Behavior of a Dynamic Covalent Library Driven by Combined Pd(II) and Biphasic Effectors for Metal Transport between Phases.

This work reports the effect of Pd(II) as chemical effector on an acylhydrazone-based dynamic covalent library (DCL) in biphasic systems (water/chloroform). The constituents of the DCL are self-built and distributed in the two phases, two of them are lipophilic enough to play the role of a carrier agent that may transfer Pd(II) from the aqueous phase to the organic phase. Upon addition of Pd(II), the DCL of components exhibits a strong amplification of the constituent that is the most adapted to stabilize Pd(II) in chloroform as well as its agonist in water. This evolution is driven by the combination of the interaction of the DCL with Pd(II) and the presence of the two phases. This study paves the way to a novel approach for liquid/liquid extraction and metal recovery by means of adaptive extractant species generated in situ by a DCL.

Ultrasonically controlled synthesis of UO2+x colloidal nanoparticles.

Actinide colloids and nanoparticles (NPs) currently constitute a topic of strong interest due to their potential role in advanced nuclear energetics and the environmental migration of radioactivity. A better understanding of the physico-chemical properties of nanoscale actinide oxides requires robust synthesis approaches. In this work, UO2+x NPs were successfully prepared by sonochemistry from U(IV) solutions previously stabilised in a hydrochloric medium (20 kHz, 65 °C, Ar/(10%)CO). Colloidal suspensions were found to be composed of crystalline and spherical NPs showing a UO2-like structure and measuring 18.0 ± 0.1 nm (SAXS, HR-TEM and PXRD techniques). In comparison with the controlled hydrolysis approach used as a reference, sonochemistry appears to be a simple and original synthesis route providing larger, better defined and more crystalline UO2+x NPs with a narrower size distribution. These well-defined NPs offer new opportunities for the preparation of reference actinide materials devoted to fundamental, technological and environmental studies.

How colloid nature drives the interactions between actinide and carboxylic surfactant in sol: Towards a mesostructured nanoporous actinide oxide material.

HYPOTHESIS: The key to prepare a mesostructured porous material by a soft-template route coupled to a colloidal sol-gel process is to control the surfactant-colloid interface. In the case of tetravalent actinide ions, their high reactivity in aqueous media always leads to uncontrolled and irreversible condensation. The addition of a complexing agent to the sol may moderate these reactions and enhances the interaction between the colloids and the surfactant to in fine prepare a mesostructured nanoporous actinide oxide material. EXPERIMENTS: Several colloidal sols were prepared without and with formic acid as complexing agent by varying the molar ratios between thorium, carboxylic surfactant and pH. Small and Wide Angle X-ray Scattering were used to characterize the nature of the colloids, their interaction with the surfactant and the final ThO2 materials. FINDINGS: Depending on the colloid nature, hexagonal or worm-like hybrid mesophase is formed. The thermal treatment of the worm-like mesophase with a sufficient amount of Th-formic acid hexameric species coated at the surface of surfactant micelles generates micrometric ThO2 nanofibers. This material having an accessible porosity opens new perspectives to be impregnated with minor actinide solutions offering a promising safety method for the fabrication of mixed oxide nuclear fuel and the minor actinide transmutation.

Facile Preparation of Macro-Microporous Thorium Oxide via a Colloidal Sol-Gel Route toward Safe MOX Fuel Fabrication.

The identification of new colloidal sol-gel routes for the preparation of actinide oxides, which have a homogeneous and accessible porosity that can easily be impregnated by any concentrated actinide solution, opens new perspectives for the preparation of homogeneous nuclear fuel for minor actinide transmutation. This homogeneity allows us to avoid "hot spot" formation due to the local accumulation of more fissile elements. Here, we report the preparation of macro-microporous ThO2 materials by a colloidal sol-gel route. Using a thorium salt with 6-aminocaproic acid as a complexing agent at a controlled pH, we were able to pilot the condensation of thorium hydroxo species forming colloids of tuned nanometric size and thus the sol stability. After a freeze-drying process to concentrate colloids and a thermal treatment allowing complexing agent removal and macroporosity formation by a brutal gas release during combustion, a loose packing of ThO2 nanoparticles with an ordered distribution of interparticular porosity and a fraction of nanometric crystallites, whose size depends on the initial colloidal size, were obtained. The sols, pastes, and final materials were characterized by small- and wide-angle X-ray scattering to determine the colloidal size and the final structure of the materials, which was also confirmed by transmission electron microscopy. The most promising material was finally successfully impregnated by a simulating minor actinide solution and thermally treated to prepare a mixed actinide oxide material. This safe technology, relying on the colloidal sol-gel process and the formulation of complex fluids forming tunable precursors, opens new perspectives for the reuse of nuclear waste solutions as new fuel.

Mutation of the proline P81 into a serine modifies the tumour suppressor function of the von Hippel-Lindau gene in the ccRCC.

BACKGROUND: The von Hippel-Lindau disease is an autosomal dominant syndrome associated with tumour formation in various tissues, such as retina, central nervous system, kidney, and adrenal glands. VHL gene deletion or mutations support the development of various cancers. Unclassified VHL variants also referred as "of unknown significance" result from gene mutations that have an unknown or unclear effect on protein functions. The P81S mutation has been linked to low penetrance Type 1 disease but its pathogenic function was not clearly determined. METHODS: We established a stable cell line expressing the pVHL213 (c.241C>T, P81S) mutant. Using biochemical and physiological approaches, we herein analysed pVHL folding, stability and function in the context of this VHL single missense mutation. RESULTS: The P81S mutation mostly affects the non-canonical function of the pVHL protein. The cells expressing the pVHL213P81S acquire invasive properties in relation with modified architecture network. CONCLUSION: We demonstrated the pathogenic role of this mutation in tumour development in vhl patients and confirm a medical follow up of family carrying the c.241C>T, P81S.

Ultrasonically assisted conversion of uranium trioxide into uranium(vi) intrinsic colloids.

Under oxidizing conditions, the corrosion of spent nuclear fuel may lead to the leaching of radionuclides including soluble uranyl-based species. The speciation of the generated chemical forms is complex and the related potential formation of colloidal species appears surprisingly poorly reported in the literature. Their formation could however contribute significantly to the mobility of radionuclides in the environment. A better knowledge in the speciation and reactivity of these species appears particularly relevant. This study describes the preparation and characterization of intrinsic uranium(vi) colloids from amorphous and crystalline UO3 in pure water assisted by 20 kHz ultrasound. In the presence of carbon monoxide preventing the sonochemical formation of hydrogen peroxide, ultrasonic treatment boosts the conversion of UO3 powder into (meta-)schoepite precipitates and yields very stable and notably concentrated uranium(vi) nanoparticles in the liquid phase. Using HR-TEM, SAXS and XAS techniques, we confirmed that the colloidal suspension is composed of quasi-spherical nanoparticles measuring ca. 3.8 ± 0.3 nm and exhibiting a schoepite-like crystallographic structure. The proposed method demonstrates the possible formation of environmentally relevant U(vi) colloidal nanoparticles appearing particularly interesting for the preparation of reference systems in the absence of added ions and capping agents.

Tuning the Regioselective Functionalization of Trifluoromethylated Dienes via Lanthanum-Mediated Single C-F Bond Activation.

The development of new fluorine-containing building blocks and their efficient synthetic access is currently a challenging research field. Herein, the highly regio- and stereoselective addition of a large range of aldehydes onto trifluoromethylated benzofulvenes was achieved using a simple La/I2 /DIBAL-Cl system via a selective C-F bond activation process. This versatile methodology provided homodienyl alcohols bearing a terminal CF2 -alkene with potential further applications, as shown by the dehydration to the first benzofulvenes carrying a difluorovinyl group. In addition, for certain electron-poor aldehydes, unprecedented ipso substitution of the CF3 group in a diene was observed, which, according to DFT studies, is related to the presence of the large, Lewis-acidic lanthanum metal.

The prefoldin complex stabilizes the von Hippel-Lindau protein against aggregation and degradation.

Loss of von Hippel-Lindau protein pVHL function promotes VHL diseases, including sporadic and inherited clear cell Renal Cell Carcinoma (ccRCC). Mechanisms controlling pVHL function and regulation, including folding and stability, remain elusive. Here, we have identified the conserved cochaperone prefoldin complex in a screen for pVHL interactors. The prefoldin complex delivers non-native proteins to the chaperonin T-complex-protein-1-ring (TRiC) or Cytosolic Chaperonin containing TCP-1 (CCT) to assist folding of newly synthesized polypeptides. The pVHL-prefoldin interaction was confirmed in human cells and prefoldin knock-down reduced pVHL expression levels. Furthermore, when pVHL was expressed in Schizosaccharomyces pombe, all prefoldin mutants promoted its aggregation. We mapped the interaction of prefoldin with pVHL at the exon2-exon3 junction encoded region. Low levels of the PFDN3 prefoldin subunit were associated with poor survival in ccRCC patients harboring VHL mutations. Our results link the prefoldin complex with pVHL folding and this may impact VHL diseases progression.

Sonochemical dissolution of nanoscale ThO2 and partial conversion into a thorium peroxo sulfate.

The influence of the sample morphology and experimental conditions towards the sonochemical dissolution of nanoscale ThO2 samples in sulfuric acid media is described. Significant sonochemical dissolution rates and yields are observed at 20 kHz under Ar/O2 atmosphere in dilute 0.5 M H2SO4 at room temperature, contrasting with the generally-reported high refractory behavior for ThO2. The dissolution of ThO2 combines the physical effects driven by acoustic cavitation phenomenon, the complexing affinity of Th(IV) in sulfuric medium and the sonochemical generation of H2O2. These sonochemical conditions further allow the observation of the partial conversion of ThO2 into a scarce Th(IV) peroxo sulfate with 1D morphology resulting from one or both following processes: dissolution/reprecipitation or formation of an intermediate Th(IV) surface complex.

Ends and middle: Global force balance and septum location in fission yeast.

The fission yeast cell is shaped as a very regular cylinder ending by hemi-spheres at both cell ends. Its conserved phenotypes are often used as read-outs for classifying interacting genes and protein networks. Using Pascal and Young-Laplace laws, we proposed a framework where scaling arguments predicted shapes. Here we probed quantitatively one of these relations which predicts that the division site would be located closer to the cell end with the larger radius of curvature. By combining genetics and quantitative imaging, we tested experimentally whether altered shapes of cell end correlate with a displaced division site, leading to asymmetric cell division. Our results show that the division site position depends on the radii of curvatures of both ends. This new geometrical mechanism for the proper division plane positioning could be essential to achieve even partitioning of cellular material at each cell division.

Direct Observation of the Surface Topography at High Temperature with SEM.

High-temperature scanning electron microscopy allows the direct study of the temperature behavior of materials. Using a newly developed heating stage, tilted images series were recorded at high temperature and 3D images of the sample surface were reconstructed. By combining 3D images recorded at different temperatures, the variations of material roughness can be accurately described and associated with local changes in the topography of the sample surface.

Probing the local structure of nanoscale actinide oxides: a comparison between PuO2 and ThO2 nanoparticles rules out PuO2+x hypothesis.

Actinide research at the nanoscale is gaining fundamental interest due to environmental and industrial issues. The knowledge of the local structure and speciation of actinide nanoparticles, which possibly exhibit specific physico-chemical properties in comparison to bulk materials, would help in a better and reliable description of their behaviour and reactivity. Herein, the synthesis and relevant characterization of PuO2 and ThO2 nanoparticles displayed as dispersed colloids, nanopowders, or nanostructured oxide powders allow to establish a clear relationship between the size of the nanocrystals constituting these oxides and their corresponding An(iv) local structure investigated by EXAFS spectroscopy. Particularly, the first oxygen shell of the probed An(iv) evidences an analogous behaviour for both Pu and Th oxides. This observation suggests that the often observed and controversial splitting of the Pu-O shell on the Fourier transformed EXAFS signal of the PuO2 samples is attributed to a local structural disorder driven by a nanoparticle surface effect rather than to the presence of PuO2+x species.

Liposomes Containing Nickel-Bis(dithiolene) Complexes for Photothermal Theranostics.

New thermosensitive liposomes with a phase transition at 42 °C, containing nickel-bis(dithiolene) complexes as efficient and stable photothermal agents, have been formulated and characterized. These liposomes are highly stable and keep their contents at 37 °C for more than 30 days. On the contrary, the mild hyperthermia generated by the nickel-bis(dithiolene) complex under 940 nm NIR irradiation allows for the fine controlled release of the liposome contents, making such liposomes highly suitable for on-demand drug delivery in the human body under NIR laser irradiation. These liposomes can also be directly used, as shown here, as nanoagents for photothermal therapy. In fact, strong cell death can be generated under laser irradiation in the presence of these photothermally active nanocargos containing less than 10% w/w of metal complex. We also demonstrate, for the first time, that nickel-bis(dithiolene) complexes are good photoacoustic agents, generating easily detectable ultrasonic signals directly proportional to the concentration of complexes and the used laser power.

Deciphering the Crystal Structure of a Scarce 1D Polymeric Thorium Peroxo Sulfate.

The preparation and structural characterization of an original Th peroxo sulfate dihydrate, crystallizing at room temperature in the form of stable 1D polymeric microfibres is described. A combination of laboratory and synchrotron techniques allowed solution of the structure of the Th(O2 )(SO4 )(H2 O)2 compound, which crystallizes in a new structure type in the space group Pna21 of the orthorhombic crystal system. Particularly, the peroxide ligand coordinates to the Th cations in an unusual µ3 -η2 :η2 :η2 bridging mode, forming an infinite 1D chain decorated with sulfato ligands exhibiting simultaneously monodentate and bidentate coordination modes.

N-Alkyl calix[4]azacrowns for the selective extraction of uranium.

The selective extraction of uranium by N-octylcalix[4]azacrown (NOCAC) and N-ethylhexylcalix[4]azacrown (NEHCAC) was investigated. The ligands were synthesised in three steps through the functionalisation of t-butyl calix[4]arene at the distal-1,3-positions of the lower rim with ethyl acetate groups followed by cyclisation with (imino)bis(ethane-2,1-diyl)diamide. A detailed investigation on the effect of various parameters, such as the aqueous phase acidity (sulfuric acid), the ionic strength, and ligand concentration, on the extraction of uranium(vi) has been conducted. The effect of the H2SO4 concentration has been studied from 0.02 to 3 M. Preliminary studies carried out on NOCAC in dodecane/octanol diluents showed that the uranium extraction from sulfuric acid is more efficient at a low H2SO4 concentrations. The stoichiometry of complexation was estimated from the slope method, NMR titration, and electrospray ionisation-mass spectrometry analysis. Both ligands were found to be highly selective for uranium(vi) over other competitive cations present in a simulated leach solution containing seven competitive cations. The successful recovery of the uranium from the organic phase has been performed thanks to stripping steps involving ammonium oxalate, ammonium carbonate, and sodium carbonate as stripping agents.

Controlled "golf ball shape" structuring of Mg surface under acoustic cavitation.

This manuscript describes the original structuring of Mg materials under ultrasound irradiation in mild conditions. Golf ball like extended structures can be prepared in dilute oxalic solutions at 20°C under high frequency ultrasound (200kHz). An original approach carried out through iterative 3D reconstruction of sonicated surfaces is used to describe surface evolutions and characterize the formed microstructures. A combination of SEM, ICP-AES, contact-angle measurements, and 3D image analyses allows to characterize the roughness and mass loss evolutions, and investigate the mechanism of formation for such architectures. A screening of the sonication experiments clearly points out an ultrasound frequency dependency for the effects generated at the surface. 200kHz sonication in 0.01M oxalic acid provides an unprecedented manufacturing of Mg samples which result from a controlled and localized dissolution of the material and characterized by a strong wetting surface with a roughness of 170nm. The additional formation of newly formed secondary phases appearing with surface dissolution progress is also deciphered. More generally, the ultrasonic procedure used to prepare these engineered surfaces opens new alternatives for the nano- and micro-structuring of metallic materials which may exhibit advanced physical and chemical properties of potential interest for a large community.

The pVHL172 isoform is not a tumor suppressor and up-regulates a subset of pro-tumorigenic genes including TGFB1 and MMP13.

The von Hippel-Lindau (VHL) tumor suppressor gene is often deleted or mutated in ccRCC (clear cell renal cell carcinoma) producing a non-functional protein. The gene encodes two mRNA, and three protein isoforms (pVHL213, pVHL160 and pVHL172). The pVHL protein is part of an E3 ligase complex involved in the ubiquitination and proteasomal degradation of different proteins, particularly hypoxia inducible factors (HIF) that drive the transcription of genes involved in the regulation of cell proliferation, angiogenesis or extracellular matrix remodelling. Other non-canonical (HIF-independent) pVHL functions have been described. A recent work reported the expression of the uncharacterized protein isoform pVHL172 which is translated from the variant 2 by alternative splicing of the exon 2. This splice variant is sometimes enriched in the ccRCCs and the protein has been identified in the respective samples of ccRCCs and different renal cell lines. Functional studies on pVHL have only concerned the pVHL213 and pVHL160 isoforms, but no function was assigned to pVHL172. Here we show that pVHL172 stable expression in renal cancer cells does not regulate the level of HIF, exacerbates tumorigenicity when 786-O-pVHL172 cells were xenografted in mice. The pVHL172-induced tumors developed a sarcomatoid phenotype. Moreover, pVHL172 expression was shown to up regulate a subset of pro-tumorigenic genes including TGFB1, MMP1 and MMP13. In summary we identified that pVHL172 is not a tumor suppressor. Furthermore our findings suggest an antagonistic function of this pVHL isoform in the HIF-independent aggressiveness of renal tumors compared to pVHL213.

Impact of the Long-Range Electronic Effect of a Fluorous Ponytail on Metal Coordination during Solvent Extraction.

With the need for a precise description of the long-range electronic effects of a perfloroalkyl chain (F-ponytail) grafted onto metal chelators, we studied in detail the effect of a spacer inserted between the polar complexing head and the F-ponytail, in relation to the metal coordination ability of the resulting molecules. The prepared molecules were then applied for the extraction of various metals from an aqueous phase into an organic phase, and the optimum spacer length could be estimated to be between three and four methylene units, according to the extraction conditions. The study also revealed the difficulty of modeling and anticipating the tiny energy differences involved in the extraction process and the importance in peculiar cases to go beyond only these studied inductive effects to understand better the factors that govern the stabilization of a metallic cation in a complex fluorous phase.

Polyoxometalate/Polyethylene Glycol Interactions in Water: From Nanoassemblies in Water to Crystal Formation by Electrostatic Screening.

In the last decade organic-inorganic hybrid materials have become essential in materials science as they combine properties of both building blocks. Nowadays the main routes for their synthesis involve electrostatic coupling, covalent grafting, and/or solvent effects. In this field, polyoxometalates (POMs) have emerged as interesting inorganic functional building blocks due to their outstanding properties. In the present work the well-known α-Keggin polyoxometalate, α-PW12 O403- (PW), is shown to form hybrid crystalline materials with industrial (neutral) polyethylene glycol oligomers (PEG) under mild conditions, that is, in aqueous medium and at room temperature. The formation of these materials originates from the spontaneous self-assembly of PW with EOx , (EO=ethylene oxide) with at least four EO units (x>4). The PW-PEG nanoassemblies, made of a POM surrounded by about two PEG oligomers, are stabilized by electrostatic repulsions between the negatively charged PW anions. Addition of NaCl, aimed at screening the inter-nanoassembly repulsions, induces aggregation and formation of hybrid crystalline materials. Single-crystal analysis showed a high selectivity of PW towards EO5 -EO6 oligomers from PEG200, which is made of a mixture of EO3-8 . Therefore, a general "soft" route to produce POM-organic composites is proposed here through the control of electrostatic repulsions between spontaneously formed nanoassemblies in water. However, this rational design of new POM hybrid (crystalline) materials with hydrophilic blocks, using such a simple mixing procedure of the components, requires a deep understanding of the molecular interactions.

Micellization in vegetable oils: A structural characterisation.

The solubilisation of polar and polyphenol antioxidant in vegetable oils was studied. It was shown that the use of a polyglyceryl-3-diisostearate (PG3DS), a bio-sourced emulsifier well known in cosmetics, increases the yield of solubilisation thanks to some aggregation properties analysed using x-ray scattering technique. We show indeed that PG3DS forms reverse aggregates with a critical concentration that depends on the oil polarity. PG3DS reverse aggregates are elongated with a polar core and cannot be really swollen by addition of water. This supramolecular organisation allows however an efficient solubilisation of polar antioxidants in vegetable oils.