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1.
J Phys Chem Lett ; : 6063-6067, 2020 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-32635727

RESUMO

Two-photon-excited fluorescence spectroscopy is a powerful tool to study the structural and electronic properties of optically active complexes and molecules. Although numerous lanthanide complexes have been characterized by two-photon-excited fluorescence in solution, this report is the first to apply such a technique to actinide compounds. Contrasting with previous observations in lanthanides, we demonstrate that the two-photon absorption properties of the complexes significantly depend on the metal (4f vs 5f), with Cm(III) complexes showing significantly higher two-photon absorption cross sections than lanthanide analogues and up to 200-fold stronger emission intensities. These results are consistent with electronic and structural differences between the lanthanide and actinide systems studied. Hence, the described methodology can provide valuable insights into the interactions between f-elements and ligands, along with promising prospects on the characterization of scarce compounds.

2.
ACS Sens ; 5(5): 1281-1286, 2020 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-32352783

RESUMO

Gadolinium-based contrast agents are widely used in magnetic resonance imaging procedures to enhance image contrast. Despite their ubiquitous use in clinical settings, gadolinium is not an innocuous element, as suggested by several disorders associated with its use. Therefore, novel analytical technologies capable of tracking contrast agent excretion through urine are necessary for optimizing patient safety after imaging procedures. Here, we describe an assay to detect and quantify contrast agents in urine based on the luminescence quenching of a metal chelate probe, Eu3+-3,4,3-LI(1,2-HOPO), which only requires 10 min incubation before measurement. Gadolinium-based contrast agents prevent the formation of the Eu3+-3,4,3-LI(1,2-HOPO) complex, subsequently decreasing the luminescence of the assay solution. Three commercial contrast agents, Magnevist, Multihance, and Omniscan, were used to demonstrate the analytical concept in synthetic human urine, and subsequent quantification of mouse urine samples. To the best of our knowledge, this is the first assay capable of detecting and quantifying gadolinium-based contrast agents in urine without sample preparation or digestion.

3.
Chemistry ; 26(11): 2354-2359, 2020 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-31914232

RESUMO

Octadentate hydroxypyridinone (HOPO) and catecholamide (CAM) siderophore analogues are known to be efficacious chelators of the actinide cations, and these ligands are also capable of facilitating both activation and reduction of actinyl species. Utilizing X-ray absorption near edge structure (XANES) and extended X-ray absorption fine structure (EXAFS) spectroscopies, as well as cyclic voltammetry measurements, herein, we elucidate chelation-based mechanisms for driving reactivity and initiating redox processes in a family of neptunyl-HOPO and CAM complexes. Based on the selected chelator, the ability to control the oxidation state of neptunium and the speed of reduction and concurrent oxo group activation was demonstrated. Most notably, reduction kinetics for the NpV O2 +/ /NpIV redox couple upon chelation by the ligands 3,4,3-LI(1,2-HOPO) and 3,4,3-LI(CAM)2 (1,2-HOPO)2 was observed to be faster than ever reported, and in fact quicker than we could measure using either X-ray absorption spectroscopy or electrochemical techniques.

4.
Inorg Chem ; 59(1): 4-7, 2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-31905501
5.
Inorg Chem ; 59(3): 2030-2036, 2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-31971379

RESUMO

The octadentate hydroxypyridinone chelator 3,4,3-LI(1,2-HOPO) is a promising therapeutic agent because of its high affinity for f-block elements and noncytotoxicity at medical dosages. The interaction between 3,4,3-LI(1,2-HOPO) and other biomedically relevant metals such as gold, however, has not been explored. Gold nanoparticles functionalized with chelators have demonstrated great potential in theranostics, yet thus far, no protocol that combines 3,4,3-LI(1,2-HOPO) and colloidal gold has been developed. Here, we characterize the solution thermodynamic properties of the complexes formed between 3,4,3-LI(1,2-HOPO) and Au3+ ions and demonstrate how under specific pH conditions the chelator promotes the growth of gold nanoparticles, acting as both reducing and stabilizing agent. 3,4,3-LI(1,2-HOPO) ligands on the nanoparticle surface remain active and selective toward f-block elements, as evidenced by gold nanoparticle selective aggregation. Finally, a new colorimetric assay capable of reaching the detection levels necessary for the quantification of lanthanides in waste from industrial processes is developed based on the inhibition of particle growth by lanthanides.

6.
Nanoscale ; 12(3): 1339-1348, 2020 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-31859321

RESUMO

Lanthanides and actinides are used in a wide variety of applications, from energy production to life sciences. To address toxicity issues due to the chemical, and often radiological, properties of these elements, methods to quantify and recover them from industrial waste are necessary. When used in biomedicine, lanthanides and actinides are incorporated in compounds that show promising therapeutic and/or bioimaging properties, but lack robust strategies to target cancer and other pathologies. Furthermore, current decorporation protocols to respond to accidental actinide exposure rely on intravenous injections of soluble chelating agents, which are inefficient for treatment of inhaled radionuclides trapped in lungs. In recent years, nanoparticles have emerged as powerful tools in both industry and clinical settings. Because some inorganic nanoparticles are sensitive to external stimuli, such as light and magnetic fields, they can be used as building blocks for sensitive bioassays and separation techniques. In addition, nanoparticles can be functionalized with multiple ligands and act as carriers for selective delivery of therapeutic and contrast agents. This review summarizes and discusses recent progress on the use of nanoparticles in lanthanide and actinide chemistry. We examine different types of nanoparticles based on composition, functionalization, and properties, and we critically analyze their performance in a comparative mode. Our focus is two-pronged, including the nanoparticles free of lanthanides and actinides that are used for the detection, separation, or decorporation of f-block elements, as well as the nanoparticles that enhance the inherent properties of lanthanides and actinides for therapeutics, imaging and catalysis.

7.
Nat Chem ; 11(12): 1075, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31758157
8.
Chem Sci ; 10(28): 6834-6843, 2019 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-31391906

RESUMO

Current methods for metal chelation are generally based on multidentate organic ligands, which are generated through cumbersome multistep synthetic processes that lack flexibility for systematically varying metal-binding motifs. Octadentate ligands incorporating hydroxypyridinone or catecholamide binding moieties onto a spermine scaffold are known to display some of the highest affinities towards f-elements. Enhancing binding affinity for specific lanthanide or actinide ions however, necessitates ligand architectures that allow for modular and high throughput synthesis. Here we introduce a high-throughput combinatorial library of 16 tetrameric N-substituted glycine oligomers (peptoids) containing hydroxypyridinone or catecholamide chelating units linked via an ethylenediamine bridge and, for comparison, we also synthesized the corresponding mixed ligands derived from the spermine scaffold: 3,4,3-LI(1,2-HOPO)2(CAM)2 and 3,4,3-LI(CAM)2(1,2-HOPO)2. Coordination-based luminescence studies were carried out with Eu3+ and Tb3+ to begin probing the properties of the new ligand architecture and revealed higher sensitization efficiency with the spermine scaffold as well as different spectroscopic features among the structural peptoid isomers. Solution thermodynamic properties of selected ligands revealed different coordination properties between the spermine and peptoid analogues with Eu3+ stability constants log ß 110 ranging from 28.88 ± 3.45 to 43.97 ± 0.49. The general synthetic strategy presented here paves the way for precision design of new specific and versatile ligands, with a variety of applications tailored towards the use of f-elements, including separations, optical device optimization, and pharmaceutical development.

9.
Nat Commun ; 10(1): 2438, 2019 06 04.
Artigo em Inglês | MEDLINE | ID: mdl-31164638

RESUMO

Metal ion separations are critical to numerous fields, including nuclear medicine, waste recycling, space exploration, and fundamental research. Nonetheless, operational conditions and performance are limited, imposing compromises between recovery, purity, and cost. Siderophore-inspired ligands show unprecedented charge-based selectivity and compatibility with harsh industry conditions, affording excellent separation efficiency, robustness and process control. Here, we successfully demonstrate a general separation strategy on three distinct systems, for Ac, Pu, and Bk purification. Separation factors (SF) obtained with model compound 3,4,3-LI(1,2-HOPO) are orders of magnitude higher than with any other ligand currently employed: 106 between Ac and relevant metal impurities, and over 108 for redox-free Pu purification against uranyl ions and trivalent actinides or fission products. Finally, a one-step separation method (SF > 3 × 106 and radiopurity > 99.999%) enables the isolation of Bk from adjacent actinides and fission products. The proposed approach offers a paradigm change for the production of strategic elements.

10.
Dalton Trans ; 48(23): 8238-8247, 2019 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-31094380

RESUMO

The solution- and solid-state interactions between the octadentate siderophore mimic 3,4,3-LI(1,2-HOPO) (343HOPO) and group IV metal ions were investigated using high-resolution mass spectrometry, liquid chromatography, UV-visible spectrophotometry, metal-competition batch titrations, and single crystal X-ray diffraction. 343HOPO forms a neutral 1 : 1 complex, [HfIV343HOPO], that exhibits extreme stability in aqueous solution, with a log ß110 value reaching 42.3. These results affirm the remarkable charge-based selectivity of 343HOPO for octacoordinated tetravalent cations with a Hf(iv) complex 1021 more stable than its Lu(iii) analogue. Moreover, [HfIV343HOPO] and its Zr(iv) counterpart show exceptional robustness, with the ligand remaining bound to the cation over a very broad pH range: from pH ∼ 11 to acidic conditions as strong as 10 M HCl. In stark contrast, Ti(iv)-343HOPO species are far less stable and undergo hydrolysis at pH as low as ∼6, likely due to the mismatch between the preferred hexacoordinated Ti(iv) ion and octadentate 343HOPO ligand. The extreme charge-based and denticity-driven selectivity of 343HOPO, now observed across the periodic table, paves the way for new selective sequestration systems for radionuclides including medical 44Ti, 89Zr or 177Lu/Hf isotopes, toxic polonium (Po) contaminants, as well as rutherfordium (Rf) research isotopes. Furthermore, despite the lack of a chiral center in 343HOPO, its complexes with metal ions are chiral and appear to form a single set of enantiomers.

11.
Nanoscale ; 11(16): 7609-7612, 2019 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-30969284

RESUMO

We present the first report of ligand-sensitized, actinide luminescence in a lanthanide nanoparticle host. Amplified luminescence of 248Cm3+ doped in a NaGdF4 lattice is achieved through optical pumping of a surface-localized metal chelator, 3,4,3-LI(1,2-HOPO), capable of sensitizing Cm3+ excited states. The data suggest the possibility of using such materials in theranostic applications, with a ligand-sensitized actinide or radio-lanthanide serving the dual roles of a nuclear decay source for radiotherapeutics, and as a luminescent center or energy transfer conduit to another emissive metal ion, for biological imaging.


Assuntos
Cúrio/química , Nanopartículas/química , Quelantes/química , Ligantes , Medições Luminescentes , Piridonas/química
12.
Inorg Chem ; 57(22): 14337-14346, 2018 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-30372069

RESUMO

The solution chemistry of a chelator developed for 227Th targeted alpha therapy was probed. The compound of interest is an octadentate ligand comprising four N-methyl-3-hydroxy-pyridine-2-one metal-binding units, two tertiary amine groups, and one carboxylate arm appended for bioconjugation. The seven p Ka values of the ligand and the stability constants of complexes formed with Th(IV), Hf(IV), Zr(IV), Gd(III), Eu(III), Al(III), and Fe(III) were determined. The ligand exhibits extreme thermodynamic selectivity toward tetravalent metal ions with a ca. 20 orders of magnitude difference between the formation constant of the Th(IV) species formed at physiological pH, namely [ThL]-, and that of its Eu(III) analogue. Likewise, log ß110 values of 41.7 ± 0.3 and 26.9 ± 0.3 (T = 25 °C) were measured for [ThL]- and [FeIIIL]2-, respectively, highlighting the high affinity and selectivity of the ligand for Th ions over potentially competing endogenous metals. Single crystal X-ray analysis of the Fe(III) complex revealed a dinuclear 2:2 metal:chelator complex crystallizing in the space group P1̅. The formation of this dimeric species is likely favored by several intramolecular hydrogen bonds and the protonation state of the chelator in acidic media. LIII edge EXAFS data on the Th(IV) complexes of both the ligand and a monoclonal antibody conjugate revealed the expected mononuclear 1:1 metal:chelator coordination environment. This was also confirmed by high resolution mass spectrometry. Finally, kinetic experiments demonstrated that labeling the bioconjugated ligand with Th(IV) could be achieved and completed after 1 h at room temperature, reinforcing the high suitability of this chelator for 227Th targeted alpha therapy.


Assuntos
Quelantes/química , Complexos de Coordenação/química , Piridonas/química , Compostos Radiofarmacêuticos/química , Tório/química , Anticorpos Monoclonais Humanizados/química , Cinética , Ligantes , Estrutura Molecular , Termodinâmica , Espectroscopia por Absorção de Raios X
13.
Chem Commun (Camb) ; 54(76): 10698-10701, 2018 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-30187044

RESUMO

Oxo group activation with reduction of neptunyl(vi) and plutonyl(vi) to tetravalent hydroxo species by the hydroxypyridinone siderophore derivative 3,4,3-LI-(1,2-HOPO) was investigated in the gas-phase via electrospray ionization mass spectrometry, in solution via Raman spectroscopy, and computationally via density functional theory. Dissociation of the gas-phase tetravalent complexes resulted in actinide-hydroxo bond cleavage.

14.
Radiat Prot Dosimetry ; 182(1): 107-111, 2018 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-30165556

RESUMO

3,4,3-LI(1,2-HOPO) has been identified as an excellent alternative for DTPA for decorporating actinides, such as Pu and Am, after internal contamination. Efforts have been focused on its application through oral administration. When 3,4,3-LI(1,2-HOPO) was encapsulated with biocompatible, biodegradable nanoparticles made of chitosan, its release from the nanoparticles to lung fluid, observed in in vitro experiments, exhibited an extended release profile. These observations were very encouraging, as this nanomedicine could lead to a reduction in the dosing frequency required to achieve the decorporation efficacy of unformulated 3,4,3-LI(1,2-HOPO) itself. In vivo release tests as well as actinide decorporation experiments, using an inhalation exposure animal model, will follow.


Assuntos
Quitosana/química , Descontaminação/métodos , Compostos Heterocíclicos com 1 Anel/administração & dosagem , Pulmão/metabolismo , Nanopartículas/administração & dosagem , Ácido Pentético/administração & dosagem , Piridonas/administração & dosagem , Elementos da Série Actinoide/efeitos adversos , Administração por Inalação , Amerício/efeitos adversos , Líquidos Corporais/metabolismo , Quelantes/administração & dosagem , Humanos , Nanopartículas/química , Plutônio/efeitos adversos , Doses de Radiação
15.
Dalton Trans ; 47(21): 7362-7369, 2018 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-29774904

RESUMO

In order to reveal subtle differences between the solution chemistries of trivalent 4f and 5f elements, the physicochemical and photophysical properties of europium(iii), terbium(iii) and curium(iii) complexes formed with a 7-methoxy-coumarin appended 1,4,7,10-tetraazadodecane-1,4,7-triacid (DO3A) ligand were studied. All three complexes were found to be kinetically inert and exhibit stability constants similar to their 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) equivalents. The Cm(iii) and Eu(iii) complexes feature strong sensitised emission, while the triplet energy of the coumarin prohibits efficient sensitisation of the Tb(iii) analogue. The data presented here indicate significant differences in perturbation of the sensitising chromophore photophysics between the 4f and 5f elements. In contrast, the size of the metal center appears to not be a determining factor for the physicochemical properties of these kinetically inert Eu(iii), Tb(iii), and Cm(iii) complexes.

16.
Inorg Chem ; 57(9): 5352-5363, 2018 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-29624372

RESUMO

The hydroxypyridinone ligand 3,4,3-LI(1,2-HOPO) is a promising agent for biological decorporation of radionuclides, and allows spectroscopic detection of many lanthanide (Ln) and actinide (An) species via sensitized luminescence. Despite the manifest uses of this ligand, the structural and thermodynamic properties of its complexes across the An series remain understudied. Theoretical investigations of the binding of An(III) and An(IV) ions, from actinium to einsteinium, by the 3,4,3-LI(1,2-HOPO) ligand, as well as experimental extended X-ray absorption fine structure (EXAFS) studies on the trivalent americium, curium, and californium complexes were employed to address the resulting structures, thermodynamic parameters, redox properties, and corresponding electronic configurations. An(IV) ions were found to form much stronger complexes than An(III) ions, consistent with experimental measurements. Complexation of both An(III) and An(IV) ions generally becomes more favorable for heavier actinides, reflecting increased energy degeneracy driven covalency and concomitant orbital mixing between the 5f orbitals of the An ions and the π orbitals of the ligand. Notably, the ability of this ligand to either accept or donate electron density as needed from its pyridine rings is found to be key to its extraordinary stability across the actinide series.

17.
Sci Rep ; 8(1): 4419, 2018 03 13.
Artigo em Inglês | MEDLINE | ID: mdl-29535330

RESUMO

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


Assuntos
Gadolínio/metabolismo , Imagem por Ressonância Magnética , Doenças Metabólicas/diagnóstico por imagem , Doenças Metabólicas/metabolismo , Animais , Quelantes/uso terapêutico , Terapia por Quelação/métodos , Meios de Contraste , Modelos Animais de Doenças , Gadolínio/efeitos adversos , Gadolínio/química , Humanos , Doenças Metabólicas/tratamento farmacológico , Doenças Metabólicas/etiologia , Camundongos , Resultado do Tratamento
18.
Angew Chem Int Ed Engl ; 57(17): 4521-4526, 2018 04 16.
Artigo em Inglês | MEDLINE | ID: mdl-29473263

RESUMO

The chemistry of trivalent transplutonium ions (Am3+ , Cm3+ , Bk3+ , Cf3+ , Es3+ …) is usually perceived as monotonic and paralleling that of the trivalent lanthanide series. Herein, we present the first extended X-ray absorption fine structure (EXAFS) study performed on a series of aqueous heavy actinide chelates, extending past Cm. The results obtained on diethylenetriaminepentaacetic acid (DTPA) complexes of trivalent Am, Cm, Bk, and Cf show a break to much shorter metal-oxygen nearest-neighbor bond lengths in the case of Cf3+ . Corroborating those results, density functional theory calculations, extended to Es3+ , suggest that the shorter Cf-O and Es-O bonds could arise from the departure of the coordinated water molecule and contraction of the ligand around the metal relative to the other [MIII DTPA(H2 O)]2- (M=Am, Cm, Bk) complexes. Taken together, these experimental and theoretical results demonstrate inhomogeneity within the trivalent transplutonium series that has been insinuated and debated in recent years, and that may also be leveraged for future nuclear waste reprocessing technologies.

19.
Inorg Chem ; 56(21): 12930-12937, 2017 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-29019408

RESUMO

Recent efforts to activate the strong uranium-oxygen bonds in the dioxo uranyl cation have been limited to single oxo-group activation through either uranyl reduction and functionalization in solution, or by collision induced dissociation (CID) in the gas-phase, using mass spectrometry (MS). Here, we report and investigate the surprising double activation of uranyl by an organic ligand, 3,4,3-LI(CAM), leading to the formation of a formal U6+ chelate in the gas-phase. The cleavage of both uranyl oxo bonds was experimentally evidenced by CID, using deuterium and 18O isotopic substitutions, and by infrared multiple photon dissociation (IRMPD) spectroscopy. Density functional theory (DFT) computations predict that the overall reaction requires only 132 kJ/mol, with the first oxygen activation entailing about 107 kJ/mol. Combined with analysis of similar, but unreactive ligands, these results shed light on the chelation-driven mechanism of uranyl oxo bond cleavage, demonstrating its dependence on the presence of ligand hydroxyl protons available for direct interactions with the uranyl oxygens.

20.
Nat Chem ; 9(9): 843-849, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28837177

RESUMO

Berkelium (Bk) has been predicted to be the only transplutonium element able to exhibit both +III and +IV oxidation states in solution, but evidence of a stable oxidized Bk chelate has so far remained elusive. Here we describe the stabilization of the heaviest 4+ ion of the periodic table, under mild aqueous conditions, using a siderophore derivative. The resulting Bk(IV) complex exhibits luminescence via sensitization through an intramolecular antenna effect. This neutral Bk(IV) coordination compound is not sequestered by the protein siderocalin-a mammalian metal transporter-in contrast to the negatively charged species obtained with neighbouring trivalent actinides americium, curium and californium (Cf). The corresponding Cf(III)-ligand-protein ternary adduct was characterized by X-ray diffraction analysis. Combined with theoretical predictions, these data add significant insight to the field of transplutonium chemistry, and may lead to innovative Bk separation and purification processes.

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