Zn-Mediated Fragmentation of N-Alkoxyphthalimides Enabling the Synthesis of gem-Difluoroalkenes.

Zn-mediated generation of alkoxyl radicals from N-alkoxyphthalimides emerged as an efficient approach for forming diverse and valuable alkyl radicals through ß-scission or a hydrogen atom transfer process. The alkyl radical species can be further trapped by α-trifluoromethyl alkenes to construct a series of gem-difluoroalkenes.

Polyoxometalate solution passivation enabling dendrite-free and high-performance zinc anodes in aqueous zinc-ion batteries.

Zinc metal anodes in aqueous electrolytes commonly face challenges such as dendrite growth and undesirable side reactions, limiting their application in the field of aqueous zinc-ion batteries (AZIBs) for energy storage. Drawing inspiration from industrial practices involving molybdenum salt solutions for metal modification, a polyoxometalate solution was formulated as a passivation solution for zinc anodes (referred to as MO solution). The formed passivation layer, referred to as the MO layer, exhibited a uniform and protective nature with a thickness of approximately 10 µm. The experimental results demonstrated that this passivation layer effectively suppressed side reactions at the zinc anode interface, as evidenced by lower corrosion current density for MO-Zn anodes. Additionally, the newly plated Zn was uniformly deposited atop the MO layer, ensuring coating integrity and inhibiting dendrite growth. As a result, under more demanding conditions such as a larger current of 8 mA cm-2, the MO-Zn anode displayed an extended cycle life exceeding 420 h in a symmetric battery, with an overpotential as low as 98 mV. This performance significantly outperformed that of commercially available pure Zn foils (with a cycle life of 60 h and an overpotential of 192 mV). Notably, a self-made Na-doped V2O5 served as the cathode (referred to as NaVO), forming the MO-Zn//NaVO full battery. Even under high current test conditions of 2 A/g, the specific capacity of the MO-Zn//NaVO full battery remained substantial at 152.83 mAh/g after 1000 cycles. Furthermore, pouch batteries assembled with NaVO//MO-Zn successfully illuminated small bulbs. This study offers a viable optimization strategy for AZIB anodes and demonstrates the potential of using polyoxometalate solution for etching zinc anodes to inhibit dendrite growth and interfacial corrosion of zinc metal anodes.

Persulfate promoted carbamoylation of N-arylacrylamides and N-arylcinnamamides with 4-carbamoyl-Hantzsch esters.

Carbamoyl-Hantzsch esters were used as carbamoyl radical precursors for oxidative carbamoylation of N-arylacrylamides and N-arylcinnamamides in the presence of inexpensive persulfates. This protocol can be applied to a broad range of substrates with various functional groups, providing a variety of 3,3-disubstituted oxindoles and 3,4-disubstituted dihydroquinolin-2(1H)-ones in moderate to good yields via an intermolecular addition/cyclization process.

Safety, Tolerability, and Pharmacokinetics of Recombinant Human Neuregulin-1 in Healthy Chinese Subjects.

BACKGROUND: We investigated the safety, tolerability, and pharmacokinetics of intravenous recombinant human Neuregulin-1 (rhNRG-1), a DNA recombinant protein for the treatment of chronic heart failure, in healthy Chinese volunteers following single and multiple dose administration. METHODS AND RESULTS: To evaluate the safety and tolerance after single-dosing escalation, 28 subjects were divided into six groups (0.2, 0.4, 0.8, 1.2, 1.6, and 2.4 µg/kg) to receive an intravenous (IV) infusion of rhNRG-1 over 10 min by a randomized, open-label design. Only the 1.2 µg/kg dose group obtained pharmacokinetic parameters: Cmax was 7.645 (24.21) ng/mL, AUC0-t was 97.088 (21.41) min·ng/mL. To assess the safety and pharmacokinetics after multiple-dosing, 32 subjects were divided into four groups (0.2, 0.4, 0.8, and 1.2 µg/kg) to receive a 10-min IV infusion of rhNRG-1 for five consecutive days. After multiple dosing of 1.2 µg/kg, the Cmax value at day 5 was 8.838 (51.6) ng/mL and the AUC0-t value at day 5 was 109.890 (32.99) min·ng/mL. RhNRG-1 is rapidly cleared from the blood and has a short t1/2 of about 10 min. The adverse events related to rhNRG-1 mainly included flat or inverted T wave and gastrointestinal reactions, all of which were mild. CONCLUSIONS: It is concluded that rhNRG-1 is safe and well tolerated in healthy Chinese subjects at the dosing levels used in this study. The severity and frequency of adverse events did not increase with the prolongation of administration time. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry ( http://www.chictr.org.cn ) Identifier No. ChiCTR2000041107.

Cross-dehydrogenative Coupling of N-Aryl Tetrahydroisoquinolines Catalyzed by an Anthraquinone-containing Polymeric Photosensitizer.

This work reports the photocatalytic application of an anthraquinone-containing polymeric photosensitizer (AQ-PHEMA) in the visible light-induced cross-dehydrogenative-coupling of N-aryl tetrahydroisoquinolines with several nucleophiles, including nitromethane, 1-methyl-2-alkyl ketone and dialkyl (aryl) phosphine oxide. The results revealed that the reaction could be catalyzed by AQ-PHEMA efficiently to afford a series of 1-substituted-2-aryl-1,2,3,4-tetrahydroisoquinolines in good to excellent yields with nice substrate tolerance under aerobic conditions at room temperature. The practical application potential was also showcased by a gram-scale synthesis. More importantly, the utilization of AQ-PHEMA as a heterogeneous photosensitizer also showed nice recyclability and reusability of the catalyst, whereas AQ-PHEMA can be easily separated and reused for at least 8 times without significant loss of photocatalytic activity.

Photoredox Generation of N-Centered Hydrazonyl Radicals Enables the Construction of Dihydropyrazole-Fused gem-Difluoroalkenes.

An efficient visible-light-promoted N-radical-mediated tandem radical cyclization/defluorinated alkylation of ß,γ-unsaturated hydrazones, and α-trifluoromethyl alkenes is described. This protocol provides a general and effective route to synthesize various dihydropyrazole-fused gem-difluoroalkenes at moderate to excellent yields under redox-neutral, metal-free, and mild conditions.

Mn(III)-Mediated Radical Cyclization of o-Alkenyl Aromatic Isocyanides with Boronic Acids: Access to N-Unprotected 2-Aryl-3-cyanoindoles.

The synthesis of N-unprotected 2-aryl-3-cyanoindoles was realized via the Mn(III)-mediated radical cascade cyclization of o-alkenyl aromatic isocyanides with boronic acids. A possible mechanism involving a sequential intermolecular radical addition, intramolecular cyclization, and cleavage of the C-C bond under mild reaction conditions is proposed. Mechanism studies show that H2O or O2 might provide the oxygen source for the elimination of benzaldehyde.

Ruthenium(II)-Catalyzed C-C/C-N Coupling of 2-Arylquinazolinones with Vinylene Carbonate: Access to Fused Quinazolinones.

In this work, ruthenium(II)-catalyzed C-C/C-N annulation of 2-arylquinazolinones with vinylene carbonate is reported to synthesize fused quinazolinones. This catalytic system tolerates a wide range of substrates with excellent functional-group compatibility. In this transformation, the vinylene carbonate acts as an ethynol surrogate without any external oxidant involved. Furthermore, preliminary mechanistic studies were conducted, and a plausible catalytic cycle was also proposed.

Synthesis of gem-Difluoroalkenes via Zn-Mediated Decarboxylative/Defluorinative Cross-Coupling.

An efficient and mild Zn-mediated decarboxylative/defluorinative alkylation of α-trifluoromethyl alkenes using N-hydroxyphthalimide esters as radical precursors was developed. Several α-trifluoromethyl alkenes were readily coupled to a wide range of primary, secondary, and tertiary radicals, affording the desired gem-difluoroethylenes in moderate to excellent yields. This reaction protocol was also successfully applied to the construction of complex molecules such as the bioactive natural dehydroabietic acid and glycosyl groups bearing the gem-difluoroethylene moiety.

Synthesis of pyrazolo[1,5-c]quinazoline derivatives through the copper-catalyzed domino reaction of o-alkenyl aromatic isocyanides with diazo compounds.

A novel copper-catalyzed domino reaction between o-alkenyl aromatic isocyanides and diazo compounds has been developed under mild reaction conditions. Various o-alkenyl aromatic isocyanides were prepared from readily available reactants. The reaction provides a general and efficient method for the synthesis of pyrazolo[1,5-c]quinazolines by the formation of two rings and three new bonds in a single step from readily available acyclic starting materials. A mechanism involving a tandem (3+2) cyclization/elimination/intramolecular aza-addition sequence was proposed.

Plastic pollution in croplands threatens long-term food security.

Plastic pollution is a global concern given its prevalence in aquatic and terrestrial ecosystems. Studies have been conducted on the distribution and impact of plastic pollution in marine ecosystems, but little is known on terrestrial ecosystems. Plastic mulch has been widely used to increase crop yields worldwide, yet the impact of plastic residues in cropland soils to soil health and crop production in the long term remained unclear. In this paper, using a global meta-analysis, we found that the use of plastic mulch can indeed increase crop yields on average by 25%-42% in the immediate season due to the increase of soil temperature (+8%) and moisture (+17%). However, the unabated accumulation of film residues in the field negatively impacts its physicochemical properties linked to healthy soil and threatens food production in the long term. It has multiple negative impacts on plant growth including crop yield (at the mean rate of -3% for every additional 100 kg/ha of film residue), plant height (-2%) and root weight (-5%), and soil properties including soil water evaporation capacity (-2%), soil water infiltration rate (-8%), soil organic matter (-0.8%) and soil available phosphorus (-5%) based on meta-regression. Using a nationwide field survey of China, the largest user of plastic mulch worldwide, we found that plastic residue accumulation in cropland soils has reached 550,800 tonnes, with an estimated 6%-10% reduction in cotton yield in some polluted sites based on current level of plastic residue content. Immediate actions should be taken to ensure the recovery of plastic film mulch and limit further increase in film residue loading to maintain the sustainability of these croplands.

Synthesis of Monofluoroalkenes through Visible-Light-Promoted Defluorinative Alkylation of gem-Difluoroalkenes with 4-Alkyl-1,4-dihydropyridines.

In this study, a facile and efficient method to synthesize monofluoroalkenes by photoredox catalytic defluorinative alkylation of gem-difluoroalkenes with 4-alkyl-1,4-dihydropyridines under mild conditions (room temperature) is described. This novel strategy is applicable for a broad range of gem-difluoroalkene substrates with good functional group tolerance and a variety of 4-alkyl-1,4-dihydropyridines (including primary, secondary, and even tertiary alkyl radicals). Moreover, it also allows the challenging radical coupling with glycosyl-based 4-alkyl-1,4-dihydropyridines (DHPs) to synthesize monofluoroalkenylated saccharides.

Anti-inflammatory effect of fucoxanthin on dextran sulfate sodium-induced colitis in mice.

The anti-inflammatory activities of fucoxanthin, a marine carotenoid derived from the macroalgae and microalgae, have been demonstrated in the previous studies. However, the effect of fucoxanthin on ulcerative colitis (UC), an inflammatory bowel disease, was still unclear. In this study, we evaluated the in vivo anti-inflammatory effect of fucoxanthin on dextran sulfate sodium(DSS)-induced colitis in mice. Fucoxanthin at the doses of 50 and 100 mg/kg/day significantly protected against DSS-induced gradual loss of body weight, exhibited inhibitory effects on the DSS-induced increase of disease activity index and colon shortening. Moreover, fucoxanthin treatment resulted in a marked amelioration of the histological damage in the colon, and reduced the colonic PGE2 levels in colitic mice. In addition, the DSS-induced overexpressions of inflammation-related molecules including COX-2 and NF-κB were significantly decreased in fucoxanthin-treated mice. These finding suggested that the use of fucoxanthin provides a new and attractive alternative to control UC.

High-Performance Ag-Cu Nanoalloy Catalyst for the Selective Catalytic Oxidation of Ammonia.

High-performance Ag-Cu alloy nanoparticles (NPs) were successfully synthesized by a solventless mix-bake-wash method and tested for NH3-SCO. The prepared Ag2Cu1 catalyst with a perfect Ag-Cu alloy structure exhibited better T100 (200 °C, the temperature at which 100% NH3 conversion was obtained), higher reaction rates, and lower Ea compared to that with ordinary bimetallic Ag-Cu (AgCuOx). The characterization data revealed much smaller Ag-Cu alloy nanoparticles of the Ag2Cu1 catalyst and more Ag/Cu metallic species on the surface, which can increase the amount of chemisorbed surface oxygen (Oß) and enhance NH3 adsorption and activation in the low-temperature range, therefore leading to a much higher NH3-SCO activity. Kinetic studies and density functional theory calculations indicated that Cu decoration at Ag by Ag-Cu alloying could enhance the adsorption/activation of NH3 and O2. It has been found that O2 was more easily transformed from the adsorption state to the transition state than NH3, which enhanced the performance of NH3 oxidation. In addition, the Ag2Cu1 catalyst exhibited excellent durability because of the stabilization of Ag sites by the Ag-Cu alloy structure.

Lightweight Splint Design for Individualized Treatment of Distal Radius Fracture.

A systematic design approach is proposed for medical splints for individualized treatment of the distal radius fracture. An initial split structural model is first constructed by 3D scanning of an injured limb. Based on the biomechanical theory and clinical experiences, the topology optimization method is applied to design the splint structure. The optimized lightweight splint is realized by additive manufacturing using polylactic acid. Compared to the traditional designs for the distal radius fracture, the optimized design by the proposed approach exhibits a weight reduction of more than 40%. Besides, the mechanical properties of the splint meet the requirements of medical treatment according to the simulation results. Numerical examples are provided to demonstrate the applicability of the approach.

Copper/B2pin2-Catalyzed Difluoroalkylation of Methylenecyclopropanes with Bromodifluorinated Acetates and Acetamides: One-Pot Synthesis of CF2-Containing Dihydronaphthalene Derivatives.

Novel copper/B2pin2-catalyzed difluoroalkylation of methylenecyclopropanes with bromodifluorinated acetates and acetamides via a tandem radical process involving ring-opening/intramolecular cyclization has been reported. This protocol is not only tolerated to a diverse range of substrates but also applicable to the synthesis of useful difluoromethylated compounds. Moreover, the reaction could be performed on a gram scale with a high yield, which opens up the possibility for practical applications.

Rhodium(III)-Catalyzed Meta-Selective C-H Alkenylation of Phenol Derivatives.

Rhodium(III)-catalyzed remote meta-selective-C-H alkenylation of phenol derivatives has been developed using a traceless organosilicon template as the directing group. This transformation proceeds smoothly with good yields and high meta-selectivities toward a series of phenol and alkene substrates. In addition, this protocol provides an effective strategy for late-stage transformations of various meta-alkenylated aromatic compounds.

A meta-selective-C-H alkenylation of phenol-derivatives employing a traceless organosilicon template.

A traceless organosilicon template-directed meta-selective-C-H alkenylation of phenols was realized with good yields and high selectivities. The template was readily removable through F--promoted O-Si cleavage under extremely mild conditions or recyclable through a p-TSA catalyzed process. The product was successfully applied in the preparation of a series of meta-alkenylated aromatic compounds.