TEMPO-Mediated Interrupted 6π-Photocyclization of ortho-Biaryl-Appended 1,3-Dicarbonyl Compounds toward 10-Phenanthrenols.

In this paper, we present an example of a photoinduced catalyst, halogen-, and base-free TEMPO-mediated interrupted 6π-photocyclization/dehydrogenative aromatization of ortho-biaryl-appended 1,3-dicarbonyl compounds for the preparation of 10-phenanthrenols. The reaction involves rapid photocycloaddition via a 1,2-biradical of 1,3-dicarbonyl compounds, followed by subsequent dehydrogenative aromatization of 1,4-biradical intermediates using TEMPO as the commercially available oxidant rather than trapped by TEMPO to form an alkoxyamine product.

Integrating Metabolomics and Network Pharmacology to Decipher the Hepatoprotective Effect Mechanisms of Magnesium Isoglycyrrhizinate Injection.

This study aimed to explore the liver protective effects of a fourth-generation glycyrrhizic acid product (magnesium isoglycyrrhizinate injection, MII) in the treatment of mice with drug-induced liver injury-specifically, to determine its effects on plasma metabolites. Moreover, the possible mechanism of its intervention in lipid metabolism and amino acid metabolism through the liver protective effect was preliminarily explored, combined with network pharmacology. The liver injury model of mice was established using acetaminophen (APAP). The protective effect of MII on the mice model was evaluated using pathological tissue sections and biochemical indices such as alanine transaminase (ALT), aspartate aminotransferase (AST), and superoxide dismutase (SOD). Metabolomics analysis of plasma was performed using the UHPLC-QTOF/MS technique to screen for potential biomarkers and enriched metabolic pathways. The potential targets and pathways of MII were predicted by network pharmacology, and the mechanism was verified by Western blot analysis. MII significantly improved the pathological liver changes in mice with liver injury. The content of ALT and AST was decreased, and the activity of SOD was increased significantly (p < 0.05, 0.01). A total of 29 potential biomarkers were identified in the metabolomics analysis, mainly involving seven pathways, such as lipid metabolism and amino acid metabolism. A total of 44 intersection targets of MII in the treatment of liver injury were obtained by network pharmacology, involving lipid metabolism and other related pathways. Western blot analysis results showed that MII could significantly reduce the expression of JAK2 and STAT3. MII can effectively ameliorate liver injury in modeled mice through related pathways such as lipid metabolism and amino acid metabolism. This study could provide not only a scientific basis for the elucidation of the mechanism of action of MII in exerting a hepatoprotective effect, but also a reference for its rational clinical application.

Visible-Light-Promoted 6π Photocyclization of ortho-Biaryl-Appended ß-Ketoesters.

A photocatalyst- and additive-free visible-light-induced 6π-photocyclization of ortho-biaryl-appended ß-ketoesters has been developed. Upon irradiation with visible light, substrates undergo 6-endo-trig cyclization/1,5-H shift to 9,10-dihydrophenanthren-9-ols with high efficiency and selectivity. The reaction proceeds via conrotatory ring closure followed by a suprafacial 1,5-hydrogen shift leading to the observed single trans-fused products. Preliminary mechanistic studies reveal the feasibility of both 1,5-H shift and intersystem crossing of the diradical intermediate.

Photoredox/Cobalt-Catalyzed Cascade Oxidative Synthesis of 2,5-Disubstituted 1,3,4-Oxadiazoles under Oxidant-Free Conditions.

An efficient oxidant-free, photoredox-mediated cascade cyclization strategy for the synthesis of 1,3,4-oxadiazoles by using an organo acridinium photocatalyst and a cobaloxime catalyst has been developed. Various acylhydrazones have been transformed into the corresponding 1,3,4-oxadiazole products in up to 96% yield, and H2 is the only byproduct. Mechanistic experiments and density functional theory (DFT) calculation studies indicate carbon-centered radicals rather than oxygen-centered radicals as π-radicals produced by the oxidation of photoexcited Mes-Acr+* along with deprotonation, which is responsible for this transformation. The practical utility of this method is highlighted by the one-pot gram-scale synthesis starting directly from commercially available aldehydes and acylhydrazides.

l-Methionine Selenoxide as an Oxidizing and Deprotection Reagent for the Synthesis of Multiple Disulfide Bonds in Peptides.

The regioselective synthesis of multiple disulfide bonds in peptides has been a significant challenge in synthetic peptide chemistry. In this work, two disulfide bonds in peptides were regioselectively synthesized via an approach of MetSeO oxidation and deprotection reaction (SeODR), in which the first disulfide bond was constructed through oxidation of dithiol by MetSeO in a neutral buffer, and the second disulfide bond was then directly constructed through the deprotection of two Acm groups or one Acm group and one Thz group by MetSeO in acidic media. Synthesis of two disulfide bonds by the SeODR approach was achieved through a one-pot manner. Moreover, the SeODR approach is compatible with the synthesis of peptides containing methionine residues. Both H+ and Br- drastically promoted the reaction rate of SeODR. The mechanistic picture for the SeODR approach was delineated, in which the formation of a stable Se-X-S bridge as the transition state plays a critical role. The SeODR approach was also utilized to construct the three disulfide bonds in linaclotide, conferring a reasonable yield.

Realizing Textured Zinc Metal Anodes through Regulating Electrodeposition Current for Aqueous Zinc Batteries.

Crystallography modulation of zinc (Zn) metal anode is promising to promote Zn reversibility in aqueous electrolytes, but efficiently constructing Zn with specific crystallographic texture remains challenging. Herein, we report a current-controlled electrodeposition strategy to texture the Zn electrodeposits in conventional aqueous electrolytes. Using the electrolytic cell with low-cost Zn(CH3 COO)2 electrolyte and Cu substrate as a model system, the texture of as-deposited Zn gradually transforms from (101) to (002) crystal plane as increasing the current density from 20 to 80 mA cm-2 . Moreover, the high current accelerates the Zn nucleation rate with abundant nuclei, enabling uniform deposition. The (002) texture permits stronger resistance to dendrite growth and interfacial side reactions than the (101) texture. The resultant (002)-textured Zn electrode achieves deep cycling stability and supports the stable operation of full batteries with conventional V/Mn-based oxide cathodes.

In-Situ Integration of a Hydrophobic and Fast-Zn2+ -Conductive Inorganic Interphase to Stabilize Zn Metal Anodes.

The irreversible issues of Zn anode stemming from dendrite growth and water-induced erosion have severely hindered the commercialization of rechargeable aqueous Zn batteries. Herein, a hydrophobic and fast-Zn2+ -conductive zinc hexacyanoferrate (HB-ZnHCF) interphase layer is in situ integrated on Zn by a rapid room-temperature wet-chemistry method to address these dilemmas. Different from currently proposed hydrophilic inorganic cases, the hydrophobic and compact HB-ZnHCF interphase effectively prevents the access of water molecules to Zn surface, thus avoiding H2 evolution and Zn corrosion. Moreover, the HB-ZnHCF with large internal ion channels, strong zincophilicity, and high Zn2+ transference number (0.86) permits fast Zn2+ transport and enables smooth Zn deposition. Remarkably, the resultant HB-ZnHCF@Zn electrode delivers unprecedented reversibility with 99.88 % Coulombic efficiency over 3000 cycles, realizes long-term cycling over 5800 h (>8 months, 1 mA cm-2 ) and 1000 h (10 mA cm-2 ), and assures the stable operation of full Zn battery with both coin- and pouch-type configurations.

Synthesis of 10-Phenanthrenols via Photosensitized Triplet Energy Transfer, Photoinduced Electron Transfer, and Cobalt Catalysis.

Due to the inert redox activity and high triplet energy, radical chemistry of 1,3-dicarbonyl compounds usually requires prefunctionalization substrates, external oxidant, and high-energy UV light. Here, we report a visible-light-driven photocatalyst/cobaloxime system composed of a photosensitized energy transfer reaction (PEnT) and photoinduced electron transfer reaction (PET) and with an interrupted 6π-photocyclization/dehydrogenative aromatization in one pot to synthesize 10-phenanthrenols. Preliminary mechanistic studies revealed that fac-Ir(ppy)3 plays the dual roles of energy transfer catalysis for photocycloaddition via 1,2-biradical intermediates of 1,3-dicarbonyl compounds and photoredox/cobaloxime catalysis dehydrogenative aromatization of 1,4-biradical rather than the intermediates via 6π photocyclization in the tandem reaction. In contrast to previous well-established radical chemistry of 1,3-dicarbonyl compounds, we provide a new strategy for the activation of 1,3-dicarbonyl compounds under visible light catalysis, affording a novel cyclization strategy with extremely high atom economy for the synthesis of 10-phenanthrenols.

Deprotection of S-Acetamidomethyl and 1,3-Thiazolidine-4-Carbonyl Protecting Groups from Cysteine Side Chains in Peptides by trans-[PtX2(CN)4]2-: One-Pot Regioselective Synthesis of Disulfide Bonds.

In this study, we developed an efficient approach for disulfide bond formation in peptides utilizing the Pt(IV) complex trans-[PtBr2(CN)4]2- to mediate Acm and Thz deprotections. [PtBr2(CN)4]2- can oxidatively deprotect two Acm groups or deprotect one Thz group and one Acm group to directly form an intramolecular disulfide bond in peptides. Several disulfide-containing peptides with excellent yields were achieved via the deprotection method in an aqueous medium under aerobic conditions. Kinetic studies indicated that the dominant path of the reaction is of first-order in both [Pt(IV)] and [peptide]; moreover, the deprotection rate increased dramatically with the addition of NaBr. A mechanism including a bromide-bridge-mediated electron transfer process was proposed. Apamin, α-conotoxin SI, and the parallel homodimer of oxytocin, all containing two disulfide bonds, were synthesized regioselectively through a one-pot method by the combined use of the above deprotection approach with oxidants l-methionine selenoxide and [PtBr2(CN)4]2-. All of the reactions were completed within 30 min to afford good yields for these peptides.

A novel thiolysis-high-performance liquid chromatography method for the determination of proanthocyanidins in grape seeds.

A novel thiolysis-high-performance liquid chromatography method for the quantitative determination of total proanthocyanidins and the mean degree of polymerization in grape seeds has been developed. Following thiolysis with formic acid and benzyl mercaptan, reaction products were separated and purified. Three proanthocyanidin monomers and three derivatives were obtained and their structures were identified by liquid chromatography-mass spectrometry, FTIR spectroscopy, and NMR spectroscopy. A decomposition model of the thiolysis products and a correction formula for proanthocyanidins concentration were established. This thiolysis-high-performance liquid chromatography method displayed good calibration linearity (R2  > 0.999 over the concentration range 0.01 to 10 mg/mL), excellent accuracy (recoveries of 97.9-99.6%), and precision (repeatability relative standard deviations of 0.45-0.75%). This method is suitable for the quantitative analysis of proanthocyanidins in grape seed products.

Risk assessment of carbofuran residues in fruits and vegetables at the Chinese market: A 7-year survey.

The United Nations designated 2021 as the International Year of Fruits and Vegetables (IYFV), with the goal of educating populations regarding the role of such produce in nutrition, food safety, and overall health. Carbofuran is a highly toxic insecticide and nematocide, and its use to treat fruit trees, vegetables, tea, and medicinal herbs is thus prohibited. However, carbofuran residues are still detectable via LC-Q-TOF/MS in fruit and vegetable samples collected from 138 sites in 31 regions. In the present study, carbofuran levels were sampled at 1388 sampling sites in 31 regions (provinces, autonomous regions, and municipalities) not including Hong Kong, Macao, or Taiwan. In total, over 36,000 samples (including 12,547 samples of 41 kinds of fruits and 23,785 samples of 83 kinds of vegetables) were randomly collected from supermarkets and farmer's markets. These data were used to conduct a risk assessment pertaining to dietary carbofuran exposure through the consumption of fruits and vegetables. In total, carbofuran residues were detectable in 2.0% of fruits and 2.3% of vegetables. Risk assessments indicated that the intake of fruits and vegetables harboring carbofuran residues did not pose a chronic health risk. However, peaches, grapes, sweet peppers, celery, Chinese chives, leaf lettuce, spinach, small rape, mustard greens, cucumbers, watermelons, Chinese wolfberry leaves, wax gourds, snap beans, bitter melons, green Chinese vegetables, lettuce, shallot, cowpeas, eggplants, tomatoes, tangerines, summer squash, oranges, lemons, Chinese cabbage, peppers, and strawberries were associated with an unacceptable acute risk to both children and adults. Moreover, crown daisies, nectarines, citrus fruits, pitayas, melons, kale, cabbages, milk Chinese cabbage, carrots, and melons were associated with an unacceptable acute risk to children. Substantial acute risk to children and adults was observed for fruits and vegetables from surveyed regions other than Inner Mongolia, Yunnan, Liaoning, Fujian, Xinjiang, and Hubei. Together, these data provide a foundation for future research aimed at the management of carbofuran residues in fruits and vegetables in an effort to better protect consumer health.

Expanding the Toolbox for Peptide Disulfide Bond Formation via l-Methionine Selenoxide Oxidation.

In this study, l-methionine selenoxide (MetSeO) was used as an oxidant for the construction of peptide disulfide bonds. Excellent yields for various disulfide-containing peptides were achieved via the MetSeO oxidation method in different solvents and on a resin. Most importantly, the construction of disulfide bonds can be performed in the trifluoroacetic acid cocktail used for the cleavage of peptides from the resin, which obviates the steps of peptide purification and lyophilization. This facilitates and simplifies the synthesis of disulfide-containing peptides. Kinetic and mechanistic studies of the reaction between MetSeO and dithiothreitol (DTT, a model compound of dicysteine-containing peptide) show that the reaction is first order in both [MetSeO] and [DTT], and a reaction mechanism is proposed that can help us gain insights into the reaction of the oxidative synthesis of disulfide bonds via MetSeO oxidation.

Recent advances in porous organic frameworks for sample pretreatment of pesticide and veterinary drug residues: a review.

Rapid and accurate detection of pesticide and veterinary drug residues is a continuing challenge because of the complex matrix effects. Thus, appropriate sample pretreatment is a crucial step for the effective extraction of the analytes and removal of the interferences. Recently, the development of nanomaterial adsorbents has greatly promoted the innovation of food sample pretreatment approaches. Porous organic frameworks (POFs), including polymers of intrinsic microporosity, covalent organic frameworks, hyper crosslinked polymers, conjugated microporous polymers, and porous aromatic frameworks, have been widely utilized due to their tailorable skeletons and pores as well as fascinating features. This review summarizes the recent advances for POFs to be utilized in adsorption and sample preparation of pesticide and veterinary drug residues. In addition, future prospects and challenges are discussed, hoping to offer a reference for further study on POFs in sample pretreatment.

Simultaneous determination and risk assessment of highly toxic pesticides in the market-sold vegetables and fruits in China: A 4-year investigational study.

This study investigated the levels of highly toxic pesticides (HTPs) in 6554 vegetable and fruit samples from 31 regions of China, along with the associated risk of dietary exposure for the population between 2014 and 2017. 18 HTPs were detected in 325 (4.96%) samples, and the levels of HTPs in 103 (1.57%) samples were found to be higher than the maximum residue limits (MRLs) of China. The rate of detection of HTPs in six types of vegetables and fruits, in a decreasing order, was found to be as follows: eggplant (8.84%) >grape (5.58%) >tomato (5.43%) >cucumber (5.43%) >pear (3.12%) >apple (2.30%). The level of contamination of HTPs was found to be higher in vegetables compared with fruits. The vegetable and fruit samples with the highest percentages of HTPs exceeding MRLs were found in eggplants from Guangxi (20%) and grapes from Inner Mongolia (12.5%), respectively. Both, the average target hazard quotient (THQ) of a single highly toxic pesticide (HTP) and the average hazard index (HI) of the mixture of HTPs for adults and children from vegetables and fruits from the 31 regions were found to be less than one. Omethoate, carbofuran, ethoprophos, triazophos, and phorate were identified as the major contributors to the average HI for vegetables, and carbofuran, ethoprophos, omethoate, phorate, and phosphamidon were identified as the primary contributors to the average HI for fruits. The results of this study revealed that HTPs in vegetables and fruits did not cause any significant chronic risk of dietary exposure. The detection of HTPs exceeding MRLs in some of the samples implied that appropriate management guidelines for HTPs should be implemented to protect the health of the consumers.

Design, Synthesis and Characterization of a Novel Type of Thermo-Responsible Phospholipid Microcapsule-Alginate Composite Hydrogel for Drug Delivery.

Liposomes are extensively used in drug delivery, while alginates are widely used in tissue engineering. However, liposomes are usually thermally unstable and drug-leaking when in liquids, while the drug carriers made of alginates show low loading capacities when used for drug delivery. Herein, we developed a type of thermo-responsible liposome-alginate composite hydrogel (TSPMAH) by grafting thermo-responsive liposomes onto alginates by using Ca2+ mediated bonding between the phosphatidic serine (PS) in the liposome membrane and the alginate. The temperature-sensitivity of the liposomes was actualized by using phospholipids comprising dipalmitoylphosphatidylcholine (DPPC) and PS and the liposomes were prepared by a thin-film dispersion method. The TSPMAH was then successfully prepared by bridge-linking the microcapsules onto the alginate hydrogel via PS-Ca2+-Carboxyl-alginate interaction. Characterizations of the TSPMAH were carried out using scanning electron microscopy, transform infrared spectroscopy, and laser scanning confocal microscopy, respectively. Their rheological property was also characterized by using a rheometer. Cytotoxicity evaluations of the TSPMAH showed that the composite hydrogel was biocompatible, safe, and non-toxic. Further, loading and thermos-inducible release of model drugs encapsulated by the TSPMAH as a drug carrier system was also studied by making protamine-siRNA complex-carrying TSPMAH drug carriers. Our results indicated that the TSPMAH described herein has great potentials to be further developed into an intelligent drug delivery system.

Pb4B6O13: A Polar Lead Oxyborate with Uncommon ∞(B6O12)6- Layers Exhibiting a Large Second Harmonic Generation Response.

A new lead oxyborate, Pb4B6O13, has been successfully synthesized by introducing stereochemically active Pb2+ cations and distorted OPb4 tetrahedra into asymmetric borates. Pb4B6O13 exhibits an unprecedented two-dimensional ∞(B6O12)6- layer structure with a large second harmonic generation (SHG) response that is 3 times that of KH2PO4. In addition, theoretical work, including dipole moment calculations, electronic structure, and SHG coefficients combined with SHG density analysis, is reported. The results suggest that the enhanced SHG of Pb4B6O13 is attributed to the synergy effect of three functional units.

Screening and Isolating Major Aldose Reductase Inhibitors from the Seeds of Evening Primrose (Oenothera biennis).

Aldose reductase (AR) is a drug target for therapies to treat complications caused by diabetes mellitus, and the development of effective AR inhibitors (ARIs) of natural origin is considered to be an attractive option for reducing these complications. In this research, the rat lens AR (RLAR) inhibitory activity of evening primrose (Oenothera biennis) seeds was investigated for the first time. In our results, the 50% (v/v) methanol extract of evening primrose seeds exhibits excellent RLAR inhibitory activity (IC50 value of 7.53 µg/mL). Moreover, after enrichment of its bioactive components, the ARIs are more likely to be present in the ethyl acetate fraction of 50% (v/v) methanol extract (EME) of evening primrose seeds, which exhibits superior RLAR inhibitory activity (IC50 value of 3.08 µg/mL). Finally, gallic acid (1), procyanidin B3 (2), catechin (3), and methyl gallate (4) were identified as the major ARIs from the EME by affinity-based ultrafiltration-high-performance liquid chromatography and were isolated by high speed countercurrent chromatography, with gallic acid (11.46 µmol/L) and catechin (14.78 µmol/L) being the more potent inhibitors of the four ARIs identified. The results demonstrated that evening primrose seeds may be a potent ingredient of ARIs.

Comparative proteomic analysis of Nostoc flagelliforme reveals the difference in adaptive mechanism in response to different ultraviolet-B radiation treatments.

Nostoc flagelliforme is a pioneer organism in the desert and highly resistant to ultraviolet B (UV-B) radiation, while the involved adaptive mechanism has not been fully explored yet. To elucidate the responsive mechanism, two doses of UV-B radiation (low: 1 W/m2 and high: 5 W/m2) were irradiated for 6 h and 48 h, respectively, and their effects on global metabolism in N. flagelliforme were comprehensively investigated. In this study, we used iTRAQ-based proteomic approach to explore the proteomes of N. flagelliforme, and 151, 172, 124 and 148 differentially expressed proteins were identified under low and high UV-B doses for 6 h and 48 h, respectively. Functional classification analysis showed these proteins were mainly involved in photosynthesis, amino acid metabolism, antioxidant activity and carbohydrate metabolism. Further analysis revealed that UV-B imposed restrictions on primary metabolism including photosynthesis, Calvin cycle, and amino acid metabolism, and cells started defense mechanism through repair of DNA and protein damage, increasing antioxidant activity, and accumulating extracellular polysaccharides to minimize the damage. Moreover, high UV-B dose imposed more severe restrictions and activated stronger defense mechanism compared with low dose. The results would improve the understanding of molecular mechanisms of UV-B-stress adaption in N. flagelliforme.

A Mild Aqueous Sonogashira Reaction as a Fluorescent Labeling Strategy for 5-Bromide-2'-Deoxyuridine.

C5-modified uridines are a valuable class of nucleoside analogues, both as potent chemotherapy agents and through their use as the conjunction site in DNA labeling strategies. As an important C5-modified uridine, BrdU has been used in cell proliferation assays since the 1980s. Currently, the detection of BrdU relies on traditional immunostaining; however, this approach has its limitations. Thus, it is desirable, albeit difficult, to develop chemistry methods to fluorescently label BrdU in a cellular context. In the present study, we report our efforts toward developing a robust chemistry methodology for BrdU fluorescent labeling. The Sonogashira reaction was chosen as the key reaction, and various alkynyl groups (aliphatic or aryl) containing fluorescent dyes were synthesized to cross-couple with BrdU. Various bases and catalyst systems were screened to evaluate the optimum conditions. A mild aqueous Sonogashira reaction (K2PdCl4, S-Phos, n-Bu4N⁺OH-, Sodium d-isoascorbate, EtOH/H2O = 1:1, 37 °C, Ar) was obtained to enable high-yielding BrdU fluorescent labeling.

Assessment of the Remediation Effect of Nano-hydroxyapatite in Exogenous Pb-contaminated Soil Using Toxicity Characteristic Leaching Procedure and Soil Enzyme Activities.

Lead (Pb) is one of the most abundant metal soil pollutants. In this research, effects of nano-hydroxyapatite (NHAP) on remediation of Pb-contaminated soil were evaluated by the measure of extractable Pb using toxicity characteristic leaching procedure (TCLP) and soil enzyme activities. Results suggested NHAP significantly decreased the concentrations of extractable Pb, achieving the maximum decrement rate of 75.71%. Activity of urease decreased with increasing Pb concentrations. Moreover, activities of alkaline phosphatase, dehydrogenase, and catalase increased at the lower Pb levels and decreased at the higher Pb levels. NHAP had a positive effect on regulating soil enzymes. Thus, soil enzyme activities, especially dehydrogenase, could be used as biological indicators of Pb pollution and NHAP remediation. Moreover, NHAP could reduce the mobility and bioavailability of Pb, while increasing enzyme activities, thereby lowering the leaching risk and biotoxicity of Pb.