90 research outputs found

    Iridium-Catalyzed Enantioselective Transfer Hydrogenation of 1,1-Dialkylethenes with Ethanol: Scope and Mechanism

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    Despite half a century’s advance in the field of transition-metal-catalyzed asymmetric alkene hydrogenation, the enantioselective hydrogenation of purely alkyl-substituted 1,1-dialkylethenes has remained an unmet challenge. Herein, we describe a chiral PCNOx-pincer iridium complex for asymmetric transfer hydrogenation of this alkene class with ethanol, furnishing all-alkyl-substituted tertiary stereocenters. High levels of enantioselectivity can be achieved in the reactions of substrates with secondary/primary and primary/primary alkyl combinations. The catalyst is further applied to the redox isomerization of disubstituted alkenols, producing a tertiary stereocenter remote to the resulting carbonyl group. Mechanistic studies reveal a dihydride species, (PCNOx)Ir(H)2, as the catalytically active intermediate, which can decay to a dimeric species (κ3-PCNOx)IrH(μ-H)2IrH(κ2-PCNOx) via a ligand-remetalation pathway. The catalyst deactivation under the hydrogenation conditions with H2 is much faster than that under the transfer hydrogenation conditions with EtOH, which explains why the (PCNOx)Ir catalyst is effective for the transfer hydrogenation but ineffective for the hydrogenation. The suppression of di-to-trisubstituted alkene isomerization by regioselective 1,2-insertion is partly responsible for the success of this system, underscoring the critical role played by the pincer ligand in enantioselective transfer hydrogenation of 1,1-dialkylethenes. Moreover, computational studies elucidate the significant influence of the London dispersion interaction between the ligand and the substrate on enantioselectivity control, as illustrated by the complete reversal of stereochemistry through cyclohexyl-to-cyclopropyl group substitution in the alkene substrates

    Iridium-Catalyzed Enantioselective Transfer Hydrogenation of 1,1-Dialkylethenes with Ethanol: Scope and Mechanism

    No full text
    Despite half a century’s advance in the field of transition-metal-catalyzed asymmetric alkene hydrogenation, the enantioselective hydrogenation of purely alkyl-substituted 1,1-dialkylethenes has remained an unmet challenge. Herein, we describe a chiral PCNOx-pincer iridium complex for asymmetric transfer hydrogenation of this alkene class with ethanol, furnishing all-alkyl-substituted tertiary stereocenters. High levels of enantioselectivity can be achieved in the reactions of substrates with secondary/primary and primary/primary alkyl combinations. The catalyst is further applied to the redox isomerization of disubstituted alkenols, producing a tertiary stereocenter remote to the resulting carbonyl group. Mechanistic studies reveal a dihydride species, (PCNOx)Ir(H)2, as the catalytically active intermediate, which can decay to a dimeric species (κ3-PCNOx)IrH(μ-H)2IrH(κ2-PCNOx) via a ligand-remetalation pathway. The catalyst deactivation under the hydrogenation conditions with H2 is much faster than that under the transfer hydrogenation conditions with EtOH, which explains why the (PCNOx)Ir catalyst is effective for the transfer hydrogenation but ineffective for the hydrogenation. The suppression of di-to-trisubstituted alkene isomerization by regioselective 1,2-insertion is partly responsible for the success of this system, underscoring the critical role played by the pincer ligand in enantioselective transfer hydrogenation of 1,1-dialkylethenes. Moreover, computational studies elucidate the significant influence of the London dispersion interaction between the ligand and the substrate on enantioselectivity control, as illustrated by the complete reversal of stereochemistry through cyclohexyl-to-cyclopropyl group substitution in the alkene substrates

    Evaluation of [<sup>18</sup>F]Favipiravir in Rodents and Nonhuman Primates (NHP) with Positron Emission Tomography

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    The COVID-19 pandemic has posed a significant challenge to global public health. In response, the search for specific antiviral drugs that can effectively treat the disease caused by the SARS-CoV-2 virus has become a priority. While significant progress has been made in this regard, much work remains to address this ongoing crisis effectively. Favipiravir is an antiviral drug initially developed for the treatment of influenza and has received approval for emergency use for COVID-19 in many countries. A better understanding of the biodistribution and pharmacokinetics of Favipiravir in vivo would facilitate the development and translation of clinical antiviral drugs for COVID-19. Herein, we report the evaluation of [18F]Favipiravir in naive mice, transgenic mice models of Alzheimer’s disease, and nonhuman primates (NHP) with positron emission tomography (PET). The [18F]Favipiravir was obtained in an overall decay-corrected radiochemical yield of 29% with a molar activity of 25 GBq/µmol at the end of synthesis (EOS). PET imaging in naive mice, transgenic mice models of Alzheimer’s disease, and nonhuman primates revealed a low initial brain uptake, followed by a slow washout of [18F]Favipiravir in vivo. The [18F]Favipiravir was eliminated by a combination of hepatobiliary and urinary excretion. The low brain uptake was probably attributed to the low lipophilicity and low passive permeability of the drug. We hope this proof-of-concept study will provide a unique feature to study antiviral drugs using their corresponding isotopologues by PET

    Bioresource Upgrade for Sustainable Energy, Environment, and Biomedicine

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    Abstract We conceptualize bioresource upgrade for sustainable energy, environment, and biomedicine with a focus on circular economy, sustainability, and carbon neutrality using high availability and low utilization biomass (HALUB). We acme energy-efficient technologies for sustainable energy and material recovery and applications. The technologies of thermochemical conversion (TC), biochemical conversion (BC), electrochemical conversion (EC), and photochemical conversion (PTC) are summarized for HALUB. Microalgal biomass could contribute to a biofuel HHV of 35.72 MJ Kg−1 and total benefit of 749 $/ton biomass via TC. Specific surface area of biochar reached 3000 m2 g−1 via pyrolytic carbonization of waste bean dregs. Lignocellulosic biomass can be effectively converted into bio-stimulants and biofertilizers via BC with a high conversion efficiency of more than 90%. Besides, lignocellulosic biomass can contribute to a current density of 672 mA m−2 via EC. Bioresource can be 100% selectively synthesized via electrocatalysis through EC and PTC. Machine learning, techno-economic analysis, and life cycle analysis are essential to various upgrading approaches of HALUB. Sustainable biomaterials, sustainable living materials and technologies for biomedical and multifunctional applications like nano-catalysis, microfluidic and micro/nanomotors beyond are also highlighted. New techniques and systems for the complete conversion and utilization of HALUB for new energy and materials are further discussed

    Equibiaxial Planar Tension Test Method and the Simulation Analysis for Hyperelastic EAP Membrane

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    The equibiaxial planar tension test is an important method for determining the mechanical properties of hyperplastic membranes, and it is also critical to designing an effective equibiaxial tension test rig to meet experimental accuracy requirements. However, any analysis addressing the accuracy of this test is not reported in the literature. In this paper, an equibiaxial planar tension apparatus is proposed for conducting single-corner-point tension tests on hyperelastic electroactive polymer (EAP) membranes. The experimental data were compared with those obtained from two-corner-point-fixed tension tests and fitted with nonlinear material models, and the model’s parameters were also evaluated. Finally, the widely-used finite element software ABAQUS was employed to simulate equibiaxial planar tension methods and investigate the impact of clamping mode and point number on test accuracy as well as the uniformity of overall deformation. The test results indicate that the stress-strain curves for the two tensions remain consistent across small stretch ratios. However, as the stretch ratio increases (about λ>2.25) in two-corner-point-fixed tension, stress shielding may lead to a degradation of strain uniformity and result in greater stresses than single-corner-point tension. Additionally, both the three-parameter Yeoh model and the four-parameter Ogden model can provide an accurate description of the EAP membrane material. The simulation results indicate that the axial strain variation amplitudes remain below 5% within a region spanning approximately 80% of the specimen’s overall length from its center to edge and even below 1% within a region spanning 85% in the single-corner-point tension; stress inaccuracies increase with stretch ratio, while the calculated error is about 2.1% when λ=4 in the single-corner-point tension test, which has the smallest stress error among the tests; when the number of tension points is increased, the overall deformation becomes more sufficient, and the test accuracy improves as well. The conclusions drawn from this paper will be beneficial in designing equibiaxial planar tension test rigs and analyzing their accuracy and uniformity of deformation

    Ecosystem Service Synergies Promote Ecological Tea Gardens: A Case Study in Fuzhou, China

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    Exploring the trade-off/synergy among ecosystem services (ESs) of agroecosystems could provide effective support for improving agricultural resilience for sustainable development. The construction of ecological tea gardens is emerging, aims to achieve a win-win situation for the tea industry and ecological environment protection. However, the effect of ES trade-offs/synergies on tea production is still not clear. In this study, we selected Fuzhou city, China, as a case study and explored the relationship among tea production and ESs in 2010 and 2020. Integrated Valuation of Ecosystem Services and Trade-offs (InVEST) and Intelligent Urban Ecosystem Management System (IUEMS) models were used to assess the ecosystem (dis)services, which were tea production, water yield, soil retention, net primary productivity (NPP), climate regulation, soil erosion and carbon emissions. Then, the sum of trade-off/synergy coefficients of ESs (Cts) were defined to reveal the trade-off/synergy in tea gardens and areas except tea gardens (ETG areas). K-means clustering was used to assess the spatiotemporal change of traditional tea garden and ecological tea garden, reflecting the effect of ecological tea garden construction. The results showed that: (1) the high-value areas of tea production were mainly distributed in Lianjiang County, with yields up to 3.6 t/ha, and the low-value areas in Yongtai County, with yields from 0.1–1.0 t/ha. Other ESs showed spatial heterogeneity. (2) The trade-offs in ETG areas intensified from 2010 to 2020, with Cts decreasing from −0.28 to −0.73, and the synergy in tea garden was at risk of decline, with Cts decreasing from 4.46 to 1.02. (3) From 2010 to 2020, 96.72% of traditional tea gardens (Area I) were transformed into ecological tea gardens (Areas IV and V). (4) Further, we classified the tea garden into five zones based on tea yield, with Zone I as the low tea yield areas and Zone V as the highest. From Zone I to Zone V, the Cts increased from 2.6 to 7.5 in 2010, and from 1.9 to 6.5 in 2020, respectively. These results demonstrate the effectiveness of the construction of ecological tea gardens in Fuzhou and provide a reference for subsequent studies on the ESs of tea gardens and governance of ecological tea gardens

    Long Noncoding RNAs in Ovarian Cancer—Functions and Clinical Applications

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    Long noncoding RNAs (lncRNAs) are RNA molecules with a length of more than 200 nt that have been discovered in recent years. LncRNAs can participate in regulating gene expression and various biological activities through multiple pathways, such as at the epigenetic level, transcriptional level, and posttranscriptional level. In recent years, with the increasing understanding of lncRNAs, a large number of studies have shown that lncRNAs are closely related to ovarian cancer and participate in its occurrence and development, providing a new method to investigate ovarian cancer. In this review, we analyzed and summarized the relationship between various lncRNAs and ovarian cancer in terms of occurrence, development, and clinical significance, in order to provide a theoretical basis for basic research and clinical application of ovarian cancer

    Synthesis and Biological Evaluation of Enantiomerically Pure (R)- and (S)-[18F]OF-NB1 for Imaging the GluN2B Subunit-Containing NMDA Receptors

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    : GluN2B subunit-containing N-methyl-d-aspartate (NMDA) receptors have been implicated in various neurological disorders. Nonetheless, a validated fluorine-18 labeled positron emission tomography (PET) ligand for GluN2B imaging in the living human brain is currently lacking. The aim of this study was to develop a novel synthetic approach that allows an enantiomerically pure radiosynthesis of the previously reported PET radioligands (R)-[18F]OF-NB1 and (S)-[18F]OF-NB1 as well as to assess their in vitro and in vivo performance characteristics for imaging the GluN2B subunit-containing NMDA receptor in rodents. A novel synthetic approach was successfully developed, which allows for the enantiomerically pure radiosynthesis of (R)-[18F]OF-NB1 and (S)-[18F]OF-NB1 and the translation of the probe to the clinic. While both enantiomers were selective over sigma2 receptors in vitro and in vivo, (R)-[18F]OF-NB1 showed superior GluN2B subunit specificity by in vitro autoradiography and higher volumes of distribution in the rodent brain by small animal PET studies

    Development of Novel <sup>11</sup>C‑Labeled Selective Orexin‑2 Receptor Radioligands for Positron Emission Tomography Imaging

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    Orexin 2 receptors (OX2R) represent a vital subtype of orexin receptors intricately involved in the regulation of wakefulness, arousal, and sleep–wake cycles. Despite their importance, there are currently no positron emission tomography (PET) tracers available for imaging the OX2R in vivo. Herein, we report [11C]1 ([11C]OX2-2201) and [11C]2 ([11C]OX2-2202) as novel PET ligands. Both compounds 1 (Ki = 3.6 nM) and 2 (Ki = 2.2 nM) have excellent binding affinity activities toward OX2R and target selectivity (OX2/OX1 > 600 folds). In vitro autoradiography in the rat brain suggested good to excellent in vitro binding specificity for [11C]1 and [11C]2. PET imaging in rat brains indicated that the low brain uptake of [11C]2 may be due to P-glycoprotein and/or breast cancer resistance protein efflux interaction and/or low passive permeability. Continuous effort in medicinal chemistry optimization is necessary to improve the brain permeability of this scaffold

    Evaluation of [18F]RoSMA-18-d6 as a CB2 PET Radioligand in Nonhuman Primates.

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    The cannabinoid type 2 receptor (CB2) has been implicated in a variety of central and peripheral inflammatory diseases, prompting significant interest in the development of CB2-targeted diagnostic and therapeutic agents. A validated positron emission tomography (PET) radioligand for imaging CB2 in the living human brain as well as in peripheral tissues is currently lacking. As part of our research program, we have recently identified the trisubstituted pyridine, [18F]RoSMA-18-d6, which proved to be highly suitable for in vitro and in vivo mapping of CB2 in rodents. The aim of this study was to assess the performance characteristics of [18F]RoSMA-18-d6 in nonhuman primates (NHPs) to pave the way for clinical translation. [18F]RoSMA-18-d6 was synthesized from the respective tosylate precursor according to previously reported procedures. In vitro autoradiograms with NHP spleen tissue sections revealed a high binding of [18F]RoSMA-18-d6 to the CB2-rich NHP spleen, which was significantly blocked by coincubation with the commercially available CB2 ligand, GW405833 (10 μM). In contrast, no specific binding was observed by in vitro autoradiography with NHP brain sections, which was in agreement with the notion of a CB2-deficient healthy mammalian brain. In vitro findings were corroborated by PET imaging experiments in NHPs, where [18F]RoSMA-18-d6 uptake in the spleen was dose-dependently attenuated with 1 and 5 mg/kg GW405833, while no specific brain signal was observed. Remarkably, we observed tracer uptake and retention in the NHP spinal cord, which was reduced by GW405833 blockade, pointing toward a potential utility of [18F]RoSMA-18-d6 in probing CB2-expressing cells in the bone marrow. If these observations are substantiated in NHP models of enhanced leukocyte proliferation in the bone marrow, [18F]RoSMA-18-d6 may serve as a valuable marker for hematopoietic activity in various pathologies. In conclusion, [18F]RoSMA-18-d6 proved to be a suitable PET radioligand for imaging CB2 in NHPs, supporting its translation to humans
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