Binding Of Plutonium Research Articles

Molecular dynamics simulations of plutonium binding and its decorporation from the binding-cleft of human serum transferrin.

The possibility of plutonium (Pu) intake by radiation workers can not be ruled out. Transportation of Pu(IV) to various organs/cells is mainly carried through iron-carrying protein, serum transferrin (sTf), by receptor-mediated endocytosis. Understanding the Pu-sTf interaction is a primary step toward future design of its decorporating agents. We report MD simulations of Pu(IV) binding with sTf and look out for its decorporation at extracellular pH using suitable ligands. MD simulations were carried out in polarizable water environment at different protonation states of the protein. Results unravel the binding motif of Pu(IV): (1) sTf binds the ion in closed conformation at extracellular serum pH with carbonate as synergistic anions, (2) change in protonation state of dilysine (K206 and K296)-trigger and that of the carbonate ion at acidic endosomal pH is found to cause conformational changes of protein, conducive for the heavy ion to be released, although; (3) strong electrostatic interaction between D63 in the binding-cleft and Pu(IV) is found not to ever set free the ion. In an endeavour to decorporate Pu(IV), fragmented molecular form of hydroxypyridinone (HOPO) and catechol (CAM)-based ligands are docked at the binding site (BS) of the protein and metadynamics simulations are conducted. Pu(IV) binding at BS is found to be so strong that it was not detached from BS with the docked HOPO. However, for the identical set of simulation parameters, CAM is found to facilitate dislodging the heavy ion from the protein's binding influence. Differential behaviour of the two chelators is further explored. Fragmented molecular form of hydroxy-pyridinone (HOPO) and catecholamide (CAM) ligands were docked at the binding-site (BS) of human serum transferrin (sTf) to explore their feasibility as plausible Pu(IV) decorporating agents by employing metadynamics method. CAM was found to dislodge Pu from the sTf BS, while HOPO could not.

Plutonium binding affinity to sediments increases with contact time

Previous research has shown that Pu binds strongly to mineral surfaces and that its tendency to desorb decreases with time. However, the mechanisms behind this aging process are not well understood, have not been conducted under controlled laboratory conditions, and have not considered natural samples aged for long durations. In this work, sediments aged for 32 years in the presence of Pu were used to investigate the reversibility of sorption with time. Experiments utilized these aged sediments to examine the fate of Pu via multi-isotope adsorption and desorption experiments and selective extractions in the presence of a suite of ligands. None of the ligands (desferrioxamine B siderophore, fulvic acid, citric acid) or elevated concentrations of salts (NaF, NaCl, CaCl2, Na2PO4) promoted desorption of significant amounts of Pu from the surface after 32 years of aging or significantly reduced sorption of freshly added Pu. Together, these results highlight that Pu has a significantly greater affinity for binding to sediment surfaces than ligand complexation, regardless of aging period. A surface complexation model further corroborated these experimental data. However, selective extractions show that Pu on the solid phase may be redistributing into a more recalcitrant fraction with time due to an aging effect. Not including long-term Pu aging effects on sediments in risk models may lead to overestimating Pu mobility in the aqueous phase while underestimating Pu mobility in the colloidal phase.

The Importance and Quantification of Plutonium Binding in Human Lungs.

Epidemiological studies have shown that the main risk arising from exposure to plutonium aerosols is lung cancer, with other detrimental effects in the bone and liver. A realistic assessment of these risks, in turn, depends on the accuracy of the dosimetric models used to calculate doses in such studies. A state-of-the-art biokinetic model for plutonium, based on the current International Commission on Radiological Protection biokinetic model, has been developed for this purpose in an epidemiological study involving the plutonium exposure of Mayak workers in Ozersk, Russia. One important consequence of this model is that the lung dose is extremely sensitive to the fraction (fb) of plutonium, which becomes bound to lung tissue after it dissolves. It has been shown that if just 1% of the material becomes bound in the bronchial region, this will double the lung dose. Furthermore, fb is very difficult to quantify from experimental measurements. This paper summarizes the work carried out thus far to quantify fb. Bayesian techniques have been used to analyze data from different sources, including both humans and dogs, and the results suggest a small, but nonzero, fraction of < 1%. A Bayesian analysis of 20 Mayak workers exposed to plutonium nitrate suggests an fb between 0 and 0.3%. Based on this work, the International Commission on Radiological Protection is currently considering the adoption of a value of 0.2% for the default bound fraction for all actinides in its forthcoming recommendations on internal dosimetry. In an attempt to corroborate these findings, further experimental work has been carried out by the US Transuranium and Uranium Registries. This work has involved direct measurements of plutonium in the respiratory tract tissues of workers who have been exposed to soluble plutonium nitrate. Without binding, one would not expect to see any activity remaining in the lungs at long times after exposure since it would have been cleared by the natural process of mucociliary clearance. Further supportive study of workers exposed to plutonium oxide is planned. This paper ascertains the extent to which these results corroborate previous inferences concerning the bound fraction.

Revisiting binding of plutonium to transferrin by CE-ICP-MS.

Capillary electrophoresis coupled with an inductively coupled plasma mass spectrometer was applied for the first time to determine the binding constant of human transferrin (Tf) for tetravalent plutonium. The experiments were carried out in a buffer 2-(N-morpholino)ethanesulfonic acid (MES) at pH 6, 0.1 M NaCl and at a temperature of 25 °C. The nitrilotriacetate anion (NTA) used in this study prevents the hydrolysis of plutonium and is an ideal competitor with Tf for Pu, both ligands sharing comparable binding strength. The separation revealed unambiguous two peaks associated with the complex Pu(NTA)2 used as the initial species and with Pu-transferrin. Two series of independent experiments were conducted and gave the first stepwise conditional bicarbonate-free Pu-transferrin binding constant of . In the absence of bicarbonate the affinity of transferrin for plutonium at pH 6 is about 104 times stronger than that of iron at pH 6.7 .

The Mayak Worker Dosimetry System (MWDS-2013): A Bayesian Analysis to Quantify Pulmonary Binding of Plutonium in Lungs Using Historic Beagle Dog Data

The revised human respiratory tract model, published in Part 1 of the International Commission on Radiological Protection's (ICRP) report on Occupational Intakes of Radionuclides (OIR), includes a bound fraction, fb, to represent radionuclides that have become chemically bound in the lungs following dissolution of particulates in lung fluid. Bound radionuclides are not subject to particle transport clearance but can be absorbed to blood at a rate, sb. The occurrence of long-term binding of plutonium can greatly increase lung doses, particularly if it occurs in the bronchial and bronchiolar regions. However, there has been little evidence that currently supports the existence of a long-term bound state for plutonium. The present work describes the analysis of measurements of lung data obtained from a life span study of Beagle dogs that were exposed by inhalation to different concentrations of plutonium-239 (239Pu) nitrate aerosol at Pacific Northwest Laboratories, USA. The data have been analysed to assess whether a bound state was required to explain the data. A Bayesian approach was adopted for the analysis that accounts for uncertainties in model parameter values, including uncertainties in the rates of particle transport clearance. Furthermore, it performs the analysis using two different modelling hypotheses: a model based on the current ICRP human respiratory tract model and its treatment of alveolar particle transport clearance; and a model of particle transport clearance that is based on the updated model developed by ICRP to calculate dose coefficients for the OIR. The current model better represents clearance in dogs at early times (up to 1 year following intake) and the latter better represents retention at greater times (>5 years following intake). The results indicate that a long-term bound fraction of between 0.16 and 1.1%, with a mean value of between 0.24 and 0.8% (depending on the model) is required to explain the data.

The Mayak Worker Dosimetry System (MWDS 2013): Soluble Plutonium Retention in the Lungs of An Occupationally Exposed USTUR Case.

For the first time, plutonium retention in human upper airways was investigated based on the dosimetric structure of the human respiratory tract proposed by the International Commission on Radiological Protection (ICRP). This paper describes analytical work methodology, case selection criteria, and summarizes findings on soluble (ICRP 68 Type M material) plutonium distribution in the lungs of a former nuclear worker occupationally exposed to plutonium nitrate [239Pu(NO3)4]. Thirty-eight years post-intake, plutonium was found to be uniformly distributed between bronchial (BB), bronchiolar (bb) and alveolar-interstitial (AI) dosimetric compartments as well as between the left and right lungs. 239+240Pu and 238Pu total body activity was estimated to be 2333±23 and 42.1±0.7 Bq, respectively. The results of this work provide key information on the extent of plutonium binding in the upper airways of the human respiratory tract.

THE MAYAK WORKER DOSIMETRY SYSTEM (MWDS 2013): A RE-ANALYSIS OF USTUR CASE 0269 TO DETERMINE WHETHER PLUTONIUM BINDS TO THE LUNGS.

Radionuclides in ionic form can become chemically bound in the airways of the lungs following dissolution of inhaled particulates in lung fluid. The presence of long-term binding can greatly increase lung doses from inhaled plutonium, particularly if it occurs in the bronchial and bronchiolar regions. However, the only published evidence that plutonium binding occurs in humans comes from an analysis of the autopsy and bioassay data of United States Transuranium and Uranium Registries Case 0269, a plutonium worker who experienced a very high (58 kBq) acute inhalation of plutonium nitrate. This analysis suggested a bound fraction of around 8 %, inferred from an unexpectedly low ratio of estimated total thoracic lymph node activity:total lung activity, at the time of death. However, there are some limitations with this study, the most significant being that measurements of the regional distribution of plutonium activity in the lungs, which provide more direct evidence of binding, were not available when the analysis was performed. The present work describes the analysis of new data, which includes measurements of plutonium activity in the alveolar-interstitial (AI) region, bronchial (BB) and bronchiolar (bb) regions, and extra-thoracic (ET) regions, at the time of death. A Bayesian approach is used that accounts for uncertainties in model parameter values, including particle transport clearance, which were not considered in the original analysis. The results indicate that a long-term bound fraction between 0.4 and 0.7 % is required to explain this data, largely because plutonium activity is present in the extra-thoracic (ET2), bronchial and bronchiolar airways at the time of death.

Kläui Ligand Thin Films for Rapid Plutonium Analysis by Alpha Spectrometry

As part of a nuclear forensics capability, rapid and effective methods to analyze for plutonium and other actinide metals are needed. A key requirement of these methods is that they afford a high chemical yield while still providing isotopic information necessary for forensic evaluation. Toward this objective, a new method for binding plutonium for analysis by alpha spectrometry has been developed. Thin films of Kläui-type tripodal oxygen donor ligands were prepared by spin-casting solutions onto glass substrates. Three different ligands were evaluated for plutonium binding, and the best results were obtained using the ethyl-substituted complex Na[Cp*Co(P(O)(OEt)2)3], which bound 80-88% of the dissolved Pu under equilibrium conditions. The thin films are simple and inexpensive to prepare and exhibit excellent alpha spectral resolution, having line widths of ~33 keV. The method has been successfully applied to analyze for plutonium in both an archived nuclear debris sample and a certified environmental soil sample. The results obtained from the soil analysis are in good agreement with the certified values, demonstrating the effectiveness of the method for rapid plutonium analysis.

Stabilization of Plutonium Nano-Colloids by Epitaxial Distortion on Mineral Surfaces

The subsurface migration of Pu may be enhanced by the presence of colloidal forms of Pu. Therefore, complete evaluation of the risk posed by subsurface Pu contamination needs to include a detailed physical/chemical understanding of Pu colloid formation and interactions of Pu colloids with environmentally relevant solid phases. Transmission electron microscopy (TEM) was used to characterize Pu nanocolloids and interactions of Pu nanocolloids with goethite and quartz. We report that intrinsic Pu nanocolloids generated in the absence of goethite or quartz were 2-5 nm in diameter, and both electron diffraction analysis and HRTEM confirm the expected Fm3m space group with the fcc, PuO2 structure. Plutonium nanocolloids formed on goethite have undergone a lattice distortion relative to the ideal fluorite-type structure, fcc, PuO2, resulting in the formation of a bcc, Pu4O7 structure. This structural distortion results from an epitaxial growth of the plutonium colloid on goethite, leading to stronger binding of plutonium to goethite compared with other minerals such as quartz, where the distortion was not observed. This finding provides new insight for understanding how molecular-scale behavior at the mineral-water interface may facilitate transport of plutonium at the field scale.

Molecular interactions of plutonium(VI) with synthetic manganese-substituted goethite

Abstract Plutonium(VI) sorption on the surface of well-characterized synthetic manganese-substituted goethite minerals (Fe1−xMnxOOH) was studied using X-ray absorption spectroscopy. We chose to study the influence of manganese as a minor component in goethite because goethite rarely exists as a pure phase in nature. Manganese X-ray absorption near-edge structure measurements indicated that essentially all the Mn in the goethite existed as Mn(III), even though Mn was added during mineral synthesis as Mn(II). Importantly, energy dispersive X-ray analysis demonstrated that Mn did not exist as discrete phases and that it was homogeneously mixed into the goethite to within the limit of detection of the method. Furthermore, Mössbauer spectra demonstrated that all Fe existed as Fe(III), with no Fe(II) present. Plutonium(VI) sorption experiments were conducted open to air and no attempt was made to exclude carbonate. The use of X-ray absorption spectroscopy allows us to directly and unambiguously measure the oxidation state of plutonium in situ at the mineral surface. Plutonium X-ray absorption near-edge structure measurements carried out on these samples showed that Pu(VI) was reduced to Pu(IV) upon contact with the mineral. This reduction appears to be strongly correlated with mineral solution pH, coinciding with pH transitions across the point of zero charge of the mineral. Furthermore, extended X-ray absorption fine structure measurements show evidence of direct plutonium binding to the metal surface as an inner-sphere complex. This combination of extensive mineral characterization and advanced spectroscopy suggests that sorption of the plutonium onto the surface of the mineral was followed by reduction of the plutonium at the surface of the mineral to form an inner-sphere complex. Because manganese is often found in the environment as a minor component associated with major mineral components, such as goethite, understanding the molecular-level interactions of plutonium with such substituted mineral phases is important for risk assessment purposes at radioactively contaminated sites and long-term underground radioactive waste repositories.

Neutron Resonance Scattering Shows Specific Binding of Plutonium to the Calcium-Binding Sites of the Protein Calmodulin and Yields Precise Distance Information

We have successfully substituted 240Pu3+ for Ca2+ in the calcium-binding protein calmodulin and used neutron resonance scattering from the bound 240Pu to demonstrate that the Pu binds specifically to the Ca2+ sites and also to measure the distance between the ion binding sites within individual domains of the protein. 240Pu has a strong nuclear resonance at 0.278 Å, and at this wavelength the coherent scattering from 240Pu is >1000 times that of any other nucleus present in a protein. The ionic radius of Pu3+ is very similar to that of Ca2+, and hence we chose this species to substitute for Ca2+ in the protein. We identified solution conditions that stablize Pu3+ in solution at near neutral pH for 6−7 h in order to form the Pu/calmodulin complex under conditions favorable for both complex formation and maintaining the structural integrity of the protein. We collected small-angle neutron scattering data from solutions of 4(240Pu3+)·calmodulin, which contain periodic terms that are directly related to the distances between the Ca2+-binding sites. The shorter Pu−Pu distance, i.e., the average distance between the two sites within each globular domain of calmodulin, is found to be 11.8 ± 0.4 Å, in excellent agreement with the value of 11.7 Å from crystallographic determinations. This is the first use of neutron resonance scattering as a structural probe in a protein.

Design and synthesis of actinide specific chelators: Synthesis of new cyclam tetrahydroxamate (CYTROX) and cyclam tetraacetonylacetone (CYTAC) chelators

Molecular modeling shows that two new chelators, the cyclam tetrahydroxamate, 1, and the cyclam tetraacetonylacetone derivative, 2, have potential for the binding of plutonium (IV). The synthesis of these chelators has been achieved using short sequences from readily available cyclam. Both the details of the molecular modeling and the synthetic route to these molecules are described.

A spectroscopic study on the binding of plutonium(IV) and its chemical analogues to transferrin

A spectroscopic study on the binding of plutonium(IV) and its chemical analogues to transferrin

The binding of plutonium to transferrin in the presence of tri-n-butyl phosphate or nitrate and its release by diethylenetriaminepenta-acetate and the tetrameric catechoylamide ligand LICAMC(C)

The binding of plutonium to human apo-transferrin and to rat serum was investigated following delivery of the metal to the protein either as the plutonium-tri-n-butyl phosphate (Pu-TBP) complex in n-dodecane or as plutonium nitrate. Chromatographic behaviour, the failure to bind to iron-saturated transferrin and the release of plutonium by the chelating agents CaNa3DTPA and 3,4,3-LICAM(C) suggest that the transferrin complexes formed from the two plutonium compounds are similar. The tetracatechoylamide ligand LICAM(C) was found to be about 500 times more effective than DTPA, on a molar basis, for the release of plutonium from transferrin in rat serum.

Plutonium in Bone: A High Resolution Autoradiographic Study Using Plutonium-241

Plutonium-241 citrate solution at pH 6-5 was injected intravenously into hamsters and an adult rabbit at a dose of 10 kBq g-1 (260 nCi g-1). The hamsters were killed serially at 15 min, 2 hours, 1 day, 10 days, 1 month and 6 months after injection and the rabbit at 1 week. Their knee-joints or femora were examined for plutonium-241 by autoradiography. Few differences were found between the pattern of plutonium distribution in the hamsters and the rabbit. The results showed that although plutonium is initially distributed on bone surfaces, at long periods after injection it becomes deposited throughout the bone matrix. Plutonium uptake by cells in resorbing areas of periosteum, in active osteoblasts, and in chondrocytes in regions of cartilage mineralization was rapid. Plutonium concentrated more slowly on the resting bone surfaces and at sites of low metabolic activity. In addition, some unlabelled sections of skeletal tissues were immersed in a plutonium-241 citrate solution. When autoradiographed, it was found that plutonium was bound by cell nuclei, tooth enamel matrix, dentine, predentine and bone matrix. Plutonium binding to cartilage matrix was weak. The results are discussed with reference to the literature, and a model is proposed to explain the distribution pattern and fate of plutonium deposits in bone.

The Binding of Thorium(IV), Plutonium(IV), Americium(III) and Curium(III) to the Constituents of Bovine Cortical Bone In Vitro

By means of a gel filtration technique it has been shown that thorium (IV), plutonium (IV), americium (III) and curium (III) bind to five glycoprotein fractions isolated from bovine cortical bone and to certain other substances. The effects of pH on the binding of plutonium to poly-L-glutamic acid and to bone chondroitin sulfate and of curium to bone sialoprotein and chondroitin sulfate-protein complex are described. Plutonium, americium, and curium were found to bind to bone glycoproteins in the presence of a 30-fold greater mass of bone mineral than glycoprotein. Some experiments on the precipitation of calcium phosphate in vitro in the presence of plutonium and americium are also presented. These observations are discussed in the light of the hypothesis that certain actinide elements are localized at bone surfaces by binding to glycoproteins.

The binding of americium and plutonium to bone glycoproteins.

By means of a gel filtration technique it is shown that plutonium and americium differ in their mode of binding to two glycoproteins isolated from bovine cortical bone. Plutonium binds more strongly than americium, plutonium binding is maximal at pH 6 and americium at pH 8, and sialic acid is involved in the binding of plutonium but not americium. The mechanisms by which these elements bind to glycoproteins in vitro are discussed.

Binding of Plutonium to Glycoproteins in Vitro

The binding of plutonium by a sialoprotein isolated from bovine cortical bone and by transferrin has been compared using a gel filtration procedure. The pH at which maximum binding of plutonium to bone sialoprotein was observed, pH 6, was different from that for transferrin, pH 7, and the magnitude of the binding was greater for bone sialoprotein. The effects of added iron and bicarbonate ions, and of removal of sialic acid on the binding of plutonium to these two glycoproteins, were also dissimilar. These results show that plutonium binds to the carboxyl groups of bone sialoprotein, and this may be responsible for the high stability of the plutoniumbone sialoprotein complex. For the plutonium-transferrin complex, the results obtained suggest that the plutonium is bound at the iron-binding sites, tyrosyl groups, and probably at other sites in the transferrin molecule.

The Binding of Plutonium to Serum Proteins in Vitro

The interactions between tetravalent plutonium and horse serum proteins were studied in vitro by electrophoresis on cellulose acetate and by gel filtration. The results show that in horse serum, as in other mammalian sera, the plutonium is associated principally with the transferrin component of the beta1-globulins. The formation of the plutonium-transferrin complex requires the presence of HCO3-, and plutonium is displaced from the complex by excess iron, thus indicating that similar binding sites may be involved in the complexing of iron and plutonium. The plutonium complex is considered to be less stable than the iron-transferrin complex, but plutonium can only be released from the transferrin complex by citrate or stronger chelating agents.

Binding of plutonium and americium to bone glycoproteins.

THE observation that plutonium, americium and yttrium are localized in bone at sites which show histological evidence of the presence of mucosubstances1 has prompted the study of the glycoproteins of bone2 and of their metal binding properties3. Four carbohydrate-containing protein fractions have been isolated; bone sialoprotein (BSP), a chondroitin sulphate–protein fraction and two glycoprotein-containing fractions designated Gl and G2 (ref. 2). The chondroitin sulphate–protein fraction has recently been separated into three components4. Collagen is also extracted during the separation procedures2.