During International Thermonuclear Experimental Reactor operation, due to plasma–wall interaction, particles/dust will be created in sizes ranging from nanometers to tens of microns. The dust properties, especially their ability to be covered by a thin oxide electrostatic insulating layer, and surface topology deeply affect their tritium inventory. Consequently, physico-chemical properties specific to tritiated tungsten particles and consequence on particle behavior in the facility and environment must be carefully assessed. For size-relevant tungsten particles, the measured tritium inventory is ~10 GBq g−1. However, it varies with the particle specific surface area. Due to tritium beta decay and the oxide-insulating layer, dust exhibits a positive electrostatic self-charging. For a 5 µm particle in diameter with a 10 GBq g−1 tritium inventory, self-charging rate could lead to 5.5 104 elementary electric charges per day. These electrostatic properties could change the adhesion of dust on walls. In the case of a single particle, the adhesion will be reinforced due to image and dielectric forces. However, if the tritiated particle is part of an aggregate, the adhesion remains unknown. Due to the limited free path of the β emission in material, the tritium inventory carried by airborne particles cannot be measured in real time by conventional continuous radioactive aerosols monitors, and a new measurement strategy is needed for atmospheric surveillance in the workplace and of facility exhaust. Toxicity studies dealing with exposure to untritiated/tritiated tungsten particles of 100 nm have been undertaken. It was shown that these particles are rapidly dissolved in biologic media. Finally, after collection, dust must be confined to avoid its spreading into the environment. Different technical solutions are presented in this paper.
Abstract The preparation of N‐heterocyclic carbene‐stabilized iridium nanoparticles and their application in hydrogen isotope exchange reactions is reported. These air‐stable and easy‐to‐handle iridium nanoparticles showed a unique catalytic activity, allowing selective and efficient hydrogen isotope incorporation on anilines using D 2 or T 2 as isotopic source. The usefulness of this transformation has been demonstrated by the deuterium and tritium labeling of diverse complex pharmaceuticals.
The preparation of N-heterocyclic carbene-stabilized iridium nanoparticles and their application in hydrogen isotope exchange reactions is reported. These air-stable and easy-to-handle iridium nanoparticles showed a unique catalytic activity, allowing selective and efficient hydrogen isotope incorporation on anilines using D2 or T2 as isotopic source. The usefulness of this transformation has been demonstrated by the deuterium and tritium labeling of diverse complex pharmaceuticals.
In preclinical models, the development and optimization of protein-drug conjugates require accurate determination of the plasma and tissue profiles of both the protein and its conjugated drug. To this aim, we developed a bioanalytical strategy based on dual radiolabeling and ex vivo digital imaging. By combining enzymatic and chemical reactions, we obtained homogeneous dual-labeled anti-MMP-14 Fabs (antigen-binding fragments) conjugated to monomethyl auristatin E where the protein scaffold was labeled with carbon-14 (14C) and the conjugated drug with tritium (3H). These antibody-drug conjugates with either a noncleavable or a cleavable linker were then evaluated in vivo. By combining liquid scintillation counting and ex vivo dual-isotope radio-imaging, it was possible not only to monitor both components simultaneously during their circulation phase but also to quantify accurately their amount accumulated within the different organs.
Nanodiamonds of detonation origin are promising delivery agents of anti-cancer therapeutic compounds in a whole organism like mouse, owing to their versatile surface chemistry and ultra-small 5 nm average primary size compatible with natural elimination routes. However, to date, little is known about tissue distribution, elimination pathways and efficacy of nanodiamonds-based therapy in mice. In this report, we studied the capacity of cationic hydrogenated detonation nanodiamonds to carry active small interfering RNA (siRNA) in a mice model of Ewing sarcoma, a bone cancer of young adults due in the vast majority to the EWS-FLI1 junction oncogene. Replacing hydrogen gas by its radioactive analog tritium gas led to the formation of labeled nanodiamonds and allowed us to investigate their distribution throughout mouse organs and their excretion in urine and feces. We also demonstrated that siRNA directed against EWS-FLI1 inhibited this oncogene expression in tumor xenografted on mice. This work is a significant step to establish cationic hydrogenated detonation nanodiamond as an effective agent for in vivo delivery of active siRNA.
This work describes the first thermally activated delayed fluorescence material enabling circularly polarized light emission through chiral perturbation. These new molecular architectures obtained through a scalable one-pot sequential synthetic procedure at room temperature (83% yield) display high quantum yield (up to 74%) and circularly polarized luminescence with an absolute luminescence dissymmetry factor, |glum|, of 1.3 × 10–3. These chiral molecules have been used as an emissive dopant in an organic light emitting diode exhibiting external quantum efficiency as high as 9.1%.
ConspectusRecently, hydrogen isotope exchange (HIE) reactions have experienced impressive development due to the growing importance of isotope containing compounds in various fields including materials and life sciences, in addition to their classical use for mechanistic studies in chemistry and biology. Tritium-labeled compounds are also of crucial interest to study the in vivo fate of a bioactive substance or in radioligand binding assays. Over the past few years, deuterium-labeled drugs have been extensively studied for the improvement of ADME (absorption, distribution, metabolism, excretion) properties of existing bioactive molecules as a consequence of the primary kinetic isotope effect. Furthermore, in the emergent "omic" fields, the need for new stable isotopically labeled internal standards (SILS) for quantitative GC- or LC-MS analyses is increasing. Because of their numerous applications, the development of powerful synthetic methods to access deuterated and tritiated molecules with either high isotope incorporation and/or selectivities is of paramount importance.HIE reactions allow a late-stage incorporation of hydrogen isotopes in a single synthetic step, thus representing an advantageous alternative to conventional multistep synthesis approaches which are time- and resource-consuming. Moreover, HIE reactions can be considered as the most fundamental C–H functionalization processes and are therefore of great interest for the chemists' community. Depending on the purpose, HIE reactions must either be highly regioselective or allow a maximal incorporation of hydrogen isotopes, sometimes both. In this context, metal-catalyzed HIE reactions are generally performed using either homogeneous or heterogeneous catalysis which may have considerable drawbacks including an insufficient isotope incorporation and a lack of chemo- and/or regioselectivity, respectively.Over the past 6 years, we have shown that nanocatalysis can be considered as a powerful tool to access complex labeled molecules (e.g., pharmaceuticals, peptides and oligonucleotides) via regio- and chemoselective or even enantiospecific labeling processes occurring at the surface of metallic nanoclusters (Ru or Ir). Numerous heterocyclic (both saturated and unsaturated) and acyclic scaffolds have been labeled with an impressive functional group tolerance, and highly deuterated compounds or high molar activity tritiated drugs have been obtained. An insight into mechanisms has also been provided by theoretical calculations to explain the regioselectivities of the isotope incorporation. Our studies have suggested that undisclosed key intermediates, including 4- and 5-membered dimetallacycles, account for the particular regioselectivities observed during the process, in contrast to the 5- or 6-membered metallacycle key intermediates usually encountered in homogeneous catalysis. These findings together with the important number of available coordination sites explain the compelling reactivity of metal nanoparticles, in between homogeneous and heterogeneous catalysis. They represent innovative tools combining the advantages of both methods for the isotopic labeling and activation of C–H bonds of complex molecules.
The paper presents complementary approaches based on experimental and numerical works to address the behavior of tokamak-relevant tungsten particles loaded with tritium. Sampling of particles inside the WEST tokamak have been realized thanks to an in situ particle collection system called Duster Box. This method allowed to identify various types of tungsten particles among them spherical shaped micro-particles between 5 µm and 30 µm in diameter. Based on these results a surrogate tungsten powder has been provided by means of spheroidization process and sieving method. Moreover, the powder tritium retention capacity was measured and specific activities of 90 MBq.g−1 and 280 MBq.g−1 were obtained for particles with 17 µm and 11.5 µm median diameters, respectively. Considering such tritium activities trapped in the particles, Monte-Carlo simulation were performed to estimate the electrostatic self-charging rates and the corresponding electrical charge carried by the radioactive tungsten dust. The results of these experiments provide robust data for the assessment of the dispersion of toxic/radioactive material in the environment that could follow a loss of containment.
Abstract The second step in the sequence includes the intramolecular Diels—Alder reaction of an aza‐quinodimethane unit with the unsaturated side chain to produce the target compounds as single trans‐isomers.
The control of tritium inventory and permeation is crucial for the safe operation of fusion reactors. To measure these phenomena, a novel tritium experiment is introduced and used to measure tritium permeation through Eurofer97 at room temperature, with several possibilities for the downstream conditions: air or water and overhead air. A pre-loading condition was shown to be required for this experiment. This direct comparison revealed that tritium is preferentially found in the water phase and secondarily in the air phase.
