hydrated) and anions are removed in two successive steps followed immediately by decomposition of the ligand molecule in the subsequent steps. The relative thermal stability of the chelates is evaluated. The final decomposition products are found to be the corresponding metal oxides. The thermodynamic activation parameters, such as E*, Δ H*, Δ S* and Δ G* are calculated from the TG curves.

  15. 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

  16. Screening of protease producing fungi for microbial digestion of seed proteins and synthesis of amino acids-metalnutrient chelates.

    PubMed

    Deore, G B; Limaye, A S; Dushing, Y A; Dhobale, S B; Kale, S; Laware, S L

    2013-01-15

    The problem of metalnutrient deficiency is becoming more serious with the introduction of modern agricultural practices. As a result, metalnutrient deficiency is recognized as one of the critical yield limiting factors. Metalnutrients are generally offered in their sulphate or oxide forms. However, it is reported that organically bound minerals generally have a higher bioavailability than inorganic minerals. Chelation makes otherwise unavailable metalnutrients plant available. Amino acids are well known among various chelating agents. In present investigation the fungus Paecilomyces variotii PR-4 was isolated from soil and was used for production of protease and determination of its activity. Proteins from germinating seeds of chick pea, mung bean, soybean and cowpea were hydrolyzed for the production of amino acids. Amino acids were recovered, estimated and utilized for chelation of metalnutrients viz., Zn, Cu, Fe, Mn, Mg, B and Mo. The resultant chelates were employed to detect with Fourier Transform Infra-Red Spectrophotometer (FTIR) analysis. The peaks of most intensive bands in the IR spectra of ligands recorded were present in the intervals of the wave numbers 3500-3300 and 1720-1700 cm(-1). Chelation of metalnutrients led to the broadening of peak and changes of the peak position of hydroxyl groups, which indicated the binding of the carboxylic groups and primary amine groups of amino acids to the metalnutrients. The resultant amino acids-metalnutrient chelates can be utilized as organic fertilizer.

  17. 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.

  18. f-Element Ion Chelation in Highly Basic Media - Final Report

    SciTech Connect

    Paine, R.T.

    2000-12-12

    A large body of data has been collected over the last fifty years on the chemical behavior of f-element ions. The ions undergo rapid hydrolysis reactions in neutral or basic aqueous solutions that produce poorly understood oxide-hydroxide species; therefore, most of the fundamental f-element solution chemistry has allowed synthetic and separations chemists to rationally design advanced organic chelating ligands useful for highly selective partitioning and separation of f-element ions from complex acidic solution matrices. These ligands and new examples under development allow for the safe use and treatment of solutions containing highly radioactive species. This DOE/EMSP project was undertaken to address the following fundamental objectives: (1) study the chemical speciation of Sr and lanthanide (Ln) ions in basic aqueous media containing classical counter anions found in waste matrices; (2) prepare pyridine N-oxide phosphonates and phosphonic acids that might act as selective chelator s for Ln ions in model basic pH waste streams; (3) study the binding of the new chelators toward Ln ions and (4) examine the utility of the chelators as decontamination and dissolution agents under basic solution conditions. The project has been successful in attacking selected aspects of the very difficult problems associated with basic pH solution f-element waste chemistry. In particular, the project has (1) shed additional light on the initial stages of Ln ion sol-gel-precipitate formulation under basic solution conditions; (2) generated new families of pyridine phosphonic acid chelators; (3) characterized the function of the chelators and (4) examined their utility as oxide-hydroxide dissolution agents. These findings have contributed significantly to an improved understanding of the behavior of Ln ions in basic media containing anions found in typical waste sludges as well as to the development of sludge dissolution agents. The new chelating reagents are easily made and could be

  19. [Physico-chemical and toxicological profile of gadolinium chelates as contrast agents for magnetic resonance imaging].

    PubMed

    Idée, J-M; Fretellier, N; Thurnher, M M; Bonnemain, B; Corot, C

    2015-07-01

    Gadolinium chelates (GC) are contrast agents widely used to facilitate or to enable diagnosis using magnetic resonance imaging (MRI). From a regulatory viewpoint, GC are drugs. GC have largely contributed to the success of MRI, which has become a major component of clinician's diagnostic armamentarium. GC are not metabolised and are excreted by the kidneys. They distribute into the extracellular compartment. Because of its high intrinsic toxicity, gadolinium must be administered as a chelate. GC can be classified according to two key molecular features: (a) nature of the chelating moiety: either macrocyclic molecules in which gadolinium is caged in the pre-organized cavity of the ligand, or linear, open-chain molecules, (b) ionicity: Gd chelates can be ionic (meglumine or sodium salts) or non-ionic. The thermodynamic and kinetic stabilities of the various GCs differ according to these structural characteristics. The kinetic stability of macrocyclic GCs is much higher than that of linear GCs and the thermodynamic stability of ionic GCs is generally higher than that of non-ionic GC, thus leading to a lower risk of gadolinium dissociation. This class of drugs has enjoyed an excellent reputation in terms of safety for a long time, until a causal link with a recently-described serious disease, nephrogenic systemic fibrosis (NSF), was evidenced. It is acknowledged that the vast majority of NSF cases are related to the administration of some linear CG in renally-impaired patients. Health authorities, worldwide, released recommendations which drastically reduced the occurrence of new cases.

  20. Actinide chelation: biodistribution and in vivo complex stability of the targeted metal ions.

    PubMed

    Kullgren, Birgitta; Jarvis, Erin E; An, Dahlia D; Abergel, Rebecca J

    2013-01-01

    Because of the continuing use of nuclear fuel sources and heightened threats of nuclear weapon use, the amount of produced and released radionuclides is increasing daily, as is the risk of larger human exposure to fission product actinides. A rodent model was used to follow the in vivo distribution of representative actinides, administered as free metal ions or complexed with chelating agents including diethylenetriamine pentaacetic acid (DTPA) and the hydroxypyridinonate ligands 3,4,3-LI(1,2-HOPO) and 5-LIO(Me-3,2-HOPO). Different metabolic pathways for the different metal ions were evidenced, resulting in intricate ligand- and metal-dependent decorporation mechanisms. While the three studied chelators are known for their unrivaled actinide decorporation efficiency, the corresponding metal complexes may undergo in vivo decomposition and release metal ions in various biological pools. This study sets the basis to further explore the metabolism and in vivo coordination properties of internalized actinides for the future development of viable therapeutic chelating agents.

  1. Cationic ruthenium alkylidene catalysts bearing phosphine ligands.

    PubMed

    Endo, Koji; Grubbs, Robert H

    2016-02-28

    The discovery of highly active catalysts and the success of ionic liquid immobilized systems have accelerated attention to a new class of cationic metathesis catalysts. We herein report the facile syntheses of cationic ruthenium catalysts bearing bulky phosphine ligands. Simple ligand exchange using silver(i) salts of non-coordinating or weakly coordinating anions provided either PPh3 or chelating Ph2P(CH2)nPPh2 (n = 2 or 3) ligated cationic catalysts. The structures of these newly reported catalysts feature unique geometries caused by ligation of the bulky phosphine ligands. Their activities and selectivities in standard metathesis reactions were also investigated. These cationic ruthenium alkylidene catalysts reported here showed moderate activity and very similar stereoselectivity when compared to the second generation ruthenium dichloride catalyst in ring-closing metathesis, cross metathesis, and ring-opening metathesis polymerization assays.

  2. Sonochemical synthesis, DNA binding, antimicrobial evaluation and in vitro anticancer activity of three new nano-sized Cu(II), Co(II) and Ni(II) chelates based on tri-dentate NOO imine ligands as precursors for metal oxides.

    PubMed

    Abdel-Rahman, Laila H; Abu-Dief, Ahmed M; El-Khatib, Rafat M; Abdel-Fatah, Shimaa Mahdy

    2016-09-01

    Three new nano sized Cu(II), Co(II) and Ni(II) complexes of imine ligand derived from the condensation of 2-amino-3-hydroxypyridine and 3-methoxysalicylaldehyde have been prepared and investigated using various chemical techniques such as NMR, elemental analysis, molar conductance, IR, electronic spectra, TGA and magnetic moment measurements. The obtained chemical analysis data showed that the synthesis of 1:1 (metal:ligand) ratio and octahedral geometry was proposed on the basis of magnetic moment and spectral data studies except the Cu(II) complex which is tetrahedral geometry. Nano-sized particles of the investigated complexes were prepared by sonochemistry method. Furthermore, metal oxides nanoparticles were gained by calcination of the prepared corresponding complexes at 500°C and their structures were characterized by powder x-ray and transmittance electron microscopy. Moreover, the free ligand, its complexes and their metal oxides have been checked in vitro against a number of bacteria and fungi in order to assess their antimicrobial activities. In addition to that, DNA binding of the prepared complexes was tested by many routes such as electronic spectra, viscosity and gel electrophoresis. The results showed that the investigated complexes could bind to DNA via an intercalative mode. The cytotoxicity of the Schiff base complexes on human colon carcinoma cells, (HCT-116 cell line) and Breast carcinoma cells, (MCF-7 cell line) showed potent cytotoxicity effect against growth of carcinoma cells compared to the clinically used Vinblastine standard.

  3. 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.

  4. 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.

  5. Objectives and Methods of Iron Chelation Therapy

    PubMed Central

    Hershko, C.; Abrahamov, A.; Konijn, A. M.; Breuer, W.; Cabantchik, I. Z.; Pootrakul, P.; Link, G.

    2003-01-01

    Recent developments in the understanding of the molecular control of iron homeostasis provided novel insights into the mechanisms responsible for normal iron balance. However in chronic anemias associated with iron overload, such mechanisms are no longer sufficient to offer protection from iron toxicity, and iron chelating therapy is the only method available for preventing early death caused mainly by myocardial and hepatic damage. Today, long-term deferoxamine (DFO) therapy is an integral part of the management of thalassemia and other transfusion-dependent anemias, with a major impact on well-being and survival. However, the high cost and rigorous requirements of DFO therapy, and the significant toxicity of deferiprone underline the need for the continued development of new and improved orally effective iron chelators. Within recent years more than one thousand candidate compounds have been screened in animal models. The most outstanding of these compounds include deferiprone (L1); pyridoxal isonicotinoyl hydrazone (PIH) and; bishydroxy- phenyl thiazole. Deferiprone has been used extensively as a substitute for DFO in clinical trials involving hundreds of patients. However, L1 treatment alone fails to achieve a negative iron balance in a substantial proportion of subjects. Deferiprone is less effective than DFO and its potential hepatotoxicity is an issue of current controversy. A new orally effective iron chelator should not necessarily be regarded as one displacing the presently accepted and highly effective parenteral drug DFO. Rather, it could be employed to extend the scope of iron chelating strategies in a manner analogous with the combined use of medications in the management of other conditions such as hypertension or diabetes. Coadministration or alternating use of DFO and a suitable oral chelator may allow a decrease in dosage of both drugs and improve compliance by decreasing the demand on tedious parenteral drug administration. Combined use of DFO

  6. New biodegradable organic-soluble chelating agents for simultaneous removal of heavy metals and organic pollutants from contaminated media.

    PubMed

    Ullmann, Amos; Brauner, Neima; Vazana, Shlomi; Katz, Zhanna; Goikhman, Roman; Seemann, Boaz; Marom, Hanit; Gozin, Michael

    2013-09-15

    Advanced biodegradable and non-toxic organic chelators, which are soluble in organic media, were synthesized on the basis of the S,S-ethylenediamine-disuccinate (S,S-EDDS) ligand. The modifications suggested in this work include attachment of a lipophilic hydrocarbon chain ("tail") to one or both nitrogen atoms of the S,S-EDDS. The new ligands were designed and evaluated for application in the Sediments Remediation Phase Transition Extraction (SR-PTE) process. This novel process is being developed for the simultaneous removal of both heavy metals and organic pollutants from contaminated soils, sediments or sludge. The new chelators were designed to bind various target metal ions, to promote extraction of these ions into organic solvents. Several variations of attached tails were synthesized and tested. The results for one of them, N,N'-bis-dodecyl-S,S-EDDS (C24-EDDS), showed that the metal-ligand complexes are concentrated in the organic-rich phase in the Phase Transition Extraction process (more than 80%). Preliminary applications of the SR-PTE process with the C24-EDDS ligand were conducted also on actually contaminated sludge (field samples). The extraction of five toxic metals, namely, Cd, Cu, Ni, Pb and Zn was examined. In general, the extraction performance of the new ligand was not less than that of S,S-EDDS when a sufficient ligand-to-extracted ion ratio (about 4:1 was applied.

  7. Synthesis and thermal characterization of new ternary chelates of piroxicam and tenoxicam with glycine and DL-phenylalanine and some transition metals

    NASA Astrophysics Data System (ADS)

    Zayed, M. A.; El-Dien, F. A. Nour; Mohamed, Gehad G.; El-Gamel, Nadia E. A.

    2006-05-01

    The ternary chelates of piroxicam (Pir) and tenoxicam (Ten) with Fe(II), Fe(III), Co(II), Ni(II), Cu(II) and Zn(II) in the presence of various amino acids such as glycine (Gly) or DL-phenylalanine (PhA) were prepared and characterized with different physicochemical methods. IR spectra confirm that Pir and Ten behave as a neutral bidentate ligand coordinated to the metal ions via the pyridine- N and carbonyl group of the amide moiety. Gly molecule acted as a uninegatively monodentate ligand and coordinate to the metal ions through its deprotonated carboxylic group. In addition, PhA acted as a uninegatively bidentate ligand and coordinate to the metal ions through its deprotonated carboxylic and amino groups. The solid reflectance spectra and magnetic moment measurements confirm that all the chelates have octahedral geometrical structures while Cu(II)- and Zn(II)-ternary chelates with PhA have square planar geometrical structures. Thermal behaviour of the complexes is extensively studied using TG and DTA techniques. TG results show that water molecules (hydrated and coordinated) and anions are removed in the first and second steps while Gly, PhA, Pir and Ten are decomposed in the next and subsequent steps. The pyrolyses of the chelates into different gases are observed in the DTA curves as exo- or endothermic peaks. Also, phase transition states are observed in some chelates. Different thermodynamic parameters are calculated using Coats-Redfern method and the results are interpreted.

  8. Synthesis and thermal characterization of new ternary chelates of piroxicam and tenoxicam with glycine and DL-phenylalanine and some transition metals.

    PubMed

    Zayed, M A; El-Dien, F A Nour; Mohamed, Gehad G; El-Gamel, Nadia E A

    2006-05-01

    The ternary chelates of piroxicam (Pir) and tenoxicam (Ten) with Fe(II), Fe(III), Co(II), Ni(II), Cu(II) and Zn(II) in the presence of various amino acids such as glycine (Gly) or dl-phenylalanine (PhA) were prepared and characterized with different physicochemical methods. IR spectra confirm that Pir and Ten behave as a neutral bidentate ligand coordinated to the metal ions via the pyridine-N and carbonyl group of the amide moiety. Gly molecule acted as a uninegatively monodentate ligand and coordinate to the metal ions through its deprotonated carboxylic group. In addition, PhA acted as a uninegatively bidentate ligand and coordinate to the metal ions through its deprotonated carboxylic and amino groups. The solid reflectance spectra and magnetic moment measurements confirm that all the chelates have octahedral geometrical structures while Cu(II)- and Zn(II)-ternary chelates with PhA have square planar geometrical structures. Thermal behaviour of the complexes is extensively studied using TG and DTA techniques. TG results show that water molecules (hydrated and coordinated) and anions are removed in the first and second steps while Gly, PhA, Pir and Ten are decomposed in the next and subsequent steps. The pyrolyses of the chelates into different gases are observed in the DTA curves as exo- or endothermic peaks. Also, phase transition states are observed in some chelates. Different thermodynamic parameters are calculated using Coats-Redfern method and the results are interpreted.

  9. New bifunctional ligands for radioimmunoimaging and radioimmunotherapy

    SciTech Connect

    Brechbiel, M.W.

    1988-01-01

    The bifunctional EDTA ligand and two bifunctional DTPA ligands were synthesized by direct aminolysis of an amino acid ester followed by reduction, alkylation, and functional group modification to introduced bifunctionality. The reactive substituent chosen for protein conjugation was the isothiocyanate group. The generality of this approach was demonstrated with 9 different amino acids to produce the respective substituted diethylenetriamines. The remaining three bifunctional DTPA ligands were synthesized via classical peptide methodology producing a dipeptide amide which, after deprotection, was reduced to the triamine and alkylated to produce the ligand. Biodistribution studies of the ligands conjugated to monoclonal antibody B72.3 and labelled with In-111 revealed that superior retention of In-111 was attained and the dose to the liver was minimized when a full intact octadentate bifunctional DTPA chelate was used, e.g. DTPA > EDTA > DTTA (diethylenetritetraacetic acid from use of DTPA dianhydride (CA-DTPA)). The best scintigraphic images were obtained after 72 hours when a DTPA ligand was used to complex the In-111. Biodistribution studies using Yttrium-88 revealed that the disubstituted bifunctional DTPA was necessary to minimize the bone dose from the Yttrium while maintaining a high dose to the tumor.

  10. High Performance Anion Chromatography of Gadolinium Chelates.

    PubMed

    Hajós, Peter; Lukács, Diana; Farsang, Evelin; Horváth, Krisztian

    2016-11-01

    High performance anion chromatography (HPIC) method to separate ionic Gd chelates, [Formula: see text], [Formula: see text], [Formula: see text] and free matrix anions was developed. At alkaline pHs, polydentate complexing agents such as ethylene-diamine-tetraacetate, diethylene-triamine pentaacetate and trans-1,2-diamine-cyclohexane-tetraacetate tend to form stable Gd chelate anions and can be separated by anion exchange. Separations were studied in the simple isocratic chromatographic run over the wide range of pH and concentration of carbonate eluent using suppressed conductivity detection. The ion exchange and complex forming equilibria were quantitatively described and demonstrated in order to understand major factors in the control of selectivity of Gd chelates. Parameters of optimized resolution between concurrent ions were presented on a 3D resolution surface. The applicability of the developed method is represented by the simultaneous analysis of Gd chelates and organic/inorganic anions. Inductively coupled plasma atomic emission spectroscopy  (ICP-AES) analysis was used for confirmation of HPIC results for Gd. Collection protocols for the heart-cutting procedure of chromatograms were applied. SPE procedures were also developed not only to extract traces of free gadolinium ions from samples, but also to remove the high level of interfering anions of the complex matrices. The limit of detection, the recoverability and the linearity of the method were also presented.

  11. Iron-chelating compound from Mycobacterium avium.

    PubMed Central

    McCullough, W G; Merkal, R S

    1976-01-01

    A iron-chelating monohydroxamate was isolated from cultures of Mycobacterium avium grown on an iron-limiting medium. The hydroxyamate metabolite was characterized by chemical degradation and spectral measurements as L-alpha-asparaginyl-L-alpha-(N-hydroxy)-asparagine. PMID:185194

  12. The effect of regioisomerism on the coordination chemistry and CEST properties of lanthanide(III) NB-DOTA-tetraamide chelates

    PubMed Central

    Slack, Jacqueline R.; Woods, Mark

    2014-01-01

    Chemical exchange saturation transfer (CEST) offers many advantages as a method of generating contrast in magnetic resonance images. However, many of the exogenous agents currently under investigation suffer from detection limits that are still somewhat short of what can be achieved with more traditional Gd3+ agents. To remedy this limitation we have undertaken an investigation of Ln3+ DOTA-tetraamide chelates (where DOTA is 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) that have unusually rigid ligand structures: the nitrobenzyl derivatives of DOTA-tetraamides with (2-phenylethyl)amide substituents. In this report we examine the effect of incorporating hydrophobic amide substituents on water exchange and CEST. The ligand systems chosen afforded a total of three CEST-active isomeric square antiprismatic chelates; each of these chelates was found to have different water exchange and CEST characteristics. The position of a nitrobenzyl substituent on the macrocyclic ring strongly influenced the way in which the chelate and Ln3+ coordination cage distorted. These differential distortions were found to affect the rate of water proton exchange in the chelates. But, by far the greatest effect arose from altering the position of the hydrophobic amide substituent, which, when forced upwards around the water binding site, caused a substantial reduction in the rate of water proton exchange. Such slow water proton exchange afforded a chelate that was 4.5 times more effective as a CEST agent than its isomeric counterparts in dry acetonitrile and at low temperatures and very low presaturation powers. PMID:24287873

  13. Properties, Solution State Behavior, and Crystal Structures of Chelates of DOTMA

    PubMed Central

    Aime, Silvio; Botta, Mauro; Garda, Zoltán; Kucera, Benjamin E.; Tircso, Gyula; Young, Victor G.; Woods, Mark

    2011-01-01

    The chemistry of polyamino carboxylates and their use as ligands for Ln3+ ions is of considerable interest from the point of view of the development of new imaging agents. Of particular interest is the chemistry of the macrocyclic ligand 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) and its derivatives. Herein we report that the tetramethylated DOTA derivative, DOTMA, possess several properties that, from an imaging agent development point of view, are more advantageous than those of the parent DOTA. In particular, the Ln3+ chelates of DOTMA exhibit a marked preference for the monocapped twisted square antiprismatic coordination isomer which imparts more rapid water exchange kinetics on the chelates; τM298 was determined to be 85 ns for GdDOTMA. Differential analysis of the 17O R2ρ temperature profiles of both GdDOTA and GdDOTMA afforded the τM298 values for the square (SAP) and twisted square antiprismatic (TSAP) isomers of each chelate that were almost identical: 365 ns (SAP) and 52 ns (TSAP). The origin of this accelerated water exchange in the TSAP isomer appears to be the slightly longer Gd–OH2 bond distance (2.50 Å) that is observed in the crystal structure of GdDOTMA which crystallizes in the P2 space group as a TSAP isomer. The Ln3+ chelates of DOTMA also exhibit high thermodynamic stabilities ranging from log KML = 20.5 for CeDOTMA, 23.5 for EuDOTMA and YbDOTMA comparable to, but a shade lower than, those of DOTA. PMID:21819052

  14. Less is more: three-coordinate c,n-chelated distannynes and digermynes.

    PubMed

    Novák, Miroslav; Bouška, Marek; Dostál, Libor; Růžička, Aleš; Hoffmann, Alexander; Herres-Pawlis, Sonja; Jambor, Roman

    2015-05-18

    We report here the synthesis of new C,N-chelated chlorostannylenes and germylenes L(3) MCl (M=Sn(1), Ge (2)) and L(4) MCl (M=Sn(3), Ge (4)) containing sterically demanding C,N-chelating ligands L(3, 4) (L(3) =[2,4-di-tBu-6-(Et2 NCH2 )C6 H2 ](-) ; L(4) =[2,4-di-tBu-6-{(C6 H3 -2',6'-iPr2 )N=CH}C6 H2 ](-) ). Reductions of 1-4 yielded three-coordinate C,N-chelated distannynes and digermynes [L(3, 4) M]2 for the first time (5: L(3) , M=Sn, 6: L(3) , M=Ge, 7: L(4) , M=Sn, 8: L(4) , M=Ge). For comparison, the four-coordinate distannyne [L(5) Sn]2 (10) stabilized by N,C,N-chelate L(5) (L(5) =[2,6-{(C6 H3 -2',6'-Me2 )NCH}2 C6 H3 ](-) ) was prepared by the reduction of chlorostannylene L(5) SnCl (9). Hence, we highlight the role of donor-driven stabilization of tetrynes. Compounds 1-10 were characterized by means of elemental analysis, NMR spectroscopy, and in the case of 1, 2, 5-7, and 10, also by single-crystal X-ray diffraction analysis. The bonding situation in either three- or four-coordinate distannynes 5, 7, and 10 was evaluated by DFT calculations. DFT calculations were also used to compare the nature of the metal-metal bond in three-coordinate C,N-chelating distannyne [L(3) Sn]2 (5) and related digermyme [L(3) Ge]2 (6).

  15. FTIR, magnetic, mass spectral, XRD and thermal studies of metal chelates of tenoxicam

    NASA Astrophysics Data System (ADS)

    Zayed, M. A.; El-Dien, F. A. Nour; Mohamed, Gehad G.; El-Gamel, Nadia E. A.

    2007-09-01

    Metal chelates of anti-inflammatory drug, tenoxicam (Ten), are synthesized and characterized using elemental analyses, IR, solid reflectance, magnetic, mass spectra, thermal analyses (TGA and DTA) and X-ray powder diffraction techniques. The chelates are found to have the general formulae [M(H 2L) 2(H 2O) x] (A) 2· yH 2O (where H 2L = neutral Ten, A = Cl in case of Ni(II) and Co(II) or AcO in case of Cu(II) and Zn(II) ions, x = 0-2 and y = 0-2.5) and [M(H 2L) 3](A) z· yH 2O (A = SO 4 in case of Fe(II) ion ( z = 1) or Cl in case of Fe(III) ( z = 3) and y = 0-4). IR spectra reveal that Ten behaves as a neutral bidentate ligand coordinated to the metal ions through the pyridyl- N and carbonyl- O of the amide moiety. The solid reflectance spectra and magnetic moment measurements reveal that these chelates have tetrahedral, square planar and octahedral geometrical structures. Mass spectra are also used to confirm the proposed formulae and the possible fragments resulted from fragmentation of Ten and its Zn(II) and Cu(II) chelates are suggested. The thermal behaviour of the chelates (TG/DTG, DTA) are discussed in detailed manner and revealed that water molecules of crystallization together with anions are removed in the first and second steps while the Ten molecules are removed in the subsequent steps. Different thermodynamic parameters are evaluated and the relative thermal stabilities of the complexes are discussed. X-ray powder diffraction patterns are used to indicate the polymorphic form of Ten and if the complexes have molecular similarity with respect to type of coordination.

  16. Spectral, biological screening of metal chelates of chalcone based Schiff bases of N-(3-aminopropyl) imidazole

    NASA Astrophysics Data System (ADS)

    Kalanithi, M.; Rajarajan, M.; Tharmaraj, P.; Sheela, C. D.

    2012-02-01

    Tridentate chelate complexes of Co(II), Ni(II), Cu(II) and Zn(II) have been synthesized from the chalcone based ligands 2-[1-(3-(1H-imidazol-1-yl)propylimino)-3-(phenylallyl)]phenol( HL1), 2-[1-(3-(1H-imidazol-1-yl)propylimino)-3-p-tolylallyl]phenol( HL2), 2-[1-(3-(1H-imidazol-1-yl)propylimino)-3-4-nitrophenylallyl]phenol( HL3). Microanalytical data, UV-vis spectrophotometric method, magnetic susceptibility measurements, IR, 1H NMR, Mass, and EPR techniques were used to characterize the structure of chelates. The electronic absorption spectra and magnetic susceptibility measurements suggest a distorted square planar geometry for the copper(II) ion. The other metal complexes show distorted tetrahedral geometry. The coordination of the ligands with metal(II) ions was further confirmed by solution fluorescence spectrum. The antimicrobial activity of the ligands and metal(II) complexes against the species Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus, Bacillus subtilis, Candida albigans and Aspergillus niger has been carried out and compared. The electrochemical behavior of copper(II) complex is studied by cyclic voltammetry.

  17. 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

  18. New Chelators for Low Temperature Al(18)F-Labeling of Biomolecules.

    PubMed

    Cleeren, Frederik; Lecina, Joan; Billaud, Emilie M F; Ahamed, Muneer; Verbruggen, Alfons; Bormans, Guy M

    2016-03-16

    The Al(18)F labeling method is a relatively new approach that allows radiofluorination of biomolecules such as peptides and proteins in a one-step procedure and in aqueous solution. However, the chelation of the {Al(18)F}(2+) core with the macrocyclic chelators NOTA or NODA requires heating to 100-120 °C. Therefore, we have developed new polydentate ligands for the complexation of {Al(18)F}(2+) with good radiochemical yields at a temperature of 40 °C. The stability of the new Al(18)F-complexes was tested in phosphate buffered saline (PBS) at pH 7.4 and in rat serum. The stability of the Al(18)F-L3 complex was found to be comparable to that of the previously reported Al(18)F-NODA complex up to 60 min in rat serum. Moreover, the biodistribution of Al(18)F-L3 in healthy mice showed the absence of in vivo defluorination since no significant bone uptake was observed, whereas the major fraction of activity at 60 min p.i. was observed in liver and intestines, indicating hepatobiliary clearance of the radiolabeled ligand. The acyclic chelator H3L3 proved to be a good lead candidate for labeling of heat-sensitive biomolecules with fluorine-18. In order to obtain a better understanding of the different factors influencing the formation and stability of the complex, we carried out more in-depth experiments with ligand H3L3. As a proof of concept, we successfully conjugated the new AlF-chelator with the urea-based PSMA inhibitor Glu-NH-CO-NH-Lys to form Glu-NH-CO-NH-Lys(Ahx)L3, and a biodistribution study in healthy mice was performed with the Al(18)F-labeled construct. This new class of AlF-chelators may have a great impact on PET radiochemical space as it will stimulate the rapid development of new fluorine-18 labeled peptides and other heat-sensitive biomolecules.

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  20. Nanogels from metal-chelating crosslinkers as versatile platforms applied to copper-64 PET imaging of tumors and metastases.

    PubMed

    Lux, Jacques; White, Alexander G; Chan, Minnie; Anderson, Carolyn J; Almutairi, Adah

    2015-01-01

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

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

    PubMed Central

    Lux, Jacques; White, Alexander G.; Chan, Minnie; Anderson, Carolyn J.; Almutairi, Adah

    2015-01-01

    Metals are essential in medicine for both therapy and diagnosis. We recently created the first metal-chelating nanogel imaging agent, which employed versatile, reproducible chemistry that maximizes chelation stability. Here we demonstrate that our metal chelating crosslinked nanogel technology is a powerful platform by incorporating 64Cu to obtain PET radiotracers. Polyacrylamide-based nanogels were crosslinked with three different polydentate ligands (DTPA, DOTA, NOTA). NOTA-based nanogels stably retained 64Cu in mouse serum and accumulated in tumors in vivo as detected by PET/CT imaging. Measurement of radioactivity in major organs ex vivo confirmed this pattern, revealing a high accumulation (12.3% ID/g and 16.6% ID/g) in tumors at 24 and 48 h following administration, with lower accumulation in the liver (8.5% ID/g at 24 h) and spleen (5.5% ID/g). Nanogels accumulated even more efficiently in metastases (29.9% and 30.4% ID/g at 24 and 48 h). These metal-chelating nanogels hold great promise for future application as bimodal PET/MRI agents; chelation of β-emitting radionuclides could enable radiation therapy. PMID:25553115

  2. Synthesis and structural features of U VI and V IV chelate complexes with (hhmmbH)Cl·H 2O [hhmmb = {3-hydroxyl-5-(hydroxymethyl)-2-methylpyridine-4-yl-methylene}benzohydrazide], a new Schiff base ligand derived from vitamin B6

    NASA Astrophysics Data System (ADS)

    Back, Davi Fernando; Ballin, Marco Aurélio; de Oliveira, Gelson Manzoni

    2009-10-01

    The Schiff base ligand {3-hydroxyl-5-(hydroxymethyl)-2-methylpyridine-4-yl-methylene}benzohydrazide hydrochloride monohydrated {(hhmmbH)Cl·H 2O} ( 1) was prepared by reaction of pyridoxine hydrochloride with benzoic acid hydrazide. The reaction of 1 with [VO(acac) 2] and triethylamine yields the neutral vanadium IV complex [VO 2(hhmmb)]·Py ( 2), with a distorted quadratic pyramidal configuration. The Schiff base 1 reacts also with UO 2(NO 3) 2·6H 2O and triethylamine under deprotonation giving the uranium VI cationic complexes [UO 2(hhmmb)(H 2O)Cl] + ( 3) and [UO 2(hhmmb)(CH 3OH)Cl] + ( 4), both showing the classical pentagonal bipyrimidal geometry of UO22+ complexes. The structural features of all compounds are discussed.

  3. 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

  4. Safety evaluation of zinc threoninate chelate.

    PubMed

    Hu, Xiao-bo; Gong, Yi; Li, Lei; Nie, Shao-ping; Wang, Yuan-xing; Xie, Ming-yong

    2010-07-01

    The acute toxicity of zinc threoninate chelate was assessed. The oral lethal dose 50% (LD(50)) was 2710 mg/kg in female rats and 3160 mg/kg in male rats. Genotoxicity was assessed by Ames test in Salmonella typhimurium strains TA97, TA98, TA100, and TA102, by bone marrow mouse micronucleus test and a sperm abnormality test with mice. Thirty-day repeat dose toxicity study was conducted at oral daily doses of 0, 42, 169, and 675 mg/kg in rats. Teratogenicity was assessed at the same daily dose in pregnant rats by gavage. No significant changes in body weight, food consumption, organ weight, relative organ weight, hematology, blood biochemistry, histopathology, behavior, mortality, sperm abnormality, mutagenicity, and micronucleus formation were observed and no clinical signs or adverse effects were detected. Zinc threoninate chelate had no significant teratogenic effect at a daily dose of 42 mg/kg.

  5. Obligatory Reduction of Ferric Chelates in Iron Uptake by Soybeans

    PubMed Central

    Chaney, Rufus L.; Brown, John C.; Tiffin, Lee O.

    1972-01-01

    The contrasting Fe2+ and Fe3+ chelating properties of the synthetic chelators ethylenediaminedi (o-hydroxyphenylacetate) (EDDHA) and 4,7-di(4-phenylsulfonate)-1, 10-phenanthroline (bathophenanthrolinedisulfonate) (BPDS) were used to determine the valence form of Fe absorbed by soybean roots supplied with Fe3+-chelates. EDDHA binds Fe3+ strongly, but Fe2+ weakly; BPDS binds Fe2+ strongly but Fe3+ weakly. Addition of an excess of BPDS to nutrient solutions containing Fe3+-chelates inhibited soybean Fe uptake-translocation by 99+%; [Fe(II) (BPDS)3]4− accumulated in the nutrient solution. The addition of EDDHA caused little or no inhibition. These results were observed with topped and intact soybeans. Thus, separation and absorption of Fe from Fe3+-chelates appear to require reduction of Fe3+-chelate to Fe2+-chelate at the root, with Fe2+ being the principal form of Fe absorbed by soybean. PMID:16658143

  6. Iron chelation therapy in thalassemia syndromes.

    PubMed

    Cianciulli, Paolo

    2009-12-29

    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.

  7. 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

  8. 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.

  9. pFe(3+) determination of multidentate ligands by a fluorescence assay.

    PubMed

    Ma, Yongmin; Zhou, Tao; Hider, Robert C

    2015-05-21

    The fluorescence intensity of the iron-CP691 complex in the presence of a competing multidentate ligand is associated with pFe(3+) of the competing ligand and the relative fluorescence has a linear correlation with the pFe(3+) values. A correlation was also found to exist between the relative fluorescence and the ratio of a competing ligand to the probe CP691. Based on this assay, the pFe(3+) value of a range of hexadentate ligands, dendrimers and polymers can be determined when they fall in the range 24.5-30.5. Only small quantities of chelators are required for this assay.

  10. Development of immobilized ligands for actinide separations. Final report, June 1991--May 1994

    SciTech Connect

    Paine, R.T.

    1994-06-01

    Primary goals during this grant period were to (1) synthesize new bifunctional chelating ligands, (2) characterize the structural features of the Ln and An coordination complexes formed by these ligands, (3) use structural data to iteratively design new classes of multifunctional ligands, and (4) explore additional routes for attachment of key ligands to solid supports that could be useful for chromatographic separations. Some highlights of recently published work as well as a summary of submitted, unpublished and/or still in progress research are outlined.

  11. Design and synthesis of chelating diamide sorbents for the separation of lanthanides

    SciTech Connect

    Fryxell, Glen E.; Chouyyok, Wilaiwan; Rutledge, Ryan D.

    2011-06-01

    A nanoporous sorbent designed around chelating iminodiacetamide (“IDA-Amide”) moiety was made on mesoporous silica (MCM-41) and evaluated for lanthanide separations (Ce3+, Nd3+, Eu3+, Gd3+, and Lu3+). The effects of solution pH on lanthanide binding were studied, as well as sorption kinetics, and competition from other metal ions. The IDA-Amide SAMMS® demonstrated an interesting difference in the kinetics of sorption of the lanthanide ions in the order of Lu3+ > Eu3+ > Gd3+ > Nd3+ > Ce3+ . The close proximity of the ligands in the IDA-Amide SAMMS® may allow for multiple metal-ligand interactions (“macromolecular chelation”).

  12. Synthesis and biological evaluation of bidentate 3-hydroxypyridin-4-ones iron chelating agents

    PubMed Central

    Saghaie, L.; Sadeghi-aliabadi, H.; Kafiri, M.

    2011-01-01

    A series of 3-hydroxypyridin-4-one derivatives (HPOs) were synthesized and their partition coefficient values (Kpart) were determined. The cytotoxic effects of these iron chelators against Hela cancer cells were also evaluated. The IC50 of HPOs was determined using MTT assay. Among these ligands, compound 4e (Kpart=5.02) with an IC50 of 30 μM and 4f (Kpart=0.1) with an IC50 of 700 μM showed the lowest and highest IC50s, respectively. In conclusion, the introduction of a more hydrophobic functional group (such as butyl in compound 4e) on the nitrogen of pyridinone ring resulted in higher cytotoxic activity of ligands. PMID:22224095

  13. Hydroxypyridinone Chelators: From Iron Scavenging to Radiopharmaceuticals for PET Imaging with Gallium-68

    PubMed Central

    Cusnir, Ruslan; Imberti, Cinzia; Hider, Robert C.; Blower, Philip J.; Ma, Michelle T.

    2017-01-01

    Derivatives of 3,4-hydroxypyridinones have been extensively studied for in vivo Fe3+ sequestration. Deferiprone, a 1,2-dimethyl-3,4-hydroxypyridinone, is now routinely used for clinical treatment of iron overload disease. Hexadentate tris(3,4-hydroxypyridinone) ligands (THP) complex Fe3+ at very low iron concentrations, and their high affinities for oxophilic trivalent metal ions have led to their development for new applications as bifunctional chelators for the positron emitting radiometal, 68Ga3+, which is clinically used for molecular imaging in positron emission tomography (PET). THP-peptide bioconjugates rapidly and quantitatively complex 68Ga3+ at ambient temperature, neutral pH and micromolar concentrations of ligand, making them amenable to kit-based radiosynthesis of 68Ga PET radiopharmaceuticals. 68Ga-labelled THP-peptides accumulate at target tissue in vivo, and are excreted largely via a renal pathway, providing high quality PET images. PMID:28075350

  14. Inhibitor Ranking through QM Based Chelation Calculations for Virtual Screening of HIV-1 RNase H Inhibition

    PubMed Central

    Poongavanam, Vasanthanathan; Steinmann, Casper; Kongsted, Jacob

    2014-01-01

    Quantum mechanical (QM) calculations have been used to predict the binding affinity of a set of ligands towards HIV-1 RT associated RNase H (RNH). The QM based chelation calculations show improved binding affinity prediction for the inhibitors compared to using an empirical scoring function. Furthermore, full protein fragment molecular orbital (FMO) calculations were conducted and subsequently analysed for individual residue stabilization/destabilization energy contributions to the overall binding affinity in order to better understand the true and false predictions. After a successful assessment of the methods based on the use of a training set of molecules, QM based chelation calculations were used as filter in virtual screening of compounds in the ZINC database. By this, we find, compared to regular docking, QM based chelation calculations to significantly reduce the large number of false positives. Thus, the computational models tested in this study could be useful as high throughput filters for searching HIV-1 RNase H active-site molecules in the virtual screening process. PMID:24897431

  15. Method for quantitative proteomics research by using metal element chelated tags coupled with mass spectrometry.

    PubMed

    Liu, Huiling; Zhang, Yangjun; Wang, Jinglan; Wang, Dong; Zhou, Chunxi; Cai, Yun; Qian, Xiaohong

    2006-09-15

    The mass spectrometry-based methods with a stable isotope as the internal standard in quantitative proteomics have been developed quickly in recent years. But the use of some stable isotope reagents is limited by the relative high price and synthetic difficulties. We have developed a new method for quantitative proteomics research by using metal element chelated tags (MECT) coupled with mass spectrometry. The bicyclic anhydride diethylenetriamine-N,N,N',N' ',N' '-pentaacetic acid (DTPA) is covalently coupled to primary amines of peptides, and the ligand is then chelated to the rare earth metals Y and Tb. The tagged peptides are mixed and analyzed by LC-ESI-MS/MS. Peptides are quantified by measuring the relative signal intensities for the Y and Tb tag pairs in MS, which permits the quantitation of the original proteins generating the corresponding peptides. The protein is then identified by the corresponding peptide sequence from its MS/MS spectrum. The MECT method was evaluated by using standard proteins as model sample. The experimental results showed that metal chelate-tagged peptides chromatographically coeluted successfully during the reversed-phase LC analysis. The relative quantitation results were accurate for proteins using MECT. DTPA modification of the N-terminal of peptides promoted cleaner fragmentation (only y-series ions) in mass spectrometry and improved the confidence level of protein identification. The MECT strategy provides a simple, rapid, and economical alternative to current mass tagging technologies available.

  16. A bis(3-hydroxy-4-pyridinone)-EDTA derivative as a strong chelator for M3+ hard metal ions: complexation ability and selectivity.

    PubMed

    Gama, Sofia; Dron, Paul; Chaves, Silvia; Farkas, Etelka; Santos, M Amélia

    2009-08-21

    The study of chelating compounds is very important to solve problems related to human metal overload. 3-Hydroxy-3-pyridinones (HP), namely deferiprone, have been clinically used for chelating therapy of Fe and Al over the last decade. A multi-disciplinary search for alternative molecules led us to develop poly-(3-hydroxy-4-pyridinones) to increase metal chelation efficacy. We present herein a complexation study of a new bis-(3-hydroxy-4-pyridinone)-EDTA derivative with a set of M(3+) hard metal ions (M = Fe, Al, Ga), as well as Zn(2+), a biologically relevant metal ion. Thus a systematic aqueous solution equilibrium study was performed using potentiometric and spectroscopic techniques (UV-Vis, NMR methods). These set of results enables the establishment of specific models as well as the determination of thermodynamic stability constants and coordination modes of the metal complexes. The results indicate that this ligand has a higher affinity for chelating to these hard metal ions than deferiprone, and that the coordination occurs mostly through the HP moieties. Furthermore, it was also found that this ligand has a higher selectivity for chelating to M(3+) hard metal ions (M = Fe, Al, Ga) than Zn(2+).

  17. Mechanism of action of diabetogenic zinc-chelating agents. Model system studies.

    PubMed

    Epand, R M; Stafford, A R; Tyers, M; Nieboer, E

    1985-03-01

    its decomposition products, diethylamine, to accelerate the dissipation of pH gradients across lipid bilayers. Diethylamine is particularly effective in stimulating a rapid dissipation of such pH gradients, even at micromolar concentrations. We have attempted to estimate quantitatively the extent of proton liberation by various zinc-chelating agents. This analysis demonstrated that partitioning of the ligand between organic and aqueous phases, ligand acidity, and zinc complex stability determine the extent of proton release.

  18. Zwitterionic Group VIII transition metal initiators supported by olefin ligands

    DOEpatents

    Bazan, Guillermo C.; Chen, Yaofeng

    2011-10-25

    A zwitterionic Group VIII transition metal complex containing the simple and relatively small 3-(arylimino)-but-1-en-2-olato ligand that catalyzes the formation of polypropylene and high molecular weight polyethylene. A novel feature of this catalyst is that the active species is stabilized by a chelated olefin adduct. The present invention also provides methods of polymerizing olefin monomers using zwitterionic catalysts, particularly polypropylene and high molecular weight polyethylene.

  19. Impact of iron chelators on short-term dissolution of basaltic glass

    NASA Astrophysics Data System (ADS)

    Perez, Anne; Rossano, Stéphanie; Trcera, Nicolas; Verney-Carron, Aurélie; Huguenot, David; van Hullebusch, Eric D.; Catillon, Gilles; Razafitianamaharavo, Angelina; Guyot, François

    2015-08-01

    Although microorganisms seem to play an important role in the alteration processes of basaltic glasses in solution, the elementary mechanisms involved remain unclear in particular with regard to the role of organic ligands excreted by the cells. Two glasses, one with Fe and one without Fe were synthesized to model basaltic glass compositions. Fe in the glass was mostly Fe(III) for enhancing interaction with siderophores, yet with small but significant amounts of Fe(II) (between 10% and 30% of iron). The prepared samples were submitted to abiotic alteration experiments in buffered (pH 6.4) diluted solutions of metal-specific ligands, namely oxalic acid (OA, 10 mM), desferrioxamine (DFA, 1 mM) or 2,2‧-bipyridyl (BPI, 1 mM). Element release from the glass into the solution after short term alteration (maximum 1 week) was measured by ICP-OES, and normalized mass losses and relative release ratios (with respect to Si) were evaluated for each element in each experimental condition. The presence of organic ligands had a significant effect on the dissolution of both glasses. Trivalent metals chelators (OA, DFA) impacted on the release of Fe3+ and Al3+, and thus on the global dissolution of both glasses, enhancing all release rates and dissolution stoichiometry (release rates were increased up to 7 times for Al or Fe). As expected, the mostly divalent metal chelator BPI interacted preferentially with Ca2+, Mg2+ and Fe2+. This study thus allows to highlight the central roles of iron and aluminium in interaction with some organic ligands in the alteration processes of basaltic glasses. It thus provides a step toward understanding the biological contribution of this fundamental geological process.

  20. A density functional theory investigation of the interaction of the tetraaqua calcium cation with bidentate carbonyl ligands.

    PubMed

    Quattrociocchi, Daniel Garcez S; Meuser, Marcos Vinicius Monsores; Ferreira, Glaucio Braga; de M Carneiro, José Walkimar; Stoyanov, Stanislav R; da Costa, Leonardo Moreira

    2017-02-01

    Calcium complexes with bidentate carbonyl ligands are important in biological systems, medicine and industry, where the concentration of Ca(2+) is controlled using chelating ligands. The exchange of two water molecules of [Ca(H2O)6](2+) for one bidentate monosubstituted and homo disubstituted dicarbonyl ligand was investigated using the B3LYP/6-311++G(d,p) method. The ligand substituents NH2, OCH3, OH, CH3, H, F, Cl, CN and NO2 are functional groups with distinct electron-donating and -withdrawing effects that bond directly to the sp(2) C atom of the carbonyl group. The geometry, charge and energy characteristics of the complexes were analyzed to help understand the effects of substituents, spacer length and chelation. Coordination strength was quantified in terms of the enthalpy and free energy of the exchange reaction. The most negative enthalpies were calculated for the coordination of bidentate ligands containing three to five methylene group spacers between carbonyls. The chelate effect contribution was analyzed based on the thermochemistry. The electronic character of the substituent modulates the strength of binding to the metal cation, as ligands containing electron-donor substituents coordinate stronger than those with electron-acceptor substituents. This is reflected in the geometric (bond length and chelating angle), electronic (atomic charges) and energetic (components of the total interacting energy) characteristics of the complexes. Energy decomposition analysis (EDA)-an approach for partitioning of the energy into its chemical origins-shows that the electrostatic component of the coordination is predominant, and yields relevant contribution of the covalent term, especially for the electron-withdrawing substituted ligands. The chelate effect of the bidentate ligands was noticeable when compared with substitution by two monodentate ligands. Graphical abstract The affinity of 18 bidentate carbonyl ligands toward the [Ca(H2O)4](2+) cation is evaluated in

  1. Paramagnetic Ligand Tagging To Identify Protein Binding Sites

    PubMed Central

    2015-01-01

    Transient biomolecular interactions are the cornerstones of the cellular machinery. The identification of the binding sites for low affinity molecular encounters is essential for the development of high affinity pharmaceuticals from weakly binding leads but is hindered by the lack of robust methodologies for characterization of weakly binding complexes. We introduce a paramagnetic ligand tagging approach that enables localization of low affinity protein–ligand binding clefts by detection and analysis of intermolecular protein NMR pseudocontact shifts, which are invoked by the covalent attachment of a paramagnetic lanthanoid chelating tag to the ligand of interest. The methodology is corroborated by identification of the low millimolar volatile anesthetic interaction site of the calcium sensor protein calmodulin. It presents an efficient route to binding site localization for low affinity complexes and is applicable to rapid screening of protein–ligand systems with varying binding affinity. PMID:26289584

  2. Preparation, spectral, X-ray powder diffraction and computational studies and genotoxic properties of new azo-azomethine metal chelates

    NASA Astrophysics Data System (ADS)

    Bitmez, Şirin; Sayin, Koray; Avar, Bariş; Köse, Muhammet; Kayraldız, Ahmet; Kurtoğlu, Mükerrem

    2014-11-01

    A new tridentate azo-azomethine ligand, N‧-[{2-hydroxy-5-[(4-nitrophenyl)diazenyl]phenyl}methylidene]benzohydrazidemonohydrate, (sbH·H2O) (1), is prepared by condensation of benzohydrazide and 2-hydroxy-5-[(4-nitrophenyl)diazenyl]benzaldehyde (a) with treatment of a solution of diazonium salt of p-nitroaniline and 2-hydroxybenzaldehyde in EtOH. The five coordination compounds, [Co(sb)2]·4H2O (2), [Ni(sb)2]·H2O (3), [Cu(sb)2]·4H2O (4), [Zn(sb)2]·H2O (5) and [Cd(sb)2]·H2O (6) are prepared by reacting the Co(II), Ni(II), Cu(II), Zn(II) and Cd(II) ions with the ligand. The structures of the compounds are elucidated from the elemental analyses data and spectroscopic studies. It is found the ligand acts as a tridentate bending through phenolic and carbonyl oxygens and nitrogen atom of the Cdbnd Nsbnd group similar to the most of salicylaldimines. Comparison of the infrared spectra of the ligand and its metal complexes confirm that azo-Schiff base behaves as a monobasic tridentate ligand towards the central metal ion with an ONO donor sequence. Upon complexation with the ligand, the Cd(II), and Zn(II) ions form monoclinic structures, while Co(II), Cu(II) and Ni(II) ions form orthorhombic structures. Quantum chemical calculations are performed on tautomers and its metal chelates by using DFT/B3LYP method. Most stable tautomer is determined as tautomer (1a). The geometrical parameters of its metal chelates are obtained as theoretically. The NLO properties of tautomer (1a) and its metal complexes are investigated. Finally, the ligand and its metal complexes are assessed for their genotoxicity.

  3. Synthesis, Characterization, and Application of Metal-Chelating Polymers for Mass Cytometric Bioassays

    NASA Astrophysics Data System (ADS)

    Majonis, Daniel

    This thesis describes the synthesis, characterization, and application of metal-chelating polymers for mass-cytometric bioassays. Mass cytometry is a cell characterization technique in which cells are injected individually into an ICP-MS detector. Signal is provided by staining cell-surface or intracellular antigens with metal-labeled antibodies (Abs). These Abs are labeled through the covalent attachment of metal-chelating polymers which carry multiple copies of a lanthanide isotope. In this work, my first goal was to develop a facile, straightforward synthesis of a new generation of metal-chelating polymers. The synthesis began with reversible addition-fragmentation chain transfer polymerization, and was followed by numerous post-polymerization pendant group transformations to introduce DTPA lanthanide chelators to every repeat unit, and a maleimide at the end of the chain. The second goal was to apply these metal-chelating polymers in bioassay experiments. The DTPA groups were loaded with lanthanide ions, and the maleimide group was used to covalently attach the polymer to an Ab. This goat anti-mouse conjugate was found to carry an average of 2.4 +/- 0.3 polymer chains. Then, primary Ab conjugates were prepared and used in an 11-plex mass cytometry assay in the characterization of umbilical cord blood cells. The third goal was to expand the multiplexity of the assay. In current technology, the number of Abs that can be monitored simultaneously is limited to the 31 commercially available, stable lanthanide isotopes. Thus, I had an interest in preparing metal-chelating polymers that could carry other metals in the 100-220 amu range. I synthesized polymers with four different polyaminocarboxylate ligands, and investigated the loading of palladium and platinum ions into these polymers. Polymer-Ab conjugates prepared with palladium- and platinum-loaded polymers gave curious results, in that only dead cells were recognized. The fourth goal was to create dual

  4. An unprecedented photochromic system with cis-oriented dithienyl-dithiolenes supported by metal chelation.

    PubMed

    Wang, Jiang; Shi, Lin-Xi; Wang, Jin-Yun; Chen, Jin-Xiang; Liu, Sheng-Hua; Chen, Zhong-Ning

    2017-02-14

    4,5-Bis(2-methyl-5-phenylthiophen-3-yl)-1,3-dithiol-2-one (L1o) was elaborately designed to afford dithienyl-dithiolene as a new photochromic ligand. We describe herein the preparation and characterization of unprecedented photochromic dithienyl-dithiolene complexes with cis-orientation of dithienylethene (DTE) stabilized by metal chelation instead of conventional cyclopentene. The treatment of L1o with sodium methoxide in methanol afforded a disodium salt of dithiolate dianion, which reacts with M(dppe)Cl2 (dppe = 1,2-bis(diphenylphosphino)ethane, M = Ni, Pd) to give neutral compounds M(dppe)(dithiolate) as established by X-ray crystallography. The reaction of L1o with NiCl2 in the presence of sodium methoxide allows the isolation of an anionic nickel(ii) bis(dithienyl-dithiolene) complex with photochemical inertness. In contrast, the corresponding reaction with ZnCl2 afforded a dianionic zinc(ii) complex chelated by two dianionic dithienyl-dithiolenes, which displays stepwise photocyclization upon irradiation with UV light at 312 nm as demonstrated experimentally and theoretically. Only when dithienyl-dithiolene behaves as a dicationic ligand instead of neutral or monoanionic species, it is possible to achieve reversible photochromism in the corresponding metal complexes.

  5. 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.

  6. D-Penicillamine tripodal derivatives as efficient copper(I) chelators.

    PubMed

    Jullien, Anne-Solène; Gateau, Christelle; Lebrun, Colette; Kieffer, Isabelle; Testemale, Denis; Delangle, Pascale

    2014-05-19

    New tripodal metal-chelating agents derived from nitrilotriacetic acid (NTA) and extended by three unnatural amino acids D-penicillamine (D-Pen) are presented. D-Pen is actually the drug most extensively used to treat copper (Cu) overload in Wilson's disease and as such is a very attractive building block for the design of chelating agents. D-Pen is also a bulkier analogue of cysteine, with the β-methylene hydrogen atoms replaced by larger methyl groups. The hindrance of the gem-dimethyl group close to the thiol functions is demonstrated to influence the speciation and stability of the metal complexes. The ligands L(4) (ester) and L(5) (amide) were obtained from NTA and commercial D-Pen synthons in four and five steps with overall yields of 14 and 24%, respectively. Their ability to bind Cu(I), thanks to their three thiolate functions, has been investigated using both spectroscopic and analytical methods. UV, CD, and NMR spectroscopy and mass spectrometry evidence the formation of two Cu(I) complexes with L(5): the mononuclear complex CuL(5) and one cluster (Cu2L(5))2. In contrast, the bulkier ethyl ester derivative L(4) cannot accommodate the mononuclear complex in solution and thus forms exclusively the cluster (Cu2L(4))2. Cu K-edge X-ray absorption spectroscopy (XAS and EXAFS) confirms that Cu(I) is bound in trigonal-planar sulfur-only environments in all of these complexes with Cu- - -S distances ranging from 2.22 to 2.23 Å. Such C3-symmetric CuS3 cores are coordination modes frequently adopted in Cu(I) proteins such as metallothioneins. These two ligands bind Cu(I) tightly and selectively, which makes them promising chelators for intracellular copper detoxification in vivo.

  7. Species-dependent effective concentration of DTPA in plasma for chelation of 241Am

    PubMed Central

    Sueda, Katsuhiko; Sadgrove, Matthew P.; Jay, Michael; Di Pasqua, Anthony J.

    2013-01-01

    Diethylenetriaminepentaacetic acid (DTPA) is a chelating agent that is used to facilitate the elimination of radionuclides, such as americium, from contaminated individuals. Its primary site of action is in the blood, where it competes with various biological ligands, including transferrin and albumin, for the binding of radioactive metals. To evaluate the chelation potential of DTPA under these conditions, the competitive binding of 241Am between DTPA and plasma proteins was studied in rat, beagle and human plasma in vitro. Following incubation of DTPA and 241Am in plasma, the 241Am-bound ligands were fractionated by ultrafiltration and ion-exchange chromatography, and each fraction was assayed for 241Am content by gamma scintillation counting. Dose-response curves of DTPA for 241Am binding were established, and these models were used to calculate the 90% maximal effective concentration, or EC90, of DTPA in each plasma system. The EC90 were determined to be 31.4, 15.9 and 10.0 μM in rat, beagle and human plasma, respectively. These values correspond to plasma concentrations of DTPA that maximize 241Am chelation while minimizing excess DTPA. Based on the pharmacokinetic profile of DTPA in humans, after a standard 30 μmol kg−1 intravenous bolus injection, the plasma concentration of DTPA remains above EC90 for approximately 5.6 h. Likewise, the effective duration of DTPA in rat and beagle were determined to be 0.67 and 1.7 h, respectively. These results suggest that species differences must be considered when translating DTPA efficacy data from animals to humans and offer further insights into improving the current DTPA treatment regimen. PMID:23799506

  8. Mn(iv) and Mn(v)-radical species supported by the redox non-innocent bis(2-amino-3,5-di-tert-butylphenyl)amine pincer ligand.

    PubMed

    Leconte, Nicolas; Moutet, Jules; Herasymchuk, Khrystyna; Clarke, Ryan M; Philouze, Christian; Luneau, Dominique; Storr, Tim; Thomas, Fabrice

    2017-02-17

    The electron-rich pincer ligand 1 has been synthesized and chelated to manganese. The octahedral Mn(iv) bis(diiminosemiquinonate) and Mn(v) (diiminobenzoquinone) (diiminosemiquinonate) radicals were structurally characterized.

  9. Chelators as antidotes of metal toxicity: therapeutic and experimental aspects.

    PubMed

    Blanusa, Maja; Varnai, Veda M; Piasek, Martina; Kostial, Krista

    2005-01-01

    The effects of chelating drugs used clinically as antidotes to metal toxicity are reviewed. Human exposure to a number of metals such as lead, cadmium, mercury, manganese, aluminum, iron, copper, thallium, arsenic, chromium, nickel and platinum may lead to toxic effects, which are different for each metal. Similarly the pharmacokinetic data, clinical use and adverse effects of most of the chelating drugs used in human metal poisoning are also different for each chelating drug. The chelating drugs with worldwide application are dimercaprol (BAL), succimer (meso-DMSA), unithiol (DMPS), D-penicillamine (DPA), N-acetyl-D-penicillamine (NAPA), calcium disodium ethylenediaminetetraacetate (CaNa(2)EDTA), calcium trisodium or zinc trisodium diethylenetriaminepentaacetate (CaNa(3)DTPA, ZnNa(3)DTPA), deferoxamine (DFO), deferiprone (L1), triethylenetetraamine (trientine), N-acetylcysteine (NAC), and Prussian blue (PB). Several new synthetic homologues and experimental chelating agents have been designed and tested in vivo for their metal binding effects. These include three groups of synthetic chelators, namely the polyaminopolycarboxylic acids (EDTA and DTPA), the derivatives of BAL (DMPS, DMSA and mono- and dialkylesters of DMSA) and the carbodithioates. Many factors have been shown to affect the efficacy of the chelation treatment in metal poisoning. Within this context it has been shown in experiments using young and adult animals that metal toxicity and chelation effects could be influenced by age. These findings may have a bearing in the design of new therapeutic chelation protocols for metal toxicity.

  10. 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.

  11. 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.

  12. The fate of Gd and chelate following intravenous injection of gadodiamide in rats

    PubMed Central

    Uran, Steinar; Friisk, Grete; Martinsen, Ivar; Skotland, Tore

    2010-01-01

    Objective The biodistribution of gadolinium (Gd) and chelate was studied in rats injected intravenously with a commercially available gadodiamide magnetic resonance contrast agent spiked with trace amounts of 14C-labelled GdDTPA-BMA. Methods Biodistribution of the 14C-labelled ligand in whole animals was visualised using quantitative whole-body autoradiography, and quantified in individual tissue samples by analysing for radioactivity using beta-counting. Biodistribution of Gd was measured by inductively coupled plasma atomic emission spectroscopy (ICP-AES) and inductively coupled plasma sector field mass spectrometry (ICP-SF-MS). Results The injected dose was rapidly excreted, with only 1.0% remaining in the body at 24 h. The radioactivity thereafter was mainly associated with kidney cortex, liver, lung, muscle and skin, with a similar rate of clearance for both ligand and Gd from these tissues. The ratio between 14C-labelled substance and Gd was not significantly different from that of the injected substance in most tissue samples up to 24 h after injection; the ratio then slowly decreased. Conclusions The data clearly show that measurements of Gd concentration alone in tissue samples from animals injected with Gd-based contrast agents (GBCAs) cannot be used as a measure of Gd released from the ligand. To our knowledge, such measurements comparing Gd and ligand concentrations and distribution in tissue samples have not been published previously for any of the commercial GBCAs. PMID:20157815

  13. Myelodysplastic Syndromes and Iron Chelation Therapy

    PubMed Central

    Angelucci, Emanuele; Urru, Silvana Anna Maria; Pilo, Federica; Piperno, Alberto

    2017-01-01

    Over recent decades we have been fortunate to witness the advent of new technologies and of an expanded knowledge and application of chelation therapies to the benefit of patients with iron overload. However, extrapolation of learnings from thalassemia to the myelodysplastic syndromes (MDS) has resulted in a fragmented and uncoordinated clinical evidence base. We’re therefore forced to change our understanding of MDS, looking with other eyes to observational studies that inform us about the relationship between iron and tissue damage in these subjects. The available evidence suggests that iron accumulation is prognostically significant in MDS, but levels of accumulation historically associated with organ damage (based on data generated in the thalassemias) are infrequent. Emerging experimental data have provided some insight into this paradox, as our understanding of iron-induced tissue damage has evolved from a process of progressive bulking of organs through high-volumes iron deposition, to one of ‘toxic’ damage inflicted through multiple cellular pathways. Damage from iron may, therefore, occur prior to reaching reference thresholds, and similarly, chelation may be of benefit before overt iron overload is seen. In this review, we revisit the scientific and clinical evidence for iron overload in MDS to better characterize the iron overload phenotype in these patients, which differs from the classical transfusional and non-transfusional iron overload syndrome. We hope this will provide a conceptual framework to better understand the complex associations between anemia, iron and clinical outcomes, to accelerate progress in this area. PMID:28293409

  14. Spectrophotometric determination and removal of unchelated europium ions from solutions containing Eu-diethylenetriaminepentaacetic acid chelate-peptide conjugates.

    PubMed

    Elshan, N G R Dayan; Patek, Renata; Vagner, Josef; Mash, Eugene A

    2014-11-01

    Europium chelates conjugated with peptide ligands are routinely used as probes for conducting in vitro binding experiments. The presence of unchelated Eu ions in these formulations gives high background luminescence and can lead to poor results in binding assays. In our experience, the reported methods for purification of these probes do not achieve adequate removal of unchelated metal ions in a reliable manner. In this work, a xylenol orange-based assay for the quantification of unchelated metal ions was streamlined and used to determine levels of metal ion contamination as well as the success of metal ion removal on attempted purification. We compared the use of Empore chelating disks and Chelex 100 resin for the selective removal of unchelated Eu ions from several Eu-diethylenetriaminepentaacetic acid chelate-peptide conjugates. Both purification methods gave complete and selective removal of the contaminant metal ions. However, Empore chelating disks were found to give much higher recoveries of the probes under the conditions used. Related to the issue of probe recovery, we also describe a significantly more efficient method for the synthesis of one such probe using Rink amide AM resin in place of Tentagel S resin.

  15. In silico strategies for the selection of chelating compounds with potential application in metal-promoted neurodegenerative diseases

    NASA Astrophysics Data System (ADS)

    Rodríguez-Rodríguez, Cristina; Rimola, Albert; Alí-Torres, Jorge; Sodupe, Mariona; González-Duarte, Pilar

    2011-01-01

    The development of new strategies to find commercial molecules with promising biochemical features is a main target in the field of biomedicine chemistry. In this work we present an in silico-based protocol that allows identifying commercial compounds with suitable metal coordinating and pharmacokinetic properties to act as metal-ion chelators in metal-promoted neurodegenerative diseases (MpND). Selection of the chelating ligands is done by combining quantum chemical calculations with the search of commercial compounds on different databases via virtual screening. Starting from different designed molecular frameworks, which mainly constitute the binding site, the virtual screening on databases facilitates the identification of different commercial molecules that enclose such scaffolds and, by imposing a set of chemical and pharmacokinetic filters, obey some drug-like requirements mandatory to deal with MpND. The quantum mechanical calculations are useful to gauge the chelating properties of the selected candidate molecules by determining the structure of metal complexes and evaluating their stability constants. With the proposed strategy, commercial compounds containing N and S donor atoms in the binding sites and capable to cross the BBB have been identified and their chelating properties analyzed.

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

    PubMed

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

    2011-12-28

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

  17. Coordination properties of a metal chelator clioquinol to Zn(2+) studied by static DFT and ab initio molecular dynamics.

    PubMed

    Rodríguez-Santiago, Luis; Alí-Torres, Jorge; Vidossich, Pietro; Sodupe, Mariona

    2015-05-28

    Several lines of evidence supporting the role of metal ions in amyloid aggregation, one of the hallmarks of Alzheimer's disease (AD), have turned metal ion chelation into a promising therapeutic treatment. The design of efficient chelating ligands requires proper knowledge of the electronic and molecular structure of the complexes formed, including their hydration properties. Among various potential chelators, clioquinol (5-chloro-7-iodo-8-hydroxyquinoline, CQH) has been evaluated with relative success in in vitro experiments and even in phase 2 clinical trials. Clioquinol interacts with Zn(ii) to lead to a binary metal/ligand 1 : 2 stoichiometric complex in which the phenolic group of CQH is deprotonated, resulting in Zn(CQ)2 neutral complexes, to which additional water molecules may coordinate. In the present work, the coordinative properties of clioquinol in aqueous solution have been analyzed by means of static, minimal cluster based DFT calculations and explicit solvent ab initio molecular dynamics simulations. Results from static calculations accounting for solvent effects by means of polarized continuum models suggest that the preferred metal coordination environment is tetrahedral Zn(CQ)2, whereas ab initio molecular dynamics simulations point to quasi degenerate penta Zn(CQ)2(H2O) and hexa Zn(CQ)2(H2O)2 coordinated complexes. The possible reasons for these discrepant results are discussed.

  18. Engineered Recognition of Tetravalent Zirconium and Thorium by Chelator-Protein Systems: Toward Flexible Radiotherapy and Imaging Platforms.

    PubMed

    Captain, Ilya; Deblonde, Gauthier J-P; Rupert, Peter B; An, Dahlia D; Illy, Marie-Claire; Rostan, Emeline; Ralston, Corie Y; Strong, Roland K; Abergel, Rebecca J

    2016-11-21

    Targeted α therapy holds tremendous potential as a cancer treatment: it offers the possibility of delivering a highly cytotoxic dose to targeted cells while minimizing damage to surrounding healthy tissue. The metallic α-generating radioisotopes (225)Ac and (227)Th are promising radionuclides for therapeutic use, provided adequate chelation and targeting. Here we demonstrate a new chelating platform composed of a multidentate high-affinity oxygen-donating ligand 3,4,3-LI(CAM) bound to the mammalian protein siderocalin. Respective stability constants log β110 = 29.65 ± 0.65, 57.26 ± 0.20, and 47.71 ± 0.08, determined for the Eu(III) (a lanthanide surrogate for Ac(III)), Zr(IV), and Th(IV) complexes of 3,4,3-LI(CAM) through spectrophotometric titrations, reveal this ligand to be one of the most powerful chelators for both trivalent and tetravalent metal ions at physiological pH. The resulting metal-ligand complexes are also recognized with extremely high affinity by the siderophore-binding protein siderocalin, with dissociation constants below 40 nM and tight electrostatic interactions, as evidenced by X-ray structures of the protein:ligand:metal adducts with Zr(IV) and Th(IV). Finally, differences in biodistribution profiles between free and siderocalin-bound (238)Pu(IV)-3,4,3-LI(CAM) complexes confirm in vivo stability of the protein construct. The siderocalin:3,4,3-LI(CAM) assembly can therefore serve as a "lock" to consolidate binding to the therapeutic (225)Ac and (227)Th isotopes or to the positron emission tomography emitter (89)Zr, independent of metal valence state.

  19. Structures and Electronic Properties of Lithium Chelate-Based Ionic Liquids.

    PubMed

    Si, Dawei; Chen, Kexian; Yao, Jia; Li, Haoran

    2016-04-28

    The conformations, electronic properties, and interaction energies of four chelate-based ionic liquids [Li(EA)][Tf2N], [Li(HDA)][Tf2N], [Li(DEA)][Tf2N], and [Li(DOBA)][Tf2N] have been theoretically explored. The reliability of the located conformers has been confirmed via the comparison between the simulated and experimental infrared spectra. Our results show that the N-Li and O-Li coordinate bonds in cation are elongated as the numbers of coordinate heteroatoms of alkanolamine ligands to Li(+) increased. Also the binding energies between Li(+) and ligands are increased and the interaction energies between cations and Tf2N anion are decreased. The cation-anion interaction energies follow the order of [Li(DOBA)][Tf2N] < [Li(HDA)][Tf2N] < [Li(DEA)][Tf2N] < [Li(EA)][Tf2N], which fall within the energetic ranges of conventional ionic liquids. Interestingly, the strongest stabilization orbital interactions in these ionic liquids and their cations revealed by the natural bond orbital analysis lie in the interaction between the lone pair (LP) of the coordinate heteroatoms in ligands or anion as donors and the vacant valence shell nonbonding orbital (LP*) of Li(+) as acceptors, which are very different from that of conventional ionic liquids. Moreover, the charges transferred from cations to anion are quite similar, and the charge of Li(+) is proposed for possibly predicting the order of the interaction energies of ionic liquids in series. The present study allows for the deeper understanding the differences between chelate-based ionic liquids and conventional ionic liquids.

  20. 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.

  1. 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…

  2. Comparison of different chelating agents to enhance reductive Cr(VI) removal by pyrite treatment procedure.

    PubMed

    Kantar, Cetin; Ari, Cihan; Keskin, Selda

    2015-06-01

    New technologies involving in-situ chemical hexavalent chromium [Cr(VI)] reduction to trivalent chromium [Cr(III)] with natural Fe(II)-containing minerals can offer viable solutions to the treatment of wastewater and subsurface systems contaminated with Cr(VI). Here, the effects of five different chelating agents including citrate, EDTA, oxalate, tartrate and salicylate on reductive Cr(VI) removal from aqueous systems by pyrite were investigated in batch reactors. The Cr(VI) removal was highly dependent on the type of ligand used and chemical conditions (e.g., ligand concentration). While salicylate and EDTA had no or little effect on Cr(VI) removal, the ligands including citrate, tartrate and oxalate significantly enhanced Cr(VI) removal at pH < 7 relative to non-ligand systems. In general, the efficiency of organic ligands on Cr(VI) removal decreased in the order: citrate ≥ oxalate ≈ tartrate > EDTA > salicylate ≈ non-ligand system. Organic ligands enhanced Cr(VI) removal by 1) removing surface oxide layer via the formation of soluble Fe-Cr-ligand complexes, and 2) enhancing the reductive iron redox cycling for the regeneration of new surface sites. While citrate, oxalate and tartrate eliminated the formation of surface Cr (III)-Fe(III)-oxides, the surface phase Cr (III) species was observed in the presence of EDTA and salicylate indicating that Cr(III) complexed with EDTA and salicylate sorbed or precipitated onto pyrite surface, thereby blocking the access of CrO4(2-) to pyrite surface. The binding of Fe(III) with the disulfide reactive sites (≡Fe-S-S-Fe(III)) was essential for the regeneration of new surface sites through pyrite oxidation. Although Fe(III)-S species was detected at the pyrite surface in the presence of citrate, oxalate and tartrate, Fe(III) complexed with EDTA and salicylate did not strongly interact with the disulfide reactive sites due to the formation of non-sorbing Fe(III)-ligand complexes. The absence of surface Fe

  3. Synthesis of zirconia-immobilized copper chelates for catalytic decomposition of hydrogen peroxide and the oxidation of polycyclic aromatic hydrocarbons.

    PubMed

    Baldrian, Petr; Merhautová, Vera; Cajthaml, Tomás; Nerud, Frantisek; Stopka, Pavel; Gorbacheva, Olga; Hrubý, Martin; Benes, Milan J

    2008-08-01

    Chelating sorbents with diethylenetriaminepenta(methylene-phosphonic acid) (DTPMPA) and ethylenediaminetetraacetic acid ligands immobilized on zirconia matrix were prepared and subsequently saturated with Cu(II). All the Cu chelates catalyzed decomposition of H(2)O(2) yielding highly reactive hydroxyl radicals. All of them were also able to catalyze degradation of polycyclic aromatic hydrocarbons (anthracene, benzo[a]pyrene and benzo[b]fluoranthene). The most effective DTPMPA-based catalysts G-32 and G-35 (10 mg ml(-1) with 100 mmol H(2)O(2)) caused almost complete decomposition of 15 ppm anthracene and benzo[a]pyrene during a five day catalytic cycle at 30 degrees C. Anthracene-1,4-dione was the main product of anthracene oxidation by all catalysts. The catalysts were active in several cycles without regeneration.

  4. 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

  5. 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.

  6. 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.

  7. Liposomal Cu-64 labeling method using bifunctional chelators: poly(ethylene glycol) spacer and chelator effects.

    PubMed

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

    2010-07-21

    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 (64)Cu-TETA, (64)Cu-TETA-PEG2k, and (64)Cu-CB-TE2A-PEG2k liposomes showed that more than 86% of the radioactivity remains associated with the liposomal fraction after 48 h of incubation with mouse serum. The in vivo time activity curves (TAC) for the three liposomal formulations showed that approximately 50% of the radioactivity cleared from the blood pool in 16-18 h. As expected, the in vivo biodistribution and TAC data obtained at 48 h demonstrate that the clearance of radioactivity from the liver slows with the incorporation of a poly(ethylene glycol)-2k (PEG2k) brush. Our data suggest that (64)Cu-TETA and (64)Cu-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 (64)Cu-TETA-chelated liposomes rather than (64)Cu-CB-TE2A-chelated liposomes.

  8. 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

  9. IR, UV-Vis, magnetic and thermal characterization of chelates of some catecholamines and 4-aminoantipyrine with Fe(III) and Cu(II)

    NASA Astrophysics Data System (ADS)

    Mohamed, Gehad G.; Zayed, M. A.; El-Dien, F. A. Nour; El-Nahas, Reham G.

    2004-07-01

    The dopamine derivatives participate in the regulation of wide variety of physiological functions in the human body and in medication life. Increase and/or decrease in the concentration of dopamine in human body reflect an indication for diseases such as Schizophrenia and/or Parkinson diseases. α-Methyldopa (α-MD) in tablets is used in medication of hypertension. The Fe(III) and Cu(II) chelates with coupled products of adrenaline hydrogen tartarate (AHT), levodopa (LD), α-MD and carbidopa (CD) with 4-aminoantipyrine (4-AAP) are prepared and characterized. Different physico-chemical methods like IR, magnetic and UV-Vis spectra are used to investigate the structure of these chelates. Fe(III) form 1:2 (M:catecholamines) chelates while Cu(II) form 1:1 chelates. Catecholamines behave as a bidentate mono- or dibasic ligands in binding to the metal ions. IR spectra show that the catecholamines are coordinated to the metal ions in a bidentate manner with O,O donor sites of the phenolic - OH. Magnetic moment measurements reveal the presence of Fe(III) chelates in octahedral geometry while the Cu(II) chelates are square planar. The thermal decomposition of Fe(III) and Cu(II) complexes is studied using thermogravimetric (TGA) and differential thermal analysis (DTA) techniques. The water molecules are removed in the first step followed immediately by decomposition of the ligand molecules. The activation thermodynamic parameters, such as, energy of activation, enthalpy, entropy and free energy change of the complexes are evaluated and the relative thermal stability of the complexes are discussed.

  10. 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.

  11. DNA nuclease activity of Rev-coupled transition metal chelates.

    PubMed

    Joyner, Jeff C; Keuper, Kevin D; Cowan, J A

    2012-06-07

    Artificial nucleases containing Rev-coupled metal chelates based on combinations of the transition metals Fe(2+), Co(2+), Ni(2+), and Cu(2+) and the chelators DOTA, DTPA, EDTA, NTA, tripeptide GGH, and tetrapeptide KGHK have been tested for DNA nuclease activity. Originally designed to target reactive transition metal chelates (M-chelates) to the HIV-1 Rev response element mRNA, attachment to the arginine-rich Rev peptide also increases DNA-binding affinity for the attached M-chelates. Apparent K(D) values ranging from 1.7 to 3.6 µM base pairs for binding of supercoiled pUC19 plasmid DNA by Ni-chelate-Rev complexes were observed, as a result of electrostatic attraction between the positively-charged Rev peptide and negatively-charged DNA. Attachment of M-chelates to the Rev peptide resulted in enhancements of DNA nuclease activity ranging from 1-fold (no enhancement) to at least 13-fold (for Cu-DTPA-Rev), for the rate of DNA nicking, with second order rate constants for conversion of DNA(supercoiled) to DNA(nicked) up to 6 × 10(6) M(-1) min(-1), and for conversion of DNA(nicked) to DNA(linear) up to 1 × 10(5) M(-1) min(-1). Freifelder-Trumbo analysis and the ratios of linearization and nicking rate constants (k(lin)/k(nick)) revealed concerted mechanisms for nicking and subsequent linearization of plasmid DNA for all of the Rev-coupled M-chelates, consistent with higher DNA residency times for the Rev-coupled M-chelates. Observed rates for Rev-coupled M-chelates were less skewed by differing DNA-binding affinities than for M-chelates lacking Rev, as a result of the narrow range of DNA-binding affinities observed, and therefore relationships between DNA nuclease activity and other catalyst properties, such as coordination unsaturation, the ability to consume ascorbic acid and generate diffusible radicals, and the identity of the metal center, are now clearly illustrated in light of the similar DNA-binding affinities of all M-chelate-Rev complexes. This work

  12. Competitive binding of Pu and Am with bone mineral and novel chelating agents.

    PubMed

    Guilmette, R A; Hakimi, R; Durbin, P W; Xu, J; Raymond, K N

    2003-01-01

    Effective direct removal of actinides such as Pu and Am from bone in vivo has not been accomplished to date, even with the strong chelating agents CaNa3DTPA or ZnNa3DTPA. This study, using an established in vitro system, compared removal of Pu and Am bound to bone mineral by ZnNa3DTPA and 10 chelating agents designed specifically to sequester actinides, including Pu and Am. Ligands tested were tetra, hexa, and octadentate, with linear or branched backbones containing sulfocatechol [CAM(S)], hydroxycatechol [CAM(C)], hydroxipyridinone (1,2-HOPO, Me-3,2-HOPO), or hydroxamate functional groups. The wide range of Pu and Am removal exhibited by the test ligands generally agreed with their metal coordination and chemical properties. The most effective agents for Pu (100 microM concentration, 24-48 h contact) are all octadentate as follows: 3,4,3-LICAM(S) (54% unbound); 3,4,3-LICAM(C) (6.2%); 3,4,3-LI(1,2-HOPO) (3.8%); H(2,2)-(Me-3,2-HOPO) (2.2%) and DFO-(1,2-HOPO) (1.8%). The other ligands removed less than 1% of the bound Pu; and ZnNa3DTPA removed only 0.086%. The most effective ligands for Am removal (100 microM, 24-48 h contact) are as follows: octadentate H(2,2)-(Me-3,2-HOPO) (21% unbound); 3,4,3-LI(1,2-HOPO) (14.5%) and 3,4,3-LICAM(C) (5.9%); hexadentate TREN-(Me-3,2-HOPO) and TREN-(1,2-HOPO) (9.6%); and tetradentate 5-LIO(Me-3,2-HOPO) (5.2%). Am removal by ZnNa3DTPA was about 1.4%. Among the ligands presently considered for possible human use, only 3,4,3-LI(1,2-HOPO) removed potentially useful amounts of both Pu and Am from bone mineral.

  13. Competitive binding of plutonium and americium with bone mineral and novel chelating agents

    SciTech Connect

    Guilmette, Ray A.; Hakimi, R.; Durbin, P. W.; Xu, J.; Raymond, K. N.

    2002-01-01

    Effective direct removal of actinides such as Pu and Am from bone in vivo has not been accomplished to date, even with the strong chelating agents CaNa{sub 3}DTPA or ZnNa{sub 3}DTPA. This study, using an established in vitro system, compared removal of Pu and Am bound to bone mineral by ZnNa{sub 3}DTPA and 10 chelating agents designed specifically to sequester actinides, including Pu and Am. Ligands tested were tetra-, hexa, and octadentate with linear or branched backbones containing sulfocatechol [CAM(S)], hydroxycatechol [CAM(C)], hydroxipyridinone (1,2-HOPO, Me-3,2-HOPO), or hydroxamate functional groups. The wide range of Pu and Am removal exhibited by the test ligands generally agreed with their metal coordination and chemical properties. The most effective agents for Pu (100 {micro}M concentration, 24-48 h contact) are all octadentate as follows: 3,4,3-LICAM(S) (54% unbound), 3,4,3-LICAM(C) (6.2%), 3,4,3-LI(1,2-HOPO) (3.8%), H(2,2)-(Me-3,2-HOPO) (2.2%) and DFO-(1,2-HOPO) (1.8%). The other ligands removed less than 1% of the bound Pu, and ZnNa{sub 3}DTPA removed only 0.086%. The most effective ligands for Am removal (100 {micro}M, 24-48 h contact) are as follows: octadentate H(2,2)-(Me-3,2-HOPO) (21% unbound), 3,4,3-LI(1,2-HOPO) (14.5%), and 3,4,3-LICAM(C) (5.9%), hexadentate TREN-(Me-3,2-HOPO) and TREN-(1,2-HOPO) (9.6%), and tetradentate 5-LIO(Me-3,2-HOPO) (5.2%). Am removal by ZnNa{sub 3}DTPA was about 1.4%. Among the ligands presently considered for possible human use, only 3,4,3-LI(1,2-HOPO) removed potentially useful amounts of both Pu and Am from bone mineral.

  14. Coupling the folding of a β-hairpin with chelation-enhanced luminescence of Tb(III) and Eu(III) ions for specific sensing of a viral RNA†

    PubMed Central

    Penas, Cristina; Mascareñas, José L; Vázquez, M. Eugenio

    2016-01-01

    Rational modification of a natural RNA-binding peptide with a lanthanide EDTA chelator, and a phenanthroline ligand yields a highly selective luminescent sensor. The sensing mechanism relies on the RNA-triggered folding of the peptide into a β-hairpin, which promotes the coordination of the phenanthroline sensitizer, and the efficient sensitization of complexed lanthanide ions. PMID:27293537

  15. Affinity purification of copper chelating peptides from chickpea protein hydrolysates.

    PubMed

    Megías, Cristina; Pedroche, Justo; Yust, Maria M; Girón-Calle, Julio; Alaiz, Manuel; Millan, Francisco; Vioque, Javier

    2007-05-16

    Chickpea protein hydrolysates obtained with alcalase and flavourzyme were used for purification of copper chelating peptides by affinity chromatography using copper immobilized on solid supports. The chelating activity of purified peptides was indirectly measured by the inhibition of beta-carotene oxidation in the presence of copper. Two protein hydrolysates, obtained after 10 and 100 min of hydrolysis, were the most inhibitory of beta-carotene oxidation. Purified copper chelating peptides from these protein hydrolysates contained 19.7 and 35.1% histidine, respectively, in comparison to 2.7 and 2.6% in the protein hydrolysates. Chelating peptides from hydrolysate obtained after 10 min of hydrolysis were the most antioxidative being 8.3 times more antioxidative than the hydrolysate, while chelating peptides purified from protein hydrolysate obtained after 100 min were 3.1 times more antioxidative than its hydrolysate. However, the histidine content was higher in peptides derived from the 100 min hydrolysate (19.7 against 35.1% in 10 min hydrolysate), indicating that this amino acid is not the only factor involved in the antioxidative activity, and other factors such as peptide size or amino acid sequence are also determinant. This manuscript shows that affinity chromatography is a useful procedure for purification of copper chelating peptides. This method can be extended to other metals of interest in nutrition, such as calcium, iron, or zinc. Purified chelating peptides, in addition to their antioxidative properties, may also be useful in food mineral fortification for increasing the bioavailability of these metals.

  16. 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

  17. In vitro copper-chelating properties of flavonoids.

    PubMed

    Ríha, Michal; Karlícková, Jana; Filipský, Tomáš; Jahodár, Ludek; Hrdina, Radomír; Mladenka, Premysl

    2014-10-01

    Copper is an indispensable trace element for human body and the association between a disruption of copper homeostasis and a series of pathological states has been well documented. Flavonoids influence the human health in a complex way and the chelation of transient metal ions indisputably contributes to their mechanism of the action, however, the information about their copper-chelating properties have been sparse. This in vitro study was thus aimed at the detailed examination of flavonoids-copper interactions by two spectrophotometric assays at four (patho)physiologically relevant pH conditions (4.5-7.5), with the emphasis on the structure-activity relationship. The tested flavonoids were compared with the clinically used copper chelator, trientine. Most of the 26 flavonoids chelated copper ions, however, in a variable extent. Only flavones and flavonols were able to form stable complexes with both cupric and cuprous ions. The 3-hydroxy-4-keto group and 5,6,7-trihydroxyl group represented the most efficient chelation sites in flavonols and flavones, respectively, and the 2,3-double bond was essential for the stable copper chelation. Interestingly, the 3´,4´-dihydroxyl (catechol) group was associated only with a weak activity. Although none of the tested flavonoids were more potent than trientine at physiological or slightly acidic conditions, 3-hydroxyflavone, kaempferol and partly baicalein surpassed trientine at acidic conditions. Conclusively, flavonoids containing appropriate structural features were efficient copper chelators and some of them were even more potent than trientine under acidic conditions.

  18. 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

  19. Synthesis and optical properties of macrocyclic lanthanide(III) chelates as new reagents for luminescent biolabeling.

    PubMed

    Deslandes, Sébastien; Galaup, Chantal; Poole, Robert; Mestre-Voegtlé, Béatrice; Soldevila, Stéphanie; Leygue, Nadine; Bazin, Hervé; Lamarque, Laurent; Picard, Claude

    2012-11-14

    The convenient and efficient synthesis of two macrocyclic ligands (15- and 18-membered) based on a dipyrido-6,7,8,9-tetrahydrophenazine (dpqc) or 2,2':6',2''-terpyridine (tpy) heterocycle and a DTTA (diethylenetriaminetriacetic acid) skeleton is described. In these ligands the DTTA skeleton contains an additional extracyclic functionality (NH(2) group) suitable for covalent attachment to bioactive molecules. These octa- and nonadentate ligands form very stable and luminescent neutral lanthanide complexes in aqueous solutions at physiological pH. The corresponding Eu(III) and Tb(III) complexes are characterized by a maximum absorption wavelength compatible with nitrogen laser excitation (337 nm) and attractive lifetimes and quantum yields. Further introduction of a maleimide bioconjugatable handle in the Eu(III) complexes was investigated and a valuable luminescence brightness above 1500 dm(3) mol(-1) cm(-1) at 337 nm was obtained with the corresponding Eu(III) tpy-derivative. Finally, these two luminescent chelates were grafted onto thiol residues of a model antibody (Mab GSS11) without loss of their luminescent properties.

  20. Chelating ligand-mediated hydrothermal synthesis of samarium orthovanadate with decavanadate as vanadium source.

    PubMed

    Li, Quanguo; Zuo, Wenli; Li, Feng

    2013-01-01

    A new ethylenediaminetetraacetic acid- (EDTA-) mediated hydrothermal route to prepare chrysanthemum-shaped samarium orthovanadate (SmVO₄) nanocrystals with decavanadate (K₆V₁₀O₂₈·9H₂O) as vanadium source has been developed. The present hydrothermal approach is simple and reproducible and employs a relatively mild reaction temperature. The EDTA, pH value, and temperature of the reaction systems play important roles in determining the morphologies and growth process of the SmVO₄ products. The products have been characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR), photoluminescence spectra (PL), and UV-Vis spectroscopy.

  1. Straightforward synthesis of novel cyclic metallasiloxanes supported by an N,C,N-chelating ligand.

    PubMed

    Fridrichová, Adéla; Mairychová, Barbora; Padělková, Zdeňka; Lyčka, Antonín; Jurkschat, Klaus; Jambor, Roman; Dostál, Libor

    2013-12-14

    The reaction of an N,C,N-intramolecularly coordinated tin(IV) carbonate LSn(Ph)(CO3) (1) and antimony(III) and bismuth(III) oxides (LMO)2 (where M = Sb (2), Bi (3) and L = C6H3-2,6-(CH2NMe2)2) with (HO)SiPh2(O)SiPh2(OH) in 1 : 1 (in the case of 1) or 1 : 2 molar ratio (in the cases of 2 and 3) gave the metallasiloxanes cyclo-LSn(Ph)(OSiPh2)2O (4) and cyclo-LM(OSiPh2)2O (where M = Sb (6) and Bi (7)) containing six-membered MSi2O3 rings. Alternatively, the compounds 4, 6 and 7 can be also prepared reacting Ph2Si(OH)2 and compounds 1, 2 and 3, respectively, in the molar ratio of either 2 : 1 (for 4) or 4 : 1 (for 6 and 7). The reaction of Ph2Si(OH)2 with 1 in 1 : 1 molar ratio gave cyclo-Ph2Si(OSnL(Ph)O)2SiPh2 (5) containing an eight-membered Sn2Si2O4 stannasiloxane ring. The analogous eight-membered stibasiloxane derivative cyclo-Ph2Si(OSbLO)2SiPh2 (8) was obtained as well, while attempts to synthesize the bismuth analogue failed. Compounds 1-3 react with the siloxane cyclo-(Me2SiO)3 providing either eight-membered metallasiloxanes cyclo-LSn(Ph)(OSiMe2O)2SiMe2 (9) and cyclo-LSb(OSiMe2O)2SiMe2 (10) or the six-membered bismutasiloxane cyclo-LBi(OSiMe2)2O (11). All compounds were characterized with the help of elemental analysis, (1)H, (13)C, (29)Si and (119)Sn NMR spectroscopy, and single crystal X-ray diffraction analyses (except 9 and 10).

  2. Ligand substitution reactions of a phenolic quinolyl hydrazone; oxidovanadium (IV) complexes

    PubMed Central

    2011-01-01

    Background Quinoline ring has therapeutic and biological activities. Quinolyl hydrazones constitute a class of excellent chelating agents. Recently, the physiological and biological activities of quinolyl hydrazones arise from their tendency to form metal chelates with transition metal ions. In this context, we have aimed to study the competency effect of a phenolic quinolyl hydrazone (H2L; primary ligand) with some auxiliary ligands (Tmen, Phen or Oxine; secondary ligands) towards oxidovanadium (IV) ions. Results Mono- and binuclear oxidovanadium (IV) - complexes were obtained from the reaction of a phenolic quinolyl hydrazone with oxidovanadium (IV)- ion in absence and presence of N,N,N',N'- tetramethylethylenediamine (Tmen), 1,10-phenanthroline (Phen) or 8-hydroxyquinoline (Oxine). The phenolic quinolyl hydrazone ligand behaves as monobasic bidentate (NO- donor with O- bridging). All the obtained complexes have the preferable octahedral geometry except the oxinato complex (2) which has a square pyramid geometry with no axial interaction; the only homoleptic complex in this study. Conclusion The ligand exchange (substitution/replacement) reactions reflect the strong competency power of the auxiliary aromatic ligands (Phen/Oxine) compared to the phenolic quinolyl hydrazone (H2L) towards oxidovanadium (IV) ion; (complexes 2 and 3). By contrast, in case of the more flexible aliphatic competitor (Tmen), an adduct was obtained (4). The obtained complexes reflect the strength of the ligand field towards the oxidovanadium (IV)- ion; Oxine or Phen >> phenolic hydrazone (H2L) > Tmen. PMID:21846387

  3. Ratiometric luminescent detection of bacterial spores with terbium chelated semiconducting polymer dots.

    PubMed

    Li, Qiong; Sun, Kai; Chang, Kaiwen; Yu, Jiangbo; Chiu, Daniel T; Wu, Changfeng; Qin, Weiping

    2013-10-01

    We report a ratiometric fluorescent sensor based on semiconducting polymer dots chelated with terbium ions to detect bacterial spores in aqueous solution. Fluorescent polyfluorene (PFO) dots serve as a scaffold to coordinate with lanthanide ions that can be sensitized by calcium dipicolinate (CaDPA), an important biomarker of bacterial spores. The absorption band of PFO dots extends to deep UV region, allowing both the reference and the sensitizer can be excited with a single wavelength (~275 nm). The fluorescence of PFO remains constant as a reference, while the Tb(3+) ions exhibit enhanced luminescence upon binding with DPA. The sharp fluorescence peaks of β-phase PFO dots and the narrow-band emissions of Tb(3+) ions enable ratiometric and sensitive CaDPA detection with a linear response over nanomolar concentration and a detection limit of ~0.2 nM. The Pdots based sensor also show excellent selectivity to CaDPA over other aromatic ligands. Our results indicate that the Tb(3+) chelated Pdots sensor is promising for sensitive and rapid detection of bacterial spores.

  4. Metal chelate affinity precipitation of RNA and purification of plasmid DNA

    NASA Technical Reports Server (NTRS)

    Balan, Sindhu; Murphy, Jason; Galaev, Igor; Kumar, Ashok; Fox, George E.; Mattiasson, Bo; Willson, Richard C.

    2003-01-01

    The affinity of metal chelates for amino acids, such as histidine, is widely used in purifying proteins, most notably through six-histidine 'tails'. We have found that metal affinity interactions can also be applied to separation of single-stranded nucleic acids through interactions involving exposed purines. Here we describe a metal affinity precipitation method to resolve RNA from linear and plasmid DNA. A copper-charged copolymer of N-isopropyl acrylamide (NIPAM) and vinyl imidazole (VI) is used to purify plasmid from an alkaline lysate of E. coli. The NIPAM units confer reversible solubility on the copolymer while the imidazole chelates metal ions in a manner accessible to interaction with soluble ligands. RNA was separated from the plasmid by precipitation along with the polymer in the presence of 800 mM NaCl. Bound RNA could be recovered by elution with imidazole and separated from copolymer by a second precipitation step. RNA binding showed a strong dependence on temperature and on the type of buffer used.

  5. Efficient Route to Highly Water-Soluble Aromatic Cyclic Hydroxamic Acid Ligands

    SciTech Connect

    Seitz, Michael; Raymond, Kenneth N.

    2008-02-06

    2-Hydroxyisoquinolin-1-one (1,2-HOIQO) is a new member of the important class of aromatic cyclic hydroxamic acid ligands which are widely used in metal sequestering applications and metal chelating therapy. The first general approach for the introduction of substituents at the aromatic ring of the chelating moiety is presented. As a useful derivative, the highly water-soluble sulfonic acid has been synthesized by an efficient route that allows general access to 1,2-HOQIO 3-carboxlic acid amides, which are the most relevant for applications.

  6. Red-Emitting Tetracoordinate Organoboron Chelates: Synthesis, Photophysical Properties, and Fluorescence Microscopy.

    PubMed

    Pais, Vânia F; Ramírez-López, Pedro; Romero-Arenas, Antonio; Collado, Daniel; Nájera, Francisco; Pérez-Inestrosa, Ezequiel; Fernández, Rosario; Lassaletta, José M; Ros, Abel; Pischel, Uwe

    2016-10-21

    Seven tetracoordinate organoboron fluorophores with heterobiaryl N,O- or N,N-chelate ligands were prepared and photophysically characterized (in toluene). The electronic variation of the heteroaromatic moiety provided a means for the fine-tuning of the UV/vis absorption and emission spectra. In the most interesting cases, the spectra were red-shifted to maximum absorbance at wavelengths longer than 500 nm and emission maxima between 620 and 660 nm. The pronounced intramolecular charge-transfer character of the dyes yielded large Stokes shifts (3500-5100 cm(-1)), while maintaining appreciable fluorescence quantum yields of up to 0.2 for emission maxima longer than 600 nm. The lipophilic character of the dyes enabled their application as stains of vesicle substructures in confocal fluorescence microscopy imaging.

  7. Spectral, Magnetic and Biological Studie on Some Bivalent 3d Metal Complexes of Hydrazine Derived Schiff-Base Ligands

    PubMed Central

    Sherazi, Syed K. A.

    1997-01-01

    Metal(II) complexes of hydrazine derived Schiff-base ligands of the type M(L)2Cl2 where M = Co, Cu, Ni and Zn and L = L1 and L2 have been prepared and characterised by molar conductance, magnetic moment, elemental analysis and electronic, IR, H-NMR and 13C spectral data.The different modes of chelation of the ligands and their comparative biological properties against different bacterial species are reported. PMID:18475770

  8. 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.

  9. 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.

  10. 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.

  11. Removal of heavy metals from water effluents using supermacroporous metal chelating cryogels.

    PubMed

    Onnby, Linda; Giorgi, Camilla; Plieva, Fatima M; Mattiasson, Bo

    2010-01-01

    Applications of IDA in, for example, immobilized metal ion affinity chromatography for purification of His-tagged proteins are well recognized. The use of IDA as an efficient chelating adsorbent for environmental separations, that is, for the capture of heavy metals, is not studied. Adsorbents based on supermacroporous gels (cryogels) bearing metal chelating functionalities (IDA residues and ligand derived from derivatization of epoxy-cryogel with tris(2-aminoethyl)amine followed by the treatment with bromoacetic acid (defined as TBA ligand)) have been prepared and evaluated on capture of heavy metal ions. The cryogels were prepared in plastic carriers, resulting in desired mechanical stability and named as macroporous gel particles (MGPs). Sorption and desorption experiments for different metals (Cu²+, Zn²+, Cd²+, and Ni²+ with IDA adsorbent and Cu²+ and Zn²+ with TBA adsorbent) were carried out in batch and monolithic modes, respectively. Obtained capacities with Cu²+ were 74 μmol/mL (TBA) and 19 μmol/mL gel (IDA). The metal removal was higher for pH values between pH 3 and 5. Both adsorbents showed improved sorption at lower temperatures (10°C) than at higher (40°C) and the adsorption significantly dropped for the TBA adsorbent and Zn²+ at 40°C. Desorption of Cu²+ by using 1 M HCl and 0.1 M EDTA was successful for the IDA adsorbent whereas the desorption with the TBA adsorbent needs further attention. The result of this work has demonstrated that MGPs are potential treatment alternatives within the field of environmental separations and the removal of heavy metals from water effluents.

  12. Species-dependent chelation of (241)Am by DTPA Di-ethyl ester.

    PubMed

    Huckle, James E; Sadgrove, Matthew P; Mumper, Russell J; Jay, Michael

    2015-04-01

    Diethylenetriaminepentaacetic acid (DTPA) is an FDA-approved chelating agent for enhancing the elimination of transuranic elements such as americium from the body. Early access to therapy minimizes deposition of these radionuclides in tissues such as the bone. Due to its poor oral bioavailability, DTPA is administered as an IV injection, delaying access. Therefore, a diethyl-ester analog of DTPA, named C2E2, was synthesized as a means to increase oral absorption. As a hexadentate ligand, it was hypothesized that C2E2 was capable of binding americium directly. Therefore, the protonation constants and americium stability constant for C2E2 were determined by potentiometric titration and a solvent extraction method, respectively. C2E2 was shown to bind americium with a log K of 19.6. The concentrations of C2E2, its metabolite C2E1, and DTPA required to achieve effective binding in rat, beagle, and human plasma were studied in vitro. Dose response curves for each ligand were established, and the 50% maximal effective concentrations were determined for each species. As expected, higher concentrations of C2E2 were required to achieve the same degree of binding as DTPA. The results indicated that chelation in beagle plasma is more representative of the human response than rats. Finally, the pharmacokinetics of C2E2 were investigated in beagles, and the data was fit to a two-compartment model with elimination from the central compartment, along with first-order absorption. Based on the in vitro data, a 100 mg kg dose of C2E2 can be expected to have an effective duration of action of 3.8 h in beagles.

  13. Species-Dependent Chelation of 241Am by DTPA Di-ethyl Ester

    PubMed Central

    Huckle, James E.; Sadgrove, Matthew P.; Mumper, Russell J.; Jay, Michael

    2014-01-01

    Diethylenetriaminepentaacetic acid (DTPA) is an FDA approved chelating agent for enhancing the elimination of transuranic elements such as americium from the body. Early access to therapy minimizes deposition of these radionuclides in tissues such as the bone. Due to its poor oral bioavailability, DTPA is administered as an IV injection, delaying access. Therefore a diethyl-ester analog of DTPA, named C2E2, was synthesized as a means to increase oral absorption. As a hexadentate ligand, it was hypothesized that C2E2 was capable of binding americium directly. Therefore, the protonation constants and americium stability constant for C2E2 were determined by potentiometric titration and a solvent extraction method, respectively. C2E2 was shown to bind americium with a log K of 19.6. The concentrations of C2E2, its metabolite C2E1, and DTPA required to achieve effective binding in rat, beagle, and human plasma were studied in vitro. Dose response curves for each ligand were established and the 50% maximal effective concentrations were determined for each species. As expected, higher concentrations of C2E2 were required to achieve the same degree of binding as DTPA. The results indicated that chelation in beagle plasma is more representative of the human response than rats. Finally, the pharmacokinetics of C2E2 were investigated in beagles and the data was fit to a two-compartment model with elimination from the central compartment, along with first-order absorption. Based on the in vitro data, a 100 mg kg−1 dose of C2E2 can be expected to have an effective duration of action of 3.8 hours in beagles. PMID:25706138

  14. Site-specific conjugation of a lanthanide chelator and its effects on the chemical synthesis and receptor binding affinity of human relaxin-2 hormone

    SciTech Connect

    Shabanpoor, Fazel; Bathgate, Ross A.D.; Belgi, Alessia; Chan, Linda J.; Nair, Vinojini B.; Wade, John D.; Hossain, Mohammed Akhter

    2012-04-06

    Highlights: Black-Right-Pointing-Pointer A mono-Eu-DTPA conjugated peptide ligand, Eu-DTPA-(A)-H2, has been developed. Black-Right-Pointing-Pointer The choice of a site for incorporation of a chelator is critical. Black-Right-Pointing-Pointer The labeled peptide retains full activity at the RXFP1 receptor. Black-Right-Pointing-Pointer It is markedly cheaper to produce and easier to use than radioactive probes. -- Abstract: Diethylenetriamine pentaacetic acid (DTPA) is a popular chelator agent for enabling the labeling of peptides for their use in structure-activity relationship study and biodistribution analysis. Solid phase peptide synthesis was employed to couple this commercially available chelator at the N-terminus of either the A-chain or B-chain of H2 relaxin. The coupling of the DTPA chelator at the N-terminus of the B-chain and subsequent loading of a lanthanide (europium) ion into the chelator led to a labeled peptide (Eu-DTPA-(B)-H2) in low yield and having very poor water solubility. On the other hand, coupling of the DTPA and loading of Eu at the N-terminus of the A-chain led to a water-soluble peptide (Eu-DTPA-(A)-H2) with a significantly improved final yield. The conjugation of the DTPA chelator at the N-terminus of the A-chain did not have any impact on the secondary structure of the peptide determined by circular dichroism spectroscopy (CD). On the other hand, it was not possible to determine the secondary structure of Eu-DTPA-(B)-H2 because of its insolubility in phosphate buffer. The B-chain labeled peptide Eu-DTPA-(B)-H2 required solubilization in DMSO prior to carrying out binding assays, and showed lower affinity for binding to H2 relaxin receptor, RXFP1, compared to the water-soluble A-chain labeled peptide Eu-DTPA-(A)-H2. The mono-Eu-DTPA labeled A-chain peptide, Eu-DTPA-(A)-H2, thus can be used as a valuable probe to study ligand-receptor interactions of therapeutically important H2 relaxin analogs. Our results show that it is critical to

  15. Quinap and congeners: atropos PN ligands for asymmetric catalysis.

    PubMed

    Fernández, Elena; Guiry, Patrick J; Connole, Kieran P T; Brown, John M

    2014-06-20

    Among the range of P,N-chelating ligands that have been employed in asymmetric catalysis, those relying on atropisomerism for the stability of individual enantiomers form a definable class. These APN (atropos P,N) ligands require a specific type of biaryl, with one component carrying a pendant phosphine unit, most commonly diaryl substituted, and the other bearing an sp(2)-nitrogen adjacent to the biaryl link. When substituents in the biaryl inhibit rotation about the linking bond, stable nonracemizing six-membered ring chelates can be formed. This Perspective relates the background to the initial synthesis in 1993 of Quinap, the original member of the series, and initial observations on its effectiveness in asymmetric catalysis. The current state of play in development of syntheses of this and other members of the APN ligand family is assessed, and their applications in asymmetric catalysis are presented. These include hydroboration and diboration of alkenes, 1,3-dipolar cycloadditions, alkynylation of iminium salts in a three-component (A(3)) condensation, and conjugate additions of Cu acetylides.

  16. Lead chelation to immobilised Symphytum officinale L. (comfrey) root tannins.

    PubMed

    Chin, Lily; Leung, David W M; Harry Taylor, H

    2009-07-01

    Reported correlations between tannin level and metal accumulation within plant tissues suggest that metal-chelating tannins may help plants to tolerate toxic levels of heavy metal contaminants. This paper supports such correlations using a new method that demonstrated the ability of plant tannins to chelate heavy metals, and showed that the relative levels of tannins in tissues were quantitatively related to lead chelation in vitro. Using this in vitro metal chelation method, we showed that immobilised tannins prepared from lateral roots of Symphytum officinale L., that contained high tannin levels, chelated 3.5 times more lead than those from main roots with lower tannin levels. This trend was confirmed using increasing concentrations of tannins from a single root type, and using purified tannins (tannic acid) from Chinese gallnuts. This study presents a new, simple, and reliable method that demonstrates direct lead-tannin chelation. In relation to phytoremediation, it also suggests that plant roots with more 'built-in' tannins may advantageously accumulate more lead.

  17. 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.

  18. Iron chelators target both proliferating and quiescent cancer cells

    PubMed Central

    Fryknäs, Mårten; Zhang, Xiaonan; Bremberg, Ulf; Senkowski, Wojciech; Olofsson, Maria Hägg; Brandt, Peter; Persson, Ingmar; D’Arcy, Padraig; Gullbo, Joachim; Nygren, Peter; Schughart, Leoni Kunz; Linder, Stig; Larsson, Rolf

    2016-01-01

    Poorly vascularized areas of solid tumors contain quiescent cell populations that are resistant to cell cycle-active cancer drugs. The compound VLX600 was recently identified to target quiescent tumor cells and to inhibit mitochondrial respiration. We here performed gene expression analysis in order to characterize the cellular response to VLX600. The compound-specific signature of VLX600 revealed a striking similarity to signatures generated by compounds known to chelate iron. Validation experiments including addition of ferrous and ferric iron in excess, EXAFS measurements, and structure activity relationship analyses showed that VLX600 chelates iron and supported the hypothesis that the biological effects of this compound is due to iron chelation. Compounds that chelate iron possess anti-cancer activity, an effect largely attributed to inhibition of ribonucleotide reductase in proliferating cells. Here we show that iron chelators decrease mitochondrial energy production, an effect poorly tolerated by metabolically stressed tumor cells. These pleiotropic features make iron chelators an attractive option for the treatment of solid tumors containing heterogeneous populations of proliferating and quiescent cells. PMID:27924826

  19. 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.

  20. 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.

  1. Surface modification of MoS2 nanoparticles with ionic liquid-ligands: towards highly dispersed nanoparticles.

    PubMed

    Osim, Wilton; Stojanovic, Anja; Akbarzadeh, Johanna; Peterlik, Herwig; Binder, Wolfgang H

    2013-10-18

    Highly dispersible MoS2 nanoparticles have been prepared via surface-modification using a novel tetraethylene glycol-based ionic liquid containing a chelating moiety attached to the cation. The choice of the respective ligand enables the generation of highly dispersible MoS2 nanoparticles with either polar, hydrophobic or "amphiphilic" surfaces, forming highly stable dispersions or microemulsions.

  2. Protection against hydrogen peroxide-mediated cytotoxicity in Friedreich's ataxia fibroblasts using novel iron chelators of the 2-pyridylcarboxaldehyde isonicotinoyl hydrazone class.

    PubMed

    Lim, C K; Kalinowski, D S; Richardson, D R

    2008-07-01

    Iron-loading diseases remain an important problem because of the toxicity of iron-catalyzed redox reactions. Iron loading occurs in the mitochondria of Friedreich's ataxia (FA) patients and may play a role in its pathogenesis. This suggests that iron chelation therapy could be useful. We developed previously the lipophilic iron chelators known as the 2-pyridylcarboxaldehyde isonicotinoyl hydrazone (PCIH) ligands and identified 2-pyridylcarboxaldehyde 2-thiophenecarboxyl hydrazone (PCTH) as the most promising analog. Hence, this study assessed the efficacy of PCTH and other PCIH analogs compared with various chelators, including deferiprone and desferrioxamine (DFO). Age- and sex-matched control and FA fibroblasts were preincubated with iron chelators and subsequently challenged with 50 microM H2O2 for up to 24 h. The current study demonstrates an interesting structure-activity relationship among the closely related PCIH series of ligands, with only PCTH being highly effective at preventing H2O2-induced cytotoxicity. PCTH increased FA fibroblast cell viability by up to 70%, whereas DFO rescued viability by 1 to 5% only. Hence, PCTH, which was well tolerated by cells was far more effective than DFO at preventing oxidative stress. It is noteworthy that kinetic studies demonstrated PCTH to rapidly penetrate cells to induce 59Fe efflux, whereas DFO, PCIH, 2-pyridylcarboxaldehyde benzoyl hydrazone, and 2-pyridylcarboxaldehyde m-bromobenzoyl hydrazone were far slower, indicating it is the rate of chelator permeation that is crucial for protection against H2O2. In addition, PCTH was found to be as effective as or more effective than conventional radical scavengers or the antioxidant idebenone (which has undergone clinical trials) at protecting cells against H2O2-mediated cytotoxicity. These findings further indicate the potential of PCTH for treatment of iron overload.

  3. Synthesis and antimalarial activity of metal complexes of cross-bridged tetraazamacrocyclic ligands

    PubMed Central

    Hubin, Timothy J.; Amoyaw, Prince N. -A.; Roewe, Kimberly D.; Simpson, Natalie C.; Maples, Randall D.; Carder Freeman, TaRynn N.; Cain, Amy N.; Le, Justin G.; Archibald, Stephen J.; Khan, Shabana I.; Tekwani, Babu L.; Khan, M. O. Faruk

    2014-01-01

    Using transition metals such as manganese(II), iron(II), cobalt(II), nickel(II), copper(II), and zinc(II), several new metal complexes of cross-bridged tetraazamacrocyclic chelators namely, cyclen- and cyclam-analogs with benzyl groups, were synthesized and screened for in vitro antimalarial activity against chloroquine-resistant (W2) and chloroquine-sensitive (D6) strains of Plasmodium falciparum. The metal-free chelators tested showed little or no antimalarial activity. All the metal complexes of the dibenzyl cross-bridged cyclam ligand exhibited potent antimalarial activity. The Mn2+ complex of this ligand was the most potent with IC50s of 0.127 and 0.157 µM against the chloroquine-sensitive (D6) and chloroquine-resistant (W2) P. falciparum strains, respectively. In general, the dibenzyl hydrophobic ligands showed better antimalarial activity compared to the activity of monobenzyl ligands, potentially because of their higher lipophilicity and thus better cell penetration ability. The higher antimalarial activity displayed by the manganese complex for the cyclam ligand in comparison to that of the cyclen, correlates with the larger pocket of cyclam compared to that of cyclen which produces a more stable complex with the Mn2+. Few of the Cu2+ and Fe2+ complexes also showed improvement in activity but Ni2+, Co2+ and Zn2+ complexes did not show any improvement in activity upon the metal-free ligands for anti-malarial development. PMID:24857776

  4. Regional siderosis: a new challenge for iron chelation therapy

    PubMed Central

    Cabantchik, Zvi Ioav; Munnich, Arnold; Youdim, Moussa B.; Devos, David

    2013-01-01

    The traditional role of iron chelation therapy has been to reduce body iron burden via chelation of excess metal from organs and fluids and its excretion via biliary-fecal and/or urinary routes. In their present use for hemosiderosis, chelation regimens might not be suitable for treating disorders of iron maldistribution, as those are characterized by toxic islands of siderosis appearing in a background of normal or subnormal iron levels (e.g., sideroblastic anemias, neuro- and cardio-siderosis in Friedreich ataxia- and neurosiderosis in Parkinson's disease). We aimed at clearing local siderosis from aberrant labile metal that promotes oxidative damage, without interfering with essential local functions or with hematological iron-associated properties. For this purpose we introduced a conservative mode of iron chelation of dual activity, one based on scavenging labile metal but also redeploying it to cell acceptors or to physiological transferrin. The “scavenging and redeployment” mode of action was designed both for correcting aberrant iron distribution and also for minimizing/preventing systemic loss of chelated metal. We first examine cell models that recapitulate iron maldistribution and associated dysfunctions identified with Friedreich ataxia and Parkinson's disease and use them to explore the ability of the double-acting agent deferiprone, an orally active chelator, to mediate iron scavenging and redeployment and thereby causing functional improvement. We subsequently evaluate the concept in translational models of disease and finally assess its therapeutic potential in prospective double-blind pilot clinical trials. We claim that any chelator applied to diseases of regional siderosis, cardiac, neuronal or endocrine ought to preserve both systemic and regional iron levels. The proposed deferiprone-based therapy has provided a paradigm for treating regional types of siderosis without affecting hematological parameters and systemic functions. PMID:24427136

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

    PubMed

    Maeng, Wan Young; Yoo, Mi

    2015-11-01

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

  6. The rates of exchange of water molecules from Al(III)-methylmalonate complexes: The effect of chelate ring size

    SciTech Connect

    Casey, W.H.; Phillips, B.L.; Nordin, J.P.; Sullivan, D.J.

    1998-08-01

    Rate coefficients are reported for exchange of hydration waters in the inner-coordination-sphere of Al(III)-methylmalonate complexes with bulk solution as determined via {sup 17}O-NMR. Surprisingly, water molecules in the thermodynamically less-stable complexes containing six-membered chelates are much more labile than those in five-membered oxalate-A(III) complexes. The surprising trend in reactivity is attributable either to differences in the Lewis basicities of oxygens in bidentate oxalate and methylmalonate ligands, or to rapid dissociation/reassociation of one of the acetate groups to the metal center. These results identify a useful case where trends in the apparent labilities of dissolved and presumed surface complexes deviate sharply. This deviation could be usefully exploited to probe surfaces if ligand-promoted dissolution rates could be compared at conditions where inner-sphere and outer-sphere chelate complexes could be distinguished spectroscopically. The authors expect inner-sphere oxalate to have a smaller labilizing effect than malonate or methylmalonate. A contrary result would indicate structural dissimilarity between complexes on the surface and in solution, or perhaps steric hindrance.

  7. 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

  8. Organic ligands reduce copper toxicity in Pseudomonas syringae

    SciTech Connect

    Azenha, M.; Vasconcelos, M.T.; Cabral, J.P.S.

    1995-03-01

    Pseudomonas syringae cells were exposed to 100 {mu}M copper alone, or to previously equilibrated copper sulfate-ligand solutions. Ligand concentrations were determined experimentally as those that reduced the free copper concentration to 5 {mu}M (determined with a Cu{sup 2+}-selective electrode). These values were in agreement with those calculated by computational equilibrium simulation based on published stability constants. Exposure of P. syringae cells to copper sulfate, chloride, or nitrate resulted in similar high mortality, suggesting that copper was responsible for cell death. Acetate, succinate, proline, lysine, cysteine, and EDTA significantly reduced both the amount of copper bound to the cells and cell death, indicating that not only strong chelating agents but also weak and moderate copper ligands can effectively antagonize copper toxicity. However, cysteine and EDTA were considerably more effective than acetate, succinate, proline, and lysine, indicating that copper toxicity is not simply a function of free copper concentration but depends on the nature of the ligand. The results suggested that a significant fraction of copper bound to acetate, succinate, proline, or lysine was displaced to the bacteria or, alternatively, mixed copper-ligand-cell complexes could be formed. On the contrary, none of these phenomena occurred for the copper complexes with cysteine or EDTA.

  9. Polyglycerol-Based Copper Chelators for the Transport and Release of Copper Ions in Biological Environments.

    PubMed

    Albrecht, Ralf; Fehse, Susanne; Pant, Kritee; Nowag, Sabrina; Stephan, Holger; Haag, Rainer; Tzschucke, Carl Christoph

    2016-03-01

    Here, the synthesis and characterization of three improved nanosystems is presented based on amino functionalized hyperbranched polyglycerol (hPG; M(w) = 16.8 kDa) as potential copper(II) chelators. The ligands, N-methyl-N-picolylglycine amide, 2,6-pyridine dicarboxylic acid monoamide, and cyclam tetraacetic acid (TETA) monoamide, are covalently attached to the polymer with amide bonds. In this paper, the Cu(II) loading capacity, the stability of the Cu(II)-loaded carriers at different pHs, with competing ligands and in human serum, as well as the transport of Cu(II) in biological systems are investigated. For the first time, a different cytotoxicity of functionalized polymer nanoparticles with and without Cu(II) is observed. The cyclam-based carrier combines the highest loading capacity (29 Cu ions/nanoparticle), best stability with respect to pH and EDTA (45% remaining Cu after 24 h), lowest cytotoxicity (IC50 > 100 × 10(-6) M (unloaded), 1500 × 10(-6) M Cu(II); Cu:carrier 29:1), and the highest stability in human serum.

  10. Ab initio coordination chemistry for nickel chelation motifs.

    PubMed

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

  11. 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.

  12. 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.

  13. 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

  14. Oxidation-Induced Degradable Nanogels for Iron Chelation

    NASA Astrophysics Data System (ADS)

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

    2016-02-01

    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.

  15. 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

  16. A chelate complex-enhanced luminol system for selective determination of Co(II), Fe(II) and Cr(III).

    PubMed

    Kim, Kyung Min; Kim, Young Ho; Oh, Sang-Hyub; Lee, Sang Hak

    2013-01-01

    A determination method for Co(II), Fe(II) and Cr(III) ions by luminol-H2 O2 system using chelating reagents is presented. A metal ion-chelating ligand complex with a Co(II) ion and a chelating reagent like ethylenediaminetetraacetic acid (EDTA) produced highly enhanced chemiluminescence (CL) intensity as well as longer lifetime in the luminol-H2 O2 system compared to metals that exist as free ions. Whereas free Cu(II) and Pb(II) ions had a strong catalytic effect on the luminol-H2 O2 system, significantly, the complexes of Cu(II) and Pb(II) with chelating reagents lost their catalytic activity due to the chelating reagents acting as masking agents. Based on the observed phenomenon, it was possible to determine Co(II), Fe(II) and Cr(III) ions with enhanced sensitivity and selectivity using the chelating reagents of the luminol-H2 O2 system. The effects of ligand, H2 O2 concentration, pH, buffer solution and concentrations of chelating reagents on CL intensity of the luminol-H2 O2 system were investigated and optimized for the determination of Co(II), Fe(II) and Cr(III) ions. Under optimized conditions, the calibration curve of metal ions was linear over the range of 2.0 × 10(-8) to 2.0 × 10(-5) M for Co(II), 1.0 × 10(-7) to 2.0 × 10(-5) M for Fe (II) and 2.0 × 10(-7) to 1.0 × 10(-4) M for Cr(III). Limits of detection (3σ/s) were 1.2 × 10(-8) , 4.0 × 10(-8) and 1.2 × 10(-7) M for Co(II), Fe(II) and Cr(III), respectively.

  17. Ligand modeling and design

    SciTech Connect

    Hay, B.P.

    1997-10-01

    The purpose of this work is to develop and implement a molecular design basis for selecting organic ligands that would be used in the cost-effective removal of specific radionuclides from nuclear waste streams. Organic ligands with metal ion specificity are critical components in the development of solvent extraction and ion exchange processes that are highly selective for targeted radionuclides. The traditional approach to the development of such ligands involves lengthy programs of organic synthesis and testing, which in the absence of reliable methods for screening compounds before synthesis, results in wasted research effort. The author`s approach breaks down and simplifies this costly process with the aid of computer-based molecular modeling techniques. Commercial software for organic molecular modeling is being configured to examine the interactions between organic ligands and metal ions, yielding an inexpensive, commercially or readily available computational tool that can be used to predict the structures and energies of ligand-metal complexes. Users will be able to correlate the large body of existing experimental data on structure, solution binding affinity, and metal ion selectivity to develop structural design criteria. These criteria will provide a basis for selecting ligands that can be implemented in separations technologies through collaboration with other DOE national laboratories and private industry. The initial focus will be to select ether-based ligands that can be applied to the recovery and concentration of the alkali and alkaline earth metal ions including cesium, strontium, and radium.

  18. The role of chelation in the treatment of other metal poisonings.

    PubMed

    Smith, Silas W

    2013-12-01

    These proceedings will review the role of chelation in five metals-aluminum, cadmium, chromium, cobalt, and uranium-in order to illustrate various chelation concepts. The process of "chelation" can often be oversimplified, leading to incorrect assumptions and risking patient harm. For chelation to be effective, two critical assumptions must be fulfilled: the presumed "metal toxicity" must correlate with a given body or a particular compartment burden, and reducing this compartmental or the body burden (through chelation) attenuates toxicity. Fulfilling these assumptions requires an established dose-response relationship, a validated, reproducible means of toxicity assessment (clinical, biochemical, or radiographical), and an appropriate assessment mechanisms of body or compartment burden. While a metal might "technically" be capable of chelation (and readily demonstrable in urine or feces), this is an insufficient endpoint. Clinical relevance must be affirmed. Deferoxamine is an accepted chelator for appropriately documented aluminum toxicity. There is a very minimal treatment window in order to address chelation in cadmium toxicity. In acute toxicity, while no definitive chelation benefit is described, succimer (DMSA), diethylenetriaminepentaacetate (DTPA), and potentially ethylenediaminetetraacetic acid (EDTA) have been considered. In chronic toxicity, chelation is unsupported. There is little evidence to suggest that currently available chromium chelators are efficacious. Similarly, scant human evidence exists with which to provide recommendation for cobalt chelation. DTPA has been recommended for cobalt radionuclide chelation, although DMSA, EDTA, and N-acetylcysteine have also been suggested. DTPA is unsupported for uranium chelation. Sodium bicarbonate is currently recommended, although animal evidence is conflicting.

  19. Biliary excretion of cadmium in rat. III. Effects of chelating agents and change in intracellular thiol content on billiary transport and tissue distribution of cadmium

    SciTech Connect

    Cherian, M.G.

    1980-03-01

    The effects of changes in sulfur-containing intracellular ligands on biliary excretion of cadmium were studied in rats. Injection of zinc or copper salts 24 h before intravenous injection of /sup 109/CdCl/sub 2/ (1 mg/kg Cd) decreased biliary excretion of Cd. Pretreatment with cysteine (25 mg/kg) had a similar effect. Depletion of intracellular thiol by injection of diethylmaleate had little effect. The effect of chelating agents on the pharmacokinetics of Cd depended on time of administration of the agents after exposure to Cd. When chelating agents were administered 1/2 h after Cd injection (before the synthesis of metallothionein), the thiol-containing agents (2,3-dimercapto-1-propanol (BAL), DL-penicillamine, N-acetylpenicillamine, and dithioerythritol increased the biliary excretion of Cd, while the carboxyl-containing ones (EDTA and nitrilotriacetate) increased the urinary excretion of Cd. BAL was the most effective chelating agent, but there was also an increase in the renal concentration of Cd. However, when these chelating agents were administered 24 h after Cd injection (after the synthesis of metallothionein), only BAL increased the biliary excretion of Cd. Renal and hepatic Cd concentrations decreased concurrently after BAL treatment.

  20. Kinetics of dissociation of trivalent actinide chelates of TMDTA

    SciTech Connect

    Muscatello, A.C.; Choppin, G.R.; D'Olieslager, W. )

    1989-03-22

    Measurements by a radiotracer technique show that the dissociation of TMDTA (trimethylenediamine-N,N-tetraacetic acid) chelates with Am, Cm, Bk, Cf, and Eu proceeds through an acid-catalyzed pathway. The rates of dissociation of An(TMDTA){sup {minus}} are 2 orders of magnitude faster than those of the corresponding EDTA chelates, presumably due to the greater lability of the nitrogen atom in the six-membered nitrogen-metal-nitrogen ring of TMDTA chelates. The rate of dissociation also decreased with decreasing metal ion radius. A proton-catalyzed mechanism similar to that for dissociation of EDTA complexes of lanthanide and actinide cations is consistent with the rate data. 19 refs., 6 figs., 2 tabs.

  1. Characterization of a metal-chelating substance in coffee.

    PubMed

    Takenaka, Makiko; Sato, Naoko; Asakawa, Hiromi; Wen, Xu; Murata, Masatsune; Homma, Seiichi

    2005-01-01

    A metal-chelating substance in brewed coffee was separated and characterized by its chemical structure. This substance was a brown polymer. The contents of sugars, amino acids and phenolics in the substance were evaluated. This polymer contained small amounts of sugars and amino acids in its partial structure. After being decomposed by alkaline fusion, the decomposition products were identified by HPLC and GC-MS. Several phenolics were detected in the decomposed products. To characterize this substance, various types of model compounds were prepared by roasting chlorogenic acid, sucrose, and (or) protein with cellulose powder. Among these model compounds, the polymer-forming ability was highest in the model prepared from all four of materials, but the metal-chelating ability was the highest in the model prepared from chlorogenic acid and cellulose. These results suggest that this metal-chelating substance was a melanoidin-like polymer formed by the decomposition and polymerization of sugars, amino acids and phenolics.

  2. A fluorescence spectroscopic study on the speciation of Cm(III) and Eu(III) in the presence of organic chelates in highly basic solutions

    SciTech Connect

    Wang, Zheming; Felmy, Andrew R.; Xia, Yuanxian; Mason, Marvin J.

    2003-07-15

    The speciation of Eu(III) and Cm(III) was investigated by time resolved laser fluorescence spectroscopy (TRLFS) over a range of base concentrations ranging from 0.01m NaOH to 7.5M NaOH and in the presence of several organic chelates including EDTA, HEDTA, NTA, and oxalate. The results of this work suggest that both Eu(III) and Cm(III) form strong mixed ligand complexes with organic chelates and the hydroxyl groups(s) in dilute NaOH solutions. However, in concentrated NaOH solutions, Eu(III)-/Cm(III)-containing colloidal nanoparticles are the primary cause for the measured Eu(III)/Cm(III) in the aqueous solutions. Therefore, the interpretation of these data solely in terms of the formation of amphoteric hydroxyl species (e.g. Eu(OH)4-) would appear to be inappropriate. The organic chelating ligands form strong complexes with surface Cm(III)/Eu(III) sites of the colloidal nanoparticles. For Cm(III), such surface complexes show largely red-shifted fluorescence spectra as compared with the aqueous complexes and unusually short fluorescence lifetimes. The decreased fluorescence lifetimes are likely due to the presence of transition metal ions, such as Fe3+, in the nanoparticle as well as reduced inter-nuclear distance between neighboring Cm(III) centers.

  3. Molecular recognition modes between adenine or adeniniun(1+) ion and binary M(II)(pdc) chelates (MCoZn; pdc=pyridine-2,6-dicarboxylate(2-) ion).

    PubMed

    Del Pilar Brandi-Blanco, María; Choquesillo-Lazarte, Duane; Domínguez-Martín, Alicia; Matilla-Hernández, Antonio; González-Pérez, Josefa María; Castiñeiras, Alfonso; Niclós-Gutiérrez, Juan

    2013-10-01

    Mixed ligand M(II)-complexes (MCoZn) with pyridine-2,6-dicarboxylate(2-) chelator (pdc) and adenine (Hade) have been synthesized and studied by X-ray diffraction and other spectral and thermal methods: [Cu(pdc)(H(N9)ade)(H2O)] (1), [Cu2(pdc)2(H2O)2(μ2-N3,N7-H(N9)ade)]·3H2O (2), trans-[M(pdc)(H(N9)ade)(H2O)2]·nH2O for MCo (3-L, 3-M, 3-H) or Zn (4-L, 4-H), where n is 0, 1 or 3 for the 'lowest' (L), 'medium' (M) and 'highest' (H) hydrated forms, and the salt trans-[Ni(pdc)(H2(N1,N9)ade)(H2O)2]Cl·2H2O (5). In all the nine compounds, both neutral and cationic adenine exist as their most stable tautomer and the molecular recognition pattern between the metal-pdc chelates and the adenine or adeninium(1+) ligands involves the MN7 bond in cooperation with an intra-molecular N6H⋯O(coordinated carboxylate) interligand interaction. In addition the dinuclear copper(II) compound (2) has the CuN3 bond and the N9H⋯O(coord. carboxylate) interaction. The structures of mononuclear ternary complexes proved that the molecular recognition pattern is the same irrespective of (a) the coordination geometry of the complex molecule, (b) the different hydrated forms of crystals with Co or Zn, and (c) the neutral of cationic form of the adenine ligand. These features are related to the mer-NO2 chelating ligand conformation (imposed by the planar rigidity of pdc) as a driving force for the observed metal binding mode.

  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. Efficacy of chelation therapy to remove aluminium intoxication.

    PubMed

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

    2015-11-01

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

  6. 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.

  7. Molecular recognition between adenine or 2,6-diaminopurine and copper(II) chelates with N,O2,S-tripodal tetradentate chelators having thioether or disulfide donor groups.

    PubMed

    González-Pérez, Josefa María; Choquesillo-Lazarte, Duane; Domínguez-Martín, Alicia; El Bakkali, Hanan; García-Rubiño, María Eugenia; Pérez-Toro, Inmaculada; Vílchez-Rodríguez, Ester; Castiñeiras, Alfonso; Nurchi, Valeria Marina; Niclós-Gutiérrez, Juan

    2015-10-01

    Five novel ternary copper(II) complexes with the N,O2,S-tripodal tetradentate chelators N,N-bis(carboxymethyl)-S-benzylcysteaminate(2-) ion (BCBC) or N,N,N',N'-tetrakis(carboxymethyl)cystaminate(4-) ion (TCC) and adenine (Hade), 2,6-diaminopurine (Hdap), 2,2'-bipyridine (bpy) or 1,10-phenanthroline (phen) as co-ligand were synthesized and characterized by X-ray diffraction and other physical methods: [Cu2(BCBC)2(μ2-N3,N7-H(N9)ade)(H2O)2]·H2O (1), [Cu2(BCBC)2(μ2-N7,N9-H(N3)dap)(H2O)2]·4H2O (2), [Cu2(μ2-TCC)(H(N9)ade)2(H2O)2]·10H2O (3), [Cu2(μ2-TCC)(bpy)2]·15H2O (4) and [Cu2(μ2-TCC)(phen)2]·14H2O (5). The crystal structure of H4TCC·3H2O was also determined. All ternary Cu(II) complexes have molecular structures. The N-(2-mercaptoethyl)-iminodiacetate moieties of BCBC or TCC ligands play a NO2+S-tripodal tetradentate role, with the S-(thioether or disulfide) atom as the apical/distal donor of the copper(II) center. In 1-3, the iminodiacetate moiety exhibits a mer-NO2 conformation (two nearly coplanar chelate rings) while in 4 and 5 (with bpy or phen as coligand) it displays a fac-NO+O (apical/distal) conformation. We conclude that the formation of the Cu-S(thioether or disulfide) bonds is strongly favored by the N-branched topology of the S-ligands in the reported compounds.

  8. 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.

  9. Dendritic poly-chelator frameworks for multimeric bioconjugation.

    PubMed

    Reich, Dominik; Wurzer, Alexander; Wirtz, Martina; Stiegler, Veronika; Spatz, Philipp; Pollmann, Julia; Wester, Hans-Jürgen; Notni, Johannes

    2017-02-23

    Starting from multifunctional triazacyclononane-triphosphinate chelator cores, dendritic molecules with the ability to bind metal ions within their framework were synthesized. A cooperative interaction of the chelator cages resulted in a markedly increased affinity towards (67/68)Ga(III). A hexameric PSMA inhibitor conjugate with high affinity (IC50 = 1.2 nM) and favorable in vivo PET imaging properties demonstrated practical applicability. The novel scaffolds are useful for synthesis of structurally well-defined multimodal imaging probes or theranostics.

  10. Ligand modeling and design

    SciTech Connect

    Hay, B.

    1996-10-01

    The purpose of this work is to develop and implement a molecular design basis for selecting organic ligands that would be used tin applications for the cost-effective removal of specific radionuclides from nuclear waste streams.

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

    PubMed

    Norkus, Eugenijus; Prusinskas, Kestutis; Vaskelis, Algirdas; Jaciauskiene, Jane; Stalnioniene, Irena; Macalady, Donald L

    2007-01-15

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

  12. Catechol versus bisphosphonate ligand exchange at the surface of iron oxide nanoparticles: towards multi-functionalization

    NASA Astrophysics Data System (ADS)

    Guénin, Erwann; Lalatonne, Yoann; Bolley, Julie; Milosevic, Irena; Platas-Iglesias, Carlos; Motte, Laurence

    2014-11-01

    We report an investigation of the ligand exchange at the surface of iron oxide nanoparticles in water. For this purpose we compared two strong chelating agents on the iron oxide surface containing catechol and bisphosphonate moieties. Interactions between the coating agents (catechol/bisphosphonate) and the nanoparticle's surface were studied by FTIR and DFT calculations. Ligand exchange experiments were performed using sonication and the exchange yield was characterized by FTIR and EDX. This methodology allowed introducing bisphosphonates with various functionalities (alkyne or biotin) permitting multi-functionalization.

  13. Rational Ligand Design for U(VI) and Pu(IV)

    SciTech Connect

    Szigethy, Geza

    2009-08-12

    Nuclear power is an attractive alternative to hydrocarbon-based energy production at a time when moving away from carbon-producing processes is widely accepted as a significant developmental need. Hence, the radioactive actinide power sources for this industry are necessarily becoming more widespread, which is accompanied by the increased risk of exposure to both biological and environmental systems. This, in turn, requires the development of technology designed to remove such radioactive threats efficiently and selectively from contaminated material, whether that be contained nuclear waste streams or the human body. Raymond and coworkers (University of California, Berkeley) have for decades investigated the interaction of biologically-inspired, hard Lewis-base ligands with high-valent, early-actinide cations. It has been established that such ligands bind strongly to the hard Lewis-acidic early actinides, and many poly-bidentate ligands have been developed and shown to be effective chelators of actinide contaminants in vivo. Work reported herein explores the effect of ligand geometry on the linear U(IV) dioxo dication (uranyl, UO2 2+). The goal is to utilize rational ligand design to develop ligands that exhibit shape selectivity towards linear dioxo cations and provides thermodynamically favorable binding interactions. The uranyl complexes with a series of tetradentate 3-hydroxy-pyridin-2-one (3,2-HOPO) ligands were studied in both the crystalline state as well as in solution. Despite significant geometric differences, the uranyl affinities of these ligands vary only slightly but are better than DTPA, the only FDA-approved chelation therapy for actinide contamination. The terepthalamide (TAM) moiety was combined into tris-beidentate ligands with 1,2- and 3,2-HOPO moieties were combined into hexadentate ligands whose structural preferences and solution thermodynamics were measured with the uranyl cation. In addition to achieving coordinative

  14. (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

  15. (S)-5-(p-nitrobenzyl)-PCTA, a promising bifunctional ligand with advantageous metal ion complexation kinetics.

    PubMed

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

    2009-03-18

    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(NO(2)-Bn-PCTA) (M = Mg(2+), Ca(2+), Cu(2+), Zn(2+)) complexes was similar to that of the corresponding PCTA complexes, while the stability of Ln(3+) complexes of the bifunctional ligand is somewhat lower than that of PCTA chelates. The rate of complex formation of Ln(NO(2)-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(NO(2)-Bn-PCTA) complexes showed that the kinetic inertness of the complexes was comparable to that of Ln(DOTA) chelates making the bifunctional ligand NO(2)-Bn-PCTA suitable for labeling biological vectors with radioisotopes for nuclear medicine applications.

  16. Characterization of metal chelate methacrylate monolithic disk for purification of polyclonal and monoclonal immunoglobulin G.

    PubMed

    Prasanna, Rajasekar R; Vijayalakshmi, Mookambeswaran A

    2010-06-04

    Dynamic binding capacity (DBC) of commercial metal-chelate methacrylate monolith-convective interaction media (CIM) was performed with commercial human immunoglobulin G (IgG) (Cohn fraction II, III). Monoliths are an attractive stationary phase for purification of large biomolecules because they exhibit very low back pressure even at high flow rates and flow-unaffected binding properties. Adsorption of IgG onto CIM-IDA disk immobilized with Cu(2+), Ni(2+) and Zn(2+) were studied with Tris-acetate (TA), phosphate-acetate (PA) and MMA (MES, MOPS and acetate) buffer systems at different flow rates. Adsorption and elution of IgG varied with different buffers and adsorption of IgG was maximum with MMA buffer. Adsorption of human IgG from Cohn fractions (II, III) was high when Cu(2+) was used as ligand. CIM-IDA disk showed dynamic binding capacity in the range of 14-16 mg/ml with Cu(2+) and 7-9 mg/ml with Ni(2+) for human IgG with MMA buffer. In the case of CIM-IDA-Zn(2+) column, the binding capacity was only about 0.5mg/ml of support. Different desorption strategies like lowering of pH and increasing of competitive agent were also studied to achieve maximum recovery. Chromatographic runs with human serum and mouse ascites fluid were also carried out with metal chelate methacrylate monolithic disk and the results indicate the potential of this technique for polyclonal human IgG and monoclonal IgG purification from complex biological samples.

  17. Application of the Ugi four-component reaction to the synthesis of ditopic bifunctional chelating agents.

    PubMed

    Tei, Lorenzo; Gugliotta, Giuseppe; Avedano, Stefano; Giovenzana, Giovanni B; Botta, Mauro

    2009-11-07

    The Ugi four-component reaction (Ugi 4CR) was exploited for the first time to obtain in a single synthetic step bifunctional ditopic chelators by using DOTA monoamide (DOTAMA) derivatives as amino and acid components. A number of ditopic systems in which the two DOTAMA units are connected by a central alpha-acylaminoamide group were synthesized by reacting different aldehydes, isocyanides and two DOTAMA chelates containing amino and acid functionalities. Variation of the components allows the insertion of another functional group into the alpha-acylaminoamide skeleton for further conjugation to biomolecules. The optimal reaction conditions were found by using methanol as solvent and ultrasound irradiation at a power of 60 W (20 kHz) for 3 h. The Gd(III) complexes of the dimeric ligands L1 and L2 (bearing a cyclohexyl ring and an octadecyl chain on the central alpha-acylaminoamide moiety, respectively) were fully characterized in aqueous media by relaxometric techniques with varying temperature and magnetic field strength. The relaxivity of Gd(2)L1 and Gd(2)L2 (in the aggregated form), at 20 MHz and 310 K, are 5.6 and 20.0 mM(-1) s(-1), respectively. The enhanced value found for Gd(2)L2 indicates that this lipophilic complex forms micelles at concentrations <0.1 mM. Finally, the binding of Gd(2)L2 to human serum albumin (HSA) was investigated by proton relaxometry, and the affinity constant of the complex and the relaxivity of the macromolecular adduct (r(1p)(b) = 38.1 mM(-1) s(-1); 20 MHz and 310 K) derived.

  18. Combined NO/sub x//SO/sub 2/ removal from flue gas using ferrous chelates of SH-containing amino acids and alkali

    SciTech Connect

    Liu, D.K.; Chang, S.G.

    1987-04-01

    We report herein the use of ferrous chelates of SH-containing amino acids including cysteine, penicillamine, N-acetylcysteine, and N-acetylpenicillamine in neutral or alkaline solutions for the combined removal of NO and SO/sub 2/ in wet flue gas clean-up systems. These SH-containing amino acids not only can stabilize ferrous ions in alkaline solutions to promote the absorption of NO, but are also capable of rapidly reducing ferric ions formed during the scrubbing process back to ferrous ions. The disulfide form of the above amino acids can be reduced by SO/sub 2/ and H/sub 2/S to regenerate the starting monomeric species. The chemistry relevant to the absorption of NO by the above ferrous chelates and the ligand regeneration process will be discussed.

  19. Combined NO/sub x//SO/sub 2/ removal from flue gas using ferrous chelates of SH-containing amino acids and alkali

    SciTech Connect

    Liu, D.K.; Chang, S.G.

    1987-01-01

    We report herein the use of ferrous chelates of SH-containing amino acids including cysteine, penicillamine, N-acetylcysteine, and N-acetylpenicillamine in neutral or alkaline solutions for the combined removal of NO and SO/sub 2/ in wet flue gas clean-up systems. These SH-containing amino acids not only can stabilize ferrous ions in alkaline solutions to promote the absorption of NO, but are also capable of rapidly reducing ferric ions formed during the scrubbing process back to ferrous ions. The disulfide from of the above amino acids can be reduced by SO/sub 2/ and H/sub 2/S to regenerate the starting monomeric species. The chemistry relevant to the absorption of NO by the above ferrous chelates and the ligand regeneration process will be discussed.

  20. NMR studies of chiral P,S-chelate platinum, rhodium, and iridium complexes and the X-ray structure of a palladium(II) allyl derivative

    SciTech Connect

    Albinati, A.; Eckert, J.; Pregosin, P.; Ruegger, H.; Salzmann, R.; Stoessel, C.

    1997-02-18

    Several Rh(I), Ir(III), and Pt(II) complexes of the chiral P,S-bidentate ligand 2 have been prepared and characterized. Detailed two-dimensional NMR studies show that (i) the boat-type chelate ring and the stereogenic sulfur center can invert rapidly at ambient temperature and (ii) the sulfur donor may dissociate, essentially destroying the chiral pocket. The solid-state structure of [Pt({eta}{sup 3}-C{sub 3}H{sub 5})(2)]PF{sub 6} (3) has been determined and the sulfur substituent shown to have an axial orientation. The six-membered chelate ring takes up a boat-like conformation. As shown by an X-ray diffraction study for 3, and via incoherent inelastic neutron scattering (IINS) measurements for the Pd analog, 4, the OH group is remote from the metal atom. 42 refs., 11 figs., 6 tabs.

  1. Triimidosulfonates as Acute Bite-Angle Chelates: Slow Relaxation of the Magnetization in Zero Field and Hysteresis Loop of a Co(II) Complex.

    PubMed

    Carl, Elena; Demeshko, Serhiy; Meyer, Franc; Stalke, Dietmar

    2015-07-06

    Starting from a polyimido sulfonate the four-coordinate, N,N'-chelated Co(II) complex [Co{(NtBu)3 SMe}2 ] (1) was synthesized, and its molecular structure was elucidated by single-crystal X-ray structural analysis. The acute N-Co-N bite angle imposed by the N,N'-chelating ligand (NtBu)3 SMe(-) leads to pronounced C2v distortion of the tetrahedral coordination environment and thus to high anisotropy of the Co(II) ion (D≈-58 cm(-1) ), favorable for single-molecule-magnet (SMM) properties. Magnetic measurements revealed a high barrier to spin reversal (Ueff =75 cm(-1) ) that gives rise to the observation of slow relaxation of the magnetization in zero field and a hysteresis loop at 2 K for this unique complex.

  2. Final report submitted to the Department of Energy [Encapsulation of metal chelate and oxo catalysts in nanoporous hosts

    SciTech Connect

    Bein, Thomas

    2000-10-27

    The focus of this project is directed at the design of novel zeolite-based hybrid catalysts, based on encapsulated transition metal chelate complexes and metal oxo species. One goal is to achieve improved control over the active species in heterogeneous catalysis, as well as improved reactant and product selectivities. This is achieved by combining the catalytic activity of transition metal catalysts with the large surface area of microporous and mesoporous hosts. Furthermore, shape selectivity may be achieved through the well-defined pore structure of zeolites. Several families of complexes have been studied, including nitrogen chelate complexes, chiral salen complexes, and supported molybdenum-oxo species. In the group of nitrogen-containing metal chelate complexes, some are derived from triazacyclononane, while others are derived from tetradentate cyclam-type ligands. These complexes have been studied in solution, encapsulated in the cages of zeolites, and attached to the channel walls of the novel mesoporous MCM-41-type materials. The latter approach is based on covalent grafting of the ligand to the host, followed by metalation. These heterogenized complexes show good activity in highly selective olefin epoxidation reactions. Furthermore, we have investigated the encapsulation of chiral metal chelate complexes, including manganese salen complexes in the cages of EMT zeolite. This large-pore host allowed us to synthesize the entire complex in the zeolite in a multistep sequence. The epoxidation activity of these hybrid systems is truly encapsulated in the host cages: large substrate molecules such as cholesterol were not oxidized. Chiral epoxidation with enantiomeric excess of 80% was achieved. Zeolite-supported molybdenum-oxo species have also been synthesized and investigated. These systems are also very active and selective epoxidation catalysts. Comprehensive characterization with spectroscopic and structural techniques has been performed, including EXAFS

  3. Nuclear magnetic resonance structural studies of an axially symmetric lanthanide ion chelate in aqueous solution

    NASA Astrophysics Data System (ADS)

    Sherry, A. D.; Singh, M.; Geraldes, C. F. G. C.

    The complexes of the macrocyclic ligand 1,4, 7-triazacyclononane- N,N',N″-triacetic acid (NOTA) with the paramagnetic trivalent lanthanide canons have been examined by proton and 13C magnetic resonance spectroscopy. Lanthanide-induced shifts (LIS) have been measured for all proton and carbon resonances in nine paramagnetic Ln(NOTA) complexes at 25 and 70°C. At both temperatures the ethylene protons appear as a pair of resonances forming an AA'XX' splitting pattern (visible only in the Eu(NOTA) spectrum) while the acetate protons remain a singlet. The directions and magnitudes of the 1H and 13C shifts indicate they are dominated by contact interactions in most of the Ln(NOTA) complexes. The 13C spectrum of Pr(NOTA) provides evidence that more than one chelate structure is present in solution. The addition of LiCl to Pr(NOTA) and Eu(NOTA) samples results in significant shifts in the bound 1H and 13C resonances whereas the spectra of Dy(NOTA) and Yb(NOTA) do not change significantly when LiCl is added. These results, along with observed breaks in plots of experimental LIS data versus theoretical pseudocontact and contact shift values, suggest that the early members of the lanthanide ion series form mixed complexes with NOTA in aqueous solution, some with NOTA bound as a hexadentate chelate and some a pentadentate species with one unbound acetate group. The smaller trivalent lanthanide cations (Dy → Yb) appear to form complexes containing only hexadentate chelated NOTA. The contact and pseudocontact contributions to each of the observed LIS have been separated and the resulting pseudocontact shifts for the Dy → Yb complexes agree reasonably well with those calculated using the axial symmetry model. The 1H and 13C relaxation rates determined for three Ln(NOTA) complexes indicate that the smaller lanthanide cations fit into the triazamacrocyclic cavity better than do the larger ions resulting in structurally more rigid Ln(NOTA) complexes.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. Synthesis and preliminary biological evaluation of the first (99m)Tc(I)-specific semi-rigid tridentate ligand based on a click chemistry strategy.

    PubMed

    Guizani, Sihem; Malek Saied, Nadia; Picard, Claude; Benoist, Eric; Saidi, Mouldi

    2014-03-01

    A novel bifunctional chelating agent based on a click chemistry strategy has been synthesized and characterized on the basis of spectroscopic techniques. The metal chelating part of this new class of tridentate N2O ligand combined a triazole unit and an aromatic ring. This latter semi-rigid framework induced a pre-organization of the chelating cavity, improving the stability of the corresponding metallic complexes (M = (99m) Tc, Re). Thus, the (99m) Tc(CO)3 complex, obtained with good yield and excellent radiochemical purity (>90%), exhibited a high in vitro serum stability. Tissue biodistribution in normal mice showed a rapid clearance, no long-term retention in organs and no in vivo reoxidation of technetium-99m, making this compound a promising (99m)Tc-chelating system.

  10. Receptor Specific Ligands for Spect Imaging

    SciTech Connect

    Kung, H. F.

    2003-02-25

    In the past funding period we have concentrated in developing new 99mTc labeled MIBG analogs. Basic chemistry of ligand synthesis, radiochemistry of Re and 99mTc complex formation, separation of stereoisomers and in vitro stability were investigated. We have prepared a number of new MIBG derivatives containing chelating moiety N2S2 and additional groups to increase lipophilicity. Unfortunately none of the new 99mTc labeled MIBG analogs showed promise as an imaging agent for myocardial neuronal function. Radioactive-iodine-labeled meta-iodobenzylguanidine (MIBG) is currently being used as an in vivo imaging agent to evaluate neuroendocrine tumors as well as the myocardial sympathetic nervous system in patients with myocardial infarct and cardiomyopathy. It is generally accepted that MIBG is an analog of norepinephrine and its uptake in the heart corresponds to the distribution of norepinephrine and the density of sympathetic neurons. A series of MIBG derivatives containing suitable chelating functional groups N2S2 for the formation of [Tcv0]+3N2S2 complex was successfully synthesized and the 99mTc-labeled complexes were prepared and tested in rats. One of the compounds, [99mTc]M2, tested showed significant, albeit lower, heart uptakes post iv injection in rats (0.18% dose/organ at 4 hours) as compared to [l25l]MIBG (1.4% dose/organ at 4 hours). The heart uptake of the 99mTc-labeled complex, [99mTc]M2, appears to be specific and can be reduced by coinjection with nonradioactive MIBG or by pretreatment with desipramine. a selective norepinephrine transporter inhibitor. Further evaluation of the in vitro uptake of [99mTc]M2 in cultured neuroblastoma cells displayed consistently lower, but measurable uptake (app. 10% of that for [125l]MlBG). These preliminary results suggested that the mechanisms of heart uptake of [99mTc]M2 may be related to those for [125l]MIBG uptake. To improve the heart uptake of the MIBG derivatives we have developed chemistry related to the

  11. Picture of a chelate in exchange: the crystal structure of NaHoDOTMA, a 'semi'-hydrated chelate.

    PubMed

    Payne, Katherine M; Valente, Edward J; Aime, Silvio; Botta, Mauro; Woods, Mark

    2013-03-21

    Crystallography generally only provides static structural information. This can render it an ineffective technique for probing dynamic solution state processes. A crystal of HoDOTMA affords unique structures that effectively represent that of a lanthanide tetra-acetate chelate mid-way through the water exchange process.

  12. 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...

  13. In Vitro Metabolism and Stability of the Actinide Chelating Agent 3,4,3-LI(1,2-HOPO)

    PubMed Central

    Choi, Taylor A.; Furimsky, Anna M.; Swezey, Robert; Bunin, Deborah I.; Byrge, Patricia; Iyer, Lalitha V.; Chang, Polly Y.; Abergel, Rebecca J.

    2015-01-01

    The hydroxypyridinonate ligand 3,4,3-LI(1,2-HOPO) is currently under development for radionuclide chelation therapy. The preclinical characterization of this highly promising ligand comprised the evaluation of its in vitro properties, including microsomal, plasma, and gastrointestinal fluid stability, cytochrome P450 inhibition, plasma protein binding, and intestinal absorption using the Caco-2 cell line. When mixed with active human liver microsomes, no loss of parent compound was observed after 60 minutes, indicating compound stability in the presence of liver microsomal P450. At the tested concentrations, 3,4,3-LI(1,2-HOPO) did not significantly influence the activities of any of the cytochromal isoforms screened. Thus, 3,4,3-LI(1,2-HOPO) is unlikely to cause drug-drug interactions by inhibiting the metabolic clearance of co-administered drugs metabolized by these enzymes. Plasma protein binding assays revealed that the compound is protein-bound in dogs and less extensively in rats and humans. In the plasma stability study, the compound was stable after 1 h at 37°C in mouse, rat, dog, and human plasma samples. Finally, a bi-directional permeability assay demonstrated that 3,4,3-LI(1,2-HOPO) is not permeable across the Caco-2 monolayer, highlighting the need to further evaluate the effects of various compounds with known permeability enhancement properties on the permeability of the ligand in future studies. PMID:25727482

  14. In Vitro Metabolism and Stability of the Actinide Chelating Agent 3,4,3-LI(1,2-HOPO)

    DOE PAGES

    Choi, Taylor A.; Furimsky, Anna M.; Swezey, Robert; ...

    2015-02-27

    We report that the hydroxypyridinonate ligand 3,4,3-LI(1,2-HOPO) is currently under development for radionuclide chelation therapy. The preclinical characterization of this highly promising ligand comprised the evaluation of its in vitro properties, including microsomal, plasma, and gastrointestinal fluid stability, cytochrome P450 inhibition, plasma protein binding, and intestinal absorption using the Caco-2 cell line. When mixed with active human liver microsomes, no loss of parent compound was observed after 60 minutes, indicating compound stability in the presence of liver microsomal P450. At the tested concentrations, 3,4,3-LI(1,2-HOPO) did not significantly influence the activities of any of the cytochromal isoforms screened. Thus, 3,4,3-LI(1,2-HOPO) ismore » unlikely to cause drug-drug interactions by inhibiting the metabolic clearance of co-administered drugs metabolized by these enzymes. Plasma protein binding assays revealed that the compound is protein-bound in dogs and less extensively in rats and humans. In the plasma stability study, the compound was stable after 1 h at 37°C in mouse, rat, dog, and human plasma samples. Finally, a bi-directional permeability assay demonstrated that 3,4,3-LI(1,2-HOPO) is not permeable across the Caco-2 monolayer, highlighting the need to further evaluate the effects of various compounds with known permeability enhancement properties on the permeability of the ligand in future studies.« less

  15. In Vitro Metabolism and Stability of the Actinide Chelating Agent 3,4,3-LI(1,2-HOPO)

    SciTech Connect

    Choi, Taylor A.; Furimsky, Anna M.; Swezey, Robert; Bunin, Deborah I.; Byrge, Patricia; Iyer, Lalitha V.; Chang, Polly Y.; Abergel, Rebecca J.

    2015-02-27

    We report that the hydroxypyridinonate ligand 3,4,3-LI(1,2-HOPO) is currently under development for radionuclide chelation therapy. The preclinical characterization of this highly promising ligand comprised the evaluation of its in vitro properties, including microsomal, plasma, and gastrointestinal fluid stability, cytochrome P450 inhibition, plasma protein binding, and intestinal absorption using the Caco-2 cell line. When mixed with active human liver microsomes, no loss of parent compound was observed after 60 minutes, indicating compound stability in the presence of liver microsomal P450. At the tested concentrations, 3,4,3-LI(1,2-HOPO) did not significantly influence the activities of any of the cytochromal isoforms screened. Thus, 3,4,3-LI(1,2-HOPO) is unlikely to cause drug-drug interactions by inhibiting the metabolic clearance of co-administered drugs metabolized by these enzymes. Plasma protein binding assays revealed that the compound is protein-bound in dogs and less extensively in rats and humans. In the plasma stability study, the compound was stable after 1 h at 37°C in mouse, rat, dog, and human plasma samples. Finally, a bi-directional permeability assay demonstrated that 3,4,3-LI(1,2-HOPO) is not permeable across the Caco-2 monolayer, highlighting the need to further evaluate the effects of various compounds with known permeability enhancement properties on the permeability of the ligand in future studies.

  16. In vitro metabolism and stability of the actinide chelating agent 3,4,3-LI(1,2-HOPO).

    PubMed

    Choi, Taylor A; Furimsky, Anna M; Swezey, Robert; Bunin, Deborah I; Byrge, Patricia; Iyer, Lalitha V; Chang, Polly Y; Abergel, Rebecca J

    2015-05-01

    The hydroxypyridinonate ligand 3,4,3-LI(1,2-HOPO) is currently under development for radionuclide chelation therapy. The preclinical characterization of this highly promising ligand comprised the evaluation of its in vitro properties, including microsomal, plasma, and gastrointestinal fluid stability, cytochrome P450 inhibition, plasma protein binding, and intestinal absorption using the Caco-2 cell line. When mixed with active human liver microsomes, no loss of parent compound was observed after 60 min, indicating compound stability in the presence of liver microsomal P450. At the tested concentrations, 3,4,3-LI(1,2-HOPO) did not significantly influence the activities of any of the cytochromal isoforms screened. Thus, 3,4,3-LI(1,2-HOPO) is unlikely to cause drug-drug interactions by inhibiting the metabolic clearance of coadministered drugs metabolized by these enzymes. Plasma protein-binding assays revealed that the compound is protein-bound in dogs and less extensively in rats and humans. In the plasma stability study, the compound was stable after 1 h at 37°C in mouse, rat, dog, and human plasma samples. Finally, a bidirectional permeability assay demonstrated that 3,4,3-LI(1,2-HOPO) is not permeable across the Caco-2 monolayer, highlighting the need to further evaluate the effects of various compounds with known permeability enhancement properties on the permeability of the ligand in future studies.

  17. How Zn can impede Cu detoxification by chelating agents in Alzheimer's disease: a proof-of-concept study.

    PubMed

    Conte-Daban, Amandine; Day, Adam; Faller, Peter; Hureau, Christelle

    2016-10-04

    The role of Cu and Zn ions in Alzheimer's disease is linked to the consequences of their coordination to the amyloid-β (Aβ) peptide, i.e. to the modulation of Aβ aggregation and to the production of Reactive Oxygen Species (ROS), two central events of the so-called amyloid cascade. The role of both ions in Aβ aggregation is still controversial. Conversely the higher toxicity of the redox competent Cu ions (compared to the redox inert Zn ions) in ROS production is acknowledged. Thus the Cu ions can be considered as the main therapeutic target. Because Zn ions are present in higher quantity than Cu ions in the synaptic cleft, they can prevent detoxification of Cu by chelators unless they have an unusually high Cu over Zn selectivity. We describe a proof-of-concept study where the role of Zn on the metal swap reaction between two prototypical ligands and the Cu(Aβ) species has been investigated by several complementary spectroscopic techniques (UV-Vis, EPR and XANES). The first ligand has a higher Cu over Zn selectivity relative to the one of Aβ peptide while the second one exhibits a classical Cu over Zn selectivity. How Zn impacts the effect of the ligands on Cu-induced ROS production and Aβ aggregation is also reported.

  18. Examining the fixation kinetics of chelated and non-chelated copper and the applications to micronutrient management in semiarid alkaline soils

    NASA Astrophysics Data System (ADS)

    Udeigwe, T. K.; Eichmann, M. B.; Menkiti, M. C.; Kusi, N. Y. O.

    2016-02-01

    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 semiarid soils of the Southern High Plains, USA, using findings from Cu extraction studies and kinetic models. Approximately, 22 % more Cu was fixed in the non-chelated system compared to the chelated 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 micronutrients over time, highlighting the significance of timing even when chelated micronutrients are used. 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 system. 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 semiarid/arid alkaline soils of the world. Findings are also more applicable to field settings, an improvement over related previous studies.

  19. 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

  20. Introducing saccharic acid as an efficient iron chelate to enhance photo-Fenton degradation of organic contaminants.

    PubMed

    Subramanian, Gokulakrishnan; Madras, Giridhar

    2016-11-01

    The identification of iron chelates that can enhance photo-Fenton degradation is of great interest in the field of advanced oxidation process. Saccharic acid (SA) is a polyhydroxy carboxylic acid and completely non-toxic. Importantly, it can effectively bind Fe(III) as well as induce photoreduction of Fe(III). Despite having these interesting properties, the effect of SA on photo-Fenton degradation has not been studied. Herein, we demonstrate the first assessment of SA as an iron chelate in photo-Fenton process using methylene blue (MB) as a model organic contaminant. Our results demonstrate that SA has the ability to (i) enhance the photo-Fenton degradation of MB by about 11 times at pH 4.5 (ii) intensify photochemical reduction of Fe(III) to Fe(II) by about 17 times and (iii) accelerate the rate of consumption of H2O2 in photo-Fenton process by about 5 times (iv) increase the TOC reduction by about 2 times and (v) improve the photo-Fenton degradation of MB in the presence of a variety of common inorganic ions and organic matter. The influential properties of SA on photo-Fenton degradation is attributed to the efficient photochemical reduction of Fe(III) via LMCT (ligand to metal charge transfer reaction) to Fe(II), which then activated H2O2 to generate OH and accelerated photo-Fenton degradation efficiency. Moreover, the effect of operational parameters such as oxidant: contaminant (H2O2: MB) ratio, catalyst: contaminant (Fe(III)SA: MB) ratio, Fe(III): SA stoichiometry and pH on the degradation of MB by photo-Fenton in the presence of SA is demonstrated. Importantly, SA assisted photo-Fenton caused effective degradation of MB and 4-Chlorophenol under natural sunlight irradiation in natural water matrix. The findings strongly support SA as a deserving iron chelate to enhance photo-Fenton degradation.

  1. Ligand fitting with CCP4

    PubMed Central

    2017-01-01

    Crystal structures of protein–ligand complexes are often used to infer biology and inform structure-based drug discovery. Hence, it is important to build accurate, reliable models of ligands that give confidence in the interpretation of the respective protein–ligand complex. This paper discusses key stages in the ligand-fitting process, including ligand binding-site identification, ligand description and conformer generation, ligand fitting, refinement and subsequent validation. The CCP4 suite contains a number of software tools that facilitate this task: AceDRG for the creation of ligand descriptions and conformers, Lidia and JLigand for two-dimensional and three-dimensional ligand editing and visual analysis, Coot for density interpretation, ligand fitting, analysis and validation, and REFMAC5 for macromolecular refinement. In addition to recent advancements in automatic carbohydrate building in Coot (LO/Carb) and ligand-validation tools (FLEV), the release of the CCP4i2 GUI provides an integrated solution that streamlines the ligand-fitting workflow, seamlessly passing results from one program to the next. The ligand-fitting process is illustrated using instructive practical examples, including problematic cases such as post-translational modifications, highlighting the need for careful analysis and rigorous validation. PMID:28177312

  2. Investigation of biologically-designed metal-specific chelators for potential metal recovery and waste remediation applications.

    SciTech Connect

    Criscenti, Louise Jacqueline; Ockwig, Nathan W.

    2009-01-01

    Bacteria, algae and plants produce metal-specific chelators to capture required nutrient or toxic trace metals. Biological systems are thought to be very efficient, honed by evolutionary forces over time. Understanding the approaches used by living organisms to select for specific metals in the environment may lead to design of cheaper and more effective approaches for metal recovery and contaminant-metal remediation. In this study, the binding of a common siderophore, desferrioxamine B (DFO-B), to three aqueous metal cations, Fe(II), Fe(III), and UO{sub 2}(VI) was investigated using classical molecular dynamics. DFO-B has three acetohydroxamate groups and a terminal amine group that all deprotonate with increasing pH. For all three metals, complexes with DFO-B (-2) are the most stable and favored under alkaline conditions. Under more acidic conditions, the metal-DFO complexes involve chelation with both acetohydroxamate and acetylamine groups. The approach taken here allows for detailed investigation of metal binding to biologically-designed organic ligands.

  3. A new tetradentate beta-diketonate--europium chelate that can be covalently bound to proteins for time-resolved fluoroimmunoassay.

    PubMed

    Yuan, J; Matsumoto, K; Kimura, H

    1998-02-01

    A new chlorosulfonylated tetradentate beta-diketone, 4,4'-bis(1",1",1",2",2",3",3"-heptafluoro-4",6"-hexanedion-6 "-yl) chlorosulfo-o-terphenyl (BHHCT), was synthesized as a chelating label for Eu3+. BHHCT can be covalently bound to proteins under mild conditions and forms a strongly fluorescent chelate with Eu3+. Bovine serum albumin (BSA) and streptavidin (SA) were labeled with BHHCH-Eu3+, and the latter was used for time-resolved fluoroimmunoassay of alpha-fetoprotein (AFP) in human sera. A remarkably high sensitivity was obtained, with a detection limit of 4.1 x 10(-3) pg/mL, which corresponds to an improvement of about 4-5 orders of magnitude, compared to those of all conventional immunoassays including fluoroimmunoassay, enzyme immunoassay, and radioimmunoassay. The high sensitivity has been attained both by strong fluorescence of the present label and by the extremely suppressed background level brought about by the direct labeling of proteins with the beta-diketone-Eu3+ complex. A general consideration and ideas are given for designing ideal label ligands for strongly fluorescent Eu3+ complexes.

  4. Switchable polarity solvent for liquid phase microextraction of Cd(II) as pyrrolidinedithiocarbamate chelates from environmental samples.

    PubMed

    Yilmaz, Erkan; Soylak, Mustafa

    2015-07-30

    A switchable polarity solvent was synthesized from triethylamine (TEA)/water/CO2 (Dry ice) via proton transfer reaction has been used for the microextraction of cadmium(II) as pyrrolidinedithiocarbamate (APDC) chelate. Cd(II)-APDC chelate was extracted into the switchable polarity solvent drops by adding 2 mL 10 M sodium hydroxide solution. Analytical parameters affecting the complex formation and microextraction efficiency such as pH, amount of ligand, volume of switchable polarity solvent and NaOH, sample volume were optimized. The effects of foreign ions were found tolerably. Under optimum conditions, the detection limit was 0.16 μg L(-1) (3Sb/m, n = 7) and the relative standard deviation was 5.4% (n = 7). The method was validated by the analysis of certified reference materials (TMDA-51.3 fortified water, TMDA-53.3 fortified water and SPS-WW2 waste water, 1573a Tomato Leaves and Oriental Basma Tobacco Leaves (INCT-OBTL-5)) and addition/recovery tests. The method was successfully applied to determination of cadmium contents of water, vegetable, fruit and cigarette samples.

  5. A Metal Chelating Porous Polymeric Support: The Missing Link for a Defect-Free Metal-Organic Framework Composite Membrane.

    PubMed

    Barankova, Eva; Tan, Xiaoyu; Villalobos, Luis Francisco; Litwiller, Eric; Peinemann, Klaus-Viktor

    2017-03-06

    Since the discovery of size-selective metal-organic frameworks (MOFs), researchers have tried to incorporate these materials into gas separation membranes. Impressive gas selectivities were found, but these MOF membranes were mostly made on inorganic supports, which are generally too bulky and expensive for industrial gas separation. Forming MOF layers on porous polymer supports is industrially attractive but technically challenging. Two features to overcome these problems are described: 1) a metal chelating support polymer to bind the MOF layer, and 2) control of MOF crystal growth by contra-diffusion, aiming at a very thin nanocrystalline MOF layer. Using a metal chelating poly-thiosemicarbazide (PTSC) support and adjusting the metal and organic ligand concentrations carefully, a very compact ZIF-8 (ZIF=zeolitic imidazolate framework) layer was produced that displayed interference colors because of its smooth surface and extreme thinness-within the range of visible light. High performances were measured in terms of hydrogen/propane (8350) and propylene/propane (150) selectivity.

  6. Controlled hydrothermal growth of ZnO nanostructures by sequestering the Zn metal ions with the chelating agent EDTA

    NASA Astrophysics Data System (ADS)

    Ram, S. D. Gopal; Ravi, G.; Manikandan, MR.; Mahalingam, T.; Anbu Kulandainathan, M.

    2011-10-01

    In the present work, a controlled growth of ZnO nanostructures by manipulating Zn metal ion concentration by the chelating action of ethylene diaminetetra acetic acid in hydrothermal method is studied. EDTA produces metal-chelate complex by the formation of bidentate ligand with Zn 2+ in the solution and diminishes the reactivity of Zn metal cations. Concentration of EDTA in the mother solution was varied in different ranges like 3, 5 and 10 mM while retaining the zinc metal salt and the NaOH concentration the same. Three different morphologies of wurtzite structured ZnO nanostructures such as nanorods-bunch, separate/discrete uniformly sized hexagonal nanorods and tapered flower petals like shapes are achieved by 3, 5 and 10 mM strengths of EDTA, respectively. The medium concentration 5 mM of EDTA is found to have moderate control over producing ZnO nanostructures of uniform diameter and a high aspect (length to diameter) ratio. An array of vertically aligned free standing ZnO nanorods with uniform spacing is successfully achieved by the addition of 5 mM of EDTA in the mother solution and the same is studied for its fluorescence property at an excitation of 325 nm and it has exhibited a characteristic UV emission of ZnO around 383 nm.

  7. Universal dispersing agent for electrophoretic deposition of inorganic materials with improved adsorption, triggered by chelating monomers.

    PubMed

    Liu, Yangshuai; Luo, Dan; Ata, Mustafa S; Zhang, Tianshi; Wallar, Cameron J; Zhitomirsky, Igor

    2016-01-15

    Poly[1-[4-(3-carboxy-4-hydroxyphenylazo)benzenesulfonamido]-1,2-ethanediyl, sodium salt] (PAZO) is a polymeric functional material with a number of unique physical properties, which attracted significant interest of different scientific communities. Films of PAZO were deposited by anodic electrophoretic deposition (EPD) under constant current and constant voltage conditions. The deposition kinetics was analyzed under different conditions and the deposition mechanism was discussed. New strategy was developed for the EPD of different inorganic materials and composites using PAZO as a dispersing, charging, binding and film forming agent. It was found that PAZO exhibits remarkable adsorption on various inorganic materials due to the presence of chelating salicylate ligands in its molecular structure. The salicylate ligands of PAZO monomers provide multiple adsorption sites by complexation of metal atoms on particle surfaces and allow for efficient electrosteric stabilization of particle suspensions. The remarkable performance of PAZO in its application in EPD have been exemplified by deposition of a wide variety of inorganic materials including the single element oxides (NiO, ZnO, Fe2O3) the complex oxides (Al2TiO5, BaTiO3, ZrSiO4, CoFe2O4) different nitrides (TiN, Si3N4, BN) as well as pure Ni metal and hydrotalcite clay. The use of PAZO can avoid limitation of other dispersing agents in deposition and co-deposition of different materials. Composite films were obtained using PAZO as a co-dispersant for different inorganic materials. The deposit composition, microstructure and deposition yield can be varied. The EPD method offers the advantages of simplicity, high deposition rate, and ability to deposit thin or thick films.

  8. Removal of cadmium from fish sauce using chelate resin.

    PubMed

    Sasaki, Tetsuya; Araki, Ryohei; Michihata, Toshihide; Kozawa, Miyuki; Tokuda, Koji; Koyanagi, Takashi; Enomoto, Toshiki

    2015-04-15

    Fish sauce that is prepared from squid organs contains cadmium (Cd), which may be present at hazardous concentrations. Cd molecules are predominantly protein bound in freshly manufactured fish sauce, but are present in a liberated form in air-exposed fish sauce. In the present study, we developed a new method for removing both Cd forms from fish sauce using chelate resin and a previously reported tannin treatment. Sixteen-fold decreases in Cd concentrations were observed (0.78-0.05 mg/100 mL) following the removal of liberated Cd using chelate resin treatment, and the removal of protein-bound Cd using tannin treatment. Major nutritional components of fish sauce were maintained, including free amino acids and peptides, and angiotensin I-converting enzyme inhibitory and antioxidant activities.

  9. NCN-chelated organoantimony(III) and organobismuth(III) phosphates: synthesis and solid-state and solution structures.

    PubMed

    Svoboda, Tomáš; Dostál, Libor; Jambor, Roman; Růžička, Aleš; Jirásko, Robert; Lyčka, Antonín

    2011-07-18

    .Organoantimony(III) and organobismuth(III) phosphates (LM)(3)(PO(4))(2) [M = Sb (3) and Bi (4)], containing the NCN-chelating ligand L [L = 2,6-(CH(2)NMe(2))(2)C(6)H(3)], were prepared by the simple treatment of parent oxides 1 and 2 with H(3)PO(4). Both compounds were characterized by elemental analysis, electrospray ionization mass spectrometry, and IR and NMR spectroscopy and in the case of 3 by X-ray diffraction techniques. Compound 3 has an interesting behavior in solution, i.e., the formation of two possible conformational isomers, which was studied by (1)H, (13)C, and (31)P NMR spectroscopy.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. Mineral Levels in Thalassaemia Major Patients Using Different Iron Chelators.

    PubMed

    Genc, Gizem Esra; Ozturk, Zeynep; Gumuslu, Saadet; Kupesiz, Alphan

    2016-03-01

    The goal of the present study was to determine the levels of minerals in chronically transfused thalassaemic patients living in Antalya, Turkey and to determine mineral levels in groups using different iron chelators. Three iron chelators deferoxamine, deferiprone and deferasirox have been used to remove iron from patients' tissues. There were contradictory results in the literature about minerals including selenium, zinc, copper, and magnesium in thalassaemia major patients. Blood samples from the 60 thalassaemia major patients (the deferoxamine group, n = 19; the deferiprone group, n = 20 and the deferasirox group, n = 21) and the controls (n = 20) were collected. Levels of selenium, zinc, copper, magnesium, and iron were measured, and all of them except iron showed no significant difference between the controls and the patients regardless of chelator type. Serum copper levels in the deferasirox group were lower than those in the control and deferoxamine groups, and serum magnesium levels in the deferasirox group were higher than those in the control, deferoxamine and deferiprone groups. Iron levels in the patient groups were higher than those in the control group, and iron levels showed a significant correlation with selenium and magnesium levels. Different values of minerals in thalassaemia major patients may be the result of different dietary intake, chelator type, or regional differences in where patients live. That is why minerals may be measured in thalassaemia major patients at intervals, and deficient minerals should be replaced. Being careful about levels of copper and magnesium in thalassaemia major patients using deferasirox seems to be beneficial.

  15. 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.

  16. 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

  17. Lipophilic chelator inhibition of electron transport in Escherichia coli.

    PubMed Central

    Crane, R T; Sun, I L; Crane, F L

    1975-01-01

    The lipophilic chelator bathophenanthroline inhibits electron transport in membranes from Escherichia coli. The less lipophilic 1,10-phenanthroline, bathophenanthroline sulfonate, and alpha,alpha-dipyridyl have little effect. Reduced nicotinamide adenine dinucleotide oxidase is more sensitive to bathophenanthroline inhibition than lactate oxidase activity. Evidence for two sites of inhibition comes from the fact that both reduced nicotinamide adenine dinucleotide menadione reductase and duroquinol oxidase activities are inhibited. Addition of uncouplers of phosphorylation before bathophenanthroline protects against inhibition. PMID:1092663

  18. Chelation therapy and vanadium: effect on reproductive organs in rats.

    PubMed

    Shrivastava, Sadhana; Jadon, Anjana; Shukla, Sangeeta; Mathur, Ramesh

    2007-06-01

    Present investigation was planned to evaluate the therapeutic effectiveness of chelating agents against vanadium intoxication on blood and reproductive organs of rats. Male and female albino rats were injected vanadyl sulphate (7.5 mg/kg, po, for 21 days, 5 days in a week). Chelating agents tiron (T) alone and in combination with lipoic acid (LA), vitamin E (vit E) and selenium (Se) were given for 2 days/week. With the administration of vanadyl sulphate to rats fructose level in seminal vesicles was significantly (P< or =0.05) declined. The activities of alkaline phosphatase and adenosine triphosphatase were also decreased, whereas glycogen content and acid phosphatase activity increased in testis, seminal vesicles, ovaries and uterus after toxicant exposure. Significant changes in serum transaminases, serum alkaline phosphatase and lactate dehydrogenase were recouped by chelation therapy. Lipid peroxidation, reduced glutathione level and triglycerides levels altered significantly after exposure to vanadium in rats. The ultrastructural damage in spermatogenic stages in treated animals showed recovery pattern after therapy. Co-treatment with antioxidants restored these activities. The most effective combination was tiron + selenium followed by tiron + vitamin E, and tiron + lipoic acid.

  19. 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.

  20. Antibacterial and antibiofilm effects of iron chelators against Prevotella intermedia.

    PubMed

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

    2013-09-01

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

  1. 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.

  2. Hydroxyurea could be a good clinically relevant iron chelator.

    PubMed

    Italia, Khushnooma; Colah, Roshan; Ghosh, Kanjaksha

    2013-01-01

    Our previous study showed a reduction in serum ferritin of β-thalassemia patients on hydroxyurea therapy. Here we aimed to evaluate the efficacy of hydroxyurea alone and in combination with most widely used iron chelators like deferiprone and deferasirox for reducing iron from experimentally iron overloaded mice. 70 BALB/c mice received intraperitonial injections of iron-sucrose. The mice were then divided into 8 groups and were orally given hydroxyurea, deferiprone or deferasirox alone and their combinations for 4 months. CBC, serum-ferritin, TBARS, sTfr and hepcidin were evaluated before and after iron overload and subsequently after 4 months of drug therapy. All animals were then killed. Iron staining of the heart and liver tissue was done using Perl's Prussian Blue stain. Dry weight of iron in the heart and liver was determined by atomic absorption spectrometry. Increased serum-ferritin, TBARS, hepcidin and dry weight of iron in the liver and heart showed a significant reduction in groups treated with iron chelators with maximum reduction in the group treated with a combination of deferiprone, deferasirox and hydroxyurea. Thus hydroxyurea proves its role in reducing iron from iron overloaded mice. The iron chelating effect of these drugs can also be increased if given in combination.

  3. Proteomic profiling reveals that collismycin A is an iron chelator

    PubMed Central

    Kawatani, Makoto; Muroi, Makoto; Wada, Akira; Inoue, Gyo; Futamura, Yushi; Aono, Harumi; Shimizu, Kenshirou; Shimizu, Takeshi; Igarashi, Yasuhiro; Takahashi-Ando, Naoko; Osada, Hiroyuki

    2016-01-01

    Collismycin A (CMA), a microbial product, has anti-proliferative activity against cancer cells, but the mechanism of its action remains unknown. Here, we report the identification of the molecular target of CMA by ChemProteoBase, a proteome-based approach for drug target identification. ChemProteoBase profiling showed that CMA is closely clustered with di-2-pyridylketone 4,4-dimethyl-3-thiosemicarbazone, an iron chelator. CMA bound to both Fe(II) and Fe(III) ions and formed a 2:1 chelator-iron complex with a redox-inactive center. CMA-induced cell growth inhibition was completely canceled by Fe(II) and Fe(III) ions, but not by other metal ions such as Zn(II) or Cu(II). Proteomic and transcriptomic analyses showed that CMA affects the glycolytic pathway due to the accumulation of HIF-1α. These results suggest that CMA acts as a specific iron chelator, leading to the inhibition of cancer cell growth. PMID:27922079

  4. 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.

  5. A waste minimization study of a chelated copper complex in wastewater -- Treatability and process analysis

    SciTech Connect

    Chang, L.Y.

    1995-12-01

    This study demonstrated an integrated waste minimization approach for the printed circuit board manufacturing shop of Lawrence Berkeley Laboratory (LBL). It included process waste assessment, process optimization and treatability analysis of the treatment system, and source reduction assessment. The results of a process waste assessment indicated that over 99.5% of the waste stream was rinsewater and less than 0.5% was characterized as hazardous waste. This finding led to a thorough source reduction assessment. From the process and treatability analysis, it was found that an organic chelating ligand in the wastewater was causing a copper precipitation problem. The results of a series of bench and process experiments indicated that optimization of pH, chemical dosage, and addition of ferrous sulfate were needed to destabilize the complexed copper. The destabilization mechanism of Cu-EDTA with ferrous sulfate at pH 6--9 was discussed. Different separation/recycling technologies were also evaluated through the source reduction assessment. A closed-loop process was simulated and designed. Through the source reduction and treatment process optimization efforts, at least 90% reduction of total acid wastes and wastewater and more than 99% metal removal were achieved. A material life-cycle analysis was also performed. The results indicated that a total quality control strategy is crucial to minimize wastes and reduce product rejection rate.

  6. Five dimeric thiogermanates with transition metal complexes of multidentate chelating amines: Syntheses, structures, magnetism and photoluminescence

    NASA Astrophysics Data System (ADS)

    Liu, Guang-Ning; Guo, Guo-Cong; Wang, Ming-Sheng; Cai, Li-Zhen; Huang, Jin-Shun

    2010-11-01

    Five new thiogermanates, [Ni II(dien) 2] 2(Ge 2S 6) (dien = diethylenetriamine) ( 1), [Ni II(dien) 2](H 2pipe)(Ge 2S 6) (pipe = piperazine) ( 2), {[Mn II(tren)] 2( μ2-Ge 2S 6)} (tren = N,N,N-tris(2-aminoethyl)amine) ( 3) and {[M II(tepa)] 2( μ2-Ge 2S 6)} (M = Mn ( 4a), Ni ( 4b); tepa = tetraethylenepentamine), have been obtained solvothermally in the presence of tri-(L 3), tetra-(L 4) and penta-dentate (L 5) chelating amines and transition metal (TM) ions. Single-crystal X-ray diffraction analyses show that compounds 1- 2 are comprised of discrete (Ge 2S 6) 4- anions and TM complex (TMC) cations, while compounds 3- 4b are composed of each dimeric (Ge 2S 6) 4- anion bridging two TMC cations via TM-S bonds to form a neutral molecule. Notably, two interesting in situ metal/ligand reactions were observed in the solvothermal syntheses of 2 and 3. The present compounds exhibit wide optical gap ranging from 2.94 to 3.39 eV and photoluminescence with the emission maxima occurring around 440 ( 1, 2, 3 and 4b) and 489 nm ( 4a). Magnetic measurements show the presence of weak antiferromagnetic interactions between magnetic centers in the five compounds.

  7. 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.

  8. LigandRNA: computational predictor of RNA-ligand interactions.

    PubMed

    Philips, Anna; Milanowska, Kaja; Lach, Grzegorz; Bujnicki, Janusz M

    2013-12-01

    RNA molecules have recently become attractive as potential drug targets due to the increased awareness of their importance in key biological processes. The increase of the number of experimentally determined RNA 3D structures enabled structure-based searches for small molecules that can specifically bind to defined sites in RNA molecules, thereby blocking or otherwise modulating their function. However, as of yet, computational methods for structure-based docking of small molecule ligands to RNA molecules are not as well established as analogous methods for protein-ligand docking. This motivated us to create LigandRNA, a scoring function for the prediction of RNA-small molecule interactions. Our method employs a grid-based algorithm and a knowledge-based potential derived from ligand-binding sites in the experimentally solved RNA-ligand complexes. As an input, LigandRNA takes an RNA receptor file and a file with ligand poses. As an output, it returns a ranking of the poses according to their score. The predictive power of LigandRNA favorably compares to five other publicly available methods. We found that the combination of LigandRNA and Dock6 into a "meta-predictor" leads to further improvement in the identification of near-native ligand poses. The LigandRNA program is available free of charge as a web server at http://ligandrna.genesilico.pl.

  9. Analysis of macromolecules, ligands and macromolecule-ligand complexes

    DOEpatents

    Von Dreele, Robert B.

    2008-12-23

    A method for determining atomic level structures of macromolecule-ligand complexes through high-resolution powder diffraction analysis and a method for providing suitable microcrystalline powder for diffraction analysis are provided. In one embodiment, powder diffraction data is collected from samples of polycrystalline macromolecule and macromolecule-ligand complex and the refined structure of the macromolecule is used as an approximate model for a combined Rietveld and stereochemical restraint refinement of the macromolecule-ligand complex. A difference Fourier map is calculated and the ligand position and points of interaction between the atoms of the macromolecule and the atoms of the ligand can be deduced and visualized. A suitable polycrystalline sample of macromolecule-ligand complex can be produced by physically agitating a mixture of lyophilized macromolecule, ligand and a solvent.

  10. SERS Activity of Silver Nanoparticles Functionalized with A Desferrioxamine B Derived Ligand for FE(III) Binding and Sensing

    NASA Astrophysics Data System (ADS)

    Galinetto, P.; Taglietti, A.; Pasotti, L.; Pallavicini, P.; Dacarro, G.; Giulotto, E.; Grandi, M. S.

    2016-01-01

    We report the SERS activity of colloidal silver nanoparticles functionalized with a ligand, derived from the siderophore desferrioxamine B (desferal, DFO), an iron chelator widely used in biological and medical applications. The ligand was equipped with a sulfur-containing moiety to ensure optimal binding with silver surfaces. By means of Raman and SERS effects we monitored the route of material preparation from the modified DFO-S molecule to the colloidal aggregates. The results indicate that the functionalization of the chelating agent does not affect its binding ability towards Fe(III). The resulting functionalized silver nanoparticles are a promising SERS tag for operation in biological environments. The Fe-O stretching signature, arising when DFO-S grafted to silver nanoparticles binds Fe(III), could provide a tool for cation sensing in solution.

  11. The Effects of Iron Complexing Ligands on the Long Term Ecosystem Response to Iron Enrichment of HNLC waters

    SciTech Connect

    Mark L. Wells; Mary Jane Perry; William P. Cochlan; Charles G. Trick

    2006-11-18

    The central hypothesis of this project is that natural iron-complexing organic ligands in seawater differentially regulate iron availability to large (microplankton) and small (nano and picoplankton) class of phytoplankton and thereby strongly influence the potential carbon sequestration in High Nitrate Low Chlorophyll (HNLC) regions of the ocean. The primary project goals are to: 1) determine how different natural and synthetic Fe chelators affect Fe availability to phytoplankton species that are representative of offshore HNLC waters, 2) elucidate how the changes in absolute concentrations of these chelators affect the longer-term ecosystem response to alleviation of Fe limitation, and 3) ascertain how changes in the ligand composition affect rates of cell sinking and aggregation - representative measures of the efficiency of carbon sequestration to the deep.

  12. Chelation therapy in Wilson's disease: from D-penicillamine to the design of selective bioinspired intracellular Cu(I) chelators.

    PubMed

    Delangle, Pascale; Mintz, Elisabeth

    2012-06-07

    Wilson's disease is an orphan disease due to copper homeostasis dysfunction. Mutations of the ATP7B gene induces an impaired functioning of a Cu-ATPase, impaired Cu detoxification in the liver and copper overload in the body. Indeed, even though copper is an essential element, which is used as cofactor by many enzymes playing vital roles, it becomes toxic when in excess as it promotes cytotoxic reactions leading to oxidative stress. In this perspective, human copper homeostasis is first described in order to explain the mechanisms promoting copper overload in Wilson's disease. We will see that the liver is the main organ for copper distribution and detoxification in the body. Nowadays this disease is treated life-long by systemic chelation therapy, which is not satisfactory in many cases. Therefore the design of more selective and efficient drugs is of great interest. A strategy to design more specific chelators to treat localized copper accumulation in the liver will then be presented. In particular we will show how bioinorganic chemistry may help in the design of such novel chelators by taking inspiration from the biological copper cell transporters.

  13. Polymer-cobalt(III) complexes: structural analysis of metal chelates on DNA interaction and comparative cytotoxic activity.

    PubMed

    Nehru, Selvan; Arunachalam, Sankaralingam; Arun, Renganathan; Premkumar, Kumpati

    2014-01-01

    A new series of pendant-type polymer-cobalt(III) complexes, [Co(LL)2(BPEI)Cl](2+), (where BPEI = branched polyethyleneimine, LL = dipyrido[3,2-a:2',3'-c](6,7,8,9-tetrahydro)phenazine (dpqc), dipyrido[3,2-d:2',3'-f]quinoxaline (dpq) and imidazo[4,5-f]1,10-phenanthroline (ip)) each with three different degrees of coordination have been synthesized and characterized. Studies to know the mode and strength of interaction between these polymer-metal complexes and calf thymus DNA have been performed by UV-Visible absorption and emission techniques. Among these series, each polymer metal complex having higher binding strength with DNA has been selected to test against human cancer/normal cell lines. On the basis of these spectral studies, it is proposed that our polymer-metal complexes bind with DNA mainly through intercalation along with some electrostatic binding. The order of binding strength for the complexes with ligand, dpqc > dpq > ip. The analysis of the results suggests that polymer-cobalt(III) complexes with higher degree of coordination effectively binds with DNA due to the presence of large number of positively charged cobalt(III) chelates in the polymer chain which cooperatively act to increase the overall binding strength. These polymer-cobalt(III) complexes with hydrophobic ligands around the cobalt(III) metal centre favour the base stacking interactions via intercalation. All the complexes show very good anticancer activities and increasing of binding strength results in higher inhibition value. The polymer-cobalt(III) complex with dpqc ligand possess two fold increased anticancer activity when compared to complexes with other ligands against MCF-7 cells. Besides, the complexes were insensitive towards the growth of normal cells (HEK-293) at the IC50 concentration.

  14. Synthesis and structure of a Zwitterionic Nd complex containing aminophenoxide ligands

    NASA Astrophysics Data System (ADS)

    Wei, Pingrong; Atwood, David A.

    1999-03-01

    In the course of attempting to prepare molecular precursors to lanthanide-aluminum oxide materials the unique Zwitterionic complex, Nd(H 2L) 3(CF 3SO 3) 3 ( 1), was discovered (L = [2,4-( tBu) 2-6-(CH 2N iPr)PhO]). In the crystal structure of ( 1) the three-triflate groups and the three oxygens of the aminophenoxide ligand (H 2L) coordinate the Nd atom. To maintain charge balance the three ligands are protonated at the amine nitrogens. This explains the fact that the ligand is monodentate and does not displace one (or more) of the triflate groups to form a chelated cation. Both hydrogens of the ammonium groups are hydrogen-bonded to oxygens of the triflates.

  15. A new morphological approach for removing acid dye from leather waste water: preparation and characterization of metal-chelated spherical particulated membranes (SPMs).

    PubMed

    Şenay, Raziye Hilal; Gökalp, Safiye Meriç; Türker, Evren; Feyzioğlu, Esra; Aslan, Ahmet; Akgöl, Sinan

    2015-03-15

    In this study, p(HEMA-GMA) poly(hydroxyethyl methacrylate-co-glycidyl methacrylate) spherical particulated membranes (SPMs) were produced by UV-photopolymerization and the synthesized SPMs were coupled with iminodiacetic acid (IDA). Finally the novel SPMs were chelated with Cr(III) ions as ligand and used for removing acid black 210 dye. Characterizations of the metal-chelated SPMs were made by SEM, FTIR and swelling test. The water absorption capacities and acid dye adsorption properties of the SPMs were investigated and the results were 245.0, 50.0, 55.0 and 51.9% for p(HEMA), p(HEMA-GMA), p(HEMA-GMA)-IDA and p(HEMA-GMA)-IDA-Cr(III) SPMs respectively. Adsorption properties of the p(HEMA-GMA)-IDA-Cr(III) SPMs were investigated under different conditions such as different initial dye concentrations and pH. The optimum pH was observed at 4.3 and the maximum adsorption capacity was determined as 885.14 mg/g at about 8000 ppm initial dye concentration. The concentrations of the dyes were determined using a UV/Vis Spectrophotometer at a wavelength of 435 nm. Reusability of p(HEMA-GMA)-IDA-Cr(III) SPMs was also shown for five adsorption-desorption cycles without considerable decrease in its adsorption capacity. Finally, the results showed that the metal-chelated p(HEMA-GMA)-IDA SPMs were effective sorbent systems removing acid dye from leather waste water.

  16. Synthesis, physicochemical characterization, and biological evaluation of 2-(1'-hydroxyalkyl)-3-hydroxypyridin-4-ones: novel iron chelators with enhanced pFe(3+) values.

    PubMed

    Liu, Z D; Khodr, H H; Liu, D Y; Lu, S L; Hider, R C

    1999-11-18

    The synthesis of a range of 2-(1'-hydroxyalkyl)-3-hydroxypyridin-4-ones as bidentate iron(III) chelators with potential for oral administration is described. The pK(a) values of the ligands and the stability constants of their iron(III) complexes have been determined. Results indicate that the introduction of a 1'-hydroxyalkyl group at the 2-position leads to a significant improvement in the pFe(3+) values. Such an effect was found to be greater with the hydroxyethyl substituent than with the hydroxymethyl substituent, particularly in the cases of 1-ethyl-2-(1'-hydroxyethyl)-3-hydroxypyridin-4-one (pFe(3+) = 21.4) and 1,6-dimethyl-2-(1'-hydroxyethyl)-3-hydroxypyridin-4-one (pFe(3+) = 21.5) where an enhancement on pFe(3+) values in the region of two orders of magnitude is observed, as compared with Deferiprone (1, 2-dimethyl-3-hydroxypyridin-4-one) (pFe(3+) = 19.4). The ability of these novel 3-hydroxypyridin-4-ones to facilitate the iron excretion in bile was investigated using a [(59)Fe]ferritin-loaded rat model. Chelators and prodrug chelators possessing high pFe(3+) values show great promise in their ability to remove iron under in vivo conditions.

  17. Transition metal complexes of the pyridylphosphine ligand o-C6H4(CH2PPy2)2.

    PubMed

    Vaughan, Teresa F; Spencer, John L

    2016-11-14

    The synthesis and coordination behaviour of the pyridylphosphine ligand o-C6H4(CH2PPy2)2 (Py = 2-pyridyl) are reported. The phosphine selenide was synthesised and the (1)JPSe value of 738 Hz indicates the phosphorus atoms have a similar basicity to PPh3. The ligand reacts with platinum(ii) and palladium(ii) complexes to give simple diphosphine complexes of the type [MX2(PP)] (M = Pt, X = Cl, I, Me, Et; M = Pd, X = Cl, Me). When the ligand is reacted with chloromethyl(hexa-1,5-diene)platinum the [PtClMe(PP)] complex results, from which a series of unsymmetrical platinum complexes of the type [PtMeL(PP)](+) (L = PPh3, PTA, SEt2 and pyridine) can be made. This enabled the comparison of the cis and trans influences of a range of ligands. The following cis influence series was compiled based on (31)P NMR data of these complexes: Py ≈ Cl > SEt2 > PTA > PPh3. Reaction of [PtClMe(PP)] with NaCH(SO2CF3)2 and carbon monoxide slowly formed an acyl complex, where the CO had inserted in the Pt-Me bond. Attempts to achieve P,P,N chelation, through abstracting the chloride ligand in [PtClMe(PP)], were unsuccessful. When the ligand reacted with platinum(0), palladium(0) and silver(i) complexes the bis-chelated complexes [M(PP)2] (M = Pt, Pd) and [Ag(PP)2](+) were formed respectively. Reaction of the ligand with [Ir(COD)(μ-Cl)]2 formed [IrCl(PP)(COD)]. When the chloride ligand was abstracted, the pyridyl nitrogens were able to interact with the iridium centre facilitating the isomerisation of the 1,2,5,6-η(4)-COD ligand to a 1-κ-4,5,6-η(3)-C8H12 ligand. The X-ray crystal structure of [Ir(1-κ-4,5,6-η(3)-C8H12)(PPN)]BPh4 confirmed the P,P,N chelation mode of the ligand. In solution, this complex displayed hemilabile behaviour, with the pyridyl nitrogens exchanging at a rate faster than the NMR time scale at room temperature.

  18. Coupling of Ligands to the Liposome Surface by Click Chemistry.

    PubMed

    Spanedda, Maria Vittoria; De Giorgi, Marcella; Hassane, Fatouma Saïd; Schuber, Francis; Bourel-Bonnet, Line; Frisch, Benoît

    2017-01-01

    Click chemistry represents a new bioconjugation strategy that can be used to conveniently attach various ligands to the surface of preformed liposomes. This efficient and chemoselective reaction involves a Cu(I)-catalyzed azide-alkyne cycloaddition which can be performed under mild experimental conditions in aqueous media. Here we describe the application of a model click reaction to the conjugation, in a single step, of unprotected α-1-thiomannosyl ligands, functionalized with an azide group, to liposomes containing a terminal alkyne-functionalized lipid anchor. Excellent coupling yields have been obtained in the presence of bathophenanthroline disulfonate, a water soluble copper-ion chelator, acting as a catalyst. No vesicle leakage is triggered by this conjugation reaction and the coupled mannose ligands are exposed at the surface of the liposomes. The major limitation of Cu(I)-catalyzed click reactions is that this conjugation is restricted to liposomes made of saturated (phospho)lipids. To circumvent that constraint, an example of alternative copper-free azide-alkyne click reaction has been developed. Molecular tools and results are presented here.

  19. EGF receptor ligands: recent advances

    PubMed Central

    Singh, Bhuminder; Carpenter, Graham; Coffey, Robert J.

    2016-01-01

    Seven ligands bind to and activate the mammalian epidermal growth factor (EGF) receptor (EGFR/ERBB1/HER1): EGF, transforming growth factor-alpha (TGFA), heparin-binding EGF-like growth factor (HBEGF), betacellulin (BTC), amphiregulin (AREG), epiregulin (EREG), and epigen (EPGN). Of these, EGF, TGFA, HBEGF, and BTC are thought to be high-affinity ligands, whereas AREG, EREG, and EPGN constitute low-affinity ligands. This focused review is meant to highlight recent studies related to actions of the individual EGFR ligands, the interesting biology that has been uncovered, and relevant advances related to ligand interactions with the EGFR. PMID:27635238

  20. 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

  1. Secondary interactions or ligand scrambling? Subtle steric effects govern the iridium(I) coordination chemistry of phosphoramidite ligands.

    PubMed

    Osswald, Tina; Rüegger, Heinz; Mezzetti, Antonio

    2010-01-25

    The like and unlike isomers of phosphoramidite (P*) ligands are found to react differently with iridium(I), which is a key to explaining the apparently inconsistent results obtained by us and other research groups in a variety of catalytic reactions. Thus, the unlike diastereoisomer (aR,S,S)-[IrCl(cod)(1 a)] (2 a; cod=1,5-cyclooctadiene, 1 a=(aR,S,S)-(1,1'-binaphthalene)-2,2'-diyl bis(1-phenylethyl)phosphoramidite) forms, upon chloride abstraction, the monosubstituted complex (aR,S,S)-[Ir(cod)(1,2-eta-1 a,kappaP)](+) (3 a), which contains a chelating P* ligand that features an eta(2) interaction between a dangling phenyl group and iridium. Under analogous conditions, the like analogue (aR,R,R)-1 a' gives the disubstituted species (aR,R,R)-[Ir(cod)(1 a',kappaP)(2)](+) (4 a') with monodentate P* ligands. The structure of 3 a was assessed by a combination of X-ray and NMR spectroscopic studies, which indicate that it is the configuration of the binaphthol moiety (and not that of the dangling benzyl N groups) that determines the configuration of the complex. The effect of the relative configuration of the P* ligand on its iridium(I) coordination chemistry is discussed in the context of our preliminary catalytic results and of apparently random results obtained by other groups in the iridium(I)-catalyzed asymmetric allylic alkylation of allylic acetates and in rhodium(I)-catalyzed asymmetric cycloaddition reactions. Further studies with the unlike ligand (aS,R,R)-(1,1'-binaphthalene)-2,2'-diyl bis{[1-(1-naphthalene-1-yl)ethyl]phosphoramidite} (1 b) showed a yet different coordination mode, that is, the eta(4)-arene-metal interaction in (aS,R,R)-[Ir(cod)(1,2,3,4-eta-1 b,kappaP)](+) (3 b).

  2. Anti-plasmodial activity of aroylhydrazone and thiosemicarbazone iron chelators: effect on erythrocyte membrane integrity, parasite development and the intracellular labile iron pool.

    PubMed

    Walcourt, Asikiya; Kurantsin-Mills, Joseph; Kwagyan, John; Adenuga, Babafemi B; Kalinowski, Danuta S; Lovejoy, David B; Lane, Darius J R; Richardson, Des R

    2013-12-01

    Iron chelators inhibit the growth of the malaria parasite, Plasmodium falciparum, in culture and in animal and human studies. We previously reported the anti-plasmodial activity of the chelators, 2-hydroxy-1-naphthylaldehyde isonicotinoyl hydrazone (311), 2-hydroxy-1-naphthylaldehyde 4-methyl-3-thiosemicarbazone (N4mT), and 2-hydroxy-1-naphthylaldehyde 4-phenyl-3-thiosemicarbazone (N4pT). In fact, these ligands showed greater growth inhibition of chloroquine-sensitive (3D7) and chloroquine-resistant (7G8) strains of P. falciparum in culture compared to desferrioxamine (DFO). The present study examined the effects of 311, N4mT and N4pT on erythrocyte membrane integrity and asexual parasite development. While the characteristic biconcave disk shape of the erythrocytes was unaffected, the chelators caused very slight hemolysis at IC50 values that inhibited parasite growth. The chelators 311, N4mT and N4pT affected all stages of the intra-erythrocytic development cycle (IDC) of P. falciparum in culture. However, while these ligands primarily affected the ring-stage, DFO inhibited primarily trophozoite and schizont-stages. Ring, trophozoite and schizont-stages of the IDC were inhibited by significantly lower concentrations of 311, N4mT, and N4pT (IC50=4.45±1.70, 10.30±4.40, and 3.64±2.00μM, respectively) than DFO (IC50=23.43±3.40μM). Complexation of 311, N4mT and N4pT with iron reduced their anti-plasmodial activity. Estimation of the intracellular labile iron pool (LIP) in erythrocytes showed that the chelation efficacy of 311, N4mT and N4pT corresponded to their anti-plasmodial activities, suggesting that the LIP may be a potential source of non-heme iron for parasite metabolism within the erythrocyte. This study has implications for malaria chemotherapy that specifically disrupts parasite iron utilization.

  3. Chromium(III) complexes of naturally occurring ligands

    NASA Astrophysics Data System (ADS)

    El-Shahawi, M. S.

    1995-02-01

    Chromium(III) complexes prepared from CrCl 3Py 3 and anhydrous CrCl 3 with L(-)-threonine, nicotinic acid, glycine, D(-)-penicillamine, L(-)-cysteine and L(-)-cystine have been characterized. The magnetic moments (3.4-4.05 B.M.) are close to the spin only value for a d3 chromium(III) ion in octahedral or pseudo octahedral symmetry. In the electronic spectra two sharp peaks are observed at (15.9-19.8) × 10 3 and (22.0-26.7) × 10 3 cm -1 and are assigned to d-d transitions in the pseudo octahedral configuration. The parameters ( Dq, B, β35) and the interelectronic repulsion parameter with the ionic charge, Z∗, are calculated and place the ligand in the middle of the spectrochemical series. In the circular dichroism spectra three Cotton effects are observed in the forbidden band of the optically active chelates and are assigned to the 2E( 2Eg), 2A 2( 2T 1g) and2E( 2T 1g) while that in the spin allowed band are a result of the splitting of the 4A 2g( 4T 2g) to 4A 1( 4T 2g) and4E( 4T 2g) transitions. The structure of threonine, cystine and cysteine chelates are likely to be fac since strong and well defined Cotton effects are observed. The Cotton effects of penicillamine chelates are weak suggesting formation of the mer structure. Prolonged heating or bubbling air through the solution of CrCl 3Py 3 containing L(-)-threonine, glycine or nicotinic acid for several hours enhances chromium(VI) formation.

  4. Fac-Re(bpy)(CO){sub 3}(COOMe): A model metallocarboxylate complex of rhenium with a bipyridyl ligand

    SciTech Connect

    Gibson, D.H.; Sleadd, B.A.; Vij, A.

    1999-05-01

    The title compound fac-(2,2{prime}-bipyridyl)(carbomethoxy)rhenium tricarbonyl, crystallizes in the monoclinic system, space group P2{sub 1}/c with the following crystal data: a = 8.37551(1), b = 6.6934(1), c = 26.2098(1) {angstrom}, V({angstrom}{sup 3}) = 1,535.93(3), Z = 4, and {beta} = 90.0971(2). The metal environment is slightly distorted octahedral with a chelating bipyridyl ligand and a facial arrangement of the carbon monoxide ligands.

  5. Selectivity in the aggregates of the chiral organolithium N-Boc-2-lithiopiperidine with a chiral ligand: a DFT study

    NASA Astrophysics Data System (ADS)

    Ince, Hasan H.; Dedeoglu, Burcu; Gul, Seref; Aviyente, Viktorya; Coldham, Iain

    2012-03-01

    In this paper the aggregates of the chiral organolithium N-Boc-2-lithiopiperidine [Boc=CO2C(CH3)3], which play an important role in the formation of chiral 2-substituted piperidines found in many alkaloid structures and medicinal compounds, have been investigated within the framework of Density Functional Theory (DFT) calculations. In the complex structures, the lithium atoms are tetra-coordinated, the diaminoalkoxide ligand is tridentate to one lithium atom and forms a chelate with the substrate which is stabilized by the solvent diethyl ether. The same type of bonding was observed for all the different ligand-bound structures; for ligands 6 and 7, which have bulky substituents, selectivity was in agreement with experiment. The results shed light on the microscopic structures of these species and suggest a potential ligand, 11, to yield high enantioselectivity.

  6. Coordination polymers of Ag(I) based on iminocarbene ligands involving metal-carbon and metal-heteroatom interactions

    NASA Astrophysics Data System (ADS)

    Netalkar, Sandeep P.; Netalkar, Priya P.; Revankar, Vidyanand K.

    2016-03-01

    The reaction of Ag2O with three novel imino-NHC ligands derived from 2-chloroacetophenone with pendant N-donor functional group incorporated by reaction with methoxyamine and 1-methyl/ethyl/n-butyl-substituted imidazoles afforded one-dimensional coordination polymers with [(-NHCarbene)Ag(NHCarbene-)PF6]n formulation involving both carbon-metal and heteroatom-metal interactions, the carbon and heteroatom involved in coordination to silver being from different molecule of the ligand. The complexes as well as the ligands were characterized by spectroscopic methods as well as the solid state structures determined in case of 2a, 3a and complex 5. The iminocarbene ligands serve as non-chelating building block for supramolecular silver assemblies.

  7. A new copper(II) Schiff base complex containing asymmetrical tetradentate N2O2 Schiff base ligand: Synthesis, characterization, crystal structure and DFT study

    NASA Astrophysics Data System (ADS)

    Grivani, Gholamhossein; Baghan, Sara Husseinzadeh; Vakili, Mohammad; Khalaji, Aliakbar Dehno; Tahmasebi, Vida; Eigner, Václav; Dušek, Michal

    2015-02-01

    A new copper (II) Schiff base complex, CuL1, was prepared from the reaction of asymmetrical Schiff base ligand of L1 and Cu(OAC)2 (L1 = salicylidene imino-ethylimino-pentan-2-one). The Schiff base ligand, L1, and its copper (II) complex, CuL1, have been characterized by elemental analysis (CHN) and FT-IR and UV-vis spectroscopy. In addition, 1H NMR was employed for characterization of the ligand. Thermogrametric analysis of the CuL1 reveals its thermal stability and its decomposition pattern shows that it is finally decomposed to the copper oxide (CuO). The crystal structure of CuL1 was determined by the single crystal X-ray analysis. The CuL1 complex crystallizes in the monoclinic system, with space group P21/n and distorted square planar coordination around the metal ion. The Schiff base ligand of L1 acts as a chelating ligand and coordinates via two nitrogen and two oxygen atoms to the copper (II) ion with C1 symmetry. The structure of the CuL1 complex was also studied theoretically at different levels of DFT and basis sets. According to calculated results the Csbnd O bond length of the salicylate fragment is slightly higher than that in the acetylacetonate fragment of ligand, which could be interpreted by resonance increasing between phenyl and chelated rings in ligand in relative to the acetylacetonate fragment.

  8. A chelate-stabilized ruthenium(sigma-pyrrolato) complex: resolving ambiguities in nuclearity and coordination geometry through 1H PGSE and 31P solid-state NMR studies.

    PubMed

    Foucault, Heather M; Bryce, David L; Fogg, Deryn E

    2006-12-11

    Reaction of RuCl2(PPh3)3 with LiNN' (NN' = 2-[(2,6-diisopropylphenyl)imino]pyrrolide) affords a single product, with the empirical formula RuCl[(2,6-iPr2C6H3)N=CHC4H3N](PPh3)2. We identify this species as a sigma-pyrrolato complex, [Ru(NN')(PPh3)2]2(mu-Cl)2 (3b), rather than mononuclear RuCl(NN')(PPh3)2 (3a), on the basis of detailed 1D and 2D NMR characterization in solution and in the solid state. Retention of the chelating, sigma-bound iminopyrrolato unit within 3b, despite the presence of labile (dative) chloride and PPh3 donors, indicates that the chelate effect is sufficient to inhibit sigma --> pi isomerization of 3b to a piano-stool, pi-pyrrolato structure. 2D COSY, SECSY, and J-resolved solid-state 31P NMR experiments confirm that the PPh3 ligands on each metal center are magnetically and crystallographically inequivalent, and 31P CP/MAS NMR experiments reveal the largest 99Ru-31P spin-spin coupling constant (1J(99Ru,31P) = 244 +/- 20 Hz) yet measured. Finally, 31P dipolar-chemical shift spectroscopy is applied to determine benchmark phosphorus chemical shift tensors for phosphine ligands in hexacoordinate ruthenium complexes.

  9. A Review on Iron Chelators in Treatment of Iron Overload Syndromes

    PubMed Central

    Mobarra, Naser; Shanaki, Mehrnoosh; Ehteram, Hassan; Nasiri, Hajar; Sahmani, Mehdi; Saeidi, Mohsen; Goudarzi, Mehdi; Pourkarim, Hoda; Azad, Mehdi

    2016-01-01

    Iron chelation therapy is used to reduce iron overload development due to its deposition in various organs such as liver and heart after regular transfusion. In this review, different iron chelators implicated in treatment of iron overload in various clinical conditions have been evaluated using more up-to-date studies focusing on these therapeutic agents. Deferoxamine, Deferiprone and Deferasirox are the most important specific US FDA-approved iron chelators. Each of these chelators has their own advantages and disadvantages, various target diseases, levels of deposited iron and clinical symptoms of the afflicted patients which may affect their selection as the best modality. Taken together, in many clinical disorders, choosing a standard chelator does not have an accurate index which requires further clarifications. The aim of this review is to introduce and compare the different iron chelators regarding their advantages and disadvantages, usage dose and specific applications. PMID:27928480

  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. Radiation protection and radiation recovery with essential metalloelement chelates

    SciTech Connect

    Sorenson, J.R.J.; Soderberg, L.S.F.; Chang, L.W.

    1995-12-01

    This review presents the roles of some essential metalloelement-dependent enzymes in tissue maintenance and function, and their responses to radiation injury in accounting for radiation protection and recovery effects observed for nontoxic doses of essential metalloelement compounds. Effects of biochemicals including water undergoing bond radiolysis and the effects of free radicals derived from diatomic oxygen account for the acute and chronic aspects of radiation injury. Copper chelates have radiation protection and radiation recovery activities and cause rapid recovery of immunocompetency and recovery from radiation-induced histopathology. Mice treated with Cu(II){sub 2}(3,5-disopropylsalicy-late){sub 4}[Cu(II){sub 2}(3,5-DIPS){sub 4}] had increased survival and corresponding increases in numbers of myeloid and multipotential progenitor cells early after irradiation and earlier recovery of immune reactivity. Examination of radiation-induced histopathology in spleen, bone marrow, thymus, and small intestine also revealed Cu(II){sub 2}(3,5-DIPS){sub 4}-mediated rapid recovery of radiation-induced histopathology. Most recently, Fe, Mn, and Zn complexes have also been found to prevent death in lethally irradiated mice. These pharmacological effects of essential metalloelement chelates can be understood as due to facilitation of de novo synthesis of essential metalloelement-dependent enzymes which have roles in preventing the accumulation of pathological concentrations of oxygen radicals or repairing biochemical damage caused by radiation-induced bond homolysis. Essential metalloelement chelates offer a physiological approach to prevention and/or treatment of radiation injury. 97 refs., 5 figs., 1 tab.

  12. Geometric isomerism in coordination cages based on tris-chelate vertices: a tool to control both assembly and host/guest chemistry.

    PubMed

    Metherell, Alexander J; Ward, Michael D

    2016-10-18

    This 'Perspective' article summarises recent work from the authors' research group on the exploitation of the simple fac/mer geometric isomerism of octahedral metal tris-chelates as a tool to control the chemistry of coordination cages based on bis(pyrazolyl-pyridine) ligands, in two different respects. Firstly this geometric isomerism plays a major role in controlling the guest binding properties of cages because a fac tris-chelate arrangement of pyrazolyl-pyridine chelates around a metal ion vertex results in formation of a convergent set of inwardly-directed C-H protons in a region of high positive electrostatic potential close to a metal cation. This collection of δ+ protons therefore provides a charge-assisted hydrogen-bond donor site, which interacts with the electron-rich regions of guest molecules that are of the correct size and shape to occupy the cage cavity, and the strength of this hydrogen-bonding interaction plays a major role in guest recognition in non-aqueous solvents. Secondly the ability to prepare mononuclear complexes with either a fac or mer arrangement of ligands provides an entry into the controlled, stepwise assembly of heterometallic cages based on a combination of kinetically inert and kinetically labile metal ions at different sites. This has allowed introduction of useful physical properties such as redox activity or luminescence, commonly associated with inert metal ions which are not amenable to participation in thermodynamic self-assembly processes, to be incorporated in a predictable way into the superstructures of coordination cages at specific sites.

  13. 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.

  14. Studies on Cu(II) ternary complexes involving an aminopenicillin drug and imidazole containing ligands

    NASA Astrophysics Data System (ADS)

    Regupathy, Sthanumoorthy; Nair, Madhavan Sivasankaran

    2010-02-01

    Equilibrium studies on the ternary complex systems involving ampicillin (amp) as ligand (A) and imidazole containing ligands viz., imidazole (Him), benzimidazole (Hbim), histamine (Hist) and histidine (His) as ligands (B) at 37 °C and I = 0.15 mol dm -3 (NaClO 4) show the presence of CuABH, CuAB and CuAB 2. The proton in the CuABH species is attached to ligand A. In the ternary complexes the ligand, amp(A) binds the metal ion via amino nitrogen and carbonyl oxygen atom. The CuAB (B = Hist/His)/CuAB 2 (B = Him/Hbim) species have also been isolated and the analytical data confirmed its formation. Non-electrolytic behavior and monomeric type of chelates have been assessed from their low conductance and magnetic susceptibility values. The electronic and vibrational spectral results were interpreted to find the mode of binding of ligands to metal and geometry of the complexes. This is also supported by the g tensor values calculated from ESR spectra. The thermal behaviour of complexes were studied by TGA/DTA. The redox behavior of the complexes has been studied by cyclic voltammetry. The antimicrobial activity and CT DNA cleavage study of the complexes show higher activity for ternary complexes.

  15. The intra-annular acylamide chelate-coordinated compound: The keto-tautomer of metal (II) milrinone complex

    NASA Astrophysics Data System (ADS)

    Gong, Yun; Liu, Jinzhi; Tang, Wang; Hu, Changwen

    2008-03-01

    In the presence of N, N'-dimethyllformamide (DMF), two isostructural metal (II)-milrinone complexes formulated as M(C 12H 8N 3O) 2 (M = Co 1 and Ni 2) have been synthesized and characterized by elemental analysis, IR, TG and single crystal X-ray diffraction. The two compounds crystallize in the tetragonal system, chiral space group P4 32 12. They exhibit similar two dimensional (2D) square grid-like framework, in which milrinone acts as a ditopic ligand with its terminal pyridine and intra-annular acylamide groups covalently bridging different metal centers. The intra-annular acylamide ligand shows a chelate-coordinated mode. Compounds 1 and 2 are stable under 200 °C. Compound 3 formulated as (C 12H 9N 3O) 4·H 2O was obtained in the presence of water, the water molecule in the structure leads to the racemization of compound 3 and it crystallizes in the monoclinic system, non-chiral space group P2 1/ c. Milrinone exhibits a keto-form in the three compounds and compounds 1- 3 exhibit different photoluminescence properties.

  16. Chelation and fluorescence properties of tetraphenylporphyrin and 5,10,15,20-tetra(4-hydroxyphenyl)porphyrin in acetonitrile

    NASA Astrophysics Data System (ADS)

    Ivanova, Yu. B.; Parfenov, A. S.; Mamardashvili, N. Zh.

    2017-01-01

    The kinetics of complex formation between zinc and 5,10,15,20-tetraphenylporphyrin and 5,10,15,20-tetra(4-hydroxyphenyl)porphyrin in acetonitrile is studied in the temperature range from 298 to 318 K. The fluorescent properties of these compounds are examined, the emission in the red region of the spectrum is measured, and the fluorescence quantum yields are determined. It is found that although the electronic absorption spectra of the studied compounds are almost identical, hydroxyl substituents are observed to have a considerable effect on the chelating ability of ligands. The rate constant of the formation of ZnT(4-OH-Ph)P is thus approximately three times higher than that of ZnTPhP, with the energy consumption being lower (about 20 kJ mol-1). The calculated fluorescence quantum yields of H2TPhP, H2T(4-OH-Ph) P, ZnTPhP, and ZnT(4-OH-Ph)P in acetonitrile are half those in toluene, while the ratio between the quantum yields of ligands and their metal complexes is a constant equal to approximately 3 and does not depend on which solvent is used.

  17. Synthesis, spectroscopic, coordination and biological activities of some organometallic complexes derived from thio-Schiff base ligands

    PubMed Central

    Abou-Hussein, Azza A.; Linert, Wolfgang

    2014-01-01

    Two series of mono- and binuclear complexes cyclic or acyclic thio-ferocine Schiff base ligands, derived from the condensation of 2-aminobenzenthiol (L) with monoacetyl ferrocene in the molar ratio 1:1 or in the molar ratio 1:2 for diacetyl ferocine have been prepared. The condensation reactions yield the corresponding Schiff Base ligands, HLa-Maf and H2Lb-Daf. The chelation of the ligands to metal ions occurs through the sulfur of the thiol group as well as the nitrogen atoms of the azomethine group of the ligands. HLa-Maf acts as monobasic bidentate or dibasic tetradentate, while H2Lb-Daf behaves as twice negatively cargend tetradentate ligand. The structures of these ligands were elucidated by elemental analysis, infrared, ultraviolet–visible spectra, as well as 1H NMR spectra. Reactions of the Schiff bases ligands with ruthenium(III), oxovanadium(IV) and dioxouranium(VI) afforded the corresponding transition metal complexes. The properties of the newly prepared complexes were analyse by elemental analyses, infrared, electronic spectra, 1H NMR as well as the magnetic susceptibility and conductivity measurement. The metal complexes exhibits different geometrical arrangements such as octahedral and square pyramidal coordination. Schiff base ligands and their metal complexes were tested against two pathogenic bacteria as Gram-positive and Gram-negative bacteria as well as one kind of fungi to study their biological activity. All the complexes exhibit antibacterial and antifungal activities against these organisms. PMID:24070648

  18. Metal complexes of ONO donor Schiff base ligand as a new class of bioactive compounds; Synthesis, characterization and biological evolution

    NASA Astrophysics Data System (ADS)

    Kumar Naik, K. H.; Selvaraj, S.; Naik, Nagaraja

    2014-10-01

    Present work reviews that, the synthesis of (E)-N";-((7-hydroxy-4-methyl-2-oxo-2H-chromen-8-yl)methylene)benzohydrazide [L] ligand and their metal complexes. The colored complexes were prepared of type [M2+L]X2, where M2+ = Mn, Co, Ni, Cu, Sr and Cd, L = (7-hydroxy-4-methyl-2-oxo-2H-chromen-8-yl)methylene)benzohydrazide, X = Cl-. Ligand derived from the condensation of 8-formyl-7-hydroxy-4-methylcoumarin and benzohydrazide in the molar ratio 1:1 and in the molar ratio 1:2 for metal complexes have been prepared. The chelation of the ligand to metal ions occurs through the both oxygen groups, as well as the nitrogen atoms of the azomethine group of the ligand. Reactions of the Schiff base ligand with Manganese(II), Cobalt(II), Nickel(II), Copper(II), Strontium(II), and Cadmium(II) afforded the corresponding metal complexes. The structures of the obtained ligand and their respective metal complexes were elucidated by infra-red, elemental analysis, Double beam UV-visible spectra, conductometric measurements, magnetic susceptibility measurements and also thermochemical studies. The metal complex exhibits octahedral coordination geometrical arrangement. Schiff base ligand and their metal complexes were tested against antioxidants, antidiabetic and antimicrobial activities have been studied. The Schiff base metal complexes emerges effective α-glucosidase inhibitory activity than free Schiff base ligand.

  19. Synthesis, spectroscopic, coordination and biological activities of some organometallic complexes derived from thio-Schiff base ligands

    NASA Astrophysics Data System (ADS)

    Abou-Hussein, Azza A.; Linert, Wolfgang

    2014-01-01

    Two series of mono- and binuclear complexes cyclic or acyclic thio-ferocine Schiff base ligands, derived from the condensation of 2-aminobenzenthiol (L) with monoacetyl ferrocene in the molar ratio 1:1 or in the molar ratio 1:2 for diacetyl ferocine have been prepared. The condensation reactions yield the corresponding Schiff Base ligands, HLa-Maf and H2Lb-Daf. The chelation of the ligands to metal ions occurs through the sulfur of the thiol group as well as the nitrogen atoms of the azomethine group of the ligands. HLa-Maf acts as monobasic bidentate or dibasic tetradentate, while H2Lb-Daf behaves as twice negatively cargend tetradentate ligand. The structures of these ligands were elucidated by elemental analysis, infrared, ultraviolet-visible spectra, as well as 1H NMR spectra. Reactions of the Schiff bases ligands with ruthenium(III), oxovanadium(IV) and dioxouranium(VI) afforded the corresponding transition metal complexes. The properties of the newly prepared complexes were analyse by elemental analyses, infrared, electronic spectra, 1H NMR as well as the magnetic susceptibility and conductivity measurement. The metal complexes exhibits different geometrical arrangements such as octahedral and square pyramidal coordination. Schiff base ligands and their metal complexes were tested against two pathogenic bacteria as Gram-positive and Gram-negative bacteria as well as one kind of fungi to study their biological activity. All the complexes exhibit antibacterial and antifungal activities against these organisms.

  20. Role of Coordination and Chelation in Utilization of Nutritionally Essential Trace Elements.

    DTIC Science & Technology

    BIOCHEMISTRY, *TRANSITION METALS), (*CHELATE COMPOUNDS, BIOCHEMISTRY), (*DIALYSIS, CHEMICAL ANALYSIS), NUTRITION , IRON, CHROMIUM, PHOSPHATES, AMINO ACIDS, HYDROXIDES, ALCOHOLS, PEPTIDES, MEMBRANES, LIQUID FILTERS

  1. Effect of metal chelators on the oxidative stability of model wine.

    PubMed

    Kreitman, Gal Y; Cantu, Annegret; Waterhouse, Andrew L; Elias, Ryan J

    2013-10-02

    Oxidation is a major problem with respect to wine quality, and winemakers have few tools at their disposal to control it. In this study, the effect of exogenous Fe(II) (bipyridine; Ferrozine) and Fe(III) chelators (ethylenediaminetetraacetic acid, EDTA; phytic acid) on nonenzymatic wine oxidation was examined. The ability of these chelators to affect the formation of 1-hydroxyethyl radicals (1-HER) and acetaldehyde was measured using a spin trapping technique with electron paramagnetic resonance (EPR) and by HPLC-PDA, respectively. The chelators were then investigated for their ability to prevent the oxidative loss of an important aroma-active thiol, 3-mercaptohexan-1-ol (3MH). The Fe(II)-specific chelators were more effective than the Fe(III) chelators with respect to 1-HER inhibition during the early stages of oxidation and significantly reduced oxidation markers compared to a control during the study. However, although the addition of Fe(III) chelators was less effective or even showed an initial pro-oxidant activity, the Fe(III) chelators proved to be more effective antioxidants compared to Fe(II) chelators after 8 days of accelerated oxidation. In addition, it is shown for the first time that Fe(II) and Fe(III) chelators can significantly inhibit the oxidative loss of 3MH in model wine.

  2. The Influence of Chelating Agents on the Kinetics of Calcite Dissolution.

    PubMed

    Fredd; Fogler

    1998-08-01

    The kinetics of calcite dissolution in the presence of calcium chelating agents was investigated over the pH range of 3.3-12 using a rotating disk apparatus. The results show that the rate of dissolution is increased significantly by the presence of chelating agents such as CDTA, DTPA, and EDTA. The rate of dissolution is influenced by the kinetics of the chelation reactions and varies considerably with pH and type of chelating agent. A surface chelation mechanism was introduced to describe the dissolution. The mechanism involves the adsorption of the chelating agent onto the calcite surface and follows Langmuir-Hinshelwood kinetics. The dissolution is different from conventional hydrogen ion attack in that the chelating agent attacks the calcium component of the lattice rather than the carbonate component. Therefore, the rate of dissolution is enhanced by the influence of hydrogen ion attack at low pH. In addition, the various ionic forms of the chelating agents react with the calcite surface at different rates depending on the number of hydrogen ions associated with the species. In general, the rate of dissolution increases with increasing protonation. The surface complexation mechanism was shown to describe the rate of calcite dissolution in the presence of chelating agents over the pH range of 4-12. Copyright 1998 Academic Press.

  3. Oxidation and reduction of bis(imino)pyridine iron dinitrogen complexes: evidence for formation of a chelate trianion.

    PubMed

    Tondreau, Aaron M; Stieber, S Chantal E; Milsmann, Carsten; Lobkovsky, Emil; Weyhermüller, Thomas; Semproni, Scott P; Chirik, Paul J

    2013-01-18

    Oxidation and reduction of the bis(imino)pyridine iron dinitrogen compound, ((iPr)PDI)FeN(2) ((iPr)PDI = 2,6-(2,6-(i)Pr(2)-C(6)H(3)-N═CMe)(2)C(5)H(3)N) has been examined to determine whether the redox events are metal or ligand based. Treatment of ((iPr)PDI)FeN(2) with [Cp(2)Fe][BAr(F)(4)] (BAr(F)(4) = B(3,5-(CF(3))(2)-C(6)H(3))(4)) in diethyl ether solution resulted in N(2) loss and isolation of [((iPr)PDI)Fe(OEt(2))][BAr(F)(4)]. The electronic structure of the compound was studied by SQUID magnetometry, X-ray diffraction, EPR and zero-field (57)Fe Mössbauer spectroscopy. These data, supported by computational studies, established that the overall quartet ground state arises from a high spin iron(II) center (S(Fe) = 2) antiferromagnetically coupled to a bis(imino)pyridine radical anion (S(PDI) = 1/2). Thus, the oxidation event is principally ligand based. The one electron reduction product, [Na(15-crown-5)][((iPr)PDI)FeN(2)], was isolated following addition of sodium naphthalenide to ((iPr)PDI)FeN(2) in THF followed by treatment with the crown ether. Magnetic, spectroscopic, and computational studies established a doublet ground state with a principally iron-centered SOMO arising from an intermediate spin iron center and a rare example of trianionic bis(imino)pyridine chelate. Reduction of the iron dinitrogen complex where the imine methyl groups have been replaced by phenyl substituents, ((iPr)BPDI)Fe(N(2))(2) resulted in isolation of both the mono- and dianionic iron dinitrogen compounds, [((iPr)BPDI)FeN(2)](-) and [((iPr)BPDI)FeN(2)](2-), highlighting the ability of this class of chelate to serve as an effective electron reservoir to support neutral ligand complexes over four redox states.

  4. Spectral, XRD, SEM and biological activities of transition metal complexes of polydentate ligands containing thiazole moiety

    NASA Astrophysics Data System (ADS)

    Neelakantan, M. A.; Marriappan, S. S.; Dharmaraja, J.; Jeyakumar, T.; Muthukumaran, K.

    2008-11-01

    Metal complexes of o-vanillidene-2-aminobenzothiazole have been prepared and characterized by elemental and spectral (vibrational, electronic, 1H NMR and EPR) data as well as magnetic susceptibility measurements and thermo gravimetric analysis (TG/DTA). The low molar conductance values reveal the non-electrolytic nature of these complexes. The elemental analysis suggests that the stoichiometry to be 1:2 (metal:ligand). Magnetic susceptibility data coupled with electronic spectra suggest that two ligands coordinate to each metal atom by phenolic oxygen and imino nitrogen to form high spin octahedral complex with Co(II), Mn(II) and Ni(II). The fifth and sixth position of metal ion is satisfied with water molecules. The thermal behaviour (TG/DTA) of the synthesised complexes shows that the complexes loss water molecules in the first step followed by decomposition of the ligand. Spin Hamiltonian parameters predict a distorted tetrahedral geometry for the copper complex. XRD and SEM analysis provide the crystalline nature and the morphology of the metal complexes. The in vitro biological activity of the metal chelates is tested against the Gram positive bacteria ( Bacillus amyloliquifacians) and gram negative bacteria ( Pseudomonas species), fungus ( Aspergillus niger) and yeast ( Sacchromyces cereviaceae). Most of the metal chelates exhibited higher biological activities.

  5. Metal chelation as a potential therapy for Alzheimer's disease.

    PubMed

    Cuajungco, M P; Fagét, K Y; Huang, X; Tanzi, R E; Bush, A I

    2000-01-01

    Alzheimer's disease is a rapidly worsening public health problem. The current lack of effective treatments for Alzheimer's disease makes it imperative to find new pharmacotherapies. At present, the treatment of symptoms includes use of acetylcholinesterase inhibitors, which enhance acetylcholine levels and improve cognitive functioning. Current reports provide evidence that the pathogenesis of Alzheimer's disease is linked to the characteristic neocortical amyloid-beta deposition, which may be mediated by abnormal metal interaction with A beta as well as metal-mediated oxidative stress. In light of these observations, we have considered the development of drugs that target abnormal metal accumulation and its adverse consequences, as well as prevention or reversal of amyloid-beta plaque formation. This paper reviews recent observations on the possible etiologic role of A beta deposition, its redox activity, and its interaction with transition metals that are enriched in the neocortex. We discuss the effects of metal chelators on these processes, list existing drugs with chelating properties, and explore the promise of this approach as a basis for medicinal chemistry in the development of novel Alzheimer's disease therapeutics.

  6. Hematein chelates of unusual metal ions for tinctorial histochemistry.

    PubMed

    Smith, A A

    2010-02-01

    Hematoxylin is oxidized easily to hematein, an excellent stain for metal ions. If it already is bound to a substrate, the metal ion becomes a mordant linking the dye to the substrate. Metal ions added to hematein in solution are chelated by the hematein to form a lake. Most of these chelates stain animal tissues. They usually are bound to the tissue by a combination of hydrogen bonding of the hematein and ionic bonding of the metal ion. When binding of the lake to the tissue occurs by way of the metal ion, the metal ion is a mordant. Mordant staining often is specific. Chromium hematoxylin binds to strong acids; it can be made selective for protein-bound sulfonic acids. Zirconyl hematoxylin is selective for acidic mucins. Mucihematein can be made selective for all acidic mucins or for sulfomucins alone. Bismuth hematoxylin appears to be selective for the guanido group of arginine and there is some evidence that the bonding is covalent. Although it is not a histochemical stain, copper-chrome hematoxylin is an excellent stain for organelles with double membranes, i.e., mitochondria and nuclei.

  7. 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.

  8. Functional characterization of the chloroplast ferric chelate oxidoreductase enzyme.

    PubMed

    Solti, Adám; Müller, Brigitta; Czech, Viktória; Sárvári, Éva; Fodor, Ferenc

    2014-05-01

    Iron (Fe) has an essential role in the biosynthesis of chlorophylls and redox cofactors, and thus chloroplast iron uptake is a process of special importance. The chloroplast ferric chelate oxidoreductase (cFRO) has a crucial role in this process but it is poorly characterized. To study the localization and mechanism of action of cFRO, sugar beet (Beta vulgaris cv Orbis) chloroplast envelope fractions were isolated by gradient ultracentrifugation, and their purity was tested by western blotting against different marker proteins. The ferric chelate reductase (FCR) activity of envelope fractions was studied in the presence of NAD(P)H (reductants) and FAD coenzymes. Reduction of Fe(III)-ethylenediaminetetraacetic acid was monitored spectrophotometrically by the Fe(II)-bathophenanthroline disulfonate complex formation. FCR activity, that is production of free Fe(II) for Fe uptake, showed biphasic saturation kinetics, and was clearly associated only to chloroplast inner envelope (cIE) vesicles. The reaction rate was > 2.5 times higher with NADPH than with NADH, which indicates the natural coenzyme preference of cFRO activity and its dependence on photosynthesis. FCR activity of cIE vesicles isolated from Fe-deficient plants also showed clear biphasic kinetics, where the KM of the low affinity component was elevated, and thus this component was down-regulated.

  9. Development of Peptoid-Based Ligands for the Removal of Cadmium from Biological Media

    PubMed Central

    Knight, Abigail S.; Zhou, Effie Y.; Francis, Matthew B.

    2015-01-01

    Cadmium poisoning poses a serious health concern due to cadmium’s increasing industrial use, yet there is currently no recommended treatment. The selective coordination of cadmium in a biological environment—i.e. in the presence of serum ions, small molecules, and proteins—is a difficult task. To address this challenge, a combinatorial library of peptoid-based ligands has been evaluated to identify structures that selectively bind to cadmium in human serum with minimal chelation of essential metal ions. Eighteen unique ligands were identified in this screening procedure, and the binding affinity of each was measured using metal titrations monitored by UV-vis spectroscopy. To evaluate the significance of each chelating moiety, sequence rearrangements and substitutions were examined. Analysis of a metal-ligand complex by NMR spectroscopy highlighted the importance of particular residues. Depletion experiments were performed in serum mimetics and human serum with exogenously added cadmium. These depletion experiments were used to compare and demonstrate the ability of these peptoids to remove cadmium from blood-like mixtures. In one of these depletion experiments, the peptoid sequence was able to deplete the cadmium to a level comparable to the reported acute toxicity limit. Evaluation of the metal selectivity in buffered solution and in human serum was performed to verify minimal off-target binding. These studies highlight a screening platform for of the identification of metal-ligands that are capable of binding in a complex environment. They additionally demonstrate the potential utility of biologically-compatible ligands for the treatment of heavy metal poisoning. PMID:26918113

  10. Development of peptoid-based ligands for the removal of cadmium from biological media

    DOE PAGES

    Knight, Abigail S.; Zhou, Effie Y.; Francis, Matthew B.

    2015-05-14

    Cadmium poisoning poses a serious health concern due to cadmium's increasing industrial use, yet there is currently no recommended treatment. The selective coordination of cadmium in a biological environment—i.e. in the presence of serum ions, small molecules, and proteins—is a difficult task. To address this challenge, a combinatorial library of peptoid-based ligands has been evaluated to identify structures that selectively bind to cadmium in human serum with minimal chelation of essential metal ions. Eighteen unique ligands were identified in this screening procedure, and the binding affinity of each was measured using metal titrations monitored by UV-vis spectroscopy. To evaluate themore » significance of each chelating moiety, sequence rearrangements and substitutions were examined. Analysis of a metal–ligand complex by NMR spectroscopy highlighted the importance of particular residues. Depletion experiments were performed in serum mimetics and human serum with exogenously added cadmium. These depletion experiments were used to compare and demonstrate the ability of these peptoids to remove cadmium from blood-like mixtures. In one of these depletion experiments, the peptoid sequence was able to deplete the cadmium to a level comparable to the reported acute toxicity limit. Evaluation of the metal selectivity in buffered solution and in human serum was performed to verify minimal off-target binding. These studies highlight a screening platform for the identification of metal–ligands that are capable of binding in a complex environment. They additionally demonstrate the potential utility of biologically-compatible ligands for the treatment of heavy metal poisoning.« less

  11. Development of peptoid-based ligands for the removal of cadmium from biological media

    SciTech Connect

    Knight, Abigail S.; Zhou, Effie Y.; Francis, Matthew B.

    2015-05-14

    Cadmium poisoning poses a serious health concern due to cadmium's increasing industrial use, yet there is currently no recommended treatment. The selective coordination of cadmium in a biological environment—i.e. in the presence of serum ions, small molecules, and proteins—is a difficult task. To address this challenge, a combinatorial library of peptoid-based ligands has been evaluated to identify structures that selectively bind to cadmium in human serum with minimal chelation of essential metal ions. Eighteen unique ligands were identified in this screening procedure, and the binding affinity of each was measured using metal titrations monitored by UV-vis spectroscopy. To evaluate the significance of each chelating moiety, sequence rearrangements and substitutions were examined. Analysis of a metal–ligand complex by NMR spectroscopy highlighted the importance of particular residues. Depletion experiments were performed in serum mimetics and human serum with exogenously added cadmium. These depletion experiments were used to compare and demonstrate the ability of these peptoids to remove cadmium from blood-like mixtures. In one of these depletion experiments, the peptoid sequence was able to deplete the cadmium to a level comparable to the reported acute toxicity limit. Evaluation of the metal selectivity in buffered solution and in human serum was performed to verify minimal off-target binding. These studies highlight a screening platform for the identification of metal–ligands that are capable of binding in a complex environment. They additionally demonstrate the potential utility of biologically-compatible ligands for the treatment of heavy metal poisoning.

  12. Ligand-induced haptotropic rearrangements in bis(indenyl)zirconium sandwich complexes.

    PubMed

    Bradley, Christopher A; Lobkovsky, Emil; Keresztes, Ivan; Chirik, Paul J

    2005-07-27

    Addition of principally sigma-donating ligands such as THF, chelating diethers, or 1,2-bis(dimethyl)phosphinoethane to eta(9),eta(5)-bis(indenyl)zirconium sandwich complexes, (eta(9)-C(9)H(5)-1,3-R(2))(eta(5)-C(9)H(5)-1,3-R(2))Zr (R = alkyl or silyl), induces haptotropic rearrangement to afford (eta(6)-C(9)H(5)-1,3-R(2))(eta(5)-C(9)H(5)-1,3-R(2))ZrL adducts. Examples where L = THF and DME have been characterized by X-ray diffraction and revealed significant buckling of the eta(6) benzo ring, consistent with reduction of the arene, and highlight the importance of the zirconium(IV) canonical form. For the THF-induced haptotropic rearrangements, the thermodynamic driving force for ring migration has been measured as a function of indenyl substituent and demonstrates silylated sandwiches favor THF coordination and the eta(6),eta(5) bonding motif over their alkylated counterparts. In the case of chelating diethers, measurement of the corresponding equilibrium constants establish more stable eta(6),eta(5) adducts with five- over four-membered chelates and with smaller oxygen and carbon backbone substituents. Kinetic studies on both THF and DME addition to (eta(9)-C(9)H(5)-1,3-(SiMe(3))(2))(eta(5)-C(9)H(5)-1,3-(SiMe(3))(2))Zr established a first-order dependence on the incoming ligand, consistent with a mechanism involving direct attack of the incoming nucleophile on the eta(9),eta(5) sandwich. These results further highlight the ability of the indenyl ligand to smoothly adjust hapticity to meet the electronic requirements of the metal center.

  13. Melatonin: functions and ligands.

    PubMed

    Singh, Mahaveer; Jadhav, Hemant R

    2014-09-01

    Melatonin is a chronobiotic substance that acts as synchronizer by stabilizing bodily rhythms. Its synthesis occurs in various locations throughout the body, including the pineal gland, skin, lymphocytes and gastrointestinal tract (GIT). Its synthesis and secretion is controlled by light and dark conditions, whereby light decreases and darkness increases its production. Thus, melatonin is also known as the 'hormone of darkness'. Melatonin and analogs that bind to the melatonin receptors are important because of their role in the management of depression, insomnia, epilepsy, Alzheimer's disease (AD), diabetes, obesity, alopecia, migraine, cancer, and immune and cardiac disorders. In this review, we discuss the mechanism of action of melatonin in these disorders, which could aid in the design of novel melatonin receptor ligands.

  14. Combining bifunctional chelator with (3 + 2)-cycloaddition approaches: synthesis of dual-function technetium complexes.

    PubMed

    Braband, Henrik; Imstepf, Sebastian; Benz, Michael; Spingler, Bernhard; Alberto, Roger

    2012-04-02

    A new concept for the synthesis of dual-functionalized technetium (Tc) compounds is presented, on the basis of the reactivity of fac-{Tc(VII)O(3)}(+) complexes. The concept combines the "classical" bifunctional chelator (BFC) approach with the new ligand centered labeling strategy of fac-{TcO(3)}(+) complexes with alkenes ((3 + 2)-cycloaddition approach). To evidence this concept, fac-{(99)TcO(3)}(+) model complexes containing functionalized 1,4,7-triazacyclononane (tacn) derivatives N-benzyl-2-(1,4,7-triazonan-1-yl)acetamide (tacn-ba) and 2,2',2″-(1,4,7-triazonane-1,4,7-triyl)triacetic acid (nota·3H) were synthesized and characterized. Whereas [(99)TcO(3)(tacn-ba)](+) [2](+) can be synthesized following a established oxidation procedure starting from the Tc(V) complex [(99)TcO(glyc)(tacn-ba)](+) [1](+), a new synthetic pathway for the synthesis of [(99)TcO(3)(nota)](2-) [5](2-) had to be developed, starting from [(99)Tc(nota·3H)(CO)(3)](+) [4](+) and using sodium perborate tetrahydrate (NaBO(3)·4H(2)O) as oxidizing reagent. While [(99)TcO(3)(nota)](2-) [5](2-) is a very attractive candidate for the development of trisubstituted novel multifunctional radioprobes, (3 + 2)-cycloaddition reactions of [(99)TcO(3)(tacn-ba)](+) [2](+) with 4-vinylbenzenesulfonate (styrene-SO(3)(-)) demonstrated the suitability of monosubstituted tacn derivatives for the new mixed "BFC-(3 + 2)-cycloaddition" approach. Kinetic studies of this reaction lead to the conclusion that the alteration of the electronic structure of the nitrogen donors by, e.g., alkylation can be used to tune the rate of the (3 + 2)-cycloaddition.

  15. From early prophylaxis to delayed treatment: Establishing the plutonium decorporation activity window of hydroxypyridinonate chelating agents.

    PubMed

    An, Dahlia D; Kullgren, Birgitta; Jarvis, Erin E; Abergel, Rebecca J

    2017-04-01

    The potential consequences of a major radiological event are not only large-scale external radiation exposure of the population, but also uncontrolled dissemination of, and internal contamination with, radionuclides. When planning an emergency response to radiological and nuclear incidents, one must consider the need for not only post-exposure treatment for contaminated individuals, but also prophylactic measures to protect the workforce facing contaminated areas and patients in the aftermath of such events. In addition to meeting the desired criteria for post-exposure treatments such as safety, ease of administration, and broad-spectrum efficacy against multiple radionuclides and levels of challenge, ideal prophylactic countermeasures must include rapid onset; induce minimal to no performance-decrementing side effects; be compatible with current military Chemical, Biological, Radiological, Nuclear, and Explosive countermeasures; and require minimal logistical burdens. Hydroxypyridinone-based actinide decorporation agents have shown the most promise as decorporation strategies for various radionuclides of concern, including the actinides plutonium and americium. The studies presented here probe the extent of plutonium decorporation efficacy for two chelating agents, 3,4,3-LI(1,2-HOPO) and 5-LIO(Me-3,2-HOPO), from early pre-exposure time points to a delay of up to 7 days in parenteral or oral treatment administration, i.e., well beyond the initial hours of emergency response. Despite delayed treatment after a contamination event, both ligands clearly enhanced plutonium elimination through the investigated 7-day post-treatment period. In addition, a remarkable prophylactic efficacy was revealed for 3,4,3-LI(1,2-HOPO) with treatment as early as 48 h before the plutonium challenge. This work provides new perspectives in the indication and use of experimental actinide decorporation treatments.

  16. A Novel Europium Chelate Coated Nanosphere for Time-Resolved Fluorescence Immunoassay.

    PubMed

    Shen, Yifeng; Xu, Shaohan; He, Donghua

    2015-01-01

    A novel europium ligand 2,2',2'',2'''-(4,7-diphenyl-1,10-phenanthroline-2,9-diyl) bis (methylene) bis (azanetriyl) tetra acetic acid (BC-EDTA) was synthesized and characterized. It shows an emission spectrum peak at 610 nm when it is excited at 360 nm, with a large Stock shift (250 nm). It is covalently coated on the surface of a bare silica nanosphere containi free amino groups, using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride and N-Hydroxysuccinimide. We also observed an interesting phenomenon that when BC-EDTA is labeled with a silica nanosphere, the chelate shows different excitation spectrum peaks of about 295 nm. We speculate that the carboxyl has a significant influence on its excitation spectrum. The BC-EDTA/Eu3+coated nanosphere could be used as a fluorescent probe for time-resolved fluorescence immunoassay. We labeled the antibody with the fluorescent nanosphere to develop a nanosphere based hepatitis B surface antigen as a time-resolved fluorescence immunoassay reagent, which is very easy to operate and eliminates potential contamination of Eu3+ contained in the environment. The analytical and functional sensitivities are 0.0037 μg/L and 0.08 μg/L (S/N≥2.0) respectively. The detection range is 0.08-166.67 μg/L, which is much wider than that of ELISA (0.2-5 μg/L). It is comparable to the commercial dissociation-enhanced lanthanide fluoro-immunoassay system (DELFIA) reagents (0.2-145 μg/L). We propose that it can fulfill clinical applications.

  17. Lead(II) binding to the chelating agent D-penicillamine in aqueous solution.

    PubMed

    Sisombath, Natalie S; Jalilehvand, Farideh; Schell, Adam C; Wu, Qiao

    2014-12-01

    A spectroscopic investigation of the complexes formed between the Pb(II) ion and D-penicillamine (H2Pen), a chelating agent used in the treatment of lead poisoning, was carried out on two sets of alkaline aqueous solutions with CPb(II) ≈ 10 and 100 mM, varying the H2Pen/Pb(II) molar ratio (2.0, 3.0, 4.0, 10.0). Ultraviolet-visible (UV-vis) spectra of the 10 mM Pb(II) solutions consistently showed an absorption peak at 298 nm for S(-) → Pb(II) ligand-to-metal charge-transfer. The downfield (13)C NMR chemical shift for the penicillamine COO(-) group confirmed Pb(II) coordination. The (207)Pb NMR chemical shifts were confined to a narrow range between 1806 ppm and 1873 ppm for all Pb(II)-penicillamine solutions, indicating only small variations in the speciation, even in large penicillamine excess. Those chemical shifts are considerably deshielded, relative to the solid-state (207)Pb NMR isotropic chemical shift of 909 ppm obtained for crystalline penicillaminatolead(II) with Pb(S,N,O-Pen) coordination. The Pb LIII-edge extended X-ray absorption fine structure (EXAFS) spectra obtained for these solutions were well-modeled with two Pb-S and two Pb-(N/O) bonds with mean distances 2.64 ± 0.04 Å and 2.45 ± 0.04 Å, respectively. The combined spectroscopic results, reporting δ((207)Pb) ≈ 1870 ppm and λmax ≈ 298 nm for a Pb(II)S2NO site, are consistent with a dominating 1:2 lead(II):penicillamine complex with [Pb(S,N,O-Pen)(S-HnPen)](2-n) (n = 0-1) coordination in alkaline solutions, and provide useful structural information on how penicillamine can function as an antidote against lead toxicity in vivo.

  18. FTIR, magnetic, 1H NMR spectral and thermal studies of some chelates of caproic acid: Inhibitory effect on different kinds of bacteria

    NASA Astrophysics Data System (ADS)

    Refat, Moamen S.; El-Korashy, Sabry A.; Kumar, Deo Nandan; Ahmed, Ahmed S.

    2008-06-01

    A convenient method for the preparation of complexes of the Cr 3+, Mn 2+, Fe 3+, Co 2+, Ni 2+, Zn 2+, ZrO 2+, UO 22+, Zr 4+ and Th 4+ ions with caproic acid (Hcap) is reported and this has enabled 10 complexes of caproate anion to be formulated: [Cr(cap) 3]·5H 2O, [Mn(cap) 2(H 2O) 2], [Fe(cap) 3]·12H 2O, [Co(cap) 2(H 2O) 2]·4H 2O, [Ni(cap) 2(H 2O) 2]·3H 2O, [Zn(cap) 2], [ZrO(cap) 2]·3H 2O, [UO 2(cap)(NO 3)], [Zr(cap) 2(Cl) 2] and [Th(cap) 4]. These new complexes were synthesized and characterized by elemental analysis, molar conductivity, magnetic measurements, spectral methods (mid infrared, 1H NMR and UV-vis spectra) and simultaneous thermal analysis (TG and DTG) techniques. It has been found from the elemental analysis as well as thermal studies that the caproate ligand behaves as bidentate ligand and forming chelates with 1:1 (metal:ligand) stoichiometry for UO 22+, 1:2 for (Mn 2+, Co 2+, Ni 2+, Zn 2+, ZrO 2+ and Zr 4+), 1:3 stoichiometry for (Cr 3+ and Fe 3+) and 1:4 for Th 4+ caproate complexes, respectively, as bidentate chelating. The molar conductance measurements proved that the caproate complexes are non-electrolytes. The kinetic thermodynamic parameters such as: E*, Δ H*, Δ S* and Δ G* are estimated from the DTG curves. The antibacterial activity of the caproic acid and their complexes was evaluated against some gram positive/negative bacteria.

  19. The removal of mercury from water by open chain ligands containing multiple sulfurs.

    PubMed

    Hutchison, Aaron; Atwood, David; Santilliann-Jiminez, Q Eduardo

    2008-08-15

    Mercury pollution is a serious challenge faced by environmental chemists over the world. For several years now, our group has been developing new compounds to precipitate and thereby remove mercury from water. In this paper, we present a new family of alkyl thiol mercury chelates to add to the aromatic ligands we have previously reported. These new compounds are effective at precipitating mercury from water and with an excess of the best compound, removal is quantitative. Furthermore, the precipitates are stable and released little to no mercury back into solution during leaching studies.

  20. Palladium Complexes with the Tridentate Dianionic Ligand Pyridine-2,6-dicarboxylate, dipic. Crystal Structure of [Pd(dipic)(PBu(3))](2).

    PubMed

    Espinet, Pablo; Miguel, Jesús A.; García-Granda, Santiago; Miguel, Daniel

    1996-04-10

    The reactions of [Pd(acac)(2)] or [Pd(OAc)(2)](3) with pyridine-2,6-dicarboxylic acid (H(2)dipic) in acetonitrile afford [Pd(dipic)(NCMe)] in high yield. This complex has been used as starting material in the preparation of a variety of neutral an anionic complexes. The dipicolinate anion behaves as a tridentate ligand in all cases, but two modes of coordination are found, depending on the ligand: as a pincer ligand O,N,O-bonded to the same palladium, giving mononuclear complexes, and as an O,N-chelate N,O'-bridging ligand in dinuclear complexes. An X-ray determination of the structure of a dimer, [Pd(dipic)(PBu(3))](2) (monoclinic, space group P2(1)/n, a = 18.144(4) Å, b = 13.191(2) Å, c = 19.571(3) Å, beta = 113.45(2) degrees, Z = 4, R = 0.050, R(w) = 0.054) shows that the ligand is coordinated to one palladium in a eta(2)-N,O chelate fashion and one oxygen atom of the other carboxylate group makes a bridge to the other palladium atom, in a novel bonding mode for the dipic ligand.

  1. Design of a Water Soluble Fluorescent 3-Hydroxy-4-Pyridinone Ligand Active at Physiological pH Values.

    PubMed

    Leite, Andreia; Silva, Ana M G; Coutinho, Catarina; Cunha-Silva, Luís; de Castro, Baltazar; Rangel, Maria

    2016-09-01

    In the present work we report the structure and the spectroscopic characterization of a new fluorescent 3-hydroxy-4-pyridinone ligand D-3,4-HPO. The synthesis of the compound was performed in two steps, which involve the reaction of the commercially available fluorophore dansyl chloride with a 3-hydroxy-4-pyridinone chelating unit and further deprotection. The new fluorescent chelator was characterized in the solid state by single-crystal X-ray diffraction and in solution by NMR, MS, absorption and fluorescence spectroscopies. The analysis of the variation of the absorption spectrum with pH allowed the determination of four pK a values (pK a1  = 3.50, pK a2  = 4.50, pK a3  = 9.60, pK a4  = 10.20) and establishment of the corresponding distribution diagram. The study of the fluorescence properties of the ligand show that in the pH range between 4 and 9 the fluorescence intensity is constant and has its maximum value thus allowing its further use at physiological pH values. The interaction of the ligand with copper(II) was accessed by fluorescence spectroscopy in MOPS buffer and the results show that the presence of copper(II) quenches the fluorescence of the ligand in ca 94 % at a ligand: metal ratio of 2:1. The latter result is consistent with the formation of a copper(II) complex with the bidentate ligand, as confirmed by the EPR spectroscopy. Graphical Abstract New water soluble fluorescent ligand active at physiological pH values.

  2. 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.

  3. 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...

  4. Infrared spectroscopic studies of dimethylglyoxime chelates of nickel, cobalt, copper, palladium and platinum

    NASA Astrophysics Data System (ADS)

    Panja, Prabhat K.; Bala, Sibsankar; Pal, Chadramadhab; Ghosh, Pradip N.

    1991-09-01

    Infrared spectra of dimethylglyoxime chelates of nickel, cobalt, copper, palladium and platinum are measured in the range 4000-200 cm -1. The shifts of the OH stretching frequencies caused by chelation provide information on hydrogen bonding. The frequency shifts and hydrogen bond distances are calculated from the Lippincott—Schroeder potential using X-ray crystallographic data and compared with the observed values.

  5. Luminescent 1-hydroxy-2-pyridinone chelates of lanthanides

    DOEpatents

    Raymond, Kenneth N.; Xu, Jide; Moore, Evan G.; Werner, Eric J.

    2013-10-15

    The present invention provides luminescent complexes between a lanthanide ion and an organic ligand which contains 1,2-hydroxypyridinone units. The complexes of the invention are stable in aqueous solutions and are useful as molecular probes, for example in medical diagnostics and bioanalytical assay systems. The invention also provides methods of using the complexes of the invention.

  6. Luminescent 1-hydroxy-2-pyridinone chelates of lanthanides

    DOEpatents

    Raymond, Kenneth N.; Xu, Jide; Moore, Evan G.; Werner, Eric J.

    2017-01-31

    The present invention provides luminescent complexes between a lanthanide ion and an organic ligand which contains 1,2-hydroxypyridinone units. The complexes of the invention are stable in aqueous solutions and are useful as molecular probes, for example in medical diagnostics and bioanalytical assay systems. The invention also provides methods of using the complexes of the invention.

  7. Comparison of 225actinium chelates: tissue distribution and radiotoxicity.

    PubMed

    Davis, I A; Glowienka, K A; Boll, R A; Deal, K A; Brechbiel, M W; Stabin, M; Bochsler, P N; Mirzadeh, S; Kennel, S J

    1999-07-01

    The biodistribution and tissue toxicity of intravenously administered 225-actinium (225Ac) complexed with acetate, ethylene diamine tetraacetic acid (EDTA), 1, 4, 7, 10, 13-pentaazacyclopentadecane-N, N', N", N"', N"-pentaacetic acid (PEPA), or the "a" isomer of cyclohexyl diethylenetriamine pentaacetic acid (CHX-DTPA), were examined. The percent of injected dose per organ and per gram of tissue for each chelate complex was determined. 225Ac-CHX-DTPA was evaluated further for radiotoxic effects. Mice receiving > or =185 kBq 225Ac-CHX-DTPA suffered 100% morbidity by 5 days and 100% mortality by 8 days postinjection, and all animals evaluated had significant organ damage. The in vivo instability of the 225Ac-CHX-DTPA complex likely allowed accumulation of free 225Ac in organs, which resulted in tissue pathology.

  8. Iron chelation therapy in myelodysplastic syndromes: where do we stand?

    PubMed Central

    Mitchell, Mhairi; Gore, Steven D; Zeidan, Amer M

    2014-01-01

    Anemia leading to transfusion dependency (TD) and iron overload (IO) is commonly observed in patients with myelodysplastic syndromes (MDS). In MDS, TD and IO have been retrospectively associated with inferior survival and worse clinical outcomes, including cardiac, hepatic and endocrine dysfunction, and, in some analyses, with leukemic progression and infectious complications. Although suggested by retrospective analyses, clear prospective documentation of the beneficial effects of iron chelation therapy (ICT) on organ function and survival in MDS patients with TD and IO is currently lacking. Consequently, the role of ICT in MDS patients with TD and IO remains a very controversial aspect in the management of MDS. In this review, the authors summarize the current knowledge regarding IO in MDS and the role of ICT. PMID:23991926

  9. 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.

  10. 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

  11. 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

  12. Copper, iron and the organic ligands that bind them - updates from San Francisco Bay and beyond

    NASA Astrophysics Data System (ADS)

    Buck, K. N.; Bundy, R.; Biller, D.; Bruland, K. W.; Barbeau, K.

    2015-12-01

    Building on more than 30 years of measurements in San Francisco Bay by Russ Flegal and others, the concentrations of dissolved manganese, iron, cobalt, nickel, copper, zinc, cadmium and lead were determined from a suite of water quality monitoring program stations in North, Central and South Bay using inductively coupled plasma- mass spectrometry following preconcentration on a Nobias-chelate PA1 resin. Given the importance of organic ligands in governing iron solubility and copper bioavailability in natural waters, the organic complexation of dissolved iron and copper in these samples was determined from multiple analytical windows applied to competitive ligand exchange- adsorptive cathodic stripping voltammetry. This study constitutes the first dataset of iron speciation in San Francisco Bay and expands upon prior work evaluating the potential for copper toxicity in this urbanized estuary. Recent advances in voltammetric techniques emerging from a Scientific Committee on Oceanic Research (SCOR) working group on metal-binding ligands in the marine environment, and insights gained from high-resolution ligand measurements from the U.S. GEOTRACES program, highlight how metal-binding ligands in San Francisco Bay compare with those of the coastal and open ocean.

  13. Metal complexes with oxygen-functionalized NHC ligands: synthesis and applications.

    PubMed

    Hameury, Sophie; de Frémont, Pierre; Braunstein, Pierre

    2017-02-06

    Ligand design has met with considerable success with both categories of hybrid ligands, which are characterized by chemically different donor groups, and of N-heterocyclic carbenes (NHCs). Their spectacular development and diversity are attracting worldwide interest and offers almost unlimited diversity and potential in e.g. coordination/organometallic main group and transition metal chemistry, catalysis, medicinal chemistry and materials science. This review aims at providing a comprehensive update on a specific class of ligands that has enjoyed much attention in the past few years, at the intersection between the two categories mentioned above, that of hybrid NHC ligands in which the functionality associated with the carbene donor is of the oxygen-donor type. For each type of oxygen-donor present in such chelating (Section 1) or bridging (Section 2) hybrid ligands, we will examine the synthesis, structures and reactivity of their metal complexes and their applications, with a special focus on homogeneous catalysis (Section 3). Thus, hydrogenation, C-H bond activation, C-C, C-N, C-O bond formation, hydrolysis of silanes, oligomerization, polymerization, metathesis, hydrosilylation, C-C bond cleavage, acceptorless dehydrogenation, dehalogenation/hydrogen transfer, oxidation and reduction reactions will be successively presented in a tabular manner, to facilitate an overview and a rapid identification of the relevant publications describing which metals associated with a given oxygen functionality are most suitable. The literature coverage includes the year 2015.

  14. Effective chelation of iron in beta thalassaemia with the oral chelator 1,2-dimethyl-3-hydroxypyrid-4-one.

    PubMed Central

    Kontoghiorghes, G J; Aldouri, M A; Hoffbrand, A V; Barr, J; Wonke, B; Kourouclaris, T; Sheppard, L

    1987-01-01

    The main iron chelator used for transfusional iron overload is desferrioxamine, which is expensive, has toxic side effects, and has to be given subcutaneously. An orally active iron chelator is therefore required. The effects of oral 1,2-dimethyl-3-hydroxypyrid-4-one on urinary iron excretion were studied in eight patients who had received multiple transfusions: four had myelodysplasia and four beta thalassaemia major. Different daily doses of the drug up to 100 mg/kg/day, alone or in combination with ascorbic acid, were used. In three patients with thalassaemia the effect of the drug was compared with that of subcutaneous desferrioxamine at the same daily dose. In all eight patients a single dose of oral 1,2-dimethyl-3-hydroxypyrid-4-one resulted in substantial urinary iron excretion, mainly in the first 12 hours. Urinary iron excretion increased with the dose and with the degree of iron loading of the patient. Giving two or three divided doses over 24 hours resulted in higher urinary iron excretion than a single dose of the same amount over the same time. In most patients coadministration of oral ascorbic acid further increased urinary iron excretion. 1,2-Dimethyl-3-hydroxypyrid-4-one caused similar iron excretion to that achieved with subcutaneous desferrioxamine at a comparable dose. In some cases the iron excretion was sufficiently high (maximum 99 mg/day) to suggest that a negative iron balance could be easily achieved with these protocols in patients receiving regular transfusions. No evidence of toxicity was observed on thorough clinical examination or haematological and biochemical testing in any of the patients. None of the patients had any symptoms that could be ascribed to the drug. These results suggest that the oral chelator 1,2-dimethyl-3-hydroxypyrid-4-one is as effective as subcutaneous desferrioxamine in increasing urinary iron excretion in patients loaded with iron. Its cheap synthesis, oral activity, and lack of obvious toxicity at effective

  15. A 1,8-naphthalenediol-based unsymmetrical dinucleating ligand.

    PubMed

    Glaser, Thorsten; Liratzis, Ioannis; Fröhlich, Roland

    2005-09-07

    A facile synthesis of 2-formyl-1,8-naphthalenediol is reported. Its potential as a general precursor for the preparation of unsymmetrical multidentate chelating ligand systems based on 1,8-naphthalenediol is demonstrated by the synthesis of the dinucleating ligand L(4-)(H(4)L=N,N'-bis(2-(1,8-naphthalenediol)methylidene)propylenediamine). Reaction of H(4) L with copper acetate results in the formation of the unsymmetrical dinuclear Cu(II) complex [LCu(2)](3), which has been structurally characterized by single-crystal X-ray diffraction. One Cu(II) ion is coordinated by a N(2)O(2) compartment of L(4-) and the other Cu(II) ion is coordinated by an O(4) compartment of L(4-) while they are bridged by two aryloxide functions of L(4-). A dimerization of two molecules of 3 to a tetranuclear entity 3(2) occurs through formation of weak apical Cu--O interactions. Analysis of the temperature dependent magnetic susceptibility measurements (2--290 K) established a strong intradimer exchange coupling J(12)=-371 cm(-1). This strong superexchange interaction fits nicely in a magneto-structural correlation which has been established for dinuclear bis(phenoxide)-bridged Cu(II) complexes demonstrating the electronic equivalence of the aryloxides of a phenol and 1,8-naphthalenediol.

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

    PubMed Central

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

    2015-01-01

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

  17. Electronic Structure Determination of Pyridine N-Heterocyclic Carbene Iron Dinitrogen Complexes and Neutral Ligand Derivatives

    PubMed Central

    2015-01-01

    The electronic structures of pyridine N-heterocyclic dicarbene (iPrCNC) iron complexes have been studied by a combination of spectroscopic and computational methods. The goal of these studies was to determine if this chelate engages in radical chemistry in reduced base metal compounds. The iron dinitrogen example (iPrCNC)Fe(N2)2 and the related pyridine derivative (iPrCNC)Fe(DMAP)(N2) were studied by NMR, Mössbauer, and X-ray absorption spectroscopy and are best described as redox non-innocent compounds with the iPrCNC chelate functioning as a classical π acceptor and the iron being viewed as a hybrid between low-spin Fe(0) and Fe(II) oxidation states. This electronic description has been supported by spectroscopic data and DFT calculations. Addition of N,N-diallyl-tert-butylamine to (iPrCNC)Fe(N2)2 yielded the corresponding iron diene complex. Elucidation of the electronic structure again revealed the CNC chelate acting as a π acceptor with no evidence for ligand-centered radicals. This ground state is in contrast with the case for the analogous bis(imino)pyridine iron complexes and may account for the lack of catalytic [2π + 2π] cycloaddition reactivity. PMID:25328270

  18. Synthesis, characterization and biological activity of ferrocene-based Schiff base ligands and their metal (II) complexes

    NASA Astrophysics Data System (ADS)

    Liu, Yu-Ting; Lian, Gui-Dan; Yin, Da-Wei; Su, Bao-Jun

    Metal (II) complexes derived from S-benzyl-N-(1-ferrocenyl-3-(4-methylbenzene)acrylketone) dithiocarbazate; HL1, S-benzyl-N-(1-ferrocenyl-3-(4-chlorobenzene)acrylketone)dithiocarbazate; HL2, all the compounds were characterized using various spectroscopic techniques. The molar conductance data revealed that the chelates were non-electrolytes. IR spectra showed that the Schiff bases were coordinated to the metal ions in a bidentate manner with N, S donor sites. The ligands and their metal complexes have been screened for in vitro antibacterial, antifungal properties. The result of these studies have revealed that zinc (II) complexes 6 and 13 of both the ligands and copper (II) complexes 9 of the HL2 were observed to be the most active against all bacterial strains, antifungal activity was overall enhanced after complexation of the ligands.

  19. Synthesis, characterization and biological activity of ferrocene-based Schiff base ligands and their metal (II) complexes.

    PubMed

    Liu, Yu-Ting; Lian, Gui-Dan; Yin, Da-Wei; Su, Bao-Jun

    2013-01-01

    Metal (II) complexes derived from S-benzyl-N-(1-ferrocenyl-3-(4-methylbenzene)acrylketone) dithiocarbazate; HL(1), S-benzyl-N-(1-ferrocenyl-3-(4-chlorobenzene)acrylketone)dithiocarbazate; HL(2), all the compounds were characterized using various spectroscopic techniques. The molar conductance data revealed that the chelates were non-electrolytes. IR spectra showed that the Schiff bases were coordinated to the metal ions in a bidentate manner with N, S donor sites. The ligands and their metal complexes have been screened for in vitro antibacterial, antifungal properties. The result of these studies have revealed that zinc (II) complexes 6 and 13 of both the ligands and copper (II) complexes 9 of the HL(2) were observed to be the most active against all bacterial strains, antifungal activity was overall enhanced after complexation of the ligands.

  20. Multiple-path dissociation mechanism for mono- and dinuclear tris(hydroxamato)iron(III) complexes with dihydroxamic acid ligands in aqueous solution.

    PubMed

    Boukhalfa, H; Crumbliss, A L

    2000-09-18

    Linear synthetic dihydroxamic acids ([CH3N(OH)C=O)]2(CH2)n; H2Ln) with short (n = 2) and long (n = 8) hydrocarbon-connecting chains form mono- and dinuclear complexes with Fe(III) in aqueous solution. At conditions where the formation of Fe2(Ln)3 is favored, complexes with each of the two ligand systems undergo [H+]-induced ligand dissociation processes via multiple sequential and parallel paths, some of which are common and some of which are different for the two ligands. The pH jump induced ligand dissociation proceeds in two major stages (I and II) where each stage is shown to be comprised of multiple components (Ix, where x = 1-3 for L2 and L8, and IIy, where y = 1-3 for L2 and y = 1-4 for L8). A reaction scheme consistent with kinetic and independent ESI-MS data is proposed that includes the tris-chelated complexes (coordinated H2O omitted for clarity) (Fe2(Ln)3, Fe2(L2)2(L2H)2, Fe(LnH)3, Fe(L8)(L8H)), bis-chelated complexes (Fe2(Ln)2(2+), Fe(LnH)2+, Fe(L8)+), and monochelated complexes (Fe(LnH)2+). Analysis of kinetic data for ligand dissociation from Fe2(Ln)(LnH)3+ (n = 2, 4, 6, 8) allows us to estimate the dielectric constant at the reactive dinuclear Fe(III) site. The existence of multiple ligand dissociation paths for the dihydroxamic acid complexes of Fe(III) is a feature that distinguishes these systems from their bidentate monohydroxamic acid and hexadentate trihydroxamic acid counterparts and may be a reason for the biosynthesis of dihydroxamic acid siderophores, despite higher environmental molar concentrations necessary to completely chelate Fe(III).

  1. 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

  2. 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.

  3. Removal of pamidronate from bone in rats using systemic and local chelation

    PubMed Central

    Howie, R. Nicole; Bhattacharyya, Maryka; Salama, Mohamed; El Refaey, Mona; Isales, Carlos; Borke, James; Daoudi, Asma; Medani, Fardous; Elsalanty, Mohammed

    2015-01-01

    Objectives Bisphosphonates become adsorbed on hydroxyapatite crystals in the bone matrix. In case of side-effects, stopping the treatment would not affect the bisphosphonates already deposited in bone. This study tests the feasibility of in-vivo targeted removal of bisphosphonates from bone using chelating agents. Design 32 Sprague Dawley rats were given an injection of fluorescent pamidronate (OsteoSense EX; 0.16 nmol/g). They were treated with either systemic (cadmium) or local [ethylenediaminetetraacetic (EDTA) or citric acid (CA)] chelating agents to induce the removal of the bisphosphonate from bone. We evaluated the decrease in fluorescence in the alveolar bone, femur, tibia, and vertebrae. We also analyzed the systemic effects of treatment. Results Systemic chelation reduced the pamidronate signal universally. However, the maximum reduction was observed in the alveolar bone and femur (22% and 21%, p values 0.008 and 0.028, respectively). Systemic chelation did not impair calcium homeostasis. The chelation effect was not due to a systemic toxic effect on the liver or kidney. On the other hand local chelation at the extraction site significantly (p=0.011) decreased the pamidronate signal at bony surfaces of the socket. Conclusions Systemic and local chelating agents can remove bisphosphonate from bone. This study establishes a new concept for the prevention of side effects of bisphosphonates during high-risk situations. PMID:26431826

  4. 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.

  5. Selective divalent copper chelation for the treatment of diabetes mellitus.

    PubMed

    Cooper, G J S

    2012-01-01

    Oxidative stress and mitochondrial dysfunction have been identified by many workers as key pathogenic mechanisms in ageing-related metabolic, cardiovascular and neurodegenerative diseases (for example diabetes mellitus, heart failure and Alzheimer's disease). However, although numerous molecular mechanisms have been advanced to account for these processes, their precise nature remains obscure. This author has previously suggested that, in such diseases, these two mechanisms are likely to occur as manifestations of a single underlying disturbance of copper regulation. Copper is an essential but highly-toxic trace metal that is closely regulated in biological systems. Several rare genetic disorders of copper homeostasis are known in humans: these primarily affect various proteins that mediate intracellular copper transport processes, and can lead either to tissue copper deficiency or overload states. These examples illustrate how impaired regulation of copper transport pathways can cause organ damage and provide important insights into the impact of defects in specific molecular processes, including those catalyzed by the copper-transporting ATPases, ATP7A (mutated in Menkes disease), ATP7B (Wilson's disease), and the copper chaperones such as those for cytochrome c oxidase, SCO1 and SCO2. In diabetes, impaired copper regulation manifests as elevations in urinary CuII excretion, systemic chelatable-CuII and full copper balance, in increased pro-oxidant stress and defective antioxidant defenses, and in progressive damage to the blood vessels, heart, kidneys, retina and nerves. Linkages between dysregulated copper and organ damage can be demonstrated by CuII-selective chelation, which simultaneously prevents/reverses both copper dysregulation and organ damage. Pathogenic structures in blood vessels that contribute to binding and localization of catalytically-active CuII probably include advanced glycation end products (AGEs), as well as atherosclerotic plaque: the

  6. Chelation and determination of labile iron in primary hepatocytes by pyridinone fluorescent probes

    PubMed Central

    Ma, Yongmin; de Groot, Herbert; Liu, Zudong; Hider, Robert C.; Petrat, Frank

    2005-01-01

    A series of fluorescent iron chelators has been synthesized such that a fluorescent function is covalently linked to a 3-hydroxypyridin-4-one. In the present study, the fluorescent iron chelators were loaded into isolated rat hepatocytes. The intracellular fluorescence was not only quenched by an addition of a highly lipophilic 8-hydroxyquinoline–iron(III) complex but also was dequenched by the addition of an excess of the membrane-permeable iron chelator CP94 (1,2-diethyl-3-hydroxypyridin-4-one). The time course of uptake of iron and iron chelation in single, intact cells was recorded on-line by using digital fluorescence microscopy. Intracellular concentrations of various fluorescent iron chelators were determined by using a spectrofluorophotometer subsequent to lysis of probe-loaded cells and were found to depend on their partition coefficients; the more hydrophobic the compound, the higher the intracellular concentration. An ex situ calibration method was used to determine the chelatable iron pool of cultured rat hepatocytes. CP655 (7-diethylamino-N-[(5-hydroxy-6-methyl-4-oxo-1,4-dihydropyridin-3-yl)methyl]-N-methyl-2-oxo-2H-chromen-3-carboxamide), which is a moderately lipophilic fluorescent chelator, was found to be the most sensitive probe for monitoring chelatable iron, as determined by the intracellular fluorescence increase induced by the addition of CP94. The concentration of the intracellular chelatable iron pool in hepatocytes was determined by this probe to be 5.4±1.3 μM. PMID:16336208

  7. 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

  8. 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.

  9. Quantifying high-affinity binding of hydrophobic ligands by isothermal titration calorimetry.

    PubMed

    Krainer, Georg; Broecker, Jana; Vargas, Carolyn; Fanghänel, Jörg; Keller, Sandro

    2012-12-18

    A fast and reliable quantification of the binding thermodynamics of hydrophobic high-affinity ligands employing a new calorimetric competition experiment is described. Although isothermal titration calorimetry is the method of choice for a quantitative characterization of intermolecular interactions in solution, a reliable determination of a dissociation constant (K(D)) is typically limited to the range 100 μM > K(D) > 1 nM. Interactions displaying higher or lower K(D) values can be assessed indirectly, provided that a suitable competing ligand is available whose K(D) falls within the directly accessible affinity window. This established displacement assay, however, requires the high-affinity ligand to be soluble at high concentrations in aqueous buffer and, consequently, poses serious problems in the study of protein binding involving small-molecule ligands dissolved in organic solvents--a familiar case in many drug-discovery projects relying on compound libraries. The calorimetric competition assay introduced here overcomes this limitation, thus allowing for a detailed thermodynamic description of high-affinity receptor-ligand interactions involving poorly water-soluble compounds. Based on a single titration of receptor into a dilute mixture of the two competing ligands, this competition assay provides accurate and precise values for the dissociation constants and binding enthalpies of both high- and moderate-affinity ligands. We discuss the theoretical background underlying the approach, demonstrate its practical application to metal ion chelation and high-affinity protein-inhibitor interactions, and explore its potential and limitations with the aid of simulations and statistical analyses.

  10. Enhancement of bismuth antibacterial activity with lipophilic thiol chelators.

    PubMed Central

    Domenico, P; Salo, R J; Novick, S G; Schoch, P E; Van Horn, K; Cunha, B A

    1997-01-01

    The antibacterial properties of bismuth are greatly enhanced when bismuth is combined with certain lipophilic thiol compounds. Antibacterial activity was enhanced from 25- to 300-fold by the following seven different thiols, in order of decreasing synergy: 1,3-propanedithiol, dimercaprol (BAL), dithiothreitol, 3-mercapto-2-butanol, beta-mercaptoethanol, 1-monothioglycerol, and mercaptoethylamine. The dithiols produced the greatest synergy with bismuth at optimum bismuth-thiol molar ratios of from 3:1 to 1:1. The monothiols were generally not as synergistic and required molar ratios of from 1:1 to 1:4 for optimum antibacterial activity. The most-active mono- or dithiols were also the most soluble in butanol. The intensity of the yellow formed by bismuth-thiol complexes reflected the degree of chelation and correlated with antibacterial potency at high molar ratios. The bismuth-BAL compound (BisBAL) was active against most bacteria, as assessed by broth dilution, agar diffusion, and agar dilution analyses. Staphylococci (MIC, 5 to 7 microM Bi3+) and Helicobacter pylori (MIC, 2.2 microM) were among the most sensitive bacteria. Gram-negative bacteria were sensitive (MIC, < 17 microM). Enterococci were relatively resistant (MIC, 63 microM Bi3+). The MIC range for anaerobes was 15 to 100 microM Bi3+, except for Clostridium difficile (MIC, 7.5 microM). Bactericidal activity averaged 29% above the MIC. Bactericidal activity increased with increasing pH and/or increasing temperature. Bismuth-thiol solubility, stability, and antibacterial activity depended on pH and the bismuth-thiol molar ratio. BisBAL was stable but ineffective against Escherichia coli at pH 4. Activity and instability (reactivity) increased with increasing alkalinity. BisBAL was acid soluble at a molar ratio of greater than 3:2 and alkaline soluble at a molar ratio of less than 2:3. In conclusion, certain lipophilic thiol compounds enhanced bismuth antibacterial activity against a broad spectrum of

  11. 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.

  12. 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.

  13. Validity of ligand efficiency metrics.

    PubMed

    Murray, Christopher W; Erlanson, Daniel A; Hopkins, Andrew L; Keserü, György M; Leeson, Paul D; Rees, David C; Reynolds, Charles H; Richmond, Nicola J

    2014-06-12

    A recent viewpoint article (Improving the plausibility of success with inefficient metrics. ACS Med. Chem. Lett. 2014, 5, 2-5) argued that the standard definition of ligand efficiency (LE) is mathematically invalid. In this viewpoint, we address this criticism and show categorically that the definition of LE is mathematically valid. LE and other metrics such as lipophilic ligand efficiency (LLE) can be useful during the multiparameter optimization challenge faced by medicinal chemists.

  14. Uncoupler-reversible inhibition of mitochondrial ATPase by metal chelates of bathophenanthroline. I. General features.

    PubMed

    Carlsson, C; Ernster, L

    1981-12-14

    (1) Certain metal chelates of 4,7-diphenyl-1,10-phenanthroline (bathophenanthroline, BPh) are potent inhibitors of soluble mitochondrial F1-ATPase. (2) The BPh-metal chelate inhibition of soluble mitochondrial F1-ATPase is relieved by uncouplers of oxidative phosphorylation. (3) The uncouplers appear to interact directly with the inhibitory chelates, forming stoichiometric adducts. (4) A complex between F1 and bPh3Fe2+, containing 3 mol BPh3Fe2+/mol F1, has been isolated. The enzymically inactive F1-BPh3Fe2+ complex binds uncouplers, yielding an enzymically active F1-BPh3Fe2+-uncoupler complex.

  15. Quantitative measurement of ligand exchange on iron oxides via radiolabeled oleic acid.

    PubMed

    Davis, Kathleen; Qi, Bin; Witmer, Michael; Kitchens, Christopher L; Powell, Brian A; Mefford, O Thompson

    2014-09-16

    Ligand exchange of hydrophilic molecules on the surface of hydrophobic iron oxide nanoparticles produced via thermal decomposition of chelated iron precursors is a common method for producing aqueous suspensions of particles for biomedical applications. Despite the wide use, relatively little is understood about the efficiency of ligand exchange on the surface of iron oxide nanoparticles and how much of the hydrophobic ligand is removed. To address this issue, we utilized a radiotracer technique to track the exchange of a radiolabeled (14)C-oleic acid ligand with hydrophilic ligands on the surface of magnetite nanoparticles. Iron oxide nanoparticles functionalized with (14)C-oleic acid were modified with poly(ethylene glycol) with terminal functional groups including, L-3,4-dihydroxyphenylalanine, a nitrated L-3,4-dihydroxyphenylalanine, carboxylic acid, a phosphonate, and an amine. Following ligand exchange, the nanoparticles and byproducts were analyzed using liquid scintillation counting and inductively coupled plasma mass spectroscopy. The labeled and unlabeled particles were further characterized by transmission electron microscopy and dynamic light scattering to determine particle size, hydrodynamic diameter, and zeta potential. The unlabeled particles were characterized via thermogravimetric analysis and vibrating sample magnetometry. Radioanalytical determination of the (14)C from (14)C-oleic acid was used to calculate the amount of oleic acid remaining on the surface of the particles after purification and ligand exchange. There was a significant loss of oleic acid on the surface of the particles after ligand exchange with amounts varying for the different functional binding groups on the poly(ethylene glycol). Nonetheless, all samples demonstrated some residual oleic acid associated with the particles. Quantification of the oleic acid remaining after ligand exchange reveals a binding hierarchy in which catechol derived anchor groups displace oleic acid on

  16. Hexadentate hydroxypyridonate iron chelators based on TREN-Me-3,2-HOPO: variation of cap size.

    PubMed

    Xu, Jide; O'Sullivan, Brendon; Raymond, Kenneth N

    2002-12-16

    TREN-Me-3,2-HOPO, TR322-Me-3,2-HOPO, TR332-Me-3,2-HOPO, and TRPN-Me-3,2-HOPO correspond to stepwise replacement of ethylene by propylene bridges. A series of tripodal, hexadentate hydroxypyridinone ligands are reported. These incorporate 1-methyl-3,2-hydroxypyridinone (Me-3,2-HOPO) bidentate chelating units for metal binding. They are varied by systematic enlargement of the capping scaffold which connects the binding units. The series of ligands and their iron complexes are reported. Single crystal X-ray structures are reported for the ferric complexes of all four tripodal ligands: FeTREN-Me-3,2-HOPO.0.375C(4)H(10)O.0.5CH(2)Cl(2) [P2(1)/n (No. 14), Z = 8, a = 20.478(3) A, b = 12.353(2) A, c = 27.360(3) A; beta = 91.60(1) degrees ]; FeTR322-Me-3,2-HOPO.CHCl(3).0.5C(6)H(14).CH(3)OH.0.5H(2)O [P2(1)/n (No. 14), Z = 4, a = 12.520(3) A, b = 22.577(5) A, c = 16.525(3) A; beta = 111.37(3) degrees ]; FeTR332-Me-3,2-HOPO.3.5CH(3)OH [C2/c (No. 15), Z = 8, a = 13.5294(3) A, b = 19.7831(4) A, c = 27.2439(4) A; beta = 101.15(3) degrees ]; FeTRPN-Me-3,2-HOPO.C(3)H(7)NO.2C(4)H(10)O [P1 (No. 2), Z = 2, a = 11.4891(2) A, b = 12.3583(2) A, c = 15.0473(2) A; alpha = 86.857(1) degrees, beta = 88.414(1) degrees, gamma = 70.124(1) degrees ]. The structures show the importance of intermolecular hydrogen bonds and the effect of cap enlargement to the stability and geometry of the metal complexes throughout the series. All protonation and iron complex formation constants have been determined from solution thermodynamic studies. The TREN-capped derivative is the most acidic, with a cumulative protonation constant, log beta(014), of 25.95. Corresponding values of 26.35, 26.93, and 27.53 were obtained for the TR322, TR332, and TRPN derivatives, respectively. The protonation constants and NMR spectroscopic data are interpreted as being due to the influence of specific hydrogen-bond interactions. The incremental enlargement of ligand size results in a decrease in iron-chelate stability, as

  17. Synthetic, crystallographic, and computational study of copper(II) complexes of ethylenediaminetetracarboxylate ligands.

    PubMed

    Matović, Zoran D; Miletić, Vesna D; Ćendić, Marina; Meetsma, Auke; van Koningsbruggen, Petra J; Deeth, Robert J

    2013-02-04

    Copper(II) complexes of hexadentate ethylenediaminetetracarboxylic acid type ligands H(4)eda3p and H(4)eddadp (H(4)eda3p = ethylenediamine-N-acetic-N,N',N'-tri-3-propionic acid; H(4)eddadp = ethylenediamine-N,N'-diacetic-N,N'-di-3-propionic acid) have been prepared. An octahedral trans(O(6)) geometry (two propionate ligands coordinated in axial positions) has been established crystallographically for the Ba[Cu(eda3p)]·8H(2)O compound, while Ba[Cu(eddadp)]·8H(2)O is proposed to adopt a trans(O(5)) geometry (two axial acetates) on the basis of density functional theory calculations and comparisons of IR and UV-vis spectral data. Experimental and computed structural data correlating similar copper(II) chelate complexes have been used to better understand the isomerism and departure from regular octahedral geometry within the series. The in-plane O-Cu-N chelate angles show the smallest deviation from the ideal octahedral value of 90°, and hence the lowest strain, for the eddadp complex with two equatorial β-propionate rings. A linear dependence between tetragonality and the number of five-membered rings has been established. A natural bonding orbital analysis of the series of complexes is also presented.

  18. Hydroxypyridinonate complex stability of group (IV) metals and tetravalent f-block elements: the key to the next generation of chelating agents for radiopharmaceuticals.

    PubMed

    Sturzbecher-Hoehne, Manuel; Choi, Taylor A; Abergel, Rebecca J

    2015-04-06

    The solution thermodynamics of the water-soluble complexes formed between 3,4,3-LI(1,2-HOPO) and Zr(IV) or Pu(IV) were investigated to establish the metal coordination properties of this octadentate chelating agent. Stability constants log β110 = 43.1 ± 0.6 and 43.5 ± 0.7 were determined for [Zr(IV)(3,4,3-LI(1,2-HOPO))] and [Pu(IV)(3,4,3-LI(1,2-HOPO))], respectively, by spectrophotometric competition titrations against Ce(IV). Such high thermodynamic stabilities not only confirm the unparalleled Pu(IV) affinity of 3,4,3-LI(1,2-HOPO) as a decorporation agent but also corroborate the great potential of hydroxypyridinonate ligands as new (89)Zr-chelating platforms for immuno-PET applications. These experimental values are in excellent agreement with previous estimates and are discussed with respect to ionic radius and electronic configuration, in comparison with those of Ce(IV) and Th(IV). Furthermore, a liquid chromatography assay combined with mass spectrometric detection was developed to probe the separation of the neutral [M(IV)(3,4,3-LI(1,2-HOPO))] complex species (M = Zr, Ce, Th, and Pu), providing additional insight into the coordination differences between group IV and tetravalent f-block metals and on the role of d and f orbitals in bonding interactions.

  19. A Novel Class of Bis- and Tris-Chelate Diam(m)inebis(dicarboxylato)platinum(IV) Complexes as Potential Anticancer Prodrugs

    PubMed Central

    Varbanov, Hristo P.; Göschl, Simone; Heffeter, Petra; Theiner, Sarah; Roller, Alexander; Jensen, Frank; Jakupec, Michael A.; Berger, Walter; Galanski, Markus; Keppler, Bernhard K.

    2015-01-01

    A novel class of platinum(IV) complexes of the type [Pt(Am)-(R(COO)2)2], where Am is a chelating diamine or two monodentate am(m)ine ligands and R(COO)2 is a chelating dicarboxylato moiety, was synthesized. For this purpose, the reaction between the corresponding tetrahydroxidoplatinum(IV) precursors and various dicarboxylic acids, such as oxalic, malonic, 3-methylmalonic, and cyclobutanedicarboxylic acid, was utilized. All new compounds were characterized in detail, using 1D and 2D NMR techniques, ESI-MS, FTIR spectroscopy, elemental analysis, TGA, and X-ray diffraction. Their in vitro cytotoxicity was determined in a panel of human tumor cell lines (CH1, SW480 and A549) by means of the MTT colorimetric assay. Furthermore, the lipophilicity and redox properties of the novel complexes were evaluated in order to better understand their pharmacological behavior. The most promising drug candidate, 4b (Pt(DACH)(mal)2), demonstrated low in vivo toxicity but profound anticancer activity against both the L1210 leukemia and CT-26 colon carcinoma models. PMID:25032896

  20. ATMP-stabilized iron nanoparticles: chelator-controlled nanoparticle synthesis

    NASA Astrophysics Data System (ADS)

    Greenlee, Lauren F.; Rentz, Nikki S.

    2014-11-01

    In this study, we characterize iron nanoparticles synthesized in water in the presence of a phosphonate chelator, amino tris(methylene phosphonic acid) (ATMP) for a range of molar ratios of ATMP to iron. An increase in the molar ratio from 0.05 to 0.8 decreases nanoparticle size from approximately 150 nm to less than 10 nm. Zeta potential measurements were used to evaluate colloidal stability. Zeta potential values varied as a function of pH, and zeta potential values decreased with increasing pH. At lower molar ratios of ATMP to iron, the zeta potential varied between 15 and -40 mV, passing through an isoelectric point at pH 7.5. At higher ratios, the zeta potential was negative across the measured pH range of 2-12 and varied from -2 to -55 mV. Diffraction analysis indicates that ATMP-stabilized iron nanoparticles may have a nano-crystalline structure, potentially with regions of amorphous iron. Characterization results of ATMP-stabilized iron nanoparticles are compared to results obtained for carboxymethyl cellulose (CMC)-stabilized iron nanoparticles. CMC stabilization caused similar peak broadening in diffraction spectra as for ATMP, suggesting similar nano-crystalline/amorphous structure; however, an increase in the molar ratio of CMC to iron did not cause the same reduction in nanoparticle size as was observed for ATMP-stabilized iron nanoparticles.

  1. Molecular evidence of Zn chelation of the procaspase activating compound B-PAC-1 in B cell lymphoma.

    PubMed

    Sarkar, Aloke; Balakrishnan, Kumudha; Chen, Jefferson; Patel, Viralkumar; Neelapu, Sattva S; McMurray, John S; Gandhi, Varsha

    2016-01-19

    The resistance of apoptosis in cancer cells is pivotal for their survival and is typically ruled by mutations or dysregulation of core apoptotic cascade. Mantle cell lymphoma (MCL) is a non-Hodgkin's B-cell malignancy expressing higher anti-apoptotic proteins providing survival advantage. B-PAC-1, a procaspase activating compound, induces apoptosis by sequestering Zn bound to procaspase-3, but the amino acids holding Zn in Caspase-3 is not known. Here we show that reintroduction of WT caspase-3 or 7 in Caspase3-7 double knock-out (DKO) mouse embryonic fibroblasts (MEF) promoted B-PAC-1 to induce apoptosis (27-43%), but not in DKO MEFs or MEFs expressing respective Casp3-7 catalytic mutants (12-13%). Using caspase-6 and -9 exosite analysis, we identified and mutated predicted Zn-ligands in caspase-3 (H108A, C148S and E272A) and overexpressed into DKO MEFs. Mutants carrying E272A abrogated Zn-reversal of apoptosis induced by B-PAC-1 via higher XIAP and smac expressions but not in H108A or C148S mutants. Co-immunoprecipitation analysis revealed stronger XIAP-caspase-3 interaction suggesting a novel mechanism of impulsive apoptosis resistance by disrupting predicted Zn-ligands in caspase-3. B-PAC-1 sponsored apoptosis in MCL cell lines (30-73%) via caspase-3 and PARP cleavages accompanied by loss of Mcl-1 and IAPs including XIAP while Zn substantially abrogated B-PAC-1-driven apoptosis (18-36%). In contrary, Zn is dispensable to inhibit staurosporin, bendamustine, ABT199 or MK206-induced apoptosis. Consistent to cell lines, B-PAC-1 stimulated cell death in primary B-lymphoma cells via caspase-3 cleavage with decline in both Mcl-1 and XIAP. This study underscores the first genetic evidence that B-PAC-1 driven apoptosis is mediated via Zn chelation.

  2. Molecular evidence of Zn chelation of the procaspase activating compound B-PAC-1 in B cell lymphoma

    PubMed Central

    Sarkar, Aloke; Balakrishnan, Kumudha; Chen, Jefferson; Patel, Viralkumar; Neelapu, Sattva S.; McMurray, John S.; Gandhi, Varsha

    2016-01-01

    The resistance of apoptosis in cancer cells is pivotal for their survival and is typically ruled by mutations or dysregulation of core apoptotic cascade. Mantle cell lymphoma (MCL) is a non-Hodgkin's B-cell malignancy expressing higher anti-apoptotic proteins providing survival advantage. B-PAC-1, a procaspase activating compound, induces apoptosis by sequestering Zn bound to procaspase-3, but the amino acids holding Zn in Caspase-3 is not known. Here we show that reintroduction of WT caspase-3 or 7 in Caspase3–7 double knock-out (DKO) mouse embryonic fibroblasts (MEF) promoted B-PAC-1 to induce apoptosis (27–43%), but not in DKO MEFs or MEFs expressing respective Casp3–7 catalytic mutants (12–13%). Using caspase-6 and -9 exosite analysis, we identified and mutated predicted Zn-ligands in caspase-3 (H108A, C148S and E272A) and overexpressed into DKO MEFs. Mutants carrying E272A abrogated Zn-reversal of apoptosis induced by B-PAC-1 via higher XIAP and smac expressions but not in H108A or C148S mutants. Co-immunoprecipitation analysis revealed stronger XIAP-caspase-3 interaction suggesting a novel mechanism of impulsive apoptosis resistance by disrupting predicted Zn-ligands in caspase-3. B-PAC-1 sponsored apoptosis in MCL cell lines (30–73%) via caspase-3 and PARP cleavages accompanied by loss of Mcl-1 and IAPs including XIAP while Zn substantially abrogated B-PAC-1-driven apoptosis (18–36%). In contrary, Zn is dispensable to inhibit staurosporin, bendamustine, ABT199 or MK206-induced apoptosis. Consistent to cell lines, B-PAC-1 stimulated cell death in primary B-lymphoma cells via caspase-3 cleavage with decline in both Mcl-1 and XIAP. This study underscores the first genetic evidence that B-PAC-1 driven apoptosis is mediated via Zn chelation. PMID:26658105

  3. Pycup – A bifunctional, cage-like ligand for 64Cu radiolabeling

    PubMed Central

    Boros, Eszter; Rybak-Akimova, Elena; Holland, Jason P.; Rietz, Tyson; Rotile, Nicholas; Blasi, Francesco; Day, Helen; Latifi, Reza; Caravan, Peter

    2014-01-01

    In developing targeted probes for positron emission tomography (PET) based on 64Cu, stable complexation of the radiometal is key, and a flexible handle for bioconjugation is highly advantageous. Here, we present the synthesis and characterization of the chelator pycup and 4 derivatives. Pycup is a cross-bridged cyclam derivative with a pyridyl donor atom integrated into the cross-bridge resulting in a pentadentate ligand. The pycup platform provides kinetic inertness toward 64Cu de-chelation and offers versatile bioconjugation chemistry. We varied the number and type of additional donor atoms by alkylation of the remaining two secondary amines, providing three model ligands, pycup2A, pycup1A1Bn and pycup2Bn in 3–4 synthetic steps from cyclam. All model copper complexes displayed very slow decomplexation in 5 M HCl and 90 °C (t1/2: 1.5 h for pycup1A1Bn, 2.7 h for pycup2A, 20.3 h for pycup2Bn). The single crystal crystal X-ray structure of the [Cu(pycup2Bn)]2+ complex showed that the copper was coordinated in a trigonal, bi-pyramidal manner. The corresponding radiochemical complexes were at least 94% stable in rat plasma after 24 h. Biodistribution studies conducted in Balb/c mice at 2 h post-injection of 64Cu labeled pycup2A revealed low residual activity in kidney, liver and blood pool with predominantly renal clearance observed. Pycup2A was readily conjugated to a fibrin-targeted peptide and labeled with 64Cu for successful PET imaging of arterial thrombosis in a rat model, demonstrating the utility of our new chelator in vivo. PMID:24294970

  4. Vanadium complexes with mixed O,S anionic ligands derived from maltol: synthesis, characterization, and biological studies.

    PubMed

    Monga, Vishakha; Thompson, Katherine H; Yuen, Violet G; Sharma, Vijay; Patrick, Brian O; McNeill, John H; Orvig, Chris

    2005-04-18

    Four mixed O,S binding bidentate ligand precursors derived from maltol (3-hydroxy-2-methyl-4-pyrone) have been chelated to vanadium to yield new bis(ligand)oxovanadium(IV) and tris(ligand)vanadium(III) complexes. The four ligand precursors include two pyranthiones, 3-hydroxy-2-methyl-4-pyranthione, commonly known as thiomaltol (Htma), and 2-ethyl-3-hydroxy-4-pyranthione, commonly known as ethylthiomaltol (Hetma), as well as two pyridinethiones, 3-hydroxy-2-methyl-4(H)-pyridinethione (Hmppt) and 3-hydroxy-1,2-dimethyl-4-pyridinethione (Hdppt). Vanadium complex formation was confirmed by elemental analysis, mass spectrometry, and IR and EPR (where possible) spectroscopies. The X-ray structure of oxobis(thiomaltolato)vanadium(IV),VO(tma)(2), was also determined; both cis and trans isomers were isolated in the same asymmetric unit. In both isomers, the two thiomaltolato ligands are arranged around the base of the square pyramid with the V=O linkage perpendicular; the vanadium atom is slightly displaced from the basal plane [V(1) = 0.656(3) A, V(2) = 0.664(2) A]. All of the new complexes were screened for insulin-enhancing effectiveness in streptozotocin-induced diabetes in rats, and VO(tma)(2) was profiled metabolically for urinary vanadium and ligand clearance by GFAAS and ESIMS, respectively. The new vanadium complexes did not lower blood glucose levels acutely, possibly because of rapid dissociation and excretion.

  5. Synthesis, crystal structure and luminescence properties of acenaphthene benzohydrazide based ligand and its zinc(II) complex

    NASA Astrophysics Data System (ADS)

    Kumar, Mukesh; Roy, Soumyabrata; Faizi, Md. Serajul Haque; Kumar, Santosh; Singh, Mantu Kumar; Kishor, Shyam; Peter, Sebastian C.; John, Rohith P.

    2017-01-01

    The complex compound of zinc(II) supported by (Z)-2-hydroxy-N‧-(1-oxoacenaphthylen-2(1H) ylidene)benzohydrazide ligand (H2L1) has been reported and discussed. The reaction of zinc acetate with H2L1 ligand leads to the formation of a mononuclear zinc(ii) complex, [Zn(HL1)2H2O]. The ligand, H2L1 has been characterized by elemental analysis, 1H, 13C and 1Hsbnd COSY -NMR, IR and ESI-MS, while the complex was characterized by elemental analysis, IR, and ESI-MS. The crystal structures of the free ligand H2L1 and the complex have also been determined by single crystal X-ray diffraction. The ligand chelates with metal centre with a nitrogen atom of imino moiety and an oxygen atom of enolic group. The complex shows distorted trigonal bipyramidal geometry around the metal centre with oxygen atoms lying in the equatorial plane and imino nitrogen atoms along the axial direction. The DFT/TD-DFT calculations were performed on both the ligand and its zinc complex to get insight into the structural, electronic and optical properties. The photoluminescence, fluorescence properties of the complex have been investigated.

  6. 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...

  7. The Management of Iron Chelation Therapy: Preliminary Data from a National Registry of Thalassaemic Patients

    PubMed Central

    Ceci, Adriana; Mangiarini, Laura; Felisi, Mariagrazia; Bartoloni, Franco; Ciancio, Angela; Capra, Marcello; D'Ascola, Domenico; Cianciulli, Paolo; Filosa, Aldo

    2011-01-01

    Thalassaemia and other haemoglobinopathies constitute an important health problem in Mediterranean countries, placing a tremendous emotional, psychological, and economic burden on their National Health systems. The development of new chelators in the most recent years had a major impact on the treatment of thalassaemia and on the quality of life of thalassaemic patients. A new initiative was promoted by the Italian Ministry of Health, establishing a Registry for thalassaemic patients to serve as a tool for the development of cost-effective diagnostic and therapeutic approaches and for the definition of guidelines supporting the most appropriate management of the iron-chelating therapy and a correct use of the available iron-chelating agents. This study represents the analysis of the preliminary data collected for the evaluation of current status of the iron chelation practice in the Italian thalassaemic population and describes how therapeutic interventions can widely differ in the different patients' age groups. PMID:21738864

  8. 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...

  9. 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.

  10. Sequestering ability of some chelating agents towards methylmercury(II).

    PubMed

    Falcone, Gabriella; Foti, Claudia; Gianguzza, Antonio; Giuffrè, Ottavia; Napoli, Anna; Pettignano, Alberto; Piazzese, Daniela

    2013-01-01

    A study on the interactions between CH(3)Hg(+) and some S, N and O donor ligands (2-mercaptopropanoic acid (thiolactic acid (H(2)TLA)), 3-mercaptopropanoic acid (H(2)MPA), 2-mercaptosuccinic acid (thiomalic acid (H(3)TMA)), D,L-penicillamine (H(2)PSH), L-cysteine (H(2)CYS), glutathione (H(3)GSH), N,N'-bis(3-aminopropyl)-1-4-diaminobutane (spermine (SPER)), 1,2,3,4,5,6-benzenehexacarboxylic acid (mellitic acid (H(6)MLT)) and ethylenediaminetetraacetic acid (H(4)EDTA)) is reported. The speciation models in aqueous solution and the possible structures of the complexes formed are discussed on the basis of potentiometric, calorimetric, UV spectrophotometric and electrospray mass spectrometric results. For the CH(3)Hg(+)-S donor ligand systems, the formation of ML(1-z) and MLH(2-z) complex species is observed, together with a diprotonated MLH(2)(3-z) species for CYS(2-), PSH(2-) and GSH(3-) and the mixed hydrolytic one ML(OH)(-z) for TLA(2-) and MPA(2-). The dependence of the stability on ionic strength and on temperature is also analysed. In the other CH(3)Hg(+)-L systems (L = MLT(6-), SPER and EDTA(4-)), ML(1-z), MLH(2-z) and MLH(2)(3-z) complex species are formed, together with the MLH(3)(4-z) species for SPER, the mixed hydrolytic ML(OH)(-z) one for SPER and EDTA, and the M(2)L(2-z) for EDTA only. On the basis of the speciation models proposed, the sequestering ability of the ligands towards methylmercury(II) cation is evaluated. All S donor ligands show a good sequestering power (at 10(-11) mol L(-1) level, in the pH range 4 to 8) following the trend MPA(2-) < PSH(2-) < GSH(3-) < TLA(2-) < CYS(2-) < TMA(3-), while significantly lower is the sequestering ability of MLT, SPER and EDTA (at 10(-3)-10(-5) mol L(-1) level, in the pH range 4 to 8).

  11. Recovery of nickel and cobalt from organic acid complexes: adsorption mechanisms of metal-organic complexes onto aminophosphonate chelating resin.

    PubMed

    Deepatana, A; Valix, M

    2006-09-21

    This study examined the recovery of nickel and cobalt from organic acid complexes using a chelating aminophosphonate Purolite S950 resin. These metal complexes are generated by bioleaching nickel laterite ores, a commercial nickel and cobalt mineral oxide, with heterotrophic organism and their metabolites or organic acid products. Equilibrium adsorption tests were conducted as a function of Ni and Co concentrations (15-2000 mg/L), solution pH (0.01 and 0.1 M acids) and three metabolic complexing agents (citrate, malate and lactate). It was shown that the adsorption of the various Ni- and Co-complexes on Purolite were quite low, 16-18 and 5.4-9 mg/g of resin, respectively, in comparison to the smaller nickel ions and nickel sulfate. This was attributed to the bulky organic ligands which promoted crowding effect or steric hindrance. The adsorption of these complexes was further hampered by the strong affinity of the resin to H+ ions under acidic conditions. Mechanisms of adsorption, as inferred from the fitted empirical Langmuir and Freundlich models, were correlated to the proposed steric hindrance and competitive adsorption effects. Nickel and cobalt elution from the resin were found be effective and were independent of the type of metal complexes and metal concentrations. This study demonstrated the relative challenges involved in recovering nickel and cobalt from bioleaching solutions.

  12. Effect of Fe-chelating complexes on a novel M2FC performance with ferric chloride and ferricyanide catholytes.

    PubMed

    Chung, Kyungmi; Lee, Ilgyu; Han, Jong-In

    2012-01-01

    As an effort to better utilize the microbial fuel cell (MFC) technology, we previously proposed an innovative MFC system named M2FC consisting of ferric-based MFC part and ferrous-based fuel cell (FC) part. In this reactor, ferric ion, the catholyte in the MFC part, was efficiently regenerated by the FC part with the generation of additional electricity. When both units were operated separately, the ferric-based MFC part produced approximately 1360 mW m(-2) of power density with FeCl(3) as catholyte and Fe-citrate as anolyte. The ferrous-based FC part with FeCl(3) as catholyte and Fe-EDTA as anolyte displayed the highest power density (1500 mW m(-2)), while that with ferricyanide as catholyte and Fe-noligand as anolyte had the lowest power density (380 mW m(-2)). The types of catholytes and chelating complexes as anolyte were found to play important roles in the reduction of ferric ions and oxidation of ferrous ion. Linear sweep voltammetry results supported that the cathode electrolytes were electrically active and these agreed well with the M2FC reactor performance. These results clearly showed that ligands played critical role in the efficiency and rate for recycling iron ion and thus the M2FC performance.

  13. Transplantation of ex vivo expanded cord blood cells using the copper chelator tetraethylenepentamine: a phase I/II clinical trial.

    PubMed

    de Lima, M; McMannis, J; Gee, A; Komanduri, K; Couriel, D; Andersson, B S; Hosing, C; Khouri, I; Jones, R; Champlin, R; Karandish, S; Sadeghi, T; Peled, T; Grynspan, F; Daniely, Y; Nagler, A; Shpall, E J

    2008-05-01

    The copper chelator tetraethylenepentamine (TEPA; StemEx) was shown to attenuate the differentiation of ex vivo cultured hematopoietic cells resulting in preferential expansion of early progenitors. A phase I/II trial was performed to test the feasibility and safety of transplantation of CD133+ cord blood (CB) hematopoietic progenitors cultured in media containing stem cell factor, FLT-3 ligand, interleukin-6, thrombopoietin and TEPA. Ten patients with advanced hematological malignancies were transplanted with a CB unit originally frozen in two fractions. The smaller fraction was cultured ex vivo for 21 days and transplanted 24 h after infusion of the larger unmanipulated fraction. All but two units contained <2 x 10(7) total nucleated cells (TNCs) per kilogram pre-expansion. All donor-recipient pairs were mismatched for one or two HLA loci. Nine patients were beyond first remission; median age and weight were 21 years and 68.5 kg. The average TNCs fold expansion was 219 (range, 2-620). Mean increase of CD34+ cell count was 6 (over the CD34+ cell content in the entire unit). Despite the low TNCs per kilogram infused (median=1.8 x 10(7)/kg), nine patients engrafted. Median time to neutrophil and platelet engraftment was 30 (range, 16-46) and 48 (range, 35-105) days. There were no cases of grades 3-4 acute graft-versus-host disease (GVHD) and 100-day survival was 90%. This strategy is feasible.

  14. Circularly Polarized Luminescence in Enantiopure Europium and Terbium Complexes with Modular, All-Oxygen Donor Ligands

    SciTech Connect

    Seitz, Michael; Do, King; Ingram, Andrew; Moore, Evan; Muller, Gilles; Raymond, Kenneth

    2009-06-04

    The modular syntheses of three new octadentate, enantiopure ligands are reported, one with the bidentate chelating unit 2-hydroxyisophthalamide (IAM) and two with bidentate 1-hydroxy-2-pyridinone (1,2-HOPO) units. A new design principle is introduced for the chiral, non-racemic hexamines which constitute the central backbones for the presented class of ligands. The terbium(III) complex of the IAM ligand, as well as the europium(III) complexes of the 1,2-HOPO ligands, are synthesized and characterized by various techniques (NMR, UV, CD, luminescence spectroscopy). All species exhibit excellent stability and moderate to high luminescence efficiency (quantum yields {phi}{sub Eu} = 0.05-0.08 and {phi}{sub Tb} = 0.30-0.57) in aqueous solution at physiological pH. Special focus is put onto the properties of the complexes in regard to circularly polarized luminescence (CPL). The maximum luminescence dissymmetry factors (glum) in aqueous solution are high with |glum|max = 0.08-0.40. Together with the very favorable general properties (good stability, high quantum yields, long lifetimes), the presented lanthanide complexes can be considered as good candidates for analytical probes based on CPL in biologically relevant environments.

  15. Group 13 and lanthanide complexes with mixed O,S anionic ligands derived from maltol.

    PubMed

    Monga, Vishakha; Patrick, Brian O; Orvig, Chris

    2005-04-18

    Four mixed O,S binding ligand precursors derived from maltol (3-hydroxy-2-methyl-4-pyrone) have been chelated to gallium(III), indium(III), and lanthanide(III) ions to yield a series of metal complexes. The four ligand precursors include two pyranthiones, 3-hydroxy-2-methyl-4-pyranthione, commonly known as thiomaltol (Htma), and 2-ethyl-3-hydroxy-4-pyranthione, commonly known as ethylthiomaltol (Hetma), and two pyridinethiones, 3-hydroxy-2-methyl-4(H)-pyridinethione (Hmppt) and 3-hydroxy-1,2-dimethyl-4-pyridinethione (Hdppt). Dimeric forms of the pyridinethiones, Hmppt dimer and Hdppt dimer, were also isolated and characterized. Complete characterization of the monomeric organic compounds is reported including acidity constants and crystal structures of Htma, Hetma, and Hdppt dimer. Reacting the four monomeric ligand precursors with Ga(3+) and In(3+) ions yielded new tris(bidentate ligand) complexes. X-ray-quality crystals of the fac isomer of Ga(tma)(3) were also obtained. New complexes with a range of lanthanides (Ln(3+)) were also synthesized with the two pyranthiones, Htma and Hetma. The synthesis reactions yielded complexes of the type LnL(3).xH(2)O and LnL(2)(OH).xH(2)O, as indicated by elemental analysis and spectroscopic evidence such as mass spectral data and IR and NMR spectra.

  16. Ligand enabling visible wavelength excitation of europium(III) for fluoroimmunoassays in aqueous micellar solutions.

    PubMed

    Valta, Timo; Puputti, Eeva-Maija; Hyppänen, Iko; Kankare, Jouko; Takalo, Harri; Soukka, Tero

    2012-09-18

    Fluorescent reporters based on lanthanide ions, such as europium chelates, enable highly sensitive detection in immunoassays and other ligand binding assays. Unfortunately they normally require UV-excitation produced by a xenon flash or nitrogen laser light source. In order to use modern solid state excitation sources such as light emitting diodes (LEDs), these reporters need to be excited at wavelengths longer than 365 nm, where high-powered ultraviolet LEDs are available. A novel ligand, 9-ethyl-3,6-bis(5',5',5',4',4'-pentafluoro-1',3'-dioxopentyl)carbazole (bdc), was synthesized to efficiently excite europium(III) at wavelengths up to 450 nm in micellar solutions, and its performance was compared to a commercially available DELFIA enhancement solution. The detection limit of Eu(III) with the bdc-ligand using 365 nm excitation was determined to be 63 fM, which is 3 times lower than with the DELFIA solution. The bdc-ligand enabled sensitive detection of europium(III) ions in solution using 365 nm excitation and displayed similar sensitivity and functionality as commercially available DELFIA enhancement solution. Therefore, this novel enhancement solution might be a feasible alternative in producing time-resolved fluorescence under LED-excitation.

  17. Chelating agents used for plutonium and uranium removal in radiation emergency medicine.

    PubMed

    Fukuda, Satoshi

    2005-01-01

    The prospects of using chelating agents for increasing the excretion of actinides are reviewed. The removal of plutonium by chelating agents is of great importance because plutonium is extremely dangerous and induces cancer due to radiation toxicity. Similarly, uranium is a radionuclide, which causes severe renal dysfunction within a short time period due to chemical toxicity. It may also induce cancers such as leukemia and osteosarcoma in cases of long-term internal radiation exposure. Investigations on chelating agents for the removal of plutonium were initiated in the 1960's and 1970's. Diethylenetriaminepentaacetic acid (DTPA) is recognized as a chelating agent that accelerates the excretion of plutonium in early treatment after an accident. Thereafter, there has long been an interest in finding new chelating agents with radionuclide removal properties for use in therapy, and many chelating agents such as 3,4,3-LIHOPO and CBMIDA have been studied for their ability to remove plutonium and uranium. Recently, the focus has turned to drugs that have been used successfully in the treatment of a variety of other diseases, for example the iron chelating drug deferiprone or 1,2-dimethyl-3-hydroxypyrid-4-one (L1), which is used in thalassaemia and ethane-1-hydroxy-1,1-bisphosphonate (EHBP), which is used in osteoporosis. Within this context, it is important to examine the clinical use of these two drugs as well as the properties of the experimental chelators 3,4,3-LIHOPO and CBMIDA in order to identify possible uses in the treatment of radiation workers contaminated with plutonium and uranium.

  18. Chromium uptake by Spirodela polyrrhiza (L. ) Schleiden in relation to metal chelators and pH

    SciTech Connect

    Tripathi, R.D.; Chandra, P. )

    1991-11-01

    This paper reports the influence of metal chelators, ethylenediaminetetraacetic acid (EDTA) and salicylic acid, and pH on the accumulation of Cr by S. polyrrhiza under the laboratory conditions. This also includes the results of K.D. pond water treatment study by cultured fronds of S. polyrrhiza. In view of the occurrence of metal chelators in natural waters and pH variation the present study would enable to assess the performance of this species under the influence of these factors.

  19. Purification of human copper, zinc superoxide dismutase by copper chelate affinity chromatography

    SciTech Connect

    Weslake, R.J.; Chesney, S.L.; Petkau, A.; Friesen, A.D.

    1986-05-15

    Copper, zinc superoxide dismutase was isolated from human red blood cell hemolysate by DEAE-Sepharose and copper chelate affinity chromatography. Enzyme preparations had specific activities ranging from 3400 to 3800 U/mg and recoveries were approximately 60% of the enzyme activity in the lysate. Copper chelate affinity chromatography resulted in a purification factor of about 60-fold. The homogeneity of the superoxide dismutase preparation was analyzed by sodium dodecyl sulfate-gel electrophoresis, analytical gel filtration chromatography, and isoelectric focusing.

  20. Removal of chelated aluminium during haemodialysis using polysulphone high-flux dialysers.

    PubMed

    Aarseth, H P; Ganss, R

    1990-01-01

    Polysulphone high-flux dialysers were used for removal of chelated aluminium in desferrioxamine-treated patients on maintenance haemodialysis. When compared with charcoal haemoperfusion in series with a cuprophane dialyser, the same aluminium clearance was obtained (34% of blood flow). During 4 h of haemodialysis serum aluminium was reduced to the concentration seen before desferrioxamine infusion. We conclude that high-flux polysulphone dialysers remove chelated aluminium as efficiently as does charcoal haemoperfusion, and at a lower cost.

  1. Fate of labeled hydroxamates during iron transport from hydroxamate-ion chelates.

    PubMed

    Arceneaux, J E; Davis, W B; Downer, D N; Haydon, A H; Byers, B R

    1973-09-01

    The fate of the hydroxamic acid-iron transport cofactors during iron uptake from the (59)Fe(3+) chelates of the (3)H-labeled hydroxamates schizokinen and aerobactin was studied by assay of simultaneous incorporation of both (59)Fe(3+) and (3)H. In the schizokinen-producing organism Bacillus megaterium ATCC 19213 transport of (59)Fe(3+) from the (3)H-schizokinen-(59)Fe(3+) chelate at 37 C was accompanied by rapid uptake and release (within 2 min) of (3)H-schizokinen, although (3)H-schizokinen discharge was temperature-dependent and did not occur at 0 C. In the schizokinen-requiring strain B. megaterium SK11 similar release of (3)H-schizokinen occurred only at elevated concentrations of the double-labeled chelate; at lower chelate concentrations, (3)H-schizokinen remained cell-associated. Temperature-dependent uptake of deferri (iron-free) (3)H-schizokinen to levels equivalent to those incorporated from the chelate form was noted in strain SK11, but strain ATCC 19213 showed only temperature-independent binding of low concentrations of deferri (3)H-schizokinen. These results indicate an initial temperature-independent binding of the ferric hydroxamate which is followed rapidly by temperature-dependent transport of the chelate into the cell and an enzyme catalyzed separation of iron from the chelate. The resulting deferri hydroxamate is discharged from the cell only when a characteristic intracellular concentration of the hydroxamate is exceeded, which happens in the schizokinen-requiring strain only at elevated concentrations of the chelate. This strain also appears to draw the deferri hydroxamate into the cell by a temperature-dependent mechanism. The aerobactin-producing organism Aerobacter aerogenes 62-1 also demonstrated rapid initial uptake and temperature-dependent discharge of (3)H-aerobactin during iron transport from (3)H-aerobactin-(59)Fe(3+), suggesting a similar ferric hydroxamate transport system in this organism.

  2. Stereoselective Arylation of Amino Aldehydes: Overriding Natural Substrate Control through Chelation.

    PubMed

    Martins, Bruna S; Moro, Angélica V; Lüdtke, Diogo S

    2017-03-03

    The chelation-controlled arylation reaction of chiral, enantiopure acyclic α-amino aldehydes enabled by a B/Zn exchange reaction between arylboronic acids and Et2Zn is reported. The presence of dibenzyl substituents at the nitrogen plays a key role in the stereochemical outcome of the reaction, and chelation is favored over the natural tendency of this type of substrate to undergo Felkin-Anh controlled additions with organomagnesium and organolithium reagents.

  3. Rapid anaerobic benzene oxidation with a variety of chelated Fe(III) forms

    USGS Publications Warehouse

    Lovley, D.R.; Woodward, J.C.; Chapelle, F.H.

    1996-01-01

    Fe(III) chelated to such compounds as EDTA, N-methyliminodiacetie acid, ethanol diglycine, humic acids, and phosphates stimulated benzene oxidation coupled to Fe(III) reduction in anaerobic sediments from a petroleum- contaminated aquifer as effectively as or more effectively than nitrilotriacetic acid did in a previously demonstrated stimulation experiment. These results indicate that many forms of chelated Fe(III) might be applicable to aquifer remediation.

  4. Removal of heavy metals from aqueous solution by chelating resin in a multistage adsorption process.

    PubMed

    Lin, S H; Lai, S L; Leu, H G

    2000-08-28

    Copper and zinc removal from aqueous solution by chelating resin was investigated theoretically and experimentally in the present study. A multistage process was proposed as an alternative for enhancement of the heavy removal of the single-stage process. Heavy metal mass balance equations with empirical Freundlich adsorption isotherm were developed to represent the multistage process and the theoretical model permits determination of the inter-stage heavy metal concentrations and the total amount of chelating resin required for achieving a desired level of heavy metal removal. Optimization of the linearized theoretical model shows that equal division of the total amount of chelating resin among all stages of the multistage process yields the best results in terms of saving of chelating resin for a given heavy metal removal or enhanced heavy metal removal for a given total amount of chelating resin. Experimental tests were also conducted to establish the equilibrium adsorption of heavy metal by the chelating resin and to empirically verify the advantages of the multistage adsorption process.

  5. The role of chelation in the treatment of arsenic and mercury poisoning.

    PubMed

    Kosnett, Michael J

    2013-12-01

    Chelation for heavy metal intoxication began more than 70 years ago with the development of British anti-lewisite (BAL; dimercaprol) in wartime Britain as a potential antidote the arsenical warfare agent lewisite (dichloro[2-chlorovinyl]arsine). DMPS (unithiol) and DMSA (succimer), dithiol water-soluble analogs of BAL, were developed in the Soviet Union and China in the late 1950s. These three agents have remained the mainstay of chelation treatment of arsenic and mercury intoxication for more than half a century. Animal experiments and in some instances human data indicate that the dithiol chelators enhance arsenic and mercury excretion. Controlled animal experiments support a therapeutic role for these chelators in the prompt treatment of acute poisoning by arsenic and inorganic mercury salts. Treatment should be initiated as rapidly as possible (within minutes to a few hours), as efficacy declines or disappears as the time interval between metal exposure and onset of chelation increases. DMPS and DMSA, which have a higher therapeutic index than BAL and do not redistribute arsenic or mercury to the brain, offer advantages in clinical practice. Although chelation following chronic exposure to inorganic arsenic and inorganic mercury may accelerate metal excretion and diminish metal burden in some organs, potential therapeutic efficacy in terms of decreased morbidity and mortality is largely unestablished in cases of chronic metal intoxication.

  6. Effect of chelators on copper metabolism and copper pools in mouse hepatocytes

    SciTech Connect

    McArdle, H.J.; Gross, S.M.; Creaser, I.; Sargeson, A.M.; Danks, D.M.

    1989-04-01

    Disorders of copper storage are usually treated by chelation therapy. It is generally thought that the chelators act by mobilizing copper from the liver, hence allowing excretion in the urine. This paper has examined the effect of chelators on copper uptake and storage in mouse hepatocytes. Penicillamine, a clinically important chelator, does not block the uptake of copper or remove copper from hepatocytes. Two other copper chelators, sar and diamsar, which form very stable and kinetically inert Cu2+ complexes by encapsulating the metal ion in an organic cage, were shown to block copper accumulation by the cells and to remove up to 80% of cell-associated copper. They also removed most (approximately 80%) of the /sup 64/Cu accumulated by the cells in 30 min, but released only a small percentage (less than 20%) of that accumulated over 18 h. The results show that copper in the hepatocyte can be divided into at least two pools, an easily accessible one, and another, not removable even after long-term incubation with any of the chelators. Most of the copper normally found in the cell appeared to be associated with the former pool.

  7. Iron overload in thalassemia and related conditions: therapeutic goals and assessment of response to chelation therapies.

    PubMed

    Porter, John B; Shah, Farrukh T

    2010-12-01

    Transfusional iron loading inevitably results in hepatic iron accumulation, with variable extrahepatic distribution that is typically less pronounced in sickle cell disease than in thalassemia disorders. Iron chelation therapy has the goal of preventing iron-mediated tissue damage through controlling tissue iron levels, without incurring chelator-mediated toxicity. Historically, target levels for tissue iron control have been limited by the increased frequency of deferoxamine-mediated toxicity and low levels of iron loading. With newer chelation regimes, these limitations are less evident. The reporting of responses to chelation therapies has typically focused on average changes in serum ferritin in patient populations. This approach has three limitations. First, changes in serum ferritin may not reflect trends in iron balance equally in all patients or for all chelation regimens. Second, this provides no information about the proportion of patients likely respond. Third, this gives insufficient information about iron trends in tissues such as the heart. Monitoring of iron overload has advanced with the increasing use of MRI techniques to estimate iron balance (changes in liver iron concentration) and extrahepatic iron distribution (myocardial T2*). The term nonresponder has been increasingly used to describe individuals who fail to show a downward trend in one or more of these variables. Lack of a response of an individual may result from inadequate dosing, high transfusion requirement, poor treatment adherence, or unfavorable pharmacology of the chelation regime. This article scrutinizes evidence for response rates to deferoxamine, deferiprone (and combinations), and deferasirox.

  8. Effect of roasting on properties of the zinc-chelating substance in coffee brews.

    PubMed

    Wen, Xu; Enokizo, Akiko; Hattori, Harumi; Kobayashi, Satiko; Murata, Masatsune; Homma, Seiichi

    2005-04-06

    ApV is a brownish polymer with zinc-chelating activity in brewed coffee. We investigated in this study the effects of roasting on the zinc-chelating, reducing, and antioxidative activities of ApV from light-, medium-, and dark-roasted coffee. We also discuss the effect on the zinc-chelating activity of adding milk to the brewed coffee. The chelating activities of ApVs were evaluated by the tetramethyl murexide method. As the intensity of roasting increased, the yield of ApV increased, and the brown color and molecular weight of ApV respectively became darker and higher. Increasing the degree of roasting also decreased the zinc-chelating activity of ApV. The reducing activities of ApVs estimated by the indophenol method were stronger than those of ascorbic acid. Both the antioxidative activity estimated by the ABTS assay and the reducing activity of ApV increased with roasting. When milk was added to instant coffee and its ApV was prepared, the zinc-chelating activity of ApV was not changed.

  9. Fatty liver-hemorrhagic syndrome observed in commercial layers fed diets containing chelated minerals.

    PubMed

    Branton, S L; Lott, B D; Maslin, W R; Day, E J

    1995-01-01

    This study was originally conducted to determine the effect of various chloride levels and consumption of chelated versus non-chelated minerals on egg production and eggshell breaking strength. However, the focus of this report changed after fatty liver-hemorrhagic syndrome (FLHS) was observed in hens that consumed diets containing chelated minerals. No FLHS was observed in hens that consumed a diet that contained non-chelated minerals. Four hundred thirty-two 35-week-old commercial laying hens were housed in individual cages in groups of nine hens each. The treatments were factorially arranged (3 x 2) such that six experimental diets differing in chloride levels and in source of minerals were fed for six 28-day laying periods. A significantly higher mortality attributed to FLHS was observed in hens that consumed the diets having chelated minerals as compared with hens that consumed the diets with non-chelated minerals. No difference in mortality was observed among the hens fed the various chloride diets.

  10. Hydroxypyri(mi)dine-based chelators as antidotes of toxicity due to aluminum and actinides.

    PubMed

    Santos, M A; Esteves, M A; Chaves, S

    2012-01-01

    This review is focused on recent developments on hydroxypyri(mi)dines, as aluminum and actinide chelating agents to combat the toxicity due to accumulations of these metal ions in human body resulting from excessive metal exposure. After a brief update revision of the most common processes of aluminum (Al) exposure, as well as the associated toxicities and pathologies, we will focus on the current available Al chelators and future perspective as potential antidotes of Al toxicity. Due to the similarity between Al and Fe, a major emphasis is given to the hydroxypyridinone and hydroxypyrimidinone chelators, since they are analogues of the current iron chelators in clinical use (DFP and DFO). This review includes issues such as molecular design strategies and corresponding effects on the associated physico-chemical properties, lipo-hydrophilic balance, toxicity, in vivo bioassays and current clinical applications. The hydroxypyri(mi)dine chelators are also suitable for other hard metal ions, such as the radiotoxic actinides, and so a brief review is included on the applications of these chelators in actinides scavenging.

  11. Iron chelators in medicinal applications - chemical equilibrium considerations in pharmaceutical activity.

    PubMed

    Manning, Thomas; Kean, Greg; Thomas, Jessica; Thomas, Khaleh; Corbitt, Michael; Gosnell, Donna; Ware, Ronald; Fulp, Sonya; Jarrard, Joey; Phillips, Dennis

    2009-01-01

    Iron chelators are being examined as a potential class of pharmaceutical agents to battle different types of cancer as well as iron overload diseases. In recent studies, iron binding species such as desferrioxamine, triapine, tachpyridine, Dp44Mt, and PIH have been tested in cell line tests and clinical trials. Using published chemical equilibrium values (stability constants, equilibrium constants), it is argued that an iron chelator cannot competitively remove iron from a heme-containing biomolecule (i.e. hemoglobin (Hb), myoglobin) causing a cancerous cell to die. This type of reaction (DFO(aq) + [Fe(2+,3+)-Hb] --> [Fe(2+,3+)-DFO] + Hb) has been proposed in a number of published studies using circumstantial evidence. It is argued that iron chelators can potentially interact with iron from ferritin or iron that has precipitated or flocculated as oxyhydroxide under physiological pH's. It is argued that chelators can interfere with various physiological processes by binding cations such as Ca(2+), Zn(2+) or K(+). A number of siderophores and natural products that have the ability to bind Fe(3+)/Fe(2+) as well as other cations are discussed in terms of their potential pharmaceutical activity as chelators. Chemical equilibria between cations and pharmaceutical agents, which are rarely quantitated in explaining medicinal mechanisms, are used to show that chelators can bind and remove iron and other cations from physiologically important systems required for cell survival and propagation.

  12. Optimization of chelators to enhance uranium uptake from tailings for phytoremediation.

    PubMed

    Jagetiya, Bhagawatilal; Sharma, Anubha

    2013-04-01

    A greenhouse experiment was set up to investigate the ability of citric acid (CA), oxalic acid (OA), nitrilotriacetic acid (NTA) and EDTA for phytoremediation of uranium tailings by Indian mustard [Brassica juncea (L.) Czern. et Coss]. Uranium tailings were collected from Umra mining region and mixed with 75% of garden soil which yielded a 25:75 mixture. Prepared pots were divided into four sets and treated with following different concentrations - 0.1, 0.5, 2.5 and 12.5 mmol kg(-1) soil additions for each of the four chelators. Control pots which were not treated with chelators. Experiments were conducted in completely randomized block design with triplicates. The optimum concentrations of these chelators were found on the basis of biomass production, tolerance and accumulation potential. The data collected were expressed statistically. EDTA produced maximum growth depression whereas, minimum occurred in the case of NTA. Maximum U uptake (3.5-fold) in the roots occurred at 2.5 mmol of CA, while NTA proved to be the weakest for the same purpose. Severe toxicity in the form of reduced growth and plant death was recorded at 12.5 mmol of each chelator. Minimum growth inhibition produced by chelators occurred in NTA which was followed by OA, moderate in CA and maximum was traced in EDTA applications. Chelator strengthened U uptake in the present study follows the order: CA>EDTA>OA>NTA.

  13. Lead(II) binding to the chelating agent d-penicillamine in aqueous solution

    DOE PAGES

    Sisombath, Natalie S.; Jalilehvand, Farideh; Schell, Adam C.; ...

    2014-11-11

    Here, a spectroscopic investigation of the complexes formed between the Pb(II) ion and d-penicillamine (H2Pen), a chelating agent used in the treatment of lead poisoning, was carried out on two sets of alkaline aqueous solutions with CPb(II) ≈ 10 and 100 mM, varying the H2Pen/Pb(II) molar ratio (2.0, 3.0, 4.0, 10.0). Ultraviolet–visible (UV-vis) spectra of the 10 mM Pb(II) solutions consistently showed an absorption peak at 298 nm for S– → Pb(II) ligand-to-metal charge-transfer. The downfield 13C NMR chemical shift for the penicillamine COO– group confirmed Pb(II) coordination. The 207Pb NMR chemical shifts were confined to a narrow range betweenmore » 1806 ppm and 1873 ppm for all Pb(II)-penicillamine solutions, indicating only small variations in the speciation, even in large penicillamine excess. Those chemical shifts are considerably deshielded, relative to the solid-state 207Pb NMR isotropic chemical shift of 909 ppm obtained for crystalline penicillaminatolead(II) with Pb(S,N,O-Pen) coordination. The Pb LIII-edge extended X-ray absorption fine structure (EXAFS) spectra obtained for these solutions were well-modeled with two Pb–S and two Pb-(N/O) bonds with mean distances 2.64 ± 0.04 Å and 2.45 ± 0.04 Å, respectively. The combined spectroscopic results, reporting δ(207Pb) ≈ 1870 ppm and λmax ≈ 298 nm for a PbIIS2NO site, are consistent with a dominating 1:2 lead(II):penicillamine complex with [Pb(S,N,O-Pen)(S-HnPen)]2–n (n = 0–1) coordination in alkaline solutions, and provide useful structural information on how penicillamine can function as an antidote against lead toxicity in vivo.« less

  14. Lead(II) binding to the chelating agent d-penicillamine in aqueous solution

    SciTech Connect

    Sisombath, Natalie S.; Jalilehvand, Farideh; Schell, Adam C.; Wu, Qiao

    2014-11-11

    Here, a spectroscopic investigation of the complexes formed between the Pb(II) ion and d-penicillamine (H2Pen), a chelating agent used in the treatment of lead poisoning, was carried out on two sets of alkaline aqueous solutions with CPb(II) ≈ 10 and 100 mM, varying the H2Pen/Pb(II) molar ratio (2.0, 3.0, 4.0, 10.0). Ultraviolet–visible (UV-vis) spectra of the 10 mM Pb(II) solutions consistently showed an absorption peak at 298 nm for S → Pb(II) ligand-to-metal charge-transfer. The downfield 13C NMR chemical shift for the penicillamine COO group confirmed Pb(II) coordination. The 207Pb NMR chemical shifts were confined to a narrow range between 1806 ppm and 1873 ppm for all Pb(II)-penicillamine solutions, indicating only small variations in the speciation, even in large penicillamine excess. Those chemical shifts are considerably deshielded, relative to the solid-state 207Pb NMR isotropic chemical shift of 909 ppm obtained for crystalline penicillaminatolead(II) with Pb(S,N,O-Pen) coordination. The Pb LIII-edge extended X-ray absorption fine structure (EXAFS) spectra obtained for these solutions were well-modeled with two Pb–S and two Pb-(N/O) bonds with mean distances 2.64 ± 0.04 Å and 2.45 ± 0.04 Å, respectively. The combined spectroscopic results, reporting δ(207Pb) ≈ 1870 ppm and λmax ≈ 298 nm for a PbIIS2NO site, are consistent with a dominating 1:2 lead(II):penicillamine complex with [Pb(S,N,O-Pen)(S-HnPen)]2–n (n = 0–1) coordination in alkaline solutions, and provide useful structural information on how penicillamine can function as an antidote against lead toxicity in vivo.

  15. XAFS Study of the Ferro- and Antiferromagnetic Binuclear Copper(II) Complexes of Azomethine Based Tridentate Ligands

    SciTech Connect

    Vlasenko, Valery G.

    2007-02-02

    Binuclear copper complexes are known to be models for metalloenzymes containing copper active sites, and some of them are of considerable interest due to their magnetic and charge transfer properties. The reactions of the complex formation of bibasic tridentate heterocyclic imines with copper acetate leads to two types of chelates with mono deprotonated ligands and with totally deprotonated ligands. Cu K-edge EXAFS has been applied to determine the local structure around the metal center in copper(II) azomethine complexes with five tridentate ligands: 1-(salycilideneimino)- or 1-(2-tosylaminobenzilideneimino)-2-amino(oxo, thio)benzimidazoles. It has been found that some of the chelates studied are bridged binuclear copper complexes, and others are mononuclear complexes. The copper-copper interatomic distances in the bridged binuclear copper complexes were found to be 2.85-3.01 A. Variable temperature magnetic susceptibility data indicate the presence of both ferromagnetic and antiferromagnetic interactions within the dimer, the former is dominating at low temperatures and the latter at high temperatures.

  16. Chelating and antibacterial properties of chitosan nanoparticles on dentin

    PubMed Central

    Bramante, Clovis Monteiro; Duarte, Marco Antonio Hungaro; de Moura, Marcia Regina; Aouada, Fauze Ahmad; Kishen, Anil

    2015-01-01

    Objectives The use of chitosan nanoparticles (CNPs) in endodontics is of interest due to their antibiofilm properties. This study was to investigate the ability of bioactive CNPs to remove the smear layer and inhibit bacterial recolonization on dentin. Materials and Methods One hundred bovine dentin sections were divided into five groups (n = 20 per group) according to the treatment. The irrigating solutions used were 2.5% sodium hypochlorite (NaOCl) for 20 min, 17% ethylenediaminetetraacetic acid (EDTA) for 3 min and 1.29 mg/mL CNPs for 3 min. The samples were irrigated with either distilled water (control), NaOCl, NaOCl-EDTA, NaOCl-EDTA-CNPs or NaOCl-CNPs. After the treatment, half of the samples (n = 50) were used to assess the chelating effect of the solutions using portable scanning electronic microscopy, while the other half (n = 50) were infected intra-orally to examine the post-treatment bacterial biofilm forming capacity. The biovolume and cellular viability of the biofilms were analysed under confocal laser scanning microscopy. The Kappa test was performed for examiner calibration, and the non-parametric Kruskal-Wallis and Dunn tests (p < 0.05) were used for comparisons among the groups. Results The smear layer was significantly reduced in all of the groups except the control and NaOCl groups (p < 0.05). The CNPs-treated samples were able to resist biofilm formation significantly better than other treatment groups (p < 0.05). Conclusions CNPs could be used as a final irrigant during root canal treatment with the dual benefit of removing the smear layer and inhibiting bacterial recolonization on root dentin. PMID:26295022

  17. Why mercury prefers soft ligands

    SciTech Connect

    Riccardi, Demian M; Guo, Hao-Bo; Gu, Baohua; Parks, Jerry M; Summers, Anne; Miller, S; Liang, Liyuan; Smith, Jeremy C

    2013-01-01

    Mercury (Hg) is a major global pollutant arising from both natural and anthropogenic sources. Defining the factors that determine the relative affinities of different ligands for the mercuric ion, Hg2+, is critical to understanding its speciation, transformation, and bioaccumulation in the environment. Here, we use quantum chemistry to dissect the relative binding free energies for a series of inorganic anion complexes of Hg2+. Comparison of Hg2+ ligand interactions in the gaseous and aqueous phases shows that differences in interactions with a few, local water molecules led to a clear periodic trend within the chalcogenide and halide groups and resulted in the well-known experimentally observed preference of Hg2+ for soft ligands such as thiols. Our approach establishes a basis for understanding Hg speciation in the biosphere.

  18. What are Nuclear Receptor Ligands?

    PubMed Central

    Sladek, Frances M.

    2010-01-01

    Nuclear receptors (NRs) are a family of highly conserved transcription factors that regulate transcription in response to small lipophilic compounds. They play a role in every aspect of development, physiology and disease in humans. They are also ubiquitous in and unique to the animal kingdom suggesting that they may have played an important role in their evolution. In contrast to the classical endocrine receptors that originally defined the family, recent studies suggest that the first NRs might have been sensors of their environment, binding ligands that were external to the host organism. The purpose of this review is to provide a broad perspective on NR ligands and address the issue of exactly what constitutes a NR ligand from historical, biological and evolutionary perspectives. This discussion will lay the foundation for subsequent reviews in this issue as well as pose new questions for future investigation. PMID:20615454

  19. Molecular Recognition and Ligand Association

    NASA Astrophysics Data System (ADS)

    Baron, Riccardo; McCammon, J. Andrew

    2013-04-01

    We review recent developments in our understanding of molecular recognition and ligand association, focusing on two major viewpoints: (a) studies that highlight new physical insight into the molecular recognition process and the driving forces determining thermodynamic signatures of binding and (b) recent methodological advances in applications to protein-ligand binding. In particular, we highlight the challenges posed by compensating enthalpic and entropic terms, competing solute and solvent contributions, and the relevance of complex configurational ensembles comprising multiple protein, ligand, and solvent intermediate states. As more complete physics is taken into account, computational approaches increase their ability to complement experimental measurements, by providing a microscopic, dynamic view of ensemble-averaged experimental observables. Physics-based approaches are increasingly expanding their power in pharmacology applications.

  20. 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.