Electrochemical Nickel-Catalyzed Hydrogenation.

Olefin hydrogenation is one of the most important transformations in organic synthesis. Electrochemical transition metal-catalyzed hydrogenation is an attractive approach to replace the dangerous hydrogen gas with electrons and protons. However, this reaction poses major challenges due to rapid hydrogen evolution reaction (HER) of metal-hydride species that outcompetes alkene hydrogenation step, and facile deposition of the metal catalyst at the electrode that stalls reaction. Here we report an economical and efficient strategy to achieve high selectivity for hydrogenation reactivity over the well-established HER. Using an inexpensive and bench-stable nickel salt as the catalyst, this mild reaction features outstanding substrate generality and functional group compatibility, and distinct chemoselectivity. In addition, hydrodebromination of alkyl and aryl bromides could be realized using the same reaction system with a different ligand, and high chemoselectivity between hydrogenation and hydrodebromination could be achieved through ligand selection. The practicability of our method has been demonstrated by the success of large-scale synthesis using catalytic amount of electrolyte and a minimal amount of solvent. Cyclic voltammetry and kinetic studies were performed, which support a NiII/0 catalytic cycle and the pre-coordination of the substrate to the nickel center.

Dual Transition Metal Electrocatalysis: Direct Decarboxylative Alkenylation of Aliphatic Carboxylic Acids.

Direct decarboxylative alkenylation of widely available aliphatic carboxylic acids with vinyl halides for the synthesis of alkenes with all substitution patterns has been accomplished by means of Ce/Ni dual transition metal electrocatalysis. The reactions employ alkyl acids as the limiting reagents and exhibit a broad scope with respect to both coupling partners. Notably, simple primary alkyl carboxylic acids could be readily engaged as carbon-centered radical precursors in the reaction. This new alkenylation protocol has been successfully demonstrated in direct modification of naturally occurring complex acids and is amenable to the enantioselective decarboxylative alkenylation of arylacetic acid. Mechanistic studies, including a series of controlled experiments and cyclic voltammetry data, allow us to probe the key intermediates and the pathway of the reaction.

Radical-Based Convergent Paired Electrolysis.

Electrochemistry offers a sustainable platform for discovering reactions involving single-electron transfer (SET) that generates highly reactive and synthetically versatile radical species. Compared with photochemistry similarly specializing in SET which requires expensive photocatalysts, electrochemistry employs low-cost electricity to drive the electron flow. Paired electrolysis makes use of both half-reactions, thus obviating the need for sacrificial reactions and maximizing the atom and energy economy. In convergent paired electrolysis, anodic oxidation and cathodic reduction occur simultaneously to generate two intermediates, which are then coupled to furnish the product. It represents a distinctive approach to challenging redox-neutral reactions. However, the gap between the two electrodes makes it hard for a reactive intermediate to come across the other coupling partner. This concept article summarizes recent state-of-the-art advances on radical-based convergent paired electrolysis, which adopted different strategies to overcome the difficulty.

Electrophotochemical Metal-Catalyzed Decarboxylative Coupling of Aliphatic Carboxylic Acids.

An electrophotochemical dual metal-catalyzed protocol for decarboxylative arylation of simple aliphatic carboxylic acids with aryl halides is reported. The relative stabilities of catalytically active metal complexes simultaneously generated at anode and cathode are the key design elements for the success of this convergent paired electrolysis. This new electrophotocatalytic method is mild, robust, and most importantly, capable of accommodating simple primary aliphatic acids including acetic acid - ubiquitous and variegated structural motifs yet remain oddly challenging substrates - directly as native functional groups for decarboxylative C(sp2 )-C(sp3 ) bond formation.

Callyspongiolide Is a Potent Inhibitor of the Vacuolar ATPase.

Callyspongiolide is a marine-derived macrolide that kills cells in a caspase-independent manner. NCI COMPARE analysis of human tumor cell line toxicity data for synthetic callyspongiolide indicated that its pattern of cytotoxicity correlated with that seen for concanamycin A, an inhibitor of the vacuolar-type H+-ATPase (V-ATPase). Using yeast as a model system, we report that treatment with synthetic callyspongiolide phenocopied a loss of V-ATPase activity including (1) inability to grow on a nonfermentable carbon source, (2) rescue of cell growth via supplementation with Fe2+, (3) pH-sensitive growth, and (4) a vacuolar acidification defect visualized using the fluorescent dye quinacrine. Crucially, in an in vitro assay, callyspongiolide was found to dose-dependently inhibit yeast V-ATPase (IC50 = 10 nM). Together, these data identify callyspongiolide as a new and highly potent V-ATPase inhibitor. Notably, callyspongiolide is the first V-ATPase inhibitor known to be expelled by Pdr5p.

Unconventional Fragment Usage Enables a Concise Total Synthesis of (-)-Callyspongiolide.

An asymmetric synthesis of (-)-callyspongiolide is described. The route builds the macrolide domain atypically from a disaccharide and a monoterpene without passing through a seco-acid. Chiral iridium catalysis selectively joins fragments. Subsequent degradation of an imbedded butyrolactone via perhemiketal fragmentation affords a stereo- and regio-defined homoallylic alcohol that is engaged directly in a carbonylative macrolactonization. Further elaboration of the polyunsaturated appendage provides the natural product in a particularly direct and flexible manner.

Rhodium(III)-catalyzed intermolecular amidation with azides via C(sp³)-H functionalization.

The amidation reactions of 8-methylquinolines with azides catalyzed by a cationic rhodium(III) complex proceed efficiently to give quinolin-8-ylmethanamine derivatives in good yields via C(sp(3))-H bond activation under external oxidant-free conditions. A catalytically competent five-membered rhodacycle has been isolated and characterized, revealing a key intermediate in the catalytic cycle.

A controlled non-radical chlorine activation pathway on hematite photoanodes for efficient oxidative chlorination reactions.

Photo(electro)catalytic chlorine oxidation has emerged as a useful method for chemical transformation and environmental remediation. However, the reaction selectivity usually remains low due to the high activity and non-selectivity characteristics of free chlorine radicals. In this study, we report a photoelectrochemical (PEC) strategy for achieving controlled non-radical chlorine activation on hematite (α-Fe2O3) photoanodes. High selectivity (up to 99%) and faradaic efficiency (up to 90%) are achieved for the chlorination of a wide range of aromatic compounds and alkenes by using NaCl as the chlorine source, which is distinct from conventional TiO2 photoanodes. A comprehensive PEC study verifies a non-radical "Cl+" formation pathway, which is facilitated by the accumulation of surface-trapped holes on α-Fe2O3 surfaces. The new understanding of the non-radical Cl- activation by semiconductor photoelectrochemistry is expected to provide guidance for conducting selective chlorine atom transfer reactions.

A systematic analysis of the global and regional burden of colon and rectum cancer and the difference between early- and late-onset CRC from 1990 to 2019.

The burden of colorectal cancer (CRC) varies substantially across different geographical locations. However, there was no further quantitative analysis of regional social development and the disease burden of CRC. In addition, the incidence of early- and late-onset CRC has increased rapidly in developed and developing regions. The main purpose of this study was to investigate the trends in CRC burden across different regions, in addition to the epidemiological differences between early and late-onset CRC and their risk factors. In this study, estimated annual percentage change (EAPC) was employed to quantify trends in age-standardized incidence rate (ASIR), mortality rate, and disability-adjusted life-years. Restricted cubic spline models were fitted to quantitatively analyze the relationship between trends in ASIR and Human Development Index (HDI). In addition, the epidemiological characteristics of early- and late-onset CRC were investigated using analyses stratified by age groups and regions. Specifically, meat consumption and antibiotic use were included to explore the differences in the risk factors for early- and late-onset CRC. The quantitative analysis showed that the ASIR of CRC was exponentially and positively correlated with the 2019 HDI in different regions. In addition, the growing trend of ASIR in recent years varied substantially across HDI regions. Specifically, the ASIR of CRC showed a significant increase in developing countries, while it remained stable or decreased in developed countries. Moreover, a linear correlation was found between the ASIR of CRC and meat consumption in different regions, especially in developing countries. Furthermore, a similar correlation was found between the ASIR and antibiotic use in all age groups, with different correlation coefficients for early-onset and late-onset CRC. It is worth mentioning that the early onset of CRC could be attributable to the unrestrained use of antibiotics among young people in developed countries. In summary, for better prevention and control of CRC, governments should pay attention to advocate self-testing and hospital visits among all age groups, especially among young people at high risk of CRC, and strictly control meat consumption and the usage of antibiotics.

Pairing Iron and Nickel Catalysis for Electrochemical Esterification of Aryl Halides with Carbazates.

We report an electrocatalytic approach for esterification of aryl halides by pairing iron and nickel electrocatalysis. The reaction involves anodically iron-catalyzed oxidation of carbazates to produce alkoxycarbonyl radicals. The carbon-centered radicals then enter nickel catalysis that is powered by cathodic reduction to deliver the radical coupling products. Mechanistic data are consistent with arylnickel(II) species as the key intermediates enabling the desired carbon-carbon bond formation.

Asymmetric Organocatalysis Enables Rapid Assembly of Portimine Precursor Chains.

Sequential organocatalytic additions of 2-furanone and dihydroxyacetone derivatives to a crotonaldehyde lynchpin provide polyhydroxylated chains reminiscent of lactonized deoxo Kdn type sugars. Further homologation via Kulinkovich ring opening of the butyrolactone and acylation of the zinc homoenolate derived from the incipient cyclopropanol allows assembly of functionalized chain precursors to portimine. Our experiments probe the stability and reactivity of monosubstituted methylidene pyrrolines and generate advanced intermediates useful for exploring the biosynthesis and de novo synthesis of portimine.

Adsorption of tetracycline by Nicandra physaloides (L.) Gaertn seed gum and Nicandra physaloides(L.) Gaertn seed gum/Carboxymethyl chitosan aerogel.

In this study, novel aerogels of Nicandra physaloides (L.) Gaertn seed gum (NPG) and Nicandra physaloides (L.) Gaertn seed gum/Carboxymethyl chitosan (NPG/CMC) were prepared by freeze-drying method for removing tetracycline (TC) from water. Scanning electron microscope (SEM), X-ray diffraction (XRD),Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), and Brunauer-Emmett-Teller (BET) were used to characterize structure and morphology of NPG and NPG/CMC aerogels. The average pore diameter of NPG and NPG/CMC were 3.04 and 1.2 nm, the specific surface areas were 2.67 and 0.73 m2/g, respectively. The maximum adsorption capacity of NPG and NPG/CMC aerogels for TC based on Langmuir isotherm was 266.7 and 332.23 mg/g respectively. Through thermodynamic and kinetic studies, it was found that the adsorption processes of the two adsorbents were spontaneous and followed the pseudo-second-order kinetic model. And the process of NPG adsorption of TC was endothermic, while NPG/CMC was exothermic.

Barium alginate as a skeleton coating graphene oxide and bentonite-derived composites: Excellent adsorbent based on predictive design for the enhanced adsorption of methylene blue.

The phenomenon that calcium alginate does not exhibit high adsorption capacity as a carrier material has not been reasonably explained or solved. In this paper, a new viewpoint that the orbital energy level of metal ions and the binding degree of the α-l-guluronate and ß-d-mannuronate units affect the adsorption performance of the composite was innovatively proposed. Taking barium alginate (BA) as an example, the possibility of replacing calcium alginate is discussed. Barium alginate/graphene oxide (BA/GO) membranes and three-dimensional (3D) barium alginate-bentonite-graphene oxide derived (3D-BA) hydrogels were prepared by vacuum freeze-drying to remove methylene blue. The structure and morphology of the prepared adsorbents were characterized by scanning electron microscopy, X-ray photoelectron spectroscopy, thermogravimetry and Fourier transform infrared spectroscopy. The effects of adsorbent dosage, doping ratio, temperature, contact time, pH value and initial dye concentration on the adsorption performance of BA composites were investigated. The adsorption capacities of the BA/GO and 3D-BA materials were 1011.3 and 710.3 mg/g, respectively. The BA/GO membrane exhibited stable filtration performance against high concentrations of dyes. Benefiting from the strong interaction between bentonite, sodium alginate and Ba2+, the 3D-BA hydrogel showed higher thermal stability and better adsorption efficiency than other materials. The Elovich kinetic model and Sips equation can appropriately describe the adsorption process. The results show that barium alginate is a better carrier material than calcium alginate.

Adsorption of methylene blue by Nicandra physaloides(L.) Gaertn seed gum/graphene oxide aerogel.

In this study, a novel composite aerogel of Nicandra physaloides(L.) Gaertn seed, gum/graphene oxide (NPG/GO), was prepared by using a vacuum freeze drying method for methylene blue (MB) adsorption. The techniques, including Brunauer-Emmett-Teller (BET), scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR), were adopted for studying the structure and surface characteristics of NPG/GO, with thermogravimetric analysis (TGA) being adopted for testing thermal properties. The effects of pH value, initial dye concentration, temperature and adsorbent dosage on adsorption performance were elaborately analysed. The adsorption kinetic studies showed that the process of adsorption follows Langmuir isotherm and a pseudo-second-order kinetic model. When the mass ratio of NPG to GO was 1.25:1, the adsorption capacity was the highest. According to Langmuir isotherm, the maximum adsorption capacity of 408.16 mg/g was higher than that of NPG. The specific surface area and average pore diameter of NPG/GO was measured as 2.70 m2/g and 4.8 nm, respectively. Thermodynamic analysis revealed that the adsorption process of methylene blue on NPG/GO was a spontaneous and endothermic process. In general, the prepared nanocomposites were excellent candidates for adsorption and removal process because of simple synthesis, low cost, high efficiency, non-toxicity, environment protection and degradability.

Study on the Adsorption Performance of Casein/Graphene Oxide Aerogel for Methylene Blue.

Casein (CS) and graphene oxide (GO) were employed for the fabrication of a casein/graphene oxide (CS/GO) aerogel by vacuum freeze drying. Fourier transform infrared spectroscopy, scanning electron microscopy, surface area and micropore analysis (BET), and thermogravimetric analysis were used to characterize the specific surface area, structure, thermal stability, and morphology of the CS/GO aerogel. The influence of experimental parameters such as the GO mass fraction in the aerogel, metering of the adsorbent, pH, contact time, and temperature on the adsorption capacity of the CS/GO aerogel on methylene blue (MB) was also investigated. According to Langmuir isotherm determination, the maximum removal rate of MB from the CS/GO aerogel was 437.29 mg/g when the temperature was 293 K and pH was 8. Through kinetic and thermodynamic studies, it is found that adsorption follows a pseudo-second-order reaction model and is also an exothermic and spontaneous process.

A colorimetric biosensor for simultaneous ochratoxin A and aflatoxins B1 detection in agricultural products.

Colorimetric biosensors have been widely applied to mycotoxins testing. However, the colorimetric assay previously reported used a single color to detect one mycotoxin, and there were few reports on the simultaneous detection of multiple mycotoxins. In this work, a colorimetric biosensor for dual mycotoxins detection was developed. A Fe3O4/GO based platform for aflatoxins B1 (AFB1) detection and a Fe3O4@Au based platform for ochratoxin A (OTA) detection were fabricated. The quantification of OTA and AFB1 was respectively achieved by the release of thymolphthalein under alkaline conditions and 3,3',5,5'-tetramethylbenzidine was catalyzed by Au NPs under acidic conditions. Because of different conditions, two sensing methods didn't interfere with each other but could provide a higher detection efficiency. The detection range of AFB1 is 5-250 ng·ml-1 and that of OTA is 0.5-80 ng·ml-1. This biosensor has been successfully applied in real sample detection, which has a broad application prospect in fields of food safety.

The modulation relationship of genomic pattern of intratumor heterogeneity and immunity microenvironment heterogeneity in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world, with the second highest mortality rate among all cancer types. Growing evidence has demonstrated the notable effects of intratumor heterogeneity (ITH) and tumor immune microenvironment heterogeneity (TIMH) on the biological processes involved in HCC. However, the interactive mechanisms between ITH and TIMH is still unclear. The present study systematically screened the mRNA expression, simple nucleotide variation data and clinical data of samples from The Cancer Genome Atlas (TCGA). The mutant-allele tumor heterogeneity (MATH) score was used to represent ITH, and TCGA cohort was divided into two groups according to the MATH score. Next, different immune-related signaling pathways and enriched immune-related genes were identified using Gene Set Enrichment Analysis of these two groups, and the results revealed that interleukin-1α (IL1A) and serine/threonine-protein kinase PAK4 were associated with prognosis. Furthermore, CIBERSORT was utilized to calculate the fractions of 22 types of leukocytes to represent TIMH, and the fractions of M1 and M2 macrophages were confirmed to be associated with prognosis. Therefore, PAK4, interleukin-1α (IL1A), and M1/M2 ratio were selected as the key factors involved in the interaction between ITH and TIMH. Afterwards, microRNAs (miRNAs) that were linearly related to the M1/M2 ratio and the potential target genes of the miRNAs were screened. Finally, the regulatory network between PAK4, IL1A, and the M1/M2 ratio was established, bridged by the above miRNAs and the target genes. In addition, PAK4, heat shock protein 105 kDa and miRNA-1911 were demonstrated to be a key factor involved in immune response via Weighted Correlation Network Analysis in HCC.

Ir(III)-Catalyzed Oxidative Coupling of NH Isoquinolones with Benzoquinone.

The oxidative coupling reactions of NH isoquinolones with 1,4-benzoquinone proceeded efficiently to form spiro compounds in the presence of an Ir(III) catalyst through C-H activation. The reactions have a broad range of substrates, with nearly quantitative yields, without the use of external oxidants. For 1,4-naphthoquinone and other substituted 1,4-benzoquinone substrates the reactions also gave high yields with Cu(OAc)2·H2O as an external oxidant. A catalytically competent five-membered iridacycle has been isolated and structurally characterized, thus revealing a key intermediate in the catalytic cycle.