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Transferrin (Tf) is a glycoprotein that transports iron from the serum to the various organs. Several studies have highlighted that Tf can interact with metals other than Fe(III), including actinides that are chemical and radiological toxics. We propose here to report on the behavior of Th(IV) and Pu(IV) in comparison with Fe(III) upon Tf complexation. We considered UV‐Vis and IR data of the M2Tf complex (M=Fe, Th, Pu) and combined experimental EXAFS data with MD models. EXAFS data of the first M−O coordination sphere are consistent with the MD model considering 1 synergistic carbonate. Further EXAFS data analysis strongly suggests that contamination by Th/Pu colloids seems to occur upon Tf complexation, but it seems limited. SAXS data have also been recorded for all complexes and also after the addition of Deferoxamine‐B (DFOB) in the medium. The Rg values are very close for apoTf, ThTf and PuTf, but slightly larger than for holoTf. Data suggest that the structure of the protein is more ellipsoidal than spherical, with a flattened oblate form. From this data, the following order of conformation size might be considered:holoTf

A spectroelectrochemical setup has been developed to investigate radioactive elements in small volumes (0.7 to 2 ml) under oxidation–reduction (redox) controlled conditions by X‐ray absorption spectroscopy (XAS). The cell design is presented together with in situ XAS measurements performed during neptunium redox reactions. Cycling experiments on the NpO22+/NpO2+ redox couple were applied to qualify the cell electrodynamics using XANES measurements and its ability to probe modifications in the neptunyl hydration shell in a 1 mol l−1 HNO3 solution. The XAS results are in agreement with previous structural studies and the NpO22+/NpO2+ standard potential, determined using Nernst methods, is consistent with measurements based on other techniques. Subsequently, the NpO2+, NpO22+ and Np4+ ion structures in solution were stabilized and measured using EXAFS. The resulting fit parameters are again compared with other results from the literature and with theoretical models in order to evaluate how this spectroelectrochemistry experiment succeeds or fails to stabilize the oxidation states of actinides. The experiment succeeded in: (i) implementing a robust and safe XAS device to investigate unstable radioactive species, (ii) evaluate in a reproducible manner the NpO22+/NpO2+ standard potential under dilute conditions and (iii) clarify mechanistic aspects of the actinyl hydration sphere in solution. In contrast, a detailed comparison of EXAFS fit parameters shows that this method is less appropriate than the majority of the previously reported chemical methods for the stabilization of the Np4+ ion. [ABSTRACT FROM AUTHOR]

Ferritin is the main protein of Fe storage in eukaryote and prokaryote cells. It is a large multifunctional, multi‐subunit protein consisting of heavy H and light L subunits. In the field of nuclear toxicology, it has been suggested that some actinide elements, such as thorium and plutonium at oxidation state +IV, have a comparable 'biochemistry' to iron at oxidation state +III owing to their very high tendency for hydrolysis and somewhat comparable ionic radii. Therefore, the possible mechanisms of interaction of such actinide elements with the Fe storage protein is a fundamental question of bio‐actinidic chemistry. We recently described the complexation of Pu(IV) and Th(IV) with horse spleen ferritin (composed mainly of L subunits). In this article, we bring another viewpoint to this question by further combining modeling with our previous EXAFS data for Pu(IV) and Th(IV). As a result, the interaction between the L subunits and both actinides appears to be non‐specific but driven only by the density of the presence of Asp and Glu residues on the protein shell. The formation of an oxyhydroxide Th or Pu core has not been observed under the experimental conditions here, nor the interaction of Th or Pu with the ferric oxyhydroxide core. [ABSTRACT FROM AUTHOR]

The impact of the contamination of living organisms by actinide elements has been a constant subject of attention since the 1950s. But to date still little is understood. Ferritin is the major storage and regulation protein of iron in many organisms, it consists of a protein ring and a ferrihydric core at the center. This work sheds light on the interactions of early actinides (Th, Pu) at oxidation state +IV with ferritin and its ability to store those elements at physiological pH compared to Fe. The ferritin–thorium load curve suggests that ThIV saturates the protein (2840 Th atoms per ferritin) in a similar way that Fe does on the protein ring. Complementary spectroscopic techniques (spectrophotometry, infrared spectroscopy, and X‐ray absorption spectroscopy) were combined with molecular dynamics to provide a structural model of the interaction of ThIV and PuIV with ferritin. Comparison of spectroscopic data together with MD calculations suggests that ThIV and PuIV are complexed mainly on the protein ring and not on the ferrihydric core. Indeed from XAS data, there is no evidence of Fe neighbors in the Th and Pu environments. On the other hand, carboxylates from amino acids of the protein ring and a possible additional carbonate anion are shaping the cation coordination spheres. This thorough description from a molecular view point of ThIV and PuIV interaction with ferritin, an essential iron storage protein, is a cornerstone in comprehensive nuclear toxicology. [ABSTRACT FROM AUTHOR]

Separation processes based on room temperature ionic liquids (RTIL) and electrochemical refining are promising strategies for the recovery of lanthanides from primary ores and electronic waste. However, they require the speciation of dissolved elements to be known with accuracy. In the present study, Eu coordination and EuIII/EuII electrochemical behavior as a function of water content in 1‐ethyl‐3‐methylimidazolium bis(trifluoromethylsulfonyl)imide ([EMIm][NTf2]) was investigated using UV–visible spectrophotometry, time‐resolved laser fluorescence spectroscopy, electrochemistry, and X‐ray absorption spectroscopy. In situ measurements were performed in spectroelectrochemical cells. Under anhydrous conditions, EuIII and EuII were complexed by NTf2, forming Eu−O and Eu−(N,O) bonds with the anion sulfoxide function and N atoms, respectively. This complexation resulted in a greater stability of EuII, and in quasi‐reversible oxidation–reduction with an E0' potential of 0.18 V versus the ferrocenium/ferrocene (Fc+/Fc) couple. Upon increasing water content, progressive incorporation of water in the EuIII coordination sphere occurred. This led to reversible oxidation–reduction reactions, but also to a decrease in stability of the +II oxidation state (E0'=−0.45 V vs. Fc+/Fc in RTIL containing 1300 mm water). [ABSTRACT FROM AUTHOR]

The magnetic properties of LnIII and AnIII complexes formed with dipicolinate ligands have been studied by NMR spectroscopy. To know precisely the geometries of these complexes, a crystallographic study by single‐crystal X‐ray diffraction (XRD) and extended X‐ray absorption fine structure (EXAFS) in solution was performed. Several methods to separate the paramagnetic shifts observed in the NMR spectra were applied to these complexes. Methods using a number of nuclei of the dipicolinate ligands revealed an abrupt change in the geometries of the complexes and a metal–ligand interaction in the middle of the lanthanide series. A study of the variation of the paramagnetic shifts with temperature demonstrated that higher‐order terms of the dipolar and contact contributions are required, especially for the lightest LnIII and almost all the studied AnIII. Bleaney's parameters a and CaD relating to the contact and dipolar terms, respectively, were deduced from experimental data and compared with the results of ab initio calculations. Quite a good agreement was found for the temperature dependencies of a and CaD. However, the CaD values obtained from cation magnetic anisotropy calculations showed some discrepancies with the values derived from Bleaney's equation defined for LnIII. Other parameters, such as the crystal field parameter and the hyperfine constants Fi obtained from the experimental data of the [An(ethyl‐dpa)3]3− complexes (ethyl‐dpa=4‐ethyl‐2,6‐dipicolinic acid), are at odds with the assumptions underlying Bleaney's theory. Valid for Ln, but for An? Is Bleaney's equation for paramagnetic NMR shifts of LnIII valid for AnIII complexes? (see figure) Several methods have been applied to separate the paramagnetic shifts observed in the NMR spectra of LnIII and AnIII complexes formed with dipicolinate ligands. Discrepancies with Bleaney's equation have been found for the AnIII complexes, and some parameters are at odds with the assumptions underlying Bleaney's theory. [ABSTRACT FROM AUTHOR]

Better understanding of uranyl-protein interactions is a prerequisite to predict uranium chemical toxicity in cells. The EF-hand motif of the calmodulin site I is about thousand times more affine for uranyl than for calcium, and threonine phosphorylation increases the uranyl affinity by two orders of magnitude at pH 7. In this study, we confront X-ray absorption spectroscopy with Fourier transform infrared (FTIR) spectroscopy, time-resolved laser-induced fluorescence spectroscopy (TRLFS), and structural models obtained by molecular dynamics simulations to analyze the uranyl coordination in the native and phosphorylated calmodulin site I. For the native site I, extended X-ray absorption fine structure (EXAFS) data evidence a short U−Oeq distance, in addition to distances compatible with mono- and bidentate coordination by carboxylate groups. Further analysis of uranyl speciation by TRLFS and thorough investigation of the fluorescence decay kinetics strongly support the presence of a hydroxide uranyl ligand. For a phosphorylated site I, the EXAFS and FTIR data support a monodentate uranyl coordination by the phosphoryl group and strong interaction with mono- and bidentate carboxylate ligands. This study confirms the important role of a phosphoryl ligand in the stability of uranyl-protein interactions. By evidencing a hydroxide uranyl ligand in calmodulin site I, this study also highlights the possible role of less studied ligands as water or hydroxide ions in the stability of protein-uranyl complexes. [ABSTRACT FROM AUTHOR]

The specific molecular interactions responsible for uranium toxicity are not yet understood. The uranyl binding sites in high-affinity target proteins have not been identified yet and the involvement of phosphoamino acids is still an important question. Short cyclic peptide sequences, with three glutamic acids and one phosphoamino acid, are used as simple models to mimic metal binding sites in phosphoproteins and to help understand the mechanisms involved in uranium toxicity. A combination of peptide design and synthesis, analytical chemistry, extended X-ray absorption fine structure (EXAFS) spectroscopy, and DFT calculations demonstrates the involvement of the phosphate group in the uranyl coordination sphere together with the three carboxylates of the glutamate moieties. The affinity constants measured with a reliable analytical competitive approach at physiological pH are significantly enhanced owing to the presence of the phosphorous moiety. These findings corroborate the importance of phosphoamino acids in uranyl binding in proteins and the relevance of considering phosphoproteins as potential uranyl targets in vivo. [ABSTRACT FROM AUTHOR]

Herein, we describe the structural investigation of one possible uranyl binding site inside a nonstructured protein. This approach couples spectroscopy, thermodynamics, and theoretical calculations (DFT) and studies the interaction of uranyl ions with a phosphopeptide, thus mimicking a possible osteopontin (OPN) hydroxyapatite growth-inhibition site. Although thermodynamical aspects were investigated by using time-resolved laser fluorescence spectroscopy (TRLFS) and isothermal titration calorimetry (ITC), structural characterization was performed by extended X-ray absorption fine structure (EXAFS) at the U LIII-edge combined with attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy. From the vibrational and fluorescence spectra, several structural models of a UO22+/peptide complex were developed and subsequently refined by using theoretical calculations to fit the experimental EXAFS obtained. The structural effect of the pH value was also considered under acidic to moderately acidic conditions (pH 1.5-5.5). Most importantly, the uranyl/peptide coordination environment was similar to that of the native protein. [ABSTRACT FROM AUTHOR]

Our previous studies on the met- and met-azido-Hc forms from Octopus vulgaris (mollusc) and Carcinus aestuarii (arthropod) at pH 7.5 and on some related binuclear models without X-ray diffraction have considered and resolved some fundamental aspects of their binuclear type-3 copper site (i.e. correct values of the Cu-Cu distances; apical distortion, when present, at the copper site; presence and type of bridging groups). In this contribution the multiple- scattering (MS) calculations performed in order to refine the EXAFS modulation of the absorption spectra are presented. It is only with a composite and advanced approach that some severe problems, mainly deriving from the presence of two absorbing atoms and from the fact that the metal-metal contribution in the absorption spectra overlaps with the Cu-His signals, have been overcome. Results are also presented which indicate the role of the MS calculations in the XANES edge region, and which show how it is possible to extract quantitative information from this zone of the spectrum in order to refine the structure of the site also in the case of a binuclear centre. [ABSTRACT FROM AUTHOR]