14 research outputs found

    SynthÚse de nouveaux séquestrants bioinspirés de radionucléides tétravalents destinés à la mise-au-point de dispositifs analytiques de terrain pour le contrÎle environnemental in situ

    No full text
    The ultimate goal of our work was to develop diffusive gradient in thin-film (DGT) devices specific for tetra- (Th4+, Pu4+) and hexavalent actinides (UO22+). The active part of a DGT accumulator is its receptor phase, consisting of a chelating resin specific to the targeted analyte embedded in a hydrophilic gel.The first part focuses on the development of a reliable method for grafting ligands onto two commercial hydrophilic organic resins. For this purpose, we selected the commercially available bacterial siderophore desferrioxamine B (DFO), a natural iron chelator that has a high affinity for all strong Lewis acid cations, including the targeted 5f ones. We took advantage of the terminal primary amine of DFO for grafting the molecule onto the polymeric chains of the support, either by creating a peptide bond with the carboxylic resin CM SephadexÂź C25, or by opening one dangling epoxy ring of the PuroliteÂź ECR8209 resin. Several tens of grams of each material were produced in order to manufacture and validate the DGT devices, using uranium(VI)-doped mineral waters before deploying them in the Oeuf river (France).The second topic dealt with the synthesis of sequestering agents of tetravalent actinides, bioinspired by exochelin MN. This siderophore incorporates a 6-membered cyclic hydroxamic acid moiety, whose donor atoms are blocked in their Z conformation. Coined PIPO, this binding unit exhibits an increased affinity towards metal cations compared to its acyclic analogs.In a first step, we synthesized substituted PIPO precursors, isolated both enantiomers, and studied their stereochemical and coordination properties. In a second step, we designed three octadentate tetrahydroxamic ligands for the chelation of tetravalent actinides. Four PIPO units were attached to three linear or branched amines of varying length and flexibility. Complexation tests with thorium(IV) and zirconium(IV), taken as plutonium(IV) surrogates, indicated the formation of 1:1 metal/ligand complexes. Based on this result, we modified the synthesis of one of the chiral tetrapods by inserting an anchoring arm that bears a terminal amine group. The chelator was appended to an antibody and the resulting bioconjugate labeled with 89Zr to produce a PET radiotracer that is currently undergoing preclinical evaluation.Le but ultime de nos travaux Ă©tait de dĂ©velopper un dispositif de gradients de diffusion en couches minces (DGT) spĂ©cifique des actinides tĂ©tra- (Th4+, Pu4+) et hexa-valents (UO22+). La partie active d'un accumulateur DGT est sa phase rĂ©ceptrice, constituĂ©e d'une rĂ©sine chĂ©latrice spĂ©ci-fique de l'analyte ciblĂ© encapsulĂ©e dans un gel hydrophile.Le premier volet se focalise sur le dĂ©veloppement d’une mĂ©thode fiable de greffage de ligands sur deux rĂ©sines organiques hydrophiles commerciales. Pour ce faire, nous nous sommes intĂ©ressĂ©s Ă  un sidĂ©rophore bactĂ©rien disponible commercialement, la desferrioxamine B (DFO), chĂ©lateur naturel du fer qui possĂšde une forte affinitĂ© pour tous les cations acides de Lewis forts, dont les ions 5f ciblĂ©s. Nous avons tirĂ© profit de l'amine primaire terminale portĂ©e par la DFO pour greffer la molĂ©cule sur les chaĂźnes polymĂ©riques du support, soit par la crĂ©ation d'une liaison peptidique avec la rĂ©sine carboxylique CM SephadexÂź C25, soit par l'ouverture de cycles Ă©poxy portĂ©s par la rĂ©sine PuroliteÂź ECR8209. Plusieurs dizaines de grammes de chaque lot ont Ă©tĂ© produits en vue de confectionner et qualifier les accumulateurs DGT Ă  l'aide d'eaux minĂ©rales dopĂ©es en uranium(VI) avant de les dĂ©ployer en milieu naturel aquatique. Le deuxiĂšme axe concerna la synthĂšse de ligands adaptĂ©s pour la complexation d’actinides tĂ©travalents, bioinspirĂ©s de l'exocheline MN. Ce sidĂ©rophore possĂšde une fonction acide hydroxamique cyclique Ă  6 atomes dont les atomes donneurs sont bloquĂ©s en conformation Z. Ce motif, dit PIPO, prĂ©sente une affinitĂ© accrue vis-Ă -vis des cations mĂ©talliques par rapport aux analogues acycliques.La premiĂšre Ă©tape consista Ă  synthĂ©tiser des prĂ©curseurs PIPO substituĂ©s, Ă  sĂ©parer les Ă©nantiomĂšres, puis Ă  Ă©tudier leurs propriĂ©tĂ©s stĂ©rĂ©ochimiques et de coordination. Dans un second temps, trois ligands tĂ©trahydroxamiques octadentes, destinĂ©s Ă  chĂ©later des actinides tĂ©travalents, ont Ă©tĂ© conçus. Quatre motifs PIPO ont Ă©tĂ© introduits sur trois squelettes carbonĂ©s linĂ©aires ou branchĂ©s, de longueur et de flexibilitĂ© variables. Les essais de complexation du thorium(IV) et du zirconium(IV), succĂ©danĂ©s du plutonium(IV), indiquent la formation de complexes de stƓchiomĂ©trie 1:1. Fort de ce rĂ©sultat, nous avons modifiĂ© la synthĂšse de l'un des tĂ©trapodes chiraux afin d'insĂ©rer un bras d'ancrage porteur d'une fonction amine terminale. Cette fonction a permis de conjuguer le chĂ©lateur Ă  un anticorps et de prĂ©parer un radiotraceur TEP marquĂ© au 89Zr en cours d'Ă©valuation prĂ©clinique

    SynthÚse de nouveaux séquestrants bioinspirés de radionucléides tétravalents destinés à la mise-au-point de dispositifs analytiques de terrain pour le contrÎle environnemental in situ

    No full text
    The ultimate goal of our work was to develop diffusive gradient in thin-film (DGT) devices specific for tetra- (Th4+, Pu4+) and hexavalent actinides (UO22+). The active part of a DGT accumulator is its receptor phase, consisting of a chelating resin specific to the targeted analyte embedded in a hydrophilic gel.The first part focuses on the development of a reliable method for grafting ligands onto two commercial hydrophilic organic resins. For this purpose, we selected the commercially available bacterial siderophore desferrioxamine B (DFO), a natural iron chelator that has a high affinity for all strong Lewis acid cations, including the targeted 5f ones. We took advantage of the terminal primary amine of DFO for grafting the molecule onto the polymeric chains of the support, either by creating a peptide bond with the carboxylic resin CM SephadexÂź C25, or by opening one dangling epoxy ring of the PuroliteÂź ECR8209 resin. Several tens of grams of each material were produced in order to manufacture and validate the DGT devices, using uranium(VI)-doped mineral waters before deploying them in the Oeuf river (France).The second topic dealt with the synthesis of sequestering agents of tetravalent actinides, bioinspired by exochelin MN. This siderophore incorporates a 6-membered cyclic hydroxamic acid moiety, whose donor atoms are blocked in their Z conformation. Coined PIPO, this binding unit exhibits an increased affinity towards metal cations compared to its acyclic analogs.In a first step, we synthesized substituted PIPO precursors, isolated both enantiomers, and studied their stereochemical and coordination properties. In a second step, we designed three octadentate tetrahydroxamic ligands for the chelation of tetravalent actinides. Four PIPO units were attached to three linear or branched amines of varying length and flexibility. Complexation tests with thorium(IV) and zirconium(IV), taken as plutonium(IV) surrogates, indicated the formation of 1:1 metal/ligand complexes. Based on this result, we modified the synthesis of one of the chiral tetrapods by inserting an anchoring arm that bears a terminal amine group. The chelator was appended to an antibody and the resulting bioconjugate labeled with 89Zr to produce a PET radiotracer that is currently undergoing preclinical evaluation.Le but ultime de nos travaux Ă©tait de dĂ©velopper un dispositif de gradients de diffusion en couches minces (DGT) spĂ©cifique des actinides tĂ©tra- (Th4+, Pu4+) et hexa-valents (UO22+). La partie active d'un accumulateur DGT est sa phase rĂ©ceptrice, constituĂ©e d'une rĂ©sine chĂ©latrice spĂ©ci-fique de l'analyte ciblĂ© encapsulĂ©e dans un gel hydrophile.Le premier volet se focalise sur le dĂ©veloppement d’une mĂ©thode fiable de greffage de ligands sur deux rĂ©sines organiques hydrophiles commerciales. Pour ce faire, nous nous sommes intĂ©ressĂ©s Ă  un sidĂ©rophore bactĂ©rien disponible commercialement, la desferrioxamine B (DFO), chĂ©lateur naturel du fer qui possĂšde une forte affinitĂ© pour tous les cations acides de Lewis forts, dont les ions 5f ciblĂ©s. Nous avons tirĂ© profit de l'amine primaire terminale portĂ©e par la DFO pour greffer la molĂ©cule sur les chaĂźnes polymĂ©riques du support, soit par la crĂ©ation d'une liaison peptidique avec la rĂ©sine carboxylique CM SephadexÂź C25, soit par l'ouverture de cycles Ă©poxy portĂ©s par la rĂ©sine PuroliteÂź ECR8209. Plusieurs dizaines de grammes de chaque lot ont Ă©tĂ© produits en vue de confectionner et qualifier les accumulateurs DGT Ă  l'aide d'eaux minĂ©rales dopĂ©es en uranium(VI) avant de les dĂ©ployer en milieu naturel aquatique. Le deuxiĂšme axe concerna la synthĂšse de ligands adaptĂ©s pour la complexation d’actinides tĂ©travalents, bioinspirĂ©s de l'exocheline MN. Ce sidĂ©rophore possĂšde une fonction acide hydroxamique cyclique Ă  6 atomes dont les atomes donneurs sont bloquĂ©s en conformation Z. Ce motif, dit PIPO, prĂ©sente une affinitĂ© accrue vis-Ă -vis des cations mĂ©talliques par rapport aux analogues acycliques.La premiĂšre Ă©tape consista Ă  synthĂ©tiser des prĂ©curseurs PIPO substituĂ©s, Ă  sĂ©parer les Ă©nantiomĂšres, puis Ă  Ă©tudier leurs propriĂ©tĂ©s stĂ©rĂ©ochimiques et de coordination. Dans un second temps, trois ligands tĂ©trahydroxamiques octadentes, destinĂ©s Ă  chĂ©later des actinides tĂ©travalents, ont Ă©tĂ© conçus. Quatre motifs PIPO ont Ă©tĂ© introduits sur trois squelettes carbonĂ©s linĂ©aires ou branchĂ©s, de longueur et de flexibilitĂ© variables. Les essais de complexation du thorium(IV) et du zirconium(IV), succĂ©danĂ©s du plutonium(IV), indiquent la formation de complexes de stƓchiomĂ©trie 1:1. Fort de ce rĂ©sultat, nous avons modifiĂ© la synthĂšse de l'un des tĂ©trapodes chiraux afin d'insĂ©rer un bras d'ancrage porteur d'une fonction amine terminale. Cette fonction a permis de conjuguer le chĂ©lateur Ă  un anticorps et de prĂ©parer un radiotraceur TEP marquĂ© au 89Zr en cours d'Ă©valuation prĂ©clinique

    Synthesis of new bioinspired sequestering agents of tetravalent radionuclides and development of analytical field devices for their in situ environmental monitoring

    No full text
    Le but ultime de nos travaux Ă©tait de dĂ©velopper un dispositif de gradients de diffusion en couches minces (DGT) spĂ©cifique des actinides tĂ©tra- (Th4+, Pu4+) et hexa-valents (UO22+). La partie active d'un accumulateur DGT est sa phase rĂ©ceptrice, constituĂ©e d'une rĂ©sine chĂ©latrice spĂ©ci-fique de l'analyte ciblĂ© encapsulĂ©e dans un gel hydrophile.Le premier volet se focalise sur le dĂ©veloppement d’une mĂ©thode fiable de greffage de ligands sur deux rĂ©sines organiques hydrophiles commerciales. Pour ce faire, nous nous sommes intĂ©ressĂ©s Ă  un sidĂ©rophore bactĂ©rien disponible commercialement, la desferrioxamine B (DFO), chĂ©lateur naturel du fer qui possĂšde une forte affinitĂ© pour tous les cations acides de Lewis forts, dont les ions 5f ciblĂ©s. Nous avons tirĂ© profit de l'amine primaire terminale portĂ©e par la DFO pour greffer la molĂ©cule sur les chaĂźnes polymĂ©riques du support, soit par la crĂ©ation d'une liaison peptidique avec la rĂ©sine carboxylique CM SephadexÂź C25, soit par l'ouverture de cycles Ă©poxy portĂ©s par la rĂ©sine PuroliteÂź ECR8209. Plusieurs dizaines de grammes de chaque lot ont Ă©tĂ© produits en vue de confectionner et qualifier les accumulateurs DGT Ă  l'aide d'eaux minĂ©rales dopĂ©es en uranium(VI) avant de les dĂ©ployer en milieu naturel aquatique. Le deuxiĂšme axe concerna la synthĂšse de ligands adaptĂ©s pour la complexation d’actinides tĂ©travalents, bioinspirĂ©s de l'exocheline MN. Ce sidĂ©rophore possĂšde une fonction acide hydroxamique cyclique Ă  6 atomes dont les atomes donneurs sont bloquĂ©s en conformation Z. Ce motif, dit PIPO, prĂ©sente une affinitĂ© accrue vis-Ă -vis des cations mĂ©talliques par rapport aux analogues acycliques.La premiĂšre Ă©tape consista Ă  synthĂ©tiser des prĂ©curseurs PIPO substituĂ©s, Ă  sĂ©parer les Ă©nantiomĂšres, puis Ă  Ă©tudier leurs propriĂ©tĂ©s stĂ©rĂ©ochimiques et de coordination. Dans un second temps, trois ligands tĂ©trahydroxamiques octadentes, destinĂ©s Ă  chĂ©later des actinides tĂ©travalents, ont Ă©tĂ© conçus. Quatre motifs PIPO ont Ă©tĂ© introduits sur trois squelettes carbonĂ©s linĂ©aires ou branchĂ©s, de longueur et de flexibilitĂ© variables. Les essais de complexation du thorium(IV) et du zirconium(IV), succĂ©danĂ©s du plutonium(IV), indiquent la formation de complexes de stƓchiomĂ©trie 1:1. Fort de ce rĂ©sultat, nous avons modifiĂ© la synthĂšse de l'un des tĂ©trapodes chiraux afin d'insĂ©rer un bras d'ancrage porteur d'une fonction amine terminale. Cette fonction a permis de conjuguer le chĂ©lateur Ă  un anticorps et de prĂ©parer un radiotraceur TEP marquĂ© au 89Zr en cours d'Ă©valuation prĂ©clinique.The ultimate goal of our work was to develop diffusive gradient in thin-film (DGT) devices specific for tetra- (Th4+, Pu4+) and hexavalent actinides (UO22+). The active part of a DGT accumulator is its receptor phase, consisting of a chelating resin specific to the targeted analyte embedded in a hydrophilic gel.The first part focuses on the development of a reliable method for grafting ligands onto two commercial hydrophilic organic resins. For this purpose, we selected the commercially available bacterial siderophore desferrioxamine B (DFO), a natural iron chelator that has a high affinity for all strong Lewis acid cations, including the targeted 5f ones. We took advantage of the terminal primary amine of DFO for grafting the molecule onto the polymeric chains of the support, either by creating a peptide bond with the carboxylic resin CM SephadexÂź C25, or by opening one dangling epoxy ring of the PuroliteÂź ECR8209 resin. Several tens of grams of each material were produced in order to manufacture and validate the DGT devices, using uranium(VI)-doped mineral waters before deploying them in the Oeuf river (France).The second topic dealt with the synthesis of sequestering agents of tetravalent actinides, bioinspired by exochelin MN. This siderophore incorporates a 6-membered cyclic hydroxamic acid moiety, whose donor atoms are blocked in their Z conformation. Coined PIPO, this binding unit exhibits an increased affinity towards metal cations compared to its acyclic analogs.In a first step, we synthesized substituted PIPO precursors, isolated both enantiomers, and studied their stereochemical and coordination properties. In a second step, we designed three octadentate tetrahydroxamic ligands for the chelation of tetravalent actinides. Four PIPO units were attached to three linear or branched amines of varying length and flexibility. Complexation tests with thorium(IV) and zirconium(IV), taken as plutonium(IV) surrogates, indicated the formation of 1:1 metal/ligand complexes. Based on this result, we modified the synthesis of one of the chiral tetrapods by inserting an anchoring arm that bears a terminal amine group. The chelator was appended to an antibody and the resulting bioconjugate labeled with 89Zr to produce a PET radiotracer that is currently undergoing preclinical evaluation

    Porous organic polymers based on cobalt corroles for carbon monoxide binding

    No full text
    International audiencePorous organic polymers (POPs), known for their high surface area and porosity, were prepared starting from tetraphenyl tetrahedral-shaped building blocks and corrole macrocyclic linkers either as free bases or cobalt complexes. This synthetic method allowed us to construct new porous frameworks with high carbon monoxide adsorption properties. Two synthetic strategies were developed for incorporatingcobalt corroles into the porous matrix. The first method is based on the copper-free Sonogashira crosscoupling reaction between a free base diodo-corrole with a tetrahedral shaped derivative followed by cobalt complexation of the resulting material, leading to POP-CorCo-1. The second strategy consists of preparing POP-CorCo-2 by directly using in the coupling reaction the metalated cobalt corrole temporarilyprotected by two ammine ligands at the axial position. The design principles as well as the relationship between the structure and the selective CO adsorption performance are presented. The adsorption capacities and selectivities of CO were calculated from a multisite Langmuir isotherm model and using IAST theory. Spectroscopic studies (NMR, FTIR, UV-visible), kinetic sorption measurements and microscopic analyses made possible to provide a fairly complete description of the structure of the POPs, their porosity and the nature of solid–gas interactions. The POPs prepared by both methods show a high permanent porosity and outstanding CO sorption properties with a high selectivity over N2, O2 and CO2, up to 15700, 4000 and 1800, respectively. The two POP-CorCo therefore offer confined molecular spaces for ascertaining a high accessibility of the metallocorrole active sites for gas binding on the cobalt atom, thus featuring high potential for applications in selective capture or sensing of CO versus N2, O2 and CO

    Combining Desferriferrioxamine B and 1‐Hydroxy‐2‐Piperidone ((PIPO)H) to Chelate Zirconium. Solution Structure of a Model Complex of the [ 89 Zr]Zr−DFOcyclo*−mAb Radioimmunoconjugate

    No full text
    International audience89Zr−immunoPET is a hot topic as 89Zr cumulates the advantages of 64Cu and 124I without their drawbacks. We report the synthesis of a model ligand of a chiral bioconjugable tetrahydroxamic chelator combining the desferriferrioxamine B siderophore and 1-hydroxy-2-piperidone ((PIPO)H), a chiral cyclic hydroxamic acid derivative, and the study by NMR spectroscopy of its zirconium complex. Nuclear Overhauser effect measurements (ROESY) indicated that the complex exists in the form of two diastereomers, in 77 : 23 ratio, resulting from the combination of the central chiralities at the 3-C of the (PIPO)H component and at the Zr4+ cation. The 44 lowest energy structures out of more than 1000 configurations/conformations returned by calculations based on density functional theory were examined. Comparison of the ROESY data and the calculated interatomic H⋅⋅⋅H distances allowed us to select the most probable configuration and conformations of the major complex

    Implementation of dihydroxamate-based binding gels in DGT devices for uranium(VI) sampling in freshwater. An intercomparison study

    No full text
    International audienceMining activities, production and use of nuclear fuel (65 kt/year), processing of spent fuel and storage of nuclear wastes may lead to the release of uranium into the environment, its transfer between the different compartments of the biosphere, and the ultimate contamination of trophic chains [1].Nowadays, the monitoring of contaminated sites requires new breakthroughs in analytical techniques in order to assess in detail the impact and bioavailability of actinides discharged into aquatic environments. In that respect, Diffusive Gradient in Thin-films (DGT) devices are particularly attractive tools for the passive sampling of various contaminants in aquatic environments.Unfortunately, the most frequently used and commercially available binding gels for uranium, namely the Chelex-100 ion-exchange resin or the TiO2-based Metsorb adsorbing material, behave poorly in carbonate-rich, hard freshwater and seawaters [2-3]. To overcome these limitations, we relied on a biomimetic approach for designing efficient pincer-like UO22+ chelators, bearing two terminal hydroxamate bidentate groups, which are able to coordinate the uranyl cation in its equatorial plane [4]. Equilibrium constants for complex formation with UO22+, Ca2+ and Mg2+ were determined by potentiometry. High affinity for the former and selectivity with respect to the two latter interfering species prompt us to graft covalently one of these binders on a hydrophilic organic resin, which was then incorporated in an agarose binding gel. Performances of the DGT samplers made thereof to accumulate uranium(VI) in natural freshwaters will be presented and compared to the experimental results obtained for a series of other binding resins, including Chelex-100 and Metsorb. These validation tests were performed both in the laboratory, using mineral water spiked with uranium, and in field by deploying the DGT samplers directly in a river

    Kinetic and thermodynamic sorption studies of Fe(III) and Zr(IV) by DFO@Purolite, a desferrioxamine B based chelating resin

    No full text
    International audienceThis paper presents the characterization of a novel solid-phase sorbent for iron(III) and zirconium(IV)obtained by the functionalization of a commercial epoxy methacrylate resin (Purolites ECR8209) withdesferrioxamine B (DFO). The sorption properties of the solid material, named DFO@Purolite, towardsFe(III) and Zr(IV) were investigated in detail. In particular, the sorption kinetics, isotherms and sorptionprofiles as a function of the solution’s pH were studied. The stoichiometry and the complexationconstants of both cations with the active sites of the sorbent were determined by applying the Gibbs–Donnan model, i.e., the model used to explain the protonation and the metal sorption on ion exchangeresins. While the chelating properties of the solid material investigated herein are in good agreementwith those of Fe(III)/DFO and Zr(IV)/DFO previously determined in homogeneous aqueous solutions, thesolid/liquid extraction studies further allow to ascertain the speciation model for the latter system that isstill subjected to controversy in the literature

    Development of efficient DGT binding gels for uranium based on molecular coordination chemistry

    No full text
    International audienceThe Diffusive Gradient in Thin-films (DGT) technique has been developed in the 1990’s with field applications that were initially limited to measuring some transition metals at trace levels in aquatic environments. Since then, a very active community of researchers have progressively created numerous binding gels with different selectivity permitting to cover almost all elements of the periodic table. However, for some elements like uranium, binding gels able to accumulate U(VI) in all types of media (river waters, sea water, soils, sediments) are still not available. Among the sixteen DGT methods developed so far for UO22+, the commercially available samplers containing either the Chelex-100 resin (polystyrene matrix functionalized with iminodiacetic acid chelating groups) or Metsorb material (TiO2-based adsorbent) are the most employed. Depending on the deployment conditions, their performances to determine the labile U(VI) concentration in aquatic environment can be unsatisfactory because these DGT samplers are not selective to UO22+ and the binding sites may become saturated by competing ions.1,2In this study, we propose to improve the DGT sampling of labile UO22+ species by employing a new strategy that relies on the knowledge of the U coordination chemistry and the development of ligands targeted for this specific element. New binding agents, including a siderophore, with strong complexation capacity for iron and actinides3–5 were grafted on a carboxylic resin and incorporated in an agarose hydrogel for their use in DGT samplers. Laboratory validation experiments were performed in simple solutions (10 mmol L–1 NaNO3 and 1 mmol L–1 NaHCO3), in which the prevailing U(VI) species are [UO2(CO3)3]4– and [UO2(CO3)2]2–. Then, time-series experiments were performed in complex matrices in which additional U(VI) species are present (i.e., Ca2UO2(CO3)3, [CaUO2(CO3)3]2–, [MgUO2(CO3)3]2– and/or [UO2(CO3)3]4–). After evaluating the DGT performances in the laboratory, a field test was finally performed in the Essonne River (Essonne, France). Results for the siderophore-based DGT sampler are compared to measurements performed with Chelex- and Metsorb-DGT samplers both in lab and in field
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