Hierarchical Porous Amidoximated Metal-Organic Framework for Highly Efficient Uranium Extraction.

With the rapid development of industry and technology, high-efficiency extraction of uranium from seawater is a research hotspot from the aspect of nuclear energy development. Herein, a new amidoximated metal-organic framework (UiO-66-DAMN-AO) constructed through a novel organic ligand of 2-diaminomaleonitrile-terephthalic acid (BDC-DAMN) is designed via one-step post-synthetic methods (PSM), which possess the merit of abundant multiaffinity sites, large specific surface area, and unique porous structure for efficient uranium extraction. Adopting one-step PSM can alleviate the destruction of structural stability and the reduction of the conversion rate of amidoxime groups. Meanwhile, introducing the BDC-DAMN ligand with abundant multiaffinity sites endow UiO-66-DAMN-AO with excellent adsorption ability (Qm = 426.3 mg g-1) and selectivity. Interestingly, the UiO-66-DAMN-AO has both micropores and mesopores, which may be attributed to the partial etching of UiO-66-DAMN-AO during the amidoximation. The presence of mesopores improves the mass transfer rate of UiO-66-DAMN-AO and provides more exposed active sites, favoring the adsorption of uranium on UiO-66-DAMN-AO. Thus, this study provides a feasible strategy for modifying metal-organic framework (MOFs) with plentiful amidoxime groups and the promising prospect for MOF-based materials to adsorb uranium from ocean.

mARC dependent NO synthesis activates CanA-Relish-AMPs signal pathway in Eriocheir sinensis during nitrite stress.

As a signal molecule, nitric oxide (NO) can induce the production of antimicrobial peptides (AMPs) in invertebrate innate immunity and is produced through NO synthase (NOS) oxidation or nitrite reduction. Although the role of NOS-derived NO has been extensively studied, studies on nitrite-dependent NO are relatively scarce. In this study, we identified a mitochondrial amidoxime reducing component (mARC), a kind of nitrite reductase, in Eriocheir sinensis. Under nitrite stress, the expression level of EsmARC in the intestine of E. sinensis increased, and the production of NO increased. Furthermore, EsmARC knockdown resulted in a remarkable decrease in NO concentration. These findings indicate that nitrite stress induces the expression of mARC, which promotes the production of NO in E. sinensis. In addition, the expression levels of AMPs in the intestine were upregulated under nitrite stress. Moreover, EsmARC knockdown resulted in the downregulated expression of AMPs. EsmARC plays a positive role in the synthesis of AMPs under nitrite stress. Calcineurin subunit A (CanA) is a serine/threonine protein phosphatase involved in the process by which NO regulates the expression of AMPs. EsCanA knockdown significantly inhibited the transcription of EsRelish and the expression of AMPs under nitrite stress, and EsRelish silencing resulted in the downregulated expression levels of AMPs under nitrite stress. These results indicate that nitrite stress activates the CanA-Relish-AMP pathway in E. sinensis. In summary, mARC-dependent NO synthesis activates the CanA-Relish-AMP signal pathway in E. sinensis during nitrite stress. This research provides novel insights into the relationship between nitrite stress and NO-dependent immune signal activation in crustaceans.

Design and Fabrication of Hypercrosslinked Covalent Organic Adsorbents for Selective Uranium Extraction.

Uranium detection and extraction are necessary for the ecological environment as the growing demand for nuclear energy. Hence, exploring stable materials with excellent performance in uranium extraction and detection is highly desired. Herein, by amidoxime-functionalizing tetrafluoroterephthalonitrile (TFTPN) crosslinked hydroquinone (bP), phloroglucinol (tP), and 4,4',4″-trihydroxytriphenylmethane (tBP), three covalent organic polymers (COPs) bPF-AO, tPF-AO, and tBPF-AO with different crosslinked architectures are fabricated. Uranium extraction and detection related to the difference in molecule construction were systemically investigated, giving some reference for the rational design and fabrication of advanced materials for the removal and monitoring of uranium in the environment. The tPF-AO with a compact steric structure achieves the highest theoretical maximum adsorption capacity of 578.9 ± 15.2 mg g-1 and the best recyclability. The scattering electron center and U(VI) selective binding sites endow tBPF-AO with excellent capability in selective detection for U(VI), with a limit of detection of 24.2 nmol L-1, which is well below the standard for U(VI) in drinking water of the World Health Organization (WHO). Moreover, the COPs possess prominent physicochemical stability and recyclability, and more importantly, the PAE-based COPs are derived from inexpensive industry materials with easy processing methods, providing an efficient and economical way for the detection and adsorption of uranium.

Novel piperine-carboximidamide hybrids: design, synthesis, and antiproliferative activity via a multi-targeted inhibitory pathway.

A new series of piperine-carboximidamide hybrids VIa-k was developed as a new cytotoxic agent targeting EGFR, BRAF, and CDK2. The antiproliferative effect against four cancer cells was investigated against erlotinib. Hybrids VIc, VIf, VIg, VIi, and VIk have the highest antiproliferative activity. Compounds VIc, VIf, VIg, VIi, and VIk inhibited EGFR with IC50 values ranging from 96 to 127 nM. Compounds VIf and VIk had the most potent inhibitory activity as BRAFV600E (IC50 = 49 and 40 nM, respectively) and were discovered to be potent inhibitors of cancer cell proliferation (GI50 = 44 and 35 nM against four cancer cell lines, respectively). Compound VIk, the most effective derivative as an antiproliferative agent, demonstrated potent anti-CDK2 action with an IC50 value of 12 nM, which is 1.5-fold more potent than the reference dinaciclib. Finally, VIc, VIf, and VIk have a high capacity to inhibit LOX-IMVI cell line survival.

Efficient adsorption of low-concentration uranium from aqueous solutions by biomass composite aerogel.

The development of nuclear energy has led to the depletion of uranium resources and now presents the challenge of treating radioactive wastewater. Extracting uranium from seawater and nuclear wastewater has been identified as an effective strategy for addressing these issues. However, extracting uranium from nuclear wastewater and seawater is still extremely challenging. In this study, an amidoxime-modified feather keratin aerogel (FK-AO aerogel) was prepared using feather keratin for efficient uranium adsorption. The FK-AO aerogel showed an impressive adsorption capacity of 585.88 mg·g-1 in an 8 ppm uranium solution, with a calculated maximum adsorption capacity of 990.10 mg·g-1. Notably, the FK-AO aerogel demonstrated excellent selectivity for U(VI) in simulated seawater that contained coexisting heavy metal ions. In a uranium solution having a salinity of 35 g·L-1 and a concentration of 0.1-2 ppm, the FK-AO aerogel achieved a uranium removal rate of greater than 90 %, indicating its effectiveness in adsorbing uranium in environments having high salinity and low concentration. This suggests that FK-AO aerogel is an ideal adsorbent for extracting uranium from seawater and nuclear wastewater, and it is also expected that it could be used in industrial applications for extracting uranium from seawater.

A biomass fiber adsorbent grafted with phosphate/amidoxime for efficient extraction of uranium from seawater by synergistic effect.

There are approximately 4 billion tons of uranium in the ocean, which is unmatched by the surface. Nevertheless, it's very challenging to extract uranium from the ocean due to the exceedingly low concentration of uranium in the ocean (about 3.3 µg L-1) as well as high salinity level. Current methods are often limited by selectivity, sustainability, economics, etc. Herein, phosphoric acid group and amidoxime group were grafted to skin collagen fibers through " initiated access" to design a new uranium extraction material, abbreviated as CGPA. Through laboratory simulation experiments, it is concluded that the maximum adsorption capacity of CGPA for uranium reaches 263.86 mg g-1. It has high adsorption, selectivity, and reusability for uranium. In the actual seawater extraction experiment, CGPA obtained 29.64 µg of uranium after extracting 10.0 L of seawater, and the extraction rate was 90.1%. The adsorbent has excellent effects in kinetics, selectivity, extraction capacity, renewability, etc. In the extraction of uranium from seawater, and is an economically feasible and industrially expandable adsorbent.

Synthesis of a boron-containing amidoxime reagent and its application to synthesize functionalized oxadiazole and quinazolinone derivatives.

Herein, we report the design, synthesis and application of a borylated amidoxime reagent for the direct synthesis of functionalized oxadiazole and quinazolinone derivatives. This reagent exhibits broad synthetic utility to obtain a variety of biologically relevant drug-like molecules. It can be easily prepared at large scale from relatively inexpensive reagents, and can undergo facile transformations to obtain target compounds. The developed amidoxime reagent was synthesized from 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzonitrile and hydroxyl amine hydrochloride using N,N-diisopropylethylamine as a base in ethanol under reflux conditions. Overall advantages include a metal-free route to boronated oxadiazoles, quinazolinone derivatives, and restriction of the multistep sequences. Importantly, the boron-rich pharmacophore derived compounds were obtained through an efficient and inexpensive strategy.

Amidoxime functionalized chitosan for uranium sequestration in vivo.

Amidoxime functionalized chitosan (AC) was recommended as a chelator for uranium sequestration in vivo in this study, and the structure-activity relationship was also explored. Compared with ZnNa3-DTPA, which was a commercial uranium mobilization drug, AC exhibited excellent biocompatibility and uranium removal efficiency, whether by injection or orally, which could reduce the amounts of uranium deposited in kidneys and femurs by up to 43.6% and 32.3%. In particular, ACs still possessed the ability to mobilize uranium in vivo even if administration was delayed for 72 h.

MTARC1 and HSD17B13 Variants Have Protective Effects on Non-Alcoholic Fatty Liver Disease in Patients Undergoing Bariatric Surgery.

The severity of hepatic steatosis is modulated by genetic variants, such as patatin-like phospholipase domain containing 3 (PNPLA3) rs738409, transmembrane 6 superfamily member 2 (TM6SF2) rs58542926, and membrane-bound O-acyltransferase domain containing 7 (MBOAT7) rs641738. Recently, mitochondrial amidoxime reducing component 1 (MTARC1) rs2642438 and hydroxysteroid 17-beta dehydrogenase 13 (HSD17B13) rs72613567 polymorphisms were shown to have protective effects on liver diseases. Here, we evaluate these variants in patients undergoing bariatric surgery. A total of 165 patients who underwent laparoscopic sleeve gastrectomy and intraoperative liver biopsies and 314 controls were prospectively recruited. Genotyping was performed using TaqMan assays. Overall, 70.3% of operated patients presented with hepatic steatosis. NASH (non-alcoholic steatohepatitis) was detected in 28.5% of patients; none had cirrhosis. The increment of liver fibrosis stage was associated with decreasing frequency of the MTARC1 minor allele (p = 0.03). In multivariate analysis MTARC1 was an independent protective factor against fibrosis ≥ 1b (OR = 0.52, p = 0.03) and ≥ 1c (OR = 0.51, p = 0.04). The PNPLA3 risk allele was associated with increased hepatic steatosis, fibrosis, and NASH (OR = 2.22, p = 0.04). The HSD17B13 polymorphism was protective against liver injury as reflected by lower AST (p = 0.04) and ALT (p = 0.03) activities. The TM6SF2 polymorphism was associated with increased ALT (p = 0.04). In conclusion, hepatic steatosis is common among patients scheduled for bariatric surgery, but the MTARC1 and HSD17B13 polymorphisms lower liver injury in these individuals.

High-Capacity Amidoxime-Functionalized ß-Cyclodextrin/Graphene Aerogel for Selective Uranium Capture.

Uranium extraction from seawater is a grand challenge of mounting severity as the energy demand increases with a growing global population. An amidoxime-functionalized carboxymethyl ß-cyclodextrin/graphene aerogel (GDC) is developed for highly efficient and selective uranium extraction via a facile one-pot hydrothermal process. GDC reaches equilibrium in 1 h, and the maximum adsorption capacity calculated from Langmuir model is 654.2 mg/g. Benefiting from the chelation and complexation reaction, the obtained GDC has an excellent selectivity even when the competitive cations, anions, and oil pollutants exist. In addition, the aerogel possesses great mechanical integrity and remains intact after 10 compression cycles. Meanwhile, the GDC can be easily regenerated and maintains a high reusability of 87.3% after 10 adsorption-desorption cycles. It is worthwhile to mention that GDC exhibits an excellent extraction capacity of 19.7 mg/g within 21 days in natural seawater, which is greatly desired in uranium extraction from seawater.

Novel chalcone/aryl carboximidamide hybrids as potent anti-inflammatory via inhibition of prostaglandin E2 and inducible NO synthase activities: design, synthesis, molecular docking studies and ADMET prediction.

Two series of chalcone/aryl carboximidamide hybrids 4a-f and 6a-f were synthesised and evaluated for their inhibitory activity against iNOS and PGE2. The most potent derivatives were further checked for their in vivo anti-inflammatory activity utilising carrageenan-induced rat paw oedema model. Compounds 4c, 4d, 6c and 6d were proved to be the most effective inhibitors of PGE2, LPS-induced NO production, iNOS activity. Moreover, 4c, 4d, 6c and 6d showed significant oedema inhibition ranging from 62.21% to 78.51%, compared to indomethacin (56.27 ± 2.14%) and celecoxib (12.32%). Additionally, 4c, 6a and 6e displayed good COX2 inhibitory activity while 4c, 6a and 6c exhibited the highest 5LOX inhibitory activity. Compounds 4c, 4d, 6c and 6d fit nicely into the pocket of iNOS protein (PDB ID: 1r35) via the important amino acid residues. Prediction of physicochemical parameters exhibited that 4c, 4d, 6c and 6d had acceptable physicochemical parameters and drug-likeness. The results indicated that chalcone/aryl carboximidamides 4c, 4d, 6c and 6d, in particular 4d and 6d, could be used as promising lead candidates as potent anti-inflammatory agents.

Amidine- and Amidoxime-Substituted Heterocycles: Synthesis, Antiproliferative Evaluations and DNA Binding.

The novel 1,2,3-triazolyl-appended N- and O-heterocycles containing amidine 4-11 and amidoxime 12-22 moiety were prepared and evaluated for their antiproliferative activities in vitro. Among the series of amidine-substituted heterocycles, aromatic diamidine 5 and coumarine amidine 11 had the most potent growth-inhibitory effect on cervical carcinoma (HeLa), hepatocellular carcinoma (HepG2) and colorectal adenocarcinoma (SW620), with IC50 values in the nM range. Although compound 5 was toxic to non-tumor HFF cells, compound 11 showed certain selectivity. From the amidoxime series, quinoline amidoximes 18 and 20 showed antiproliferative effects on lung adenocarcinoma (A549), HeLa and SW620 cells emphasizing compound 20 that exhibited no cytostatic effect on normal HFF fibroblasts. Results of CD titrations and thermal melting experiments indicated that compounds 5 and 10 most likely bind inside the minor groove of AT-DNA and intercalate into AU-RNA. Compounds 6, 9 and 11 bind to AT-DNA with mixed binding mode, most probably minor groove binding accompanied with aggregate binding along the DNA backbone.

Leveraging Actinide Hydrolysis Chemistry for Targeted Th and U Separations using Amidoxime-Functionalized Poly(HIPE)s.

Polymerized high internal phase emulsions (poly(HIPE)s) are porous polymer monoliths whose synthesis can easily be tailored to allow incorporation of functional units. In this work, nitrile containing poly(HIPE)s have been prepared with either acrylonitrile (AN) or 4-cyanostyrene (4CS) comonomers. Post-synthetic modification of these nitrile-containing poly(HIPE)s yields their corresponding amidoximated analogues, which were studied for actinide uptake. These amidoxime-functionalized, porous polymers were shown to adsorb 95 % Th4+ species from aqueous solution within 30 minutes. In contrast to other amidoxime containing polymers the uptake of UO2 2+ in these poly(HIPE)s is lower under similar conditions. A critical analysis of actinide separations and high-energy X-ray scattering data provides insight into the polymers' selectivity, enabled by the uptake of multinuclear Th clusters.

Design, synthesis and molecular modeling of novel aryl carboximidamides and 3-aryl-1,2,4-oxadiazoles derived from indomethacin as potent anti-inflammatory iNOS/PGE2 inhibitors.

The development of NSAIDs/iNOS inhibitor hybrids is a new strategy for the treatment of inflammatory diseases by suppression of the overproduction of PGE2 and NO. A novel series of aryl carboximidamides 4a-g and their cyclized 3-aryl-1,2,4-oxadiazoles 5a-g counterparts derived from indomethacin 1 were synthesized. Most of the target compounds displayed lower LPS-induced NO production IC50 in RAW 264.7 cells and potent in vitro iNOS and PGE2 inhibitory activity than indomethacin. Moreover, in carrageenan-induced rat paw oedema method, most of them exhibited higher in vivo anti-inflammatory activity than the reference drug indomethacin. Notably, 4 hrs after carrageenan injection, compound 4a proved to be the most potent anti-inflammatory agent in this study, with almost two- and eight-fold more active than the reference drugs indomethacin (1) and celecoxib, respectively. Compound 4a proved to be inhibitor to LPS-induced NO production, iNOS activity and PGE2 with IC50 of 10.70 µM, 2.31 µM, and 29 nM; respectively. Compounds 4a and 5b possessed the lowest ulcerogenic liabilities (35% and 38%, respectively) compared to 1. Histopathological analysis revealed that compounds 4a and 5b demonstrated reduced degeneration and healing of ulcers. Molecular docking studies into the catalytic binding pocket of the iNOS protein receptor (PDB ID: 1r35) showed good correlation with the obtained biological results. Parameters of Lipinski's rule of five and ADMET analysis were calculated where compound 4a had reasonable drug-likeness with acceptable physicochemical properties so it could be used as promising orally absorbed anti-inflammatory therapy and entitled to be used as future template for further investigations.

Preparation and modification of forcespun polypropylene nanofibers for adsorption of uranium (VI) from simulated seawater.

In this paper, polypropylene (PP) nanofibers were prepared using the melt forcespinning technology by a handmade device. Then, the surface of PP nanofibers was grafted through the high energy electron beams (EB) pre-irradiation method by acrylonitrile and methacrylic acid monomers with grafting percentage of 145.55%. The 92% of grafted cyano functional groups on nanofibers were converted to amidoxime groups, then modified by an alkaline solution. Characterization and surface morphology of nanofibers were investigated by Fourier Transform Infrared (FTIR) spectroscopy and scanning electron microscopy (SEM). The produced adsorbent was used to adsorb U(VI) ions from simulated seawater. The maximum adsorption was 83.24 mg/g in the optimal time of 60 min and optimal pH of 4. The optimum desorption efficiency was 80% in HCl 0.5 M. The kinetic data in optimum conditions showed that the adsorption followed an S-shaped kinetic model. The Adsorption equilibrium studies presented S-shape isotherm model that confirmed the adsorption occurs both on the adsorbent surface and in its pores The thermodynamic studies indicated spontaneous adsorption of uranyl ions and the higher efficiency adsorption at higher temperatures. The selectivity of adsorbent for metal ions followed the order V(V)>U(VI)>CO(II)>Ni(II)>Fe(II). These results shows that the prepared and modified nanofibers in this work can be considered as an effective and promising adsorbents for removal of uranium ions from seawater with high efficiency.

Amidoximes and Oximes: Synthesis, Structure, and Their Key Role as NO Donors.

Nitric oxide (NO) is naturally synthesized in the human body and presents many beneficial biological effects; in particular on the cardiovascular system. Recently; many researchers tried to develop external sources to increase the NO level in the body; for example by using amidoximes and oximes which can be oxidized in vivo and release NO. In this review; the classical methods and most recent advances for the synthesis of both amidoximes and oximes are presented first. The isomers of amidoximes and oximes and their stabilities will also be described; (Z)-amidoximes and (Z)-oximes being usually the most energetically favorable isomers. This manuscript details also the biomimetic and biological pathways involved in the oxidation of amidoximes and oximes. The key role played by cytochrome P450 or other dihydronicotinamide-adenine dinucleotide phosphate (NADPH)-dependent reductase pathways is demonstrated. Finally, amidoximes and oximes exhibit important effects on the relaxation of both aortic and tracheal rings alongside with other effects as the decrease of the arterial pressure and of the thrombi formation.

A Dual-Surface Amidoximated Halloysite Nanotube for High-Efficiency Economical Uranium Extraction from Seawater.

By chemical cross-linking the amidoxime group onto dual-surfaces of natural ore materials, namely halloysite nanotubes (HNTs), an efficient adsorbent, AO-HNTs, is developed. AO-HNTs show high uranium adsorption capacity of 456.24 mg g-1 in 32 ppm uranium-spiked simulated seawater. In natural seawater, AO-HNTs reach the high uranium extraction capacity of 9.01 mg g-1 after 30 days' field test. The dual-surface amidoximated hollow nanotubular AO-HNTs exhibit more coordination active sites for uranium adsorption, which is attributed to the high and fast uranium adsorption capacity. Because of the stable natural ore structure, AO-HNTs also show long service life. Benefiting from the low cost of HNTs, the cost for uranium extraction from seawater is close to the uranium price in the spot uranium market, suggesting that AO-HNTs could be used for economical extraction of uranium from the oceans.

Tris-amidoximate uranyl complexes via η2 binding mode coordinated in aqueous solution shown by X-ray absorption spectroscopy and density functional theory methods.

The present study sheds some light on the long-standing debate concerning the coordination properties between uranyl ions and the amidoxime ligand, which is a key ingredient for achieving efficient extraction of uranium. Using X-ray absorption fine structure combined with theoretical simulation methods, the binding mode and bonding nature of a uranyl-amidoxime complex in aqueous solution were determined for the first time. The results show that in a highly concentrated amidoxime solution the preferred binding mode between UO22+ and the amidoxime ligand is η2 coordination with tris-amidoximate species. In such a uranyl-amidoximate complex with η2 binding motif, strong covalent interaction and orbital hybridization between U 5f/6d and (N, O) 2p should be responsible for the excellent binding ability of the amidoximate ligand to uranyl. The study was performed directly in aqueous solution to avoid the possible binding mode differences caused by crystallization of a single-crystal sample. This work also is an example of the simultaneous study of local structure and electronic structure in solution systems using combined diagnostic tools.

A BODIPY Based Fluorescent Probe for the Rapid Detection of Hypochlorite.

A new boron-dipyrromethene (BODIPY) fluorescent dye aimed at sensitively detecting hypochlorite anion (ClO-) has been designed, synthesized and characterized. The probe is comprised of a BODIPY fluorophore unit and a ClO- specific reactive group of amidoxime. The addition of hypochlorite results in a red-shift of absorption and emission spectra of the probe accompanied by a decrease of intensity and spectra changes (A500 and 1/I512) of the probe can achieve a good linearity to the concentration of ClO-. The fluorescence probe can react to ClO- rapidly (within 60 s) in a wide pH range (4-10) with high sensitivity (detection limit of 6.81 µM) and selectivity. The reaction mechanism has been proposed and confirmed by MS analysis, ClO- anion oxidizes amidoxime moiety to hydroxyl group and hydroxyl group is further oxidized to formyl group in the formation of a corresponding aldehyde compound. In addition, the probe has also been successfully applied to detect ClO- in tap water and river water samples by spiking a known amount of standard ClO-.

Study of Different Variants of Mo Enzyme crARC and the Interaction with Its Partners crCytb5-R and crCytb5-1.

The mARC (mitochondrial Amidoxime Reducing Component) proteins are recently discovered molybdenum (Mo) Cofactor containing enzymes. They are involved in the reduction of several N-hydroxylated compounds (NHC) and nitrite. Some NHC are prodrugs containing an amidoxime structure or mutagens such as 6-hydroxylaminopurine (HAP). We have studied this protein in the green alga Chlamydomonas reinhardtii (crARC). Interestingly, all the ARC proteins need the reducing power supplied by other proteins. It is known that crARC requires a cytochrome b5 (crCytb5-1) and a cytochrome b5 reductase (crCytb5-R) that form an electron transport chain from NADH to the substrates. Here, we have investigated NHC reduction by crARC, the interaction with its partners and the function of important conserved amino acids. Interactions among crARC, crCytb5-1 and crCytb5-R have been studied by size-exclusion chromatography. A protein complex between crARC, crCytb5-1 and crCytb5-R was identified. Twelve conserved crARC amino acids have been substituted by alanine by in vitro mutagenesis. We have determined that the amino acids D182, F210 and R276 are essential for NHC reduction activity, R276 is important and F210 is critical for the Mo Cofactor chelation. Finally, the crARC C-termini were shown to be involved in protein aggregation or oligomerization.