Molecular Hosts for the Sensing and Separation of 99TcO4.

In recent years, European Union member states have hastened energy policy deliberations to address supply and sustainability concerns, placing a significant emphasis on nuclear energy as a means to achieve decarbonization goals. However, despite its significant role in power generation, nuclear energy faces significant challenges linked to fuel reprocessing and waste disposal, that hinder its broader expansion. In this context, the separation of technetium represents a concerning issue. Indeed, technetium's catalytic activity can impede the extraction of uranium, neptunium, and plutonium, affecting waste reprocessing efficiency. Additionally, the stable form of technetium in aerobic conditions, pertechnetate (TcO4 -), poses risks of groundwater contamination due to its mobility and solubility. Hence, sensing and separation of TcO4 - is imperative for both nuclear fuel processing and minimising radioactive contamination in the environment. However, the binding of TcO4 - and its separation from contaminated solutions present challenges due to the acidic (or basic) waste components and the high ionic strength in real matrices. Supramolecular chemists have addressed these issues by designing receptors inspired by molecular recognition principles. This article explores recent advancements and future directions in TcO4 - sensing and separation (using extraction and sorption) with a focus on molecular hosts. Metal-organic receptors will also be discussed.

Investigation of the Plutonium(IV) Interactions with Two Variants of the EF-Hand Ca-Binding Site I of Calmodulin.

Due to its presence in the nuclear industry and its strong radiotoxicity, plutonium is an actinide of major interest in the event of internal contamination. To improve the understanding of its mechanisms of transport and accumulation in the body, the complexation of Pu(IV) to the most common protein calcium-binding motif found in cells, the EF-hand motif of calmodulin, was investigated. Visible and X-ray absorption spectroscopies (XAS) in solution made it possible to investigate the speciation of plutonium at physiological pH (pH 7.4) and pH 6 in two variants of the calmodulin Ca-binding site I and using Pu(IV) in different media: carbonate, chloride, or nitrate solutions. Three different species of Pu were identified in the samples, with formation of 1:1 Pu(IV):calmodulin peptide complexes, Pu(IV) reduction, and formation of peptide-mediated Pu(IV) hexanuclear cluster.

Optimized Coordination of Uranyl in Engineered Calmodulin Site 1 Provides a Subnanomolar Affinity for Uranyl and a Strong Uranyl versus Calcium Selectivity.

As an alpha emitter and chemical toxicant, uranium toxicity in living organisms is driven by its molecular interactions. It is therefore essential to identify main determinants of uranium affinity for proteins. Others and we showed that introducing a phosphoryl group in the coordination sphere of uranyl confers a strong affinity of proteins for uranyl. In this work, using calmodulin site 1 as a template, we modulate the structural organization of a metal-binding loop comprising carboxylate and/or carbonyl ligands and reach affinities for uranyl comparable to that provided by introducing a strong phosphoryl ligand. Shortening the metal binding loop of calmodulin site 1 from 12 to 10 amino acids in CaMΔ increases the uranyl-binding affinity by about 2 orders of magnitude to log KpH7 = 9.55 ± 0.11 (KdpH7 = 280 ± 60 pM). Structural analysis by FTIR, XAS, and molecular dynamics simulations suggests an optimized coordination of the CaMΔ-uranyl complex involving bidentate and monodentate carboxylate groups in the uranyl equatorial plane. The main role of this coordination sphere in reaching subnanomolar dissociation constants for uranyl is supported by similar uranyl affinities obtained in a cyclic peptide reproducing CaMΔ binding loop. In addition, CaMΔ presents a uranyl/calcium selectivity of 107 that is even higher in the cyclic peptide.

Force Field Parameterization of Actinyl Molecular Cations Using the 12-6-4 Model.

In this work, a set of 12-6-4 force fields (FFs) parameters were developed for the actinyl molecular cations, AnO2n+ (n = 1, 2), from uranium to plutonium for classical molecular dynamics (MD) for four water models: TIP3P, SPC/E, OPC3, and TIP4Pew. Such a non-bonded potential model taking into account the induced dipole between the metallic center and the surrounding molecules has shown better performances for various cations than the classic 12-6 non-bonded potentials. The parametrization method proposed elsewhere for metallic cations has been extended to these molecular cations. In contrast to the actinyl 12-6 FFs from the literature, the new models reproduce correctly both solvation and thermodynamic properties, thanks to the inclusion of the induced dipole term (C4). The transferability of such force fields was assessed by performing MD simulations of carbonato actinyl species, which are highly implicated in actinide migration or actinide extraction from seawater. A highly satisfying agreement was found when comparing the EXAFS signals computed from our MD simulation to the experimental ones. The set of FFs developed here opens new possibilities for the study of actinide chemistry.

Effect of metal complexation on diglycolamide radiolysis: a comparison between ex situ gamma and in situ alpha irradiation.

Radiolytic degradation is an important aspect to consider when developing a ligand or a complexant for radionuclides. Diglycolamide extractants (DGAs) have been playing an important role in many partition processes for spent nuclear fuel. In particular, the extractant N,N,N'N'-tetraoctyl diglycolamide (TODGA) has been studied intensively for the purpose of solvent extraction processes such as ARTIST, i-Sanex, EURO-GANEX and EURO-EXAM, which have been developed around the TODGA extractant. For the first time, the radiolytic stability of TODGA was investigated both by in situ alpha irradiation using a macroconcentration of americum(III) and by ex situ gamma irradiation in the presence of a macroconcentration of neodymium(III). It was shown that metal ions complexed in the organic phase protect TODGA from degradation by irradiation and that the degradation was slower using in situ alpha irradiation compared to ex situ gamma irradiation. By comparison to gamma irradiation of Nd-TODGA solution, alpha irradiation of Am-TODGA solutions showed the presence of 2 additional compounds identified as a TODGA molecule with a CC bond and a TODGA molecule with the addition of a NO3 group. The major degradation products were identified and a degradation schema was proposed. The direct analysis of the solution containing Am(III) or Nd(III) showed that the degradation compounds retaining a diglycolamide skeleton are involved in heteroleptic complexes with TODGA, without a negative impact on An(III) or Ln(III) complexation.

Liquid/liquid interface in periodic boundary condition.

We study how surface phenomena can change the interface geometry in liquid-liquid two-phase systems with periodic boundary conditions. Without any curvature effect on surface tension, planar (slab), cylindrical, and spherical structures are successively obtained as a function of the total composition and elongation of the box, in accordance with molecular dynamics simulations for a water/heptane system. The curvature effects described by Tolman relationship desymmetrize the phase diagram by stabilizing a concavity but it leads to inconsistencies with high curvature. Helfrich model partially resolves this and predicts the possible presence of shells reflecting a frustrated system.

Insight of the Metal-Ligand Interaction in f-Element Complexes by Paramagnetic NMR Spectroscopy.

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 C a D 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 C a D . However, the C a D 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.

UO22+ structure in solvent extraction phases resolved at molecular and supramolecular scales: a combined molecular dynamics, EXAFS and SWAXS approach.

A new polarizable force field for describing the solvation of the uranyl (UO22+) cation in solvent extraction phases has been developed for molecular dynamics simulations. The validity of the polarizable force field has been established by comparison with EXAFS and SWAXS experiments. This new force field allows for describing both the UO22+ hydration and solvation properties in good agreement with the experiments. In aqueous phases we demonstrated that the UO22+ force field has been improved from the previous one we developed. Indeed, the UO22+ structural and dynamics properties, i.e., the dynamics of the water molecules in the vicinity of the uranyl cation, calculated from molecular dynamics are in better agreement with the EXAFS experiments. Furthermore, the transferability of the UO22+ force field proposed here has been validated on typical solvent extraction phases containing uranyl nitrate salts with extractant molecules, namely DMDOHEMA molecules, in n-heptane. The good agreements observed between the theoretical (MD simulations) and experimental UO22+ structures at the molecular (EXAFS) and supramolecular (SWAXS) scales prove the accuracy of the UO22+ force field developed and proposed in the present paper.

Coordination of Tetravalent Actinides (An=ThIV , UIV , NpIV , PuIV ) with DOTA: From Dimers to Hexamers.

Three tetravalent actinide (AnIV ) hexanuclear clusters with the octahedral core [An6 (OH)4 O4 ]12+ (AnIV =UIV , NpIV , PuIV ) were structurally characterized in the solid state and in aqueous solution by using single-crystal X-ray diffraction, X-ray absorption, IR, Raman, and UV/Vis spectroscopy. The observed structure, [An6 (OH)4 O4 (H2 O)8 (HDOTA)4 ]⋅HCl/HNO3 ⋅n H2 O (An=U(I), Np(II), Pu(III)), consists of a AnIV hexanuclear pseudo-octahedral cluster stabilized by DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) ligands. The six actinide atoms are connected through alternate µ3 -O2- and µ3 -OH- groups. Extended X-ray absorption fine structure (EXAFS) investigations combined with UV/Vis spectroscopy provide evidence for the same local structure in moderate acidic and neutral aqueous solutions. The synthesis mechanism was partially elucidated and the main physicochemical properties (pH range stability, solubility, and protonation constant) of the cluster were determined. The results underline the importance of: 1) considering such polynuclear species in thermodynamic models, and 2) competing reactions between hydrolysis and complexation. It is interesting to note that the same synthesis route with thorium(IV) led to the formation of a dimer, Th2 (H2 O)10 (H2 DOTA)2 ⋅4 NO3 ⋅x H2 O (IV), which contrasts to the structure of the other AnIV hexamers.

Structural Analysis of Uranyl Complexation by the EF-Hand Motif of Calmodulin: Effect of Phosphorylation.

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.

The role of curvature effects in liquid-liquid extraction: assessing organic phase mesoscopic properties from MD simulations.

The bending rigidity of small reverse aggregates involved in liquid-liquid extraction processes has been investigated by molecular dynamics simulations. Simulations of a common extractant (DMDOHEMA) with four hydrophobic chains in explicit solvent (n-heptane) and in vacuum have been performed to determine the effect of solvent penetration on film stiffness. Elastic film bending energy that is needed for mesoscopic modelling of transfer of species between complex fluids is harmonic in terms of curvature (Helfrich formalism) and the packing parameter only if the solvent is explicitly taken into account. In terms of the packing parameter of the real molecular film constituting the reverse water in oil aggregates and taking into account molecular volume, area and film thickness (that is in agreement with Tanford's model), the bending rigidity is calculated to be about 16 kBT per extractant molecule (about 40 kJ mol-1), which is smaller than the free energy of transfer from an isolated "monomer" molecule to a weak aggregate, but of the order of magnitude of the free energy of transfer used in liquid-liquid extraction processes.

Complexation of Actinide(III) and Lanthanide(III) with H4TPAEN for a Separation of Americium from Curium and Lanthanides.

Previous studies have identified the TPAEN ligand as a potentially appropriate complexing agent in solvent extraction processes for the separation of americium (Am(III)) from the fission products including lanthanide (Ln(III)) and curium (Cm(III)) ions, a challenging issue for advanced nuclear fuel recycling. To get insight into the selectivity of this ligand, the complexation of selected trivalent Ln(III) and actinide (An(III)) cations with TPAEN was investigated in solution. First, the structure and stoichiometry of the TPAEN complex with Am(III) were characterized by extended X-ray absorption fine structure spectroscopy (EXAFS). Then complexation constants and thermodynamics data were acquired for the complexes using different methods: microcalorimetry for the Ln(III) cations, time-resolved laser fluorescence spectroscopy (TRLFS) for Eu(III) and Cm(III), and UV-visible spectroscopy for Nd(III) and Am(III).

Stability of reverse micelles in rare-earth separation: a chemical model based on a molecular approach.

Molecular complexes formed in the organic phase during solvent extraction may self-assemble as reverse micelles, and therefore induce a supramolecular organization of this phase. In most of the cases, water molecules play an essential role in the organization of this non polar medium. The aim of this work is to investigate the speciation of the aggregates formed in the organic phase during solvent extraction, and especially to assess their stability as a function of the number of water molecules included in their polar core. We have focused on malonamide extractants that have already been investigated experimentally. Different stoichiometries of reverse micelles in the organic phase have been studied by means of classical molecular dynamics simulations. Furthermore, umbrella-sampling molecular dynamics simulations have been used to calculate the equilibrium constant (K°) representing the association/dissociation pathways of water molecules in the aggregates and the corresponding reaction free energies (ΔrG°).

Thermodynamics of Calcium binding to the Calmodulin N-terminal domain to evaluate site-specific affinity constants and cooperativity.

Calmodulin (CaM) is an essential Ca(II)-dependent regulator of cell physiology. To understand its interaction with Ca(II) at a molecular level, it is essential to examine Ca(II) binding at each site of the protein, even if it is challenging to estimate the site-specific binding properties of the interdependent CaM-binding sites. In this study, we evaluated the site-specific Ca(II)-binding affinity of sites I and II of the N-terminal domain by combining site-directed mutagenesis and spectrofluorimetry. The mutations had very low impact on the protein structure and stability. We used these binding constants to evaluate the inter-site cooperativity energy and compared it with its lower limit value usually reported in the literature. We found that site I affinity for Ca(II) was 1.5 times that of site II and that cooperativity induced an approximately tenfold higher affinity for the second Ca(II)-binding event, as compared to the first one. We further showed that insertion of a tryptophan at position 7 of site II binding loop significantly increased site II affinity for Ca(II) and the intra-domain cooperativity. ΔH and ΔS parameters were studied by isothermal titration calorimetry for Ca(II) binding to site I, site II and to the entire N-terminal domain. They showed that calcium binding is mainly entropy driven for the first and second binding events. These findings provide molecular information on the structure-affinity relationship of the individual sites of the CaM N-terminal domain and new perspectives for the optimization of metal ion binding by mutating the EF-hand loops sequences.

Multi-scale modelling of uranyl chloride solutions.

Classical molecular dynamics simulations with explicit polarization have been successfully used to determine the structural and thermodynamic properties of binary aqueous solutions of uranyl chloride (UO2Cl2). Concentrated aqueous solutions of uranyl chloride have been studied to determine the hydration properties and the ion-ion interactions. The bond distances and the coordination number of the hydrated uranyl are in good agreement with available experimental data. Two stable positions of chloride in the second hydration shell of uranyl have been identified. The UO2(2+)-Cl(-) association constants have also been calculated using a multi-scale approach. First, the ion-ion potential averaged over the solvent configurations at infinite dilution (McMillan-Mayer potential) was calculated to establish the dissociation/association processes of UO2 (2+)-Cl(-) ion pairs in aqueous solution. Then, the association constant was calculated from this potential. The value we obtained for the association constant is in good agreement with the experimental result (KUO2Cl(+) = 1.48 l mol(-1)), but the resulting activity coefficient appears to be too low at molar concentration.

Complexation-induced supramolecular assembly drives metal-ion extraction.

Combining experiment with theory reveals the role of self-assembly and complexation in metal-ion transfer through the water-oil interface. The coordinating metal salt Eu(NO3)3 was extracted from water into oil by a lipophilic neutral amphiphile. Molecular dynamics simulations were coupled to experimental spectroscopic and X-ray scattering techniques to investigate how local coordination interactions between the metal ion and ligands in the organic phase combine with long-range interactions to produce spontaneous changes in the solvent microstructure. Extraction of the Eu(3+)-3(NO3(-)) ion pairs involves incorporation of the "hard" metal complex into the core of "soft" aggregates. This seeds the formation of reverse micelles that draw the water and "free" amphiphile into nanoscale hydrophilic domains. The reverse micelles interact through attractive van der Waals interactions and coalesce into rod-shaped polynuclear Eu(III) -containing aggregates with metal centers bridged by nitrate. These preorganized hydrophilic domains, containing high densities of O-donor ligands and anions, provide improved Eu(III) solvation environments that help drive interfacial transfer, as is reflected by the increasing Eu(III) partitioning ratios (oil/aqueous) despite the organic phase approaching saturation. For the first time, this multiscale approach links metal-ion coordination with nanoscale structure to reveal the free-energy balance that drives the phase transfer of neutral metal salts.

Elucidation of the structure of organic solutions in solvent extraction by combining molecular dynamics and X-ray scattering.

Knowledge of the supramolecular structure of the organic phase containing amphiphilic ligand molecules is mandatory for full comprehension of ionic separation during solvent extraction. Existing structural models are based on simple geometric aggregates, but no consensus exists on the interaction potentials. Herein, we show that molecular dynamics crossed with scattering techniques offers key insight into the complex fluid involving weak interactions without any long-range ordering. Two systems containing mono- or diamide extractants in heptane and contacted with an aqueous phase were selected as examples to demonstrate the advantages of coupling the two approaches for furthering fundamental studies on solvent extraction.

Modeling Lanthanide Ions in Solution: A Versatile Force Field in Aqueous and Organic Solvents.

In this paper, we propose a new nonpolarizable force field for describing the Ln3+ (Ln = lanthanide) series based on a 12-6-4 Lennard-Jones potential. The development of the force field was performed in pure water by adjusting both the ion-oxygen distance and the hydration free energy. This force field accurately reproduces the Ln3+ hydration properties through the series, especially the coordination number that is hardly accessible using a nonpolarizable force field. Then, the validity and the transferability of the current force field were evaluated for two different systems containing Ln3+ in various solvents, namely, 0.1 mol L-1 La(NO3)3 salts in methanol and Eu(NO3)3 salts in solvent organic phases composed of DMDOHEMA molecules in n-heptane. The good agreement between our simulations and the data available in the literature confirms the accuracy of the force field for describing the lanthanide cations in both aqueous and nonaqueous media.

Specific interaction between uranium anionic complexes and the cations of bis(trifluoromethylsulfonyl)imide based ionic liquids.

The redox properties of uranium(IV) hexachloro complex have been investigated with a glassy carbon electrode in four bis(trifluoromethylsulfonyl)imide (Tf2N(-)) based ionic liquids (ILs): the 1-butyl-3-methylimidazolium ([BuMeIm](+)), the 1-butyl-2,3-dimethylimidazolium ([BuMe2Im](+)), the N-butylmethylpyrrolidinium ([BuMePyr](+)), and the tributyl-methylammonium ([MeBu3N](+)). The cyclic voltammetric analysis has revealed two main redox systems: U(V)Cl6(-)/U(IV)Cl6(2-) around 0.2 V and U(IV)Cl6(2-)/U(III)Cl6(3-) around -2 V. The formation of U(V)Cl6(-), a non-dioxo uranium(V) species, can then be observed at the electrode in [Tf2N](-) based ILs. This work also provides evidence of a specific interaction between the uranium anionic species and the IL cations because the standard potentials of both redox couples depend on the IL. The interaction extent has been evaluated by comparison of the IL cation number associated with the uranium anionic complex. For that purpose, the standard potentials of both systems have been measured in the less interacting medium [MeBu3N][Tf2N] as a function of the [BuMeIm](+), [BuMe2Im](+), and [BuMePyr](+) concentration. Predominance diagrams for uranium hexachloro complexes, analogous to the Pourbaix diagram, have then been built in [MeBu3N][Tf2N] depending on the IL cations concentration. The exploitation of these diagrams leads to the conclusion that the interaction is function of the charge of the uranium hexachloro complex (U(V)Cl6(-) < U(IV)Cl6(2-) < U(III)Cl6(3-)) and the IL cation ([BuMe2Im](+) < [BuMePyr](+) < [BuMeIm](+)). The influence of the IL cation could be correlated to the size and the electropositivity of the IL cation. The association would occur by H-bonding and electrostatic interaction. Ab initio calculations were also carried out to evaluate the strength of the interaction between the anionic uranium(IV) chloro complex and the IL cations. The results show that [BuMeIm](+) interacts the most and [MeBu3N](+) the least with U(IV)Cl6(2-), and the magnitude of the interaction is comparable for [BuMe2Im](+) and [BuMePyr](+).