Pegylated Phosphine Ligands in Iridium(I) Catalyzed Hydrogen Isotope Exchange Reactions in Aqueous Buffers.

The synthesis of a water-soluble, phosphine-pegylated iridium(I) catalyst and its application in hydrogen isotope exchange (HIE) reactions in buffer is reported. The longer polyethylene glycol side chains on the phosphine increased the water solubility independently from the pH. HIE reactions of polar substrates in protic solvents were studied. DFT calculations gave further insights into the catalytic processes. The scope and limitation of the pegylated catalyst was studied in HIE reactions of several complex compounds in borax buffer at pH 9 and the best conditions were applied in a tritium experiment with the drug telmisartan.

Estimation of accumulation potential for tritium in olive flounder on exposure of treated water derived from Fukushima Daiichi Nuclear Power Station: Tritium transfer from seawater and food chain into organically bound tritium in the targeted fish.

This study estimated the accumulation potential of tritium, a major radionuclide released from the Fukushima Daiichi Nuclear Power Station (FDNPS), into the olive flounder as organically bound tritium (OBT) using a computer simulation model. In this estimation, two transfer pathways into the OBT were assumed: formation from tritiated water (HTO) in the tricarboxylic acid (TCA) cycle, and ingestion of OBT through the food chain (from phytoplankton, small fish, to the flounder). The food chain structure was reconstructed based on fish growth model. The OBT concentration in the flounder was estimated on three scenarios: Tritium was supplied to the flounder as only HTO in seawater (Scenario 1), as HTO in seawater and OBT formed from HTO in the small fish (Scenario 2), and as HTO in seawater and OBT accumulated in the small fish through the formation and ingestion of OBT in phytoplankton (Scenario 3). The estimated OBT concentrations in the flounder were in the following order: Scenario 3 > 2 > 1. The ratio of the estimated concentration in Scenario 1 to that in Scenario 3 reached a certain value (66 % after a year from the start of HTO exposure), indicating that the tritium transfer from the seawater into the flounder more significantly contributed to this concentration than ingestions of the small fish and the phytoplankton. Additionally, the difference between the estimations of Scenarios 1 and 2 is significantly larger than that between Scenarios 2 and 3. This suggests that phytoplankton contributed weakly to the OBT concentration in the flounder compared to the small fish.

Tritium and deuterium labelling of a kainate receptor antagonist and evaluation as a radioligand.

Kainate receptors play a crucial role in mediating synaptic transmission within the central nervous system. However, the lack of selective pharmacological tool compounds for the GluK3 subunit represents a significant challenge in studying these receptors. Recently presented compound 1 stands out as a potent antagonist of GluK3 receptors, exhibiting nanomolar affinity at GluK3 receptors and strongly inhibiting glutamate-induced currents at homomeric GluK1 and GluK3 receptors in HEK293 cells with Kb values of 65 and 39 nM, respectively. This study presents the synthesis of two potent GluK3-preferring iodine derivatives of compound 1, serving as precursors for radiolabelling. Furthermore, we demonstrate the optimisation of dehalogenation conditions using hydrogen and deuterium, resulting in [2H]-1, and demonstrate the efficient synthesis of the radioligand [3H]-1 with a specific activity of 1.48 TBq/mmol (40.1 Ci/mmol). Radioligand binding studies conducted with [3H]-1 as a radiotracer at GluK1, GluK2, and GluK3 receptors expressed in Sf9 and rat P2 membranes demonstrated its potential applicability for selectively studying native GluK3 receptors in the presence of GluK1 and 2-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor-blocking ligands.

Tritium-Labeled Nanodiamonds as an Instrument to Analyze Bioprosthetic Valve Coatings: A Case of Using a Nanodiamond Containing Coating on a Pork Aorta.

Coatings with xenogenic materials, made of detonation nanodiamonds, provide additional strength and increase elasticity. A functionally developed surface of nanodiamonds makes it possible to apply antibiotics. Previous experiments show the stability of such coatings; however, studies on stability in the bloodstream and calcification of the material in natural conditions have yet to be conducted. Tritium-labeled nanodiamonds (negative and positive) were obtained by the tritium activation method and used to develop coatings for a pork aorta to analyze their stability in a pig's bloodstream using a radiotracer technique. A chitosan layer was applied from a solution of carbonic acid under high-pressure conditions to prevent calcification. The obtained materials were used to prepare a porcine conduit, which was surgically stitched inside the pig's aorta for four months. The aorta samples, including nanodiamond-coated and control samples, were analyzed for nanodiamond content and calcium, using the radiotracer and ICP-AES methods. A histological analysis of the materials was also performed. The obtained coatings illustrate a high in vivo stability and low levels of calcification for all types of nanodiamonds. Even though we did not use additional antibiotics in this case, the development of infection was not observed for negatively charged nanodiamonds, opening up prospects for their use in developing coatings.

A method for tritiation of iboxamycin permits measurement of its ribosomal binding.

Hydrogen-tritium exchange is widely employed for radioisotopic labeling of molecules of biological interest but typically involves the metal-promoted exchange of sp2-hybridized carbon-hydrogen bonds, a strategy that is not directly applicable to the antibiotic iboxamycin, which possesses no such bonds. We show that ruthenium-induced 2'-epimerization of 2'-epi-iboxamycin in HTO (200 mCi) of low specific activity (10 Ci/g, 180 mCi/mmol) at 80 °C for 18 h affords after purification tritium-labeled iboxamycin (3.55 µCi) with a specific activity of 53 mCi/mmol. Iboxamycin displayed an apparent inhibition constant (Ki, app) of 41 ± 30 nM towards Escherichia coli ribosomes, binding approximately 70-fold more tightly than the antibiotic clindamycin (Ki, app = 2.7 ± 1.1 µM).

Tritium and Carbon-14 Contamination Reshaping the Microbial Community Structure, Metabolic Network, and Element Cycle in the Seawater Environment.

The potential ecological risks caused by entering radioactive wastewater containing tritium and carbon-14 into the sea require careful evaluation. This study simulated seawater's tritium and carbon-14 pollution and analyzed the effects on the seawater and sediment microenvironments. Tritium and carbon-14 pollution primarily altered nitrogen and phosphorus metabolism in the seawater environment. Analysis by 16S rRNA sequencing showed changes in the relative abundance of microorganisms involved in carbon, nitrogen, and phosphorus metabolism and organic matter degradation in response to tritium and carbon-14 exposure. Metabonomics and metagenomic analysis showed that tritium and carbon-14 exposure interfered with gene expression involving nucleotide and amino acid metabolites, in agreement with the results seen for microbial community structure. Tritium and carbon-14 exposure also modulated the abundance of functional genes involved in carbohydrate, phosphorus, sulfur, and nitrogen metabolic pathways in sediments. Tritium and carbon-14 pollution in seawater adversely affected microbial diversity, metabolic processes, and the abundance of nutrient-cycling genes. These results provide valuable information for further evaluating the risks of tritium and carbon-14 in marine environments.

Development of a Novel Passive Monitoring Technique to Showcase the 3D Distribution of Tritiated Water (HTO) Vapor in Indoor Air of a Nuclear Facility.

Tritiated water (HTO), a ubiquitous byproduct of the nuclear industry, is a radioactive contaminant of major concern for environmental authorities. Although understanding spatiotemporal heterogeneity of airborne HTO vapor holds great importance for radiological safety as well as diagnosing a reactor's status, comprehensive HTO distribution dynamics inside nuclear facilities has not been studied routinely yet due to a lack of appropriate monitoring techniques. For current systems, it is difficult to simultaneously achieve high representativeness, sensitivity, and spatial resolution. Here, we developed a passive monitoring scheme, including a newly designed passive sampler and a tailored analytical protocol for the first comprehensive 3D distribution characterization of HTO inside a nuclear reactor facility. The technique enables linear sampling in any environment at a one-day resolution and simultaneous preparation of hundreds of samples within 1 day. Validation experiments confirmed the method's good metrological properties and sensitivity to the HTO's spatial dynamics. The air in TU Wien's reactor hall exhibits a range of 3H concentrations from 75-946 mBq m-3 in the entire 3D matrix. The HTO release rate estimated by the mass-balance model (3199 ± 306 Bq h-1) matches the theoretical calculation (2947 ± 254 Bq h-1), suggesting evaporation as the dominant HTO source in the hall. The proposed method provides reliable and quality-controlled 3D monitoring at low cost, which can be adopted not only for HTO and may also inspire monitoring schemes of other indoor pollutants.

Changes in the Structure of Potato Virus A Virions after Limited in situ Proteolysis According to Tritium Labeling Data and Computer Simulation.

Coat proteins (CP) of the potato virus A virions (PVA) contain partially disordered N-terminal domains, which are necessary for performing vital functions of the virus. Comparative analysis of the structures of coat proteins (CPs) in the intact PVA virions and in the virus particles lacking N-terminal 32 amino acids (PVAΔ32) was carried out in this work based on the tritium planigraphy data. Using atomic-resolution structure of the potato virus Y potyvirus (PVY) protein, which is a homolog of the CP PVA, the available CP surfaces in the PVY virion were calculated and the areas of intersubunit/interhelix contacts were determined. For this purpose, the approach of Lee and Richards [Lee, B., and Richards, F. M. (1971) J. Mol. Biol., 55, 379-400] was used. Comparison of incorporation profiles of the tritium label in the intact and trypsin-degraded PVAΔ32 revealed position of the ΔN-peptide shielding the surface domain (a.a. 66-73, 141-146) and the interhelix zone (a.a. 161-175) of the PVA CP. Presence of the channels/cavities was found in the virion, which turned out to be partially permeable to tritium atoms. Upon removal of the ΔN-peptide, decrease in the label incorporation within the virion (a.a. 184-200) was also observed, indicating possible structural transition leading to the virion compactization. Based on the obtained data, we can conclude that part of the surface ΔN-peptide is inserted between the coils of the virion helix thus increasing the helix pitch and providing greater flexibility of the virion, which is important for intercellular transport of the viruses in the plants.

Thoughts, perceptions and concerns of coastal residents regarding the discharge of tritium-containing treated water from the Fukushima Daiichi Nuclear Power Plant into the Pacific Ocean.

BACKGROUND: As a part of the decontamination process after the Fukushima Daiichi Nuclear Power Plant accident of 2011, 1.32 million tonnes of tritium-containing water will be discharged from the power plant into the Pacific Ocean. Although radiobiological impacts of the treated water discharge on the public and the environment were reported to be minimal, Tomioka and Okuma locals expressed unease regarding the long-term recovery of their towns, which are economically dependent on the agricultural, fishery, and tourism sectors. This study presents thoughts, perceptions and concerns of Tomioka and Okuma locals regarding the discharge of FDNPP-treated water containing tritium into the Pacific Ocean to facilitate a more inclusive decision-making process that respects local stakeholder interests. METHODS: Conducted from November to December 2022, surveys were mailed to current residents and evacuees aged 20 years or older registered with the town councils. RESULTS: Out of 1268 included responses, 71.5% were from those > 65 years. 65.6% were unemployed, 76.2% routinely visited hospitals, and 85.5% did not live with children. 61% did not want to return to Okuma/Tomioka. Anxiety about radiation-related health effects (38.7%), consuming food produced in Okuma/Tomioka (48.0%) and genetic effects (45.3%) were low. >50% reported poor physical and mental health. 40% were acceptive, 31.4% were unsure, and 29.7% objected to the discharge plans. Multinomial regression analysis revealed that, compared to acceptive responders, those who objected were more likely to be female, unemployed, and have anxiety about radiation-related genetic effects and poor mental health. Unsure responders were similarly more likely to be female, anxious about radiation-related genetic effects and have poor mental health. CONCLUSION: The poor mental health of the locals, connected to high levels of risk perception and anxiety about the loss of economic opportunities related to the discharge plans, must be addressed. The 30-year discharge process could handicap local industries and hamper post-disaster socioeconomic recovery due to the circulation of false rumours among consumers. These results highlight the need to actively involve residents in the towns' recovery process to address local concerns. The focus should be on the judicious combination of transparent science with the human aspect of recovery and narratives highlighting dialogues between local stakeholders and experts to enable the locals and the general public to make informed decisions about their protection and future.

Tritium NMR: A compilation of data and a practical guide.

The present review is focused on experimental methods and structural applications of tritium NMR. It consists of five parts covering accordingly, introduction, brief overview, early (based on the papers appearing before 2000), more recent (based on the papers appeared in the interim of 2000 to 2015), and recent (based on the papers that appeared after 2015) reports. A special interest in this review is focused on practical aspects of tritium NMR spectroscopy, which is thoroughly illustrated by its numerous applications in chemistry and biochemistry.

Site-Specific Tritium Labeling at the Predefined Internal Position of the Chemically-Modified RNA.

In nucleic acid drug discovery, it is extremely important to develop a technology to understand the distribution in target organs and to trace the degradation process in the body in order to optimize the structure and improve the efficiency of the clinical trial process. Since nucleic acid drugs are essentially metabolically degraded into numerous fragments, labeling at the internal position is preferable to that at the terminus. Due to the high molar specific activity of tritium, various approaches for tritium-labeling have been studied for nucleic acid drugs. Nevertheless, a generally-applicable method for tritium labeling of the internal position of a nucleic acid has not been established. In this study, we have demonstrated a new and efficient method for site-specific tritium labeling of the cytosine base at a predefined internal position in nucleic acid drugs. This method was developed by the chemical modification of the cytosine 4-amino group with the pyridinyl vinyl keto group by the functionality-transfer reaction using the reactive oligodeoxynucleotide (ODN), followed by reduction with NaBT4. Applicability to a variety of chemical structures, such as 5-methyl cytosine, 2'-O-methyl, 2'-fluoro ribose derivatives, Locked/Bridged nucleic acid (LNA/BNA) derivatives, as well as phosphorothioate bonds, has been evidenced using nine oligoribonucleic acid (ORN) substrates. It has been clearly demonstrated that this method is an excellent method for tritium-labeling of nucleic acid with an average conversion efficiency of 74%, an average isolated labeling yield of 60%, and an average specific activity of 61 GBq/mmol. This method is expected to contribute to the preclinical absorption, distribution, metabolism, excretion (ADME) studies of nucleic acid drug candidates.

Enzymatic synthesis of halogen derivatives of L-phenylalanine and phenylpyruvic acid stereoselectively labeled with hydrogen isotopes in the side chain.

Halogenated, labeled with deuterium, tritium or doubly labeled with deuterium and tritium in the 3S position of the side chain isotopomers of L-phenylalanine and phenylpyruvic acid were synthesized. Isotopomers of halogenated L-phenylalanine were obtained by addition of ammonia from isotopically enriched buffer solution to the halogenated derivative of (E)-cinnamic acid catalyzed by phenylalanine ammonia lyase. Isotopomers of halogenated phenylpyruvic acid were obtained enzymatically by conversion of the appropriate isotopomer of halogenated L-phenylalanine in the presence of phenylalanine dehydrogenase. As a source of deuterium was used deuterated water, as a source of tritium was used a solution of highly diluted tritiated water. The labeling takes place in good yields and with high deuterium atom% abundance.

Small-scale two-dimensional liquid chromatography for a preparative re-purification of a highly labile tritium-labeled compound.

Tritium-labeled compounds are generally less stable than their non-labeled counterparts. This requires storage at low temperatures, a constant workflow of quality checks, and subsequent re-purifications. As the amount of tritium-labeled material is typically purified in the µg range, repeated injections on analytical-scale ultra high-performance liquid chromatography systems can provide high-resolution re-purification results. Yet, degradants can be undesirably included in the compound isolation because the amount of decomposition can vary dramatically depending on the structure. We report a case of a sensitive molecule that could not be isolated in pure form even though the chromatographic separation was successful. In this case, the use of a small-scale two-dimensional preparative liquid chromatography approach with a direct transfer interface to a second (trapping) column resulted in a highly pure compound (>98% radiochemical purity). This approach combines high chromatographic resolution, accurate control over the re-purification process, minimal sample manipulation, and higher overall safety for the handling of radioactive samples.

Novel Calibration Approach for Monitoring Aerosol Hydrogen Isotopes Using Laser-Induced Breakdown Spectroscopy for Molten Salt Reactor Off-Gas Streams.

Online monitoring is a key challenge for the continued development of molten salt reactor (MSR) technology. Laser-induced breakdown spectroscopy (LIBS) has previously been demonstrated to be a viable tool for monitoring aerosolized species and noble gases in real time, but the ability to discern varying isotopes in these streams has not yet been investigated for MSR applications. Tritium will form in MSRs from ternary fission and from (n,α)-reactions occurring in lithium-containing salts. This study compares three spectrometers of varying resolutions and types for measuring hydrogen isotope shifts in LIBS spectra of wetted filter paper. For each spectrometer, multivariate models were built (i.e., principal component regression, partial least squares regression, and multivariate curve resolution) to quantify the isotope ratio. The top models were then modified and corrected to apply the models to aerosol samples with varying isotope ratios. This novel calibration strategy offers an 82% reduction in volume of the calibration samples needed and is a more viable pathway for calibrating deployable LIBS systems. Lastly, this calibration model was compared with an all-aerosol trained model for monitoring hydrogen isotopes during a real-time test where the protium/deuterium ratio, along with representative salt species (i.e., lithium, sodium, and potassium) were adjusted dynamically. Results of this test validated the predictive capabilities of the transferred model and highlighted the capabilities of LIBS for real-time monitoring of MSR effluent streams.

Impact of the Fukushima Accident on 3H and 14C Environmental Levels: A Review of Ten Years of Investigation.

The investigation of the impact of the Fukushima accident is still going on although more than ten years have passed since the disaster. The main goal of this paper was to summarize the results of tritium and radiocarbon determinations in different environmental samples, possibly connected with the Fukushima Dai-ichi Nuclear Power Plant (FDNPP) accident. A document containing compiled data may serve as a solid basis for further research in the selected fields. To accomplish such effort, we went through dozens of relevant published papers, reporting 3H and 14C activity concentrations in precipitations, groundwater, seawater, river systems, tree rings, and, in some more extraordinary samples, such as herbaceous plants or debris from the damaged reactor buildings. As the referenced results would not be obtainable without adequate analytical techniques, the most common methods for routine measurement of tritium and radiocarbon concentrations are discussed as well. We believe that the correct identification of the affected environmental compartments could help quantify the released 3H and 14C activities and track their following fate, which could be especially important for plans to discharge contaminated water from the FDNPP in the upcoming years.

Hydrogeochemical and isotopic evolution of groundwater in shallow and deep aquifers of the Kabul Plain, Afghanistan.

Groundwater from shallow and deep aquifers are widely used for drinking, agricultural and industrial use in Kabul, the capital of Afghanistan. However, unplanned urbanization and rapid population growth has led to the installation of numerous unlicensed wells to meet the public demand. This has caused to extraction of huge amounts of groundwater from the subsurface and further deterioration of groundwater quality. Therefore, understanding the hydrogeochemical characteristics of groundwater in shallow aquifers and deep aquifers is imperative for sustainable management of the groundwater resource in Kabul Plain. Thus, in this study, we used a multi-parameter approach, involving hydrochemical and environmental isotopes to understand the geochemical evolution of entire groundwater system of the Kabul Plain including river and dam water. The results of this study show that shallow and deep aquifers are dominantly of Mg-(Ca)-HCO3 and Na-Cl water type, respectively. We observed that (1) water-rock interaction is the major contributing factor to the chemical compositions of groundwater in the Kabul Plain; (2) groundwater in deep aquifer is mainly influenced by silicate weathering, and dissolution of evaporitic and carbonate minerals and reverse cation exchange; (3) dissolution of carbonates and silicate weathering plays a pivotal role in the groundwater chemistry of shallow aquifer; (4) the stable isotopes of groundwater display that the shallow aquifer is principally recharged by river water and local precipitation; (5) the tritium analysis exhibited that groundwater of shallow aquifer was primarily recharged recently, whereas groundwater of deep aquifer is the mixture of pre 1953 with post 1953 groundwater. This study revealed that there are hydraulic interactions between the two aquifers and the deep aquifer is recharged through shallow aquifer. The findings of this study would be useful for Afghanistan's water authorities to develop an effective strategy for sustainable water resources management in the Kabul Basin.

Geochemical and isotopic tracers to define the aquifer's vulnerability: the case study of the alluvial multi-aquifer system of the Friulian plain.

The Friuli-Venezia Giulia Region (north of Italy) is characterized by the presence of high-quality freshwater resources which benefit local citizens, animals, environmental habitats, and also agriculture and production activities. Waters from wells, canal, and wastewater selected in the Fiume Veneto area, through a detailed lithological modeling, were sampled and analyzed to characterize them from a geochemical point of view. The chemical and isotopic characterization made it possible to establish provenance, and the average age of water used, making available the estimation of the relationships between recharge capacity and water use in the Fiume Vento area. The focus of this study is to define the average age of the resources based on the time required for the recharge contributions to compensate the losses induced by exploitation. The results made it possible to support the plans for a water balance using the provenance and average age of water sources for the protection of water reserves formed by the multi-aquifer system of the high and medium Friuli plain. The methodology applied has followed the legislation of the water directive considering the overexploitation due to unauthorized withdrawals of the sampling area.

Perfluoroalkyl and Polyfluoroalkyl Substances in Groundwater Used as a Source of Drinking Water in the Eastern United States.

In 2019, 254 samples were collected from five aquifer systems to evaluate perfluoroalkyl and polyfluoroalkyl substance (PFAS) occurrence in groundwater used as a source of drinking water in the eastern United States. The samples were analyzed for 24 PFAS, major ions, nutrients, trace elements, dissolved organic carbon (DOC), volatile organic compounds (VOCs), pharmaceuticals, and tritium. Fourteen of the 24 PFAS were detected in groundwater, with 60 and 20% of public-supply and domestic wells, respectively, containing at least one PFAS detection. Concentrations of tritium, chloride, sulfate, DOC, and manganese + iron; percent urban land use within 500 m of the wells; and VOC and pharmaceutical detection frequencies were significantly higher in samples containing PFAS detections than in samples with no detections. Boosted regression tree models that consider 57 chemical and land-use variables show that tritium concentration, distance to the nearest fire-training area, percentage of urban land use, and DOC and VOC concentrations are the top five predictors of PFAS detections, consistent with the hydrologic position, geochemistry, and land use being important controls on PFAS occurrence in groundwater. Model results indicate that it may be possible to predict PFAS detections in groundwater using existing data sources.

Synthesis of N-acetyl-l-aspartyl-l-glutamic acid; [3 H]NAAG.

[3 H]NAAG, N-acetyl-l-aspartyl-l-glutamic acid, has been widely used as a substrate in glutamate carboxypeptidase II (GCPII) reactions, either to determine the inhibitory constants at 50% inhibition (IC50 ) of novel compounds or to measure GCPII activities in different tissues harvested from various disease models. The importance of [3 H]NAAG, combined with its current commercial unavailability, prompted the development of a reliable eight-step synthetic procedure towards [3 H2 ]NAAG starting from commercially available pyroglutamate. Pure [3 H]NAAG of high molar activity (49.8 Ci/mmol) and desired stereochemistry was isolated in high radiochemical yield (67 mCi) and radiochemical purity (>99%). The identity was confirmed by mass spectrometry and co-injection with unlabeled reference.

µRA-A New Compact Easy-to-Use Raman System for All Hydrogen Isotopologues.

We have developed a new compact and cost-efficient Laser-Raman system for the simultaneous measurement of all six hydrogen isotopologues. The focus of this research was set on producing a tool that can be implemented in virtually any existing setup providing in situ process control and analytics. The "micro Raman (µRA)" system is completely fiber-coupled for an easy setup consisting of (i) a spectrometer/CCD unit, (ii) a 532 nm laser, and (iii) a commercial Raman head coupled with a newly developed, tritium-compatible all-metal sealed DN16CF flange/Raman window serving as the process interface. To simplify the operation, we developed our own software suite for instrument control, data acquisition, and data evaluation in real-time. We have given a detailed description of the system, showing the system's capabilities in terms of the lower level of detection, and presented the results of a dedicated campaign using the accurate reference mixtures of all of the hydrogen isotopologues benchmarking µRA against two of the most sensitive Raman systems for tritium operation. Due to its modular nature, modifications that allow for the detection of various other gas species can be easily implemented.