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EJNMMI Radiopharmacy and Chemistry Apr 20246-Bromo-7-[C]methylpurine ([C]BMP) is a radiotracer for positron emission tomography (PET) to measure multidrug resistance-associated protein 1 (MRP1) transport activity...
BACKGROUND
6-Bromo-7-[C]methylpurine ([C]BMP) is a radiotracer for positron emission tomography (PET) to measure multidrug resistance-associated protein 1 (MRP1) transport activity in different tissues. Previously reported radiosyntheses of [C]BMP afforded a mixture of 7- and 9-[C]methyl regioisomers. To prepare for clinical use, we here report an improved regioselective radiosynthesis of [C]BMP, the results of a non-clinical toxicity study as well as human dosimetry estimates based on mouse PET data.
RESULTS
[C]BMP was synthesised by regioselective N-methylation of 6-bromo-7H-purine (prepared under good manufacturing practice) with [C]methyl triflate in presence of 2,2,6,6-tetramethylpiperidine magnesium chloride in a TRACERlab™ FX2 C synthesis module. [C]BMP was obtained within a total synthesis time of approximately 43 min in a decay-corrected radiochemical yield of 20.5 ± 5.2%, based on starting [C]methyl iodide, with a radiochemical purity > 99% and a molar activity at end of synthesis of 197 ± 130 GBq/μmol (n = 28). An extended single-dose toxicity study conducted in male and female Wistar rats under good laboratory practice after single intravenous (i.v.) administration of unlabelled BMP (2 mg/kg body weight) revealed no test item related adverse effects. Human dosimetry estimates, based on dynamic whole-body PET data in female C57BL/6J mice, suggested that an i.v. injected activity amount of 400 MBq of [C]BMP will deliver an effective dose in the typical range of C-labelled radiotracers.
CONCLUSIONS
[C]BMP can be produced in sufficient amounts and acceptable quality for clinical use. Data from the non-clinical safety evaluation showed no adverse effects and suggested that the administration of [C]BMP will be safe and well tolerated in humans.
PubMed: 38683266
DOI: 10.1186/s41181-024-00265-z -
Chemosphere Jun 20241,2-dichloropropane (1,2-DCP) and 1,2,3-trichloropropane (1,2,3-TCP) are hazardous chemicals frequently detected in groundwater near agricultural zones due to their...
1,2-dichloropropane (1,2-DCP) and 1,2,3-trichloropropane (1,2,3-TCP) are hazardous chemicals frequently detected in groundwater near agricultural zones due to their historical use in chlorinated fumigant formulations. In this study, we show that the organohalide-respiring bacterium Dehalogenimonas alkenigignens strain BRE15 M can grow during the dihaloelimination of 1,2-DCP and 1,2,3-TCP to propene and allyl chloride, respectively. Our work also provides the first application of dual isotope approach to investigate the anaerobic reductive dechlorination of 1,2-DCP and 1,2,3-TCP. Stable carbon and chlorine isotope fractionation values for 1,2-DCP (Ɛ = -13.6 ± 1.4 ‰ and Ɛ = -27.4 ± 5.2 ‰) and 1,2,3-TCP (Ɛ = -3.8 ± 0.6 ‰ and Ɛ = -0.8 ± 0.5 ‰) were obtained resulting in distinct dual isotope slopes (Λ = 0.5 ± 0.1, Λ = 4 ± 2). However direct comparison of Λ among different substrates is not possible and investigation of the C and Cl apparent kinetic isotope effects lead to the hypothesis that concerted dichloroelimination mechanism is more likely for both compounds. In fact, whole cell activity assays using cells suspensions of the Dehalogenimonas-containing culture grown with 1,2-DCP and methyl viologen as electron donor suggest that the same set of reductive dehalogenases was involved in the transformation of 1,2-DCP and 1,2,3-TCP. This study opens the door to the application of isotope techniques for evaluating biodegradation of 1,2-DCP and 1,2,3-TCP, which often co-occur in groundwaters near agricultural fields.
Topics: Biodegradation, Environmental; Propane; Water Pollutants, Chemical; Groundwater; Chlorine; Carbon Isotopes; Halogenation; Chloroflexi; Chemical Fractionation; 2,4-Dichlorophenoxyacetic Acid
PubMed: 38679177
DOI: 10.1016/j.chemosphere.2024.142170 -
International Journal of Molecular... Apr 2024Sodium chloride (NaCl) activates Th17 and dendritic cells in hypertension by stimulating serum/glucocorticoid kinase 1 (SGK1), a sodium sensor. Memory T cells also play...
Sodium chloride (NaCl) activates Th17 and dendritic cells in hypertension by stimulating serum/glucocorticoid kinase 1 (SGK1), a sodium sensor. Memory T cells also play a role in hypertension by infiltrating target organs and releasing proinflammatory cytokines. We tested the hypothesis that the role of T cell SGK1 extends to memory T cells. We employed mice with a T cell deletion of SGK1, SGK1 × tgCD4 mice, and used SGK1 mice as controls. We treated the mice with L-NAME (0.5 mg/mL) for 2 weeks and allowed a 2-week washout interval, followed by a 3-week high-salt (HS) diet (4% NaCl). L-NAME/HS significantly increased blood pressure and memory T cell accumulation in the kidneys and bone marrow of SGK1 mice compared to knockout mice on L-NAME/HS or groups on a normal diet (ND). SGK1 mice exhibited increased albuminuria, renal fibrosis, and interferon-γ levels after L-NAME/HS treatment. Myography demonstrated endothelial dysfunction in the mesenteric arterioles of SGK1 mice. Bone marrow memory T cells were adoptively transferred from either mouse strain after L-NAME/HS administration to recipient CD45.1 mice fed the HS diet for 3 weeks. Only the mice that received cells from SGK1 donors exhibited increased blood pressure and renal memory T cell infiltration. Our data suggest a new therapeutic target for decreasing hypertension-specific memory T cells and protecting against hypertension.
Topics: Animals; Male; Mice; Blood Pressure; Hypertension; Immediate-Early Proteins; Kidney; Mice, Inbred C57BL; Mice, Knockout; NG-Nitroarginine Methyl Ester; Protein Serine-Threonine Kinases; Sodium Chloride, Dietary; T-Lymphocytes
PubMed: 38673987
DOI: 10.3390/ijms25084402 -
International Journal of Molecular... Apr 2024Over the past three decades, the synthesis of new ionic liquids (ILs) and the expansion of their use in newer applications have grown exponentially. From the beginning...
Over the past three decades, the synthesis of new ionic liquids (ILs) and the expansion of their use in newer applications have grown exponentially. From the beginning of this vertiginous period, it was known that many of them were hygroscopic, which in some cases limited their use or altered the value of their measured physical properties with all the problems that this entails. In an earlier article, we addressed the hygroscopic grade achieved by the ILs 1-ethyl-3-methylimidazolium chloride, 1-ethyl-3-methylimidazolium bromide, 1-ethyl-3-methylimidazolium methyl sulfate, 1-ethyl-3-methylimidazolium ethyl sulfate, 1-ethyl-3-methylpyridinium ethyl sulfate, 1-ethyl-3-methylimidazolium tosylate, 1-ethyl-3-methylimidazolium tetrafluoroborate, 1-butyl-3-methylimidazolium tetrafluoroborate, 1-dodecyl-3-methylimidazolium tetrafluoroborate, 1-butyl-3-methylpyridinium tetrafluoroborate, 1-butyl-1-methylpiperidinium bis(trifluoromethyl sulfonyl)imide, 1-methyl-1-propylpyrrolidinium bis(trifluoromethyl sulfonyl)imide, 1-butyl-1-methylpyrrolidinium bis(trifluoromethyl sulfonyl)imide, and methyl trioctyl ammonium bis(trifluoromethyl sulfonyl)imide. The objective was to determine the influence of the chemical nature of the compounds, exposed surface area, sample volume, agitation, and temperature. For this purpose, we exposed the samples to abrupt increases in relative humidity from 15 to 100% for days in an atmosphere chamber and then proceeded with the reverse process in a gentle manner. The results show that the sorption of water from the atmosphere depends on the nature of the IL, especially the anion, with the chloride anion being of particular importance (chloride ≫ alkyl sulfates~bromide > tosylate ≫ tetrafluoroborate). It has also been proven for the EMIM-ES and EMIM-BF samples that the mechanism of moisture capture is both absorption and adsorption, and that the smaller the exposed surface area, the higher the ratio of the mass of water per unit area.
Topics: Ionic Liquids; Anions; Cations; Imidazoles; Wettability; Water
PubMed: 38673814
DOI: 10.3390/ijms25084229 -
Journal of Agricultural and Food... May 2024In the past, taste interactions between sodium chloride (NaCl) and bitter tastants were investigated in human sensory studies, and the suppression of bitterness by...
In the past, taste interactions between sodium chloride (NaCl) and bitter tastants were investigated in human sensory studies, and the suppression of bitterness by sodium was observed. It is currently not clear if this phenomenon occurs predominantly peripherally or centrally and if the effect is general or only particular bitter compounds are blocked. Therefore, the influence of NaCl at the receptor level was tested by functional expression assays using four out of ∼25 human bitter taste receptors together with prototypical agonists. It was observed that NaCl affected only the responses of particular bitter taste receptor-compound pairs, whereas other bitter responses remained unchanged upon variations of the sodium concentrations. Among the tested receptors, TAS2R16 showed a reduction in signaling in the presence of NaCl. This demonstrates that for some receptor-agonist pairs, NaCl reduces the activation at the receptor level, whereas central effects may dominate the NaCl-induced bitter taste inhibition for other substances.
Topics: Humans; HEK293 Cells; Receptors, G-Protein-Coupled; Sodium Chloride; Taste; Taste Buds
PubMed: 38663860
DOI: 10.1021/acs.jafc.3c08775 -
The Science of the Total Environment Jun 2024The global concern regarding the ubiquitous presence of plastics in the environment has led to intensified research on the impact of these materials on wildlife. In the...
The global concern regarding the ubiquitous presence of plastics in the environment has led to intensified research on the impact of these materials on wildlife. In the Australian context, marsupials represent a unique and diverse group of mammals, yet little is known about their exposures to plastics. This study aimed to assess the contamination levels of seven common plastics (i.e., polystyrene (PS), polycarbonate (PC), poly-(methyl methacrylate) (PMMA), polypropylene (PP), polyethylene terephthalate (PET), polyethylene (PE), and polyvinyl chloride (PVC)) in both the diet and faeces of kangaroos, wallabies and koalas sampled from a sanctuary in Northeastern Australia. Quantitative analysis was performed by pressurized liquid extraction followed by double-shot microfurnace pyrolysis coupled to gas chromatography mass spectrometry. Interestingly, the analysis of the food and faeces samples revealed the absence of detectable plastic particles; with this preliminary finding suggesting a relatively limited exposure of captive Australian marsupials to plastics. This study contributes valuable insights into the current state of plastic contamination in Australian marsupials, shedding light on the limited exposures and potential risks, and highlighting the need for continued monitoring and conservation efforts. The results underscore the importance of proactive measures to mitigate plastic pollution and protect vulnerable wildlife populations in Australia's unique ecosystems.
Topics: Animals; Plastics; Marsupialia; Australia; Environmental Pollutants; Environmental Monitoring; Feces; Environmental Exposure
PubMed: 38663626
DOI: 10.1016/j.scitotenv.2024.172716 -
Scientific Reports Apr 2024The effects of sulfate salts under low and high salinity conditions and pH of 3.5-11 on interfacial tension (IFT) reduction and IL adsorption using resinous (RSO) and...
The effects of sulfate salts under low and high salinity conditions and pH of 3.5-11 on interfacial tension (IFT) reduction and IL adsorption using resinous (RSO) and asphaltenic (8 wt/wt%) synthetic oils are investigated. The measurements showed the increasing effect of pH on the IFT of RSO/DW from 23.5 to 27.3 mN/m (pH = 3.5 → 7) in the first place and a reducing effect (0.4 mN/m) if pH = 7 → 11. Using a high concentration of 50,000 ppm for MgSO, and NaSO revealed an extensive IFT reduction for a pH value of 11 with the value of 0.20 mN/m for NaSO. The measured IFT values showed the significant impact of IL (500 ppm) on the IFT (minimum value of 0.01 mN/m for RSO/50,000 NaSO + 500 ppm 1-decyl-3-methyl imidazolium triflate ([Cmim][TfO])) for pH = 11. The IL adsorption measurements showed the role of in-situ surfactant production (saponification process) on the 1-decyl-3-methyl imidazolium chloride ([Cmim][Cl]) and [Cmim][TfO] adsorption reduction from 3.67 to 2.33 and 4.21 to 3.34 mg IL/g rock, respectively. The performed core flooding experiments using the optimum chemical formulation showed the possibility of tertiary oil recovery with maximum oil recovery of 28.8% based on original oil in place in the presence of 500 ppm.
PubMed: 38658645
DOI: 10.1038/s41598-024-59472-y -
Bioresources and Bioprocessing Aug 2023Ursodeoxycholic acid (UDCA) is not only safer than chenodeoxycholic acid in the treatment of hepatobiliary diseases, but also has a wide range of applications in Acute...
Ursodeoxycholic acid (UDCA) is not only safer than chenodeoxycholic acid in the treatment of hepatobiliary diseases, but also has a wide range of applications in Acute Kidney Injury and Parkinson's Disease. The purpose of this experiment is to improve the conversion rate of 7-ketocholic acid (7K-LCA) and the yield of ursodeoxycholic acid in aprotic solvents during electrochemical reduction process. Three aprotic solvents were investigated as electrolytes. 1,3-Dimethyl-2-imidazolidinone (DMI) has a stable five-membered ring structure, and 7K-LCA has undergone two nucleophilic reactions and "Walden" inversion, the 7K-LCK was stereoselectively reduced to UDCA. Hexamethylphosphoramide (HMPA) and 1,3-methyl-3,4,5,6-Tetrahydro-2(1H)-pyrimidinone (DMPU) can be attacked by chloride ions to produce by-products. Molecular orbital theory-based simulations were conducted to study the reducibility of three aprotic solvents [hexamethylphosphoramide (HMPA), 1,3-methyl-3,4,5,6-Tetrahydro-2(1H)-pyrimidinone (DMPU), and 1,3-Dimethyl-2-imidazolidinone (DMI)] in combination with experiments. Choose the best solvent based on the simulation results, the electrolysis reaction can be carried out by applying current and voltage when lithium chloride is used as electrolytes. Calculations using Materials Studio showed that Cu, Pb, Hg-Cu, and Ni exhibited the highest binding energies to the substrate in this system. Using Cu as the electrode when the solvent is a 1:1 mix of DMI and HMPA, the conversion rate of 7-ketocholic acid (could reach 98%, the yield of ursodeoxycholic acid was up to 80%. Under the same conditions, linear voltammetry was performed on the electrochemical workstation to study the electrolysis behavior, and the obtained results were consistent with the experiment.
PubMed: 38647780
DOI: 10.1186/s40643-023-00668-x -
Materials (Basel, Switzerland) Apr 2024A novel hyperbranched polymer with polyacrylamide side chains (HAPAM) was synthesized by aqueous solution polymerization using acrylic acid, acrylamide,...
A novel hyperbranched polymer with polyacrylamide side chains (HAPAM) was synthesized by aqueous solution polymerization using acrylic acid, acrylamide, 2-acrylamido-2-methyl-1-propanesulfonic acid, hydrophobic monomer of dimethyl octadecyl ammonium chloride, and the homemade skeleton monomer of modified-M as raw materials and (NH)SO-NaHSO as initiator. The molecular structure, functional groups, and surface morphology of HAPAM were characterized by Fourier transform infrared spectroscopy, nuclear magnetic resonance hydrogen spectroscopy, and scanning electron microscopy. It was found that the performance of HAPAM solution was higher than that of ordinary polyacrylamide solution in terms of thickening ability, shearing resistance, thermal endurance, salt-resistance, resistance-coefficient and residual-resistance-coefficient, ability to reduce interfacial tension between polymer solution and crude oil, and oil-displacement-efficiency. In particular, the enhanced oil recovery of the HAPAM solution was 13.03%, and the improvement of shearing resistance and immunity to chromatographic separation were simultaneously achieved by the HAPAM solution. These results indicate that the successful synthesis of the novel HAPAM opens a promising strategy for developing new high-performance oil-displacing polymers.
PubMed: 38612133
DOI: 10.3390/ma17071619 -
Molecules (Basel, Switzerland) Mar 2024Easy-to-handle -hydroxyacridinecarbimidoyl chloride hydrochlorides were synthesized as convenient nitrile oxide precursors in the preparation of...
Easy-to-handle -hydroxyacridinecarbimidoyl chloride hydrochlorides were synthesized as convenient nitrile oxide precursors in the preparation of 3-(acridin-9/2-yl)isoxazole derivatives via 1,3-dipolar cycloaddition with terminal alkynes, 1,1-dichloroethene, and acrylonitrile. Azirines with an acridin-9/2-yl substituent attached directly or via the 1,2,3-triazole linker to the azirine C2 were also synthesized. The three-membered rings of the acridine-azirine hybrids were found to be resistant to irradiation in the UV/visible boundary region, despite their long-wave absorption at 320-420 nm, indicating that the acridine moiety cannot be used as an antenna to transfer light energy to generate nitrile ylides from azirines for photoclick cycloaddition. The acridine-isoxazole hybrids linked at the C9-C3 or C2-C3 atoms under blue light irradiation underwent the addition of such hydrogen donor solvents, such as, toluene, -xylene, mesitylene, 4-chlorotoluene, THF, 1,4-dioxane, or methyl -butyl ether (MTBE), to the acridine system to give the corresponding 9-substituted acridanes in good yields. The synthesized acridine-azirine, acridine-isoxazole, and acridane-isoxazole hybrids exhibited cytotoxicity toward both all tested cancer cell lines (HCT 116, MCF7, and A704) and normal cells (WI-26 VA4).
PubMed: 38611817
DOI: 10.3390/molecules29071538