Fate of Oxidation States at Actinide Centers in Redox-Active Ligand Systems Governed by Energy Levels of 5 f Orbitals.

We report the formation of a NpIV complex from the complexation of NpVI O2 2+ with the redox-active ligand tBu-pdiop2- =2,6-bis[N-(3,5-di-tert-butyl-2-hydroxyphenyl)iminomethyl]pyridine. To the best of our knowledge, this is the first example of the direct complexation-induced chemical reduction of NpVI O2 2+ to NpIV . In contrast, the complexation of UVI O2 2+ with tBu-pdiop2- did not induce the reduction of UVI O2 2+ , not even after the two-electron electrochemical reduction of [UVI O2 (tBu-pdiop)]. This contrast between the Np and U systems may be ascribed to the decrease of the energy of the 5 f orbitals in Np compared to those in U. The present findings indicate that the redox chemistry between UVI O2 2+ and NpVI O2 2+ should be clearly differentiated in redox-active ligand systems.

Interaction Between the Transferrin Protein and Plutonium (and Thorium), What's New?

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 M2 Tf 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

Crystal Structures of Ce(IV) Nitrates with Bis(2-pyrrolidone) Linker Molecules Deposited from Aqueous Solutions with Different HNO3 Concentrations.

We investigated the molecular and crystal structures of Ce(IV) compounds deposited under different [HNO3] with bis(2-pyrrolidone) linker molecules having a trans-1,4-cyclohexyl bridging moiety (L). As a result, we found that, after loading L, Ce(IV) in HNO3(aq) exclusively provides one of different crystalline phases, (HL)2[Ce(NO3)6] or [Ce2(µ-O)-(NO3)6(L)2]n 2D MOF, depending on [HNO3]. The former has been obtained at [HNO3] = 4.70-9.00 M and is isomorphous with the analogous (HL)2[An(NO3)6] we reported previously. In contrast, the deposition of the latter phase at the lower [HNO3] conditions (1.00-4.30 M) demonstrates that hydrolysis and oxolation of Ce4+ proceed even below pH 0 to provide a [Ce-O-Ce]6+ unit included in this compound. These different Ce(IV) phases are exchangeable with each other under soaking in HNO3(aq), implying that chemical equilibria of dissolution/deposition of these crystalline phases and hydrolysis and oxolation of Ce4+ and its complexation with NO3- occur in parallel. Indeed, such coordination chemistry of Ce(IV) in HNO3(aq) was well corroborated by 17O NMR, Raman, and IR spectroscopy.

Europium(III) Meets Etidronic Acid (HEDP): A Coordination Study Combining Spectroscopic, Spectrometric, and Quantum Chemical Methods.

Etidronic acid (1-Hydroxyethylidene-1,1-diphosphonic acid, HEDP, H4L) is a proposed decorporation agent for U(VI). This paper studied its complex formation with Eu(III), an inactive analog of trivalent actinides, over a wide pH range, at varying metal-to-ligand ratios (M:L) and total concentrations. Combining spectroscopic, spectrometric, and quantum chemical methods, five distinct Eu(III)-HEDP complexes were found, four of which were characterized. The readily soluble EuH2L+ and Eu(H2L)2- species with log ß values of 23.7 ± 0.1 and 45.1 ± 0.9 are formed at acidic pH. At near-neutral pH, EuHL0s forms with a log ß of ~23.6 and, additionally, a most probably polynuclear complex. The readily dissolved EuL- species with a log ß of ~11.2 is formed at alkaline pH. A six-membered chelate ring is the key motif in all solution structures. The equilibrium between the Eu(III)-HEDP species is influenced by several parameters, i.e., pH, M:L, total Eu(III) and HEDP concentrations, and time. Overall, the present work sheds light on the very complex speciation in the HEDP-Eu(III) system and indicates that, for risk assessment of potential decorporation scenarios, side reactions of HEDP with trivalent actinides and lanthanides should also be taken into account.

Eu(III) and Cm(III) Complexation by the Aminocarboxylates NTA, EDTA, and EGTA Studied with NMR, TRLFS, and ITC-An Improved Approach to More Robust Thermodynamics.

The complex formation of Eu(III) and Cm(III) was studied via tetradentate, hexadentate, and octadentate coordinating ligands of the aminopolycarboxylate family, viz., nitrilotriacetate (NTA3-), ethylenediaminetetraacetate (EDTA4-), and ethylene glycol-bis(2-aminoethyl ether)-N,N,N',N'-tetraacetate (EGTA4-), respectively. Based on the complexones' pKa values obtained from 1H nuclear magnetic resonance (NMR) spectroscopic pH titration, complex formation constants were determined by means of the parallel-factor-analysis-assisted evaluation of Eu(III) and Cm(III) time-resolved laser-induced fluorescence spectroscopy (TRLFS). This was complemented by isothermal titration calorimetry (ITC), providing the enthalpy and entropy of the complex formation. This allowed us to obtain genuine species along with their molecular structures and corresponding reliable thermodynamic data. The three investigated complexones formed 1:1 complexes with both Eu(III) and Cm(III). Besides the established Eu(III)-NTA 1:1 and 1:2 complexes, we observed, for the first time, the existence of a Eu(III)-NTA 2:2 complex of millimolar metal and ligand concentrations. Demonstrated for thermodynamic studies on Eu(III) and Cm(III) interaction with complexones, the utilized approach is commonly applicable to many other metal-ligand systems, even to high-affinity ligands.

Interaction of Th(IV), Pu(IV) and Fe(III) with ferritin protein: how similar?

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.

Fully Chelating N3O2-Pentadentate Planar Ligands Designed for the Strongest and Selective Capture of Uranium from Seawater.

Based on the unique fivefold equatorial coordination of UO22+, water-compatible pentadentate planar ligands, H2saldian and its derivatives, were designed for the strong and selective capture of UO22+ in seawater. In the simulated seawater condition (0.5 M NaCl + 2.3 mM HCO3-/CO32-, pH 8), saldian2- shows the strongest complexation with UO22+ to form UO2(saldian) (log ß11 = 28.05 ± 0.07), which is more than 10 order of magnitude greater than amidoxime-based or -inspired ligand systems most commonly employed for U capture from seawater. Good selectivity for UO22+ from other metal ions coexisting in seawater was also demonstrated.

Hydrophobic core formation and secondary structure elements in uranyl(VI)-binding peptides.

Cyclic peptides as well as a modified EF-hand motif of calmodulin have been newly designed to achieve high affinity towards uranyl(VI). Cyclic peptides may be engineered to bind uranyl(VI) to its backbone under acidic conditions, which may enhance its selectivity. For the modified EF-hand motif of calmodulin, strong electrostatic interactions between uranyl(VI) and negatively charged side chains play an important role in achieving high affinity; however, it is also essential to have a secondary structure element and formation of hydrophobic cores in the metal-bound state of the peptide.

2-Phosphonobutane-1,2,4,-Tricarboxylic Acid (PBTC): pH-Dependent Behavior Studied by Means of Multinuclear NMR Spectroscopy.

Although 2-phosphonobutane-1,2,4,-tricarboxylic acid, PBTC, has manifold industrial applications, relevant and reliable data on the protonation of PBTC are poor. However, these data are critical parameters for ascertaining PBTC speciation, especially with regard to a sound structural and thermodynamic characterization of its metal ion complexes. A rigorous evaluation of pH-dependent 1H, 13C, and 31P chemical shifts along with accessible scalar spin-spin coupling constants (J) was performed in order to determine the pKa values of PBTC in 0.5 molal NaCl aqueous solution by means of nuclear magnetic resonance (NMR) spectroscopy. The phosphonate group revealed pKa values of 0.90 ± 0.02 and 9.79 ± 0.02, and the pKa values associated with the carboxylic groups are 3.92 ± 0.02, 4.76 ± 0.03, and 6.13 ± 0.03. Supported by DFT-calculated structures revealing strong intramolecular hydrogen bonding, the sequence of deprotonation could be unambiguously determined.

How Does Iron Storage Protein Ferritin Interact with Plutonium (and Thorium)?

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.

Effects of Substituents on the Molecular Structure and Redox Behavior of Uranyl(V/VI) Complexes with N3O2-Donating Schiff Base Ligands.

Uranyl(VI) complexes with pentadentate N3O2-donating Schiff base ligands having various substituents at the ortho (R1) and/or para (R2) positions on phenolate moieties, R1,R2-Mesaldien2-, were synthesized and thoroughly characterized by 1H nuclear magnetic resonance, infrared, elemental analysis, and single-crystal X-ray diffraction. Molecular structures of UO2(R1,R2-Mesaldien) are more or less affected by the electron-donating or -withdrawing nature of the substituents. The redox behavior of all UO2(R1,R2-Mesaldien) complexes was investigated to understand how substituents introduced onto the ligand affect the redox behavior of these uranyl(VI) complexes. As a result, the redox potentials of UO2(R1,R2-Mesaldien) in dimethyl sulfoxide increased from -1.590 to -1.213 V with an increase in the electron-withdrawing nature of the substituents at the R1 and R2 positions. The spectroelectrochemical measurements and theoretical calculation [density functional theory (DFT) and time-dependent DFT calculations] revealed that the center U6+ of each UO2(R1,R2-Mesaldien) complex undergoes one-electron reduction to afford the corresponding uranyl(V) complex, [UO2(R1,R2-Mesaldien)]-, regardless of the difference in the substituents. Consequently, the redox active center of uranyl(VI) complexes seems not to be governed by the redox potentials but to be determined by whether the LUMO is centered on a U 5f orbital or on one π* orbital of a surrounding ligand.

Dimeric and Trimeric Uranyl(VI)-Citrate Complexes in Aqueous Solution.

This research addresses a subject discussed controversially for almost 70 years. The interactions between the uranyl(VI) ion, U(VI), and citric acid, H3Cit, were examined using a multi-method approach comprising nuclear magnetic resonance (NMR), ultraviolet-visible (UV-vis), attenuated total reflectance Fourier-transform infrared (ATR FT-IR), and extended X-ray absorption fine-structure (EXAFS) spectroscopies as well as density functional theory (DFT) calculations. Combining 17O NMR spectroscopy and DFT calculation provided an unambiguous decision on complex configurations, evidencing for the first time that the dimeric complex, (UO2)2(HCit-H)22-, exists as two diastereomers with the syn-isomer in aqueous solution strongly favored over the anti-isomer. Both isomers interconvert mutually with exchange rates of ∼30 s-1 at -6 °C and ∼249 s-1 at 60 °C in acidic solution corresponding to an activation barrier of about 24 kJ mol-1. Upon increasing the pH value, ternary dimeric mono- and bis-hydroxo as well as trimeric complexes form, that is, (UO2)2(HCit-H)2(OH)3-, (UO2)2(HCit-H)2(OH)24-, (UO2)3(O)(Cit-H)38-, and (UO2)3(O)(OH)(Cit-H)25-, respectively. Stability constants were determined for all dimeric and trimeric species, with log ß° = -(8.6 ± 0.2) for the 3:3 species being unprecedented. Additionally, in the 6:6 sandwich complex, formed from two units of 3:3 species, the 17O NMR resonance of the trinuclear uranyl(VI) core bridging µ3-O is shown for the first time. Species distribution calculations suggest that the characterized polynuclear U(VI)-citrate species do not significantly increase uranium(VI) mobility in the environment. Furthermore, we revise the misconceptions in the aqueous U(VI)-citric acid solution chemistry, that is, structures proposed and repeatedly taken up, and outline generalized isostructural considerations to provide a basis for future U(VI) complexation studies.

Impact of the Microbial Origin and Active Microenvironment on the Shape of Biogenic Elemental Selenium Nanomaterials.

The shape of nanomaterials affects their colloidal properties, cellular uptake, and fate in the environment. The microbial origin and microenvironment can play a role in altering the shape of the nanomaterial. However, such studies have never been conducted. Here, we demonstrate that the selenium nanomaterials produced by Escherichia coli K-12 are stable and remain as BioSe-Nanospheres under thermophilic conditions, while those produced by anaerobic granular sludge transform to BioSe-Nanorods, due to a lower quantity of proteins coating these nanoparticles, which has been verified by proteomics analysis as well as using chemically synthesized selenium nanomaterials. Furthermore, the presence of Bacillus safensis JG-B5T transform the purified BioSe-Nanospheres produced by E. coli K-12 to BioSe-Nanorods, though they are not transformed in the absence of B. safensis JG-B5T. This is due to the production of peptidases by B. safensis JG-B5T that cleaves the protein coating the BioSe-Nanospheres produced by E. coli K-12, leading to their transformation to trigonal BioSe-Nanorods, which is the thermodynamically more stable state. These findings suggest that the fate of selenium and probably other redox-active elements released from the biological wastewater treatment units needs to be reevaluated and improved by including microbial criteria for better accuracy.

Quenching Mechanism of Uranyl(VI) by Chloride and Bromide in Aqueous and Non-Aqueous Solutions.

A major hindrance in utilizing uranyl(VI) luminescence as a standard analytical tool, for example, in environmental monitoring or nuclear industries, is quenching by other ions such as halide ions, which are present in many relevant matrices of uranyl(VI) speciation. Here, we demonstrate through a combination of time-resolved laser-induced fluorescence spectroscopy, transient absorption spectroscopy, and quantum chemistry that coordinating solvent molecules play a crucial role in U(VI) halide luminescence quenching. We show that our previously suggested quenching mechanism based on an internal redox reaction of the 1:2-uranyl-halide-complex holds also true for bromide-induced quenching of uranyl(VI). By adopting specific organic solvents, we were able to suppress the separation of the oxidized halide ligand X2·- and the formed uranyl(V) into fully solvated ions, thereby "reigniting" U(VI) luminescence. Time-dependent density functional theory calculations show that quenching occurs through the outer-sphere complex of U(VI) and halide in water, while the ligand-to-metal charge transfer is strongly reduced in acetonitrile.

DNA-Mediated Stack Formation of Nanodiscs.

Membrane-scaffolding proteins (MSPs) derived from apolipoprotein A-1 have become a versatile tool in generating nano-sized discoidal membrane mimetics (nanodiscs) for membrane protein research. Recent efforts have aimed at exploiting their controlled lipid protein ratio and size distribution to arrange membrane proteins in regular supramolecular structures for diffraction studies. Thereby, direct membrane protein crystallization, which has remained the limiting factor in structure determination of membrane proteins, would be circumvented. We describe here the formation of multimers of membrane-scaffolding protein MSP1D1-bounded nanodiscs using the thiol reactivity of engineered cysteines. The mutated positions N42 and K163 in MSP1D1 were chosen to support chemical modification as evidenced by fluorescent labeling with pyrene. Minimal interference with the nanodisc formation and structure was demonstrated by circular dichroism spectroscopy, differential light scattering and size exclusion chromatography. The direct disulphide bond formation of nanodiscs formed by the MSP1D1_N42C variant led to dimers and trimers with low yield. In contrast, transmission electron microscopy revealed that the attachment of oligonucleotides to the engineered cysteines of MSP1D1 allowed the growth of submicron-sized tracts of stacked nanodiscs through the hybridization of nanodisc populations carrying complementary strands and a flexible spacer.

Lanthanide-induced conformational change of methanol dehydrogenase involving coordination change of cofactor pyrroloquinoline quinone.

There is emerging interest in the role of lanthanides as cofactors for XoxF-type methanol dehydrogenase (MDH). Here, classical molecular dynamics simulations combined with fragment molecular orbital calculations were employed to rationalize the enzymatic activities of MDH (both XoxF- and MxaF-types) carrying different lanthanides. In XoxF-type MDH, lanthanide binding to cofactor pyrroloquinoline quinone was found to switch from tridentate to unidentate fashion as it switches from lighter to heavier lanthanides. This fact possibly plays a crucial role in the enzymatic activity exclusive to XoxF-type MDH incorporating lighter lanthanides.

Cm3+/Eu3+ induced structural, mechanistic and functional implications for calmodulin.

Trivalent actinides and their lanthanide homologues are being scrutinized for their potential health risk when ingested as a result of a range of industrial activities such as mining. Importantly, these ions are known to exhibit high affinity towards calmodulin (CaM). In case of their inadvertent uptake, the holoproteins that are occupied by these cations may block signal transduction pathways or increase the concentration of these ions in intact cells, which could lead to accumulation in human organs. Accordingly, this investigation employed spectroscopy, computational chemistry, calorimetry, and biochemistry to study the results of metal ion substitution on the protein structure, enzymatic activity and chemo- and cytotoxicity of An3+/Ln3+ ions. As will be demonstrated herein, our data confirm the higher affinity of Cm3+ and Eu3+ compared to Ca2+ to all 4 binding sites of CaM, with one site differing from the remaining three. This higher-affinity site will complex Eu3+ in an exothermic fashion; in contrast, ion binding to the three lower-affinity EF-hands was found to be endothermic. The overall endothermic binding process is ascribed to the loss of the hydration shells of the trivalent ions upon protein binding. These findings are supported by extensive quantum chemical calculations of full holo-CaM, which were performed at the MP2 level using the fragment molecular orbital method. The exceptional binding site (EF-hand 3) features fewer negatively charged residues compared to the other EF-hands, thereby allowing Eu3+ and Cm3+ to carry one or two additional waters compared to Ca2+-CaM, while also causing the structure of Cm3+/Eu3+-CaM to become slightly disordered. Moreover, the enzymatic activity decreases somewhat in comparison to Ca2+-CaM. By utilizing a combination of techniques, we were able to generate a comprehensive picture of the CaM-actinide/lanthanide system from the molecular level to its functional impact. Such knowledge could also be applied to other metal-binding proteins.

Crystal Structure of Regularly Th -Symmetric [U(NO3 )6 ]2- Salts with Hydrogen Bond Polymers of Diamide Building Blocks.

Hexanitratouranate(IV), [U(NO3 )6 ]2- , has been crystallized with anhydrous H+ -involving hydrogen bond polymers connected by selected diamide building blocks. Thanks to the significant moderation of electrostatic interactions between the anions and cations, the molecular structure of [U(NO3 )6 ]2- in these compounds is regularly Th -symmetric. The f-f transitions stemming from 5f2 configuration of U4+ are strictly forbidden by the Laporte selection rule in such a centrosymmetric system, so that the obtained compounds are nearly colourless in contrast to other UIV species usually coloured in green.

Ultrafast Transient Absorption Spectroscopy of UO22+ and [UO2Cl].

For the only water coordinated "free" uranyl(VI) aquo ion in perchlorate solution we identified and assigned several different excited states and showed that the 3Δ state is the luminescent triplet state from transient absorption spectroscopy. With additional data from other spectroscopic methods (TRLFS, UV/vis) we generated a detailed Jablonski diagram and determined rate constants for several state transitions, like the inner conversion rate constant from the 3Φ state to the 3Δ state transition to be 0.35 ps-1. In contrast to luminescence measurements, it was possible to observe the highly quenched uranyl(VI) ion in highly concentrated chloride solution by TAS and we were able to propose a dynamic quenching mechanism, where chloride complexation is followed by the charge transfer from the excited state uranyl(VI) to chloride. This proposed quenching route is supported by TD-DFT calculations.

Molecular and Crystal Structures of Uranyl Nitrate Coordination Polymers with Double-Headed 2-Pyrrolidone Derivatives.

Double-headed 2-pyrrolidone derivatives (DHNRPs) were designed and synthesized as bridging ligands for the efficient and selective separation of UO22+ from a HNO3 solution by precipitation. The building blocks, UO2(NO3)2 and DHNRPs, were successfully connected to form an infinite 1D coordination polymer. The solubility of [UO2(NO3)2(DHNRP)]n is no longer correlated to the hydrophobicity of the ligand but is exclusively governed by the ligand symmetry and packing efficiency. The newly designed DHNRP family can be used to establish a new spent nuclear fuel reprocessing scheme.