Palladium-Catalyzed Benzylic C(sp3 )-H Carbonylative Arylation with Aryl Bromides.

A novel, selective and high-yielding palladium-catalyzed carbonylative arylation of a variety of weakly acidic (pKa 25-35 in DMSO) benzylic and heterobenzylic C(sp3 )-H bonds with aryl bromides has been achieved. This system is applicable to a range of pro-nucleophiles for access to sterically and electronically diverse α-aryl or α,α-diaryl ketones, which are ubiquitous substructures in biologically active compounds. The Josiphos SL-J001-1-based palladium catalyst was identified as the most efficient and selective, enabling carbonylative arylation with aryl bromides under 1 atm CO to provide the ketone products without the formation of direct coupling byproducts. Additionally, (Josiphos)Pd(CO)2 was identified as the catalyst resting state. A kinetic study suggests that the oxidative addition of aryl bromides is the turnover-limiting step. Key catalytic intermediates were also isolated.

Borane-Catalyzed Tandem Cyclization/Hydrosilylation Towards Enantio- and Diastereoselective Construction of trans-2,3-Disubstituted-1,2,3,4-Tetrahydroquinoxalines.

Recent years have witnessed marked progress in the efficient synthesis of various enantioenriched 1,2,3,4-tetrahydroquinoxalines. However, enantio- and diastereoselective access to trans-2,3-disubstituted 1,2,3,4-tetrahydroquinoxalines remains much less explored. Herein we report that a frustrated Lewis pair-based catalyst generated via in situ hydroboration of 2-vinylnaphthalene with HB(C6 F5 )2 allows for the one-pot tandem cyclization/hydrosilylation of 1,2-diaminobenzenes and 1,2-diketones with commercially available PhSiH3 to exclusively afford trans-2,3-disubstituted 1,2,3,4-tetrahydroquinoxalines in high yields with excellent diastereoselectivities (>20 : 1 dr). Furthermore, this reaction can be rendered asymmetric by using an enantioenriched borane-based catalyst derived from HB(C6 F5 )2 and a binaphthyl-based chiral diene to give rise to enantioenriched trans-2,3-disubstituted 1,2,3,4-tetrahydroquinoxalines in high yields with almost complete diastereo- and enantiocontrol (>20 : 1 dr, up to >99 % ee). A wide substrate scope, good tolerance of diverse functionality and up to 20-gram scale production are demonstrated. The enantio- and diastereocontrol are achieved by the judicious choice of borane catalyst and hydrosilane. The catalytic pathway and the origin of the excellent stereoselectivity are elucidated by mechanistic experiments and DFT calculations.

A transporter for delivering zinc to the developing tiller bud and panicle in rice.

Tiller number is one of the most important agronomic traits that determine rice (Oryza sativa) yield. Active growth of tiller bud (TB) requires high amount of mineral nutrients; however, the mechanism underlying the distribution of mineral nutrients to TB with low transpiration is unknown. Here, we found that the distribution of Zn to TB is mediated by OsZIP4, one of the ZIP (ZRT, IRT-like protein) family members. The expression of OsZIP4 was highly detected in TB and nodes, and was induced by Zn deficiency. Immunostaining analysis revealed that OsZIP4 was mainly expressed in phloem of diffuse vascular bundles in the nodes and the axillary meristem. The mutation of OsZIP4 did not affect the total Zn uptake, but altered Zn distribution; less Zn was delivered to TB and new leaf, but more Zn was retained in the basal stems at the vegetative growth stage. Bioimaging analysis showed that the mutant aberrantly accumulated Zn in enlarged and transit vascular bundles of the basal node, whereas in wild-type high accumulation of Zn was observed in the meristem part. At the reproductive stage, mutation of OsZIP4 resulted in delayed panicle development, which is associated with decreased Zn distribution to the panicles. Collectively, OsZIP4 is involved in transporting Zn to the phloem of diffuse vascular bundles in the nodes for subsequent distribution to TBs and other developing tissues. It also plays a role in transporting Zn to meristem cells in the TBs.

Ligand-Promoted RhI -Catalyzed C2-Selective C-H Alkenylation and Polyenylation of Imidazoles with Alkenyl Carboxylic Acids.

The first RhI -catalyzed, directed decarbonylative C2-H alkenylation of imidazoles with readily available alkenyl carboxylic acids is reported. The reaction proceeds in a highly regio- and stereoselective manner, providing efficient access to C2-alkenylated imidazoles that are generally inaccessible by known C-H alkenylation methods. This transformation accommodates a wide range of alkenyl carboxylic acids, including challenging conjugated polyene carboxylic acids, and diversely decorated imidazoles with high functional group compatibility. The presence of a removable pyrimidine directing group and the use of a bidentate phosphine ligand are pivotal to the success of the catalytic reaction. This process is also suitable for benzimidazoles. Importantly, the scalability and diversification of the products highlight the potential of this protocol in practical applications. Detailed experimental and computational studies provide important insights into the underlying reaction mechanism.

Rhodium(I)-catalyzed directed trideuteromethylation of (hetero)arene C-H bonds with CD3CO2D.

A Rh(I)-catalyzed trideuteromethylation of heteroarenes with inexpensive and readily available deuterated acetic acid (CD3CO2D) with the aid of a N-containing directing groups is developed. The oxidant-free reaction is applicable to a wide range of heteroarene substrates, including 2-pyridones, indoles, aryl rings, pyrroles and carbazoles. It allows installation of CD3 groups under straightforward reaction conditions. It is expected that the salient and practical features of this trideuteromethylation protocol will be of use to academic and industrial researchers.

The role of intramolecular relaxations on the structure and stability of vapor-deposited glasses.

Stable glasses (SGs) are formed through surface-mediated equilibration (SME) during physical vapor deposition (PVD). Unlike intermolecular interactions, the role of intramolecular degrees of freedom in this process remains unexplored. Here, using experiments and coarse-grained molecular dynamics simulations, we demonstrate that varying dihedral rotation barriers of even a single bond, in otherwise isomeric molecules, can strongly influence the structure and stability of PVD glasses. These effects arise from variations in the degree of surface mobility, mobility gradients, and mobility anisotropy, at a given deposition temperature (Tdep). At high Tdep, flexible molecules have access to more configurations, which enhances the rate of SME, forming isotropic SGs. At low Tdep, stability is achieved by out of equilibrium aging of the surface layer. Here, the poor packing of rigid molecules enhances the rate of surface-mediated aging, producing stable glasses with layered structures in a broad range of Tdep. In contrast, the dynamics of flexible molecules couple more efficiently to the glass layers underneath, resulting in reduced mobility and weaker mobility gradients, producing unstable glasses. Independent of stability, the flattened shape of flexible molecules can also promote in-plane orientational order at low Tdep. These results indicate that small changes in intramolecular relaxation barriers can be used as an approach to independently tune the structure and mobility profiles of the surface layer and, thus, the stability and structure of PVD glasses.

Thermodynamics driving phytochemical self-assembly morphological change and efficacy enhancement originated from single and co-decoction of traditional chinese medicine.

Through the self-assembled strategy to improve the clinical efficacy of the existing drugs is the focus of current research. Herbal formula granule is a kind of modern dosage form of traditional Chinese medicine (TCM) which has sprung up in recent decades. However, whether it is equivalent to the TCM decoction that has been used for thousands of years has always been a controversial issue. In this paper, taking the herb pair of Coptidis Rhizoma-Scutellariae Radix and its main component berberine-baicalin as examples, the differences and mechanisms of self-assemblies originated from the co-decoction and physical mixture were studied, respectively. Moreover, the relationship between the morphology and antibacterial effects of self-assemblies was illuminated via multi-technology. Our study revealed that the physical mixture's morphology of both the herb pair and the phytochemicals was nanofibers (NFs), while their co-decoction's morphology was nanospheres (NPs). We also found that the antibacterial activity was enhanced with the change of self-assemblies' morphology after the driving by thermal energy. This might be attributed to that NPs could influence amino acid biosynthesis and metabolism in bacteria. Current study provides a basis that co-decoction maybe beneficial to enhance activity and reasonable use of herbal formula granule in clinic.

Ameliorative effect of betulinic acid against zearalenone exposure triggers testicular dysfunction and oxidative stress in mice via p38/ERK MAPK inhibition and Nrf2-mediated antioxidant defense activation.

Zearalenone (ZEA) is a nonsteroidal estrogenic mycotoxin, which mainly contaminates grains and has estrogen-like effects on the reproductive system. Betulinic acid (BA), a natural lupane-type pentacyclic triterpene, has anti-oxidative and anti-inflammatory properties. This study aimed to investigate whether BA alleviates ZEA-induced testicular damage and explore the possible mechanism. Here, BA ameliorated testicular damage by mitigating the disordered arrangement of seminiferous tubules, the exfoliation of lumen cells, and the increase of cell apoptosis caused by ZEA. Meanwhile, BA alleviated ZEA-triggered testicular damage by restoring hormone levels and sperm motility, and reconstructing the blood-testis-barrier. Moreover, BA alleviated ZEA-exposed testicular oxidative stress by activating Nrf2 pathway. Furthermore, BA moderated ZEA-evoked testicular inflammation by inhibiting p38/ERK MAPK pathway. Overall, our results revealed that BA has a therapeutic protective effect on ZEA-induced testicular injury and oxidative stress via p38/ERK MAPK inhibition and Nrf2-mediated antioxidant defense activation, which provides a viable alternative to alleviate ZEA-induced male reproductive toxicology.

Progress on the functional role of oleosin gene family in plants.

Oil bodies, also known as lipid droplets or oil droplets, are important organelles for oil storage in plant cells. The oil body is composed of a monolayer of phospholipid membrane encapsulating neutral fatty acids, and a variety of membrane proteins are embedded in the membrane, including oleosin, caleosin and steroleosin, of which oleosin accounts for 80%-90%. Oleosin plays important biological roles in various biological roles, such as affecting the size and stability of oil bodies, formation and degradation of oil bodies, lipid metabolism, and seed maturation and germination. In this review, we summarize the sequence and structural characteristics of oleosin and its important role in plant growth and development based on the research progress of plant oleosin gene families at home and abroad in recent years. Additionally, we discuss the application of oleosin in actual production and problems in the research and application, in order to provide a useful reference for people to further study the functions of oleosin-related molecules and their application in production practice.

Rhodium(III)-Catalyzed C-H Bond Functionalization of 2-Pyridones with Alkynes: Switchable Alkenylation, Alkenylation/Directing Group Migration and Rollover Annulation.

Cp*Rh(III)-catalyzed chelation-assisted direct C-H bond functionalization of 1-(2-pyridyl)-2-pyridones with internal alkynes that can be controlled to give three different products in good yields has been realized. Depending on the reaction conditions, solvents and additives, the reaction pathway can be switched between alkenylation, alkenylation/directing group migration and rollover annulation. These reaction manifolds allow divergent access to a variety of valuable C6-alkenylated 1-(2-pyridyl)-2-pyridones, (Z)-6-(1,2-diaryl-2-(pyridin-2-yl)vinyl)pyridin-2(1H)-ones and 10H-pyrido[1,2-a][1,8]naphthyridin-10-ones from the same starting materials. These protocols exhibit excellent regio- and stereoselectivity, broad substrate scope, and good tolerance of functional groups. A combination of experimental and computational approaches have been employed to uncover the key mechanistic features of these reactions.

Design of a homologous series of molecular glassformers.

We design and synthesize a set of homologous organic molecules by taking advantage of facile and tailorable Suzuki cross coupling reactions to produce triarylbenzene derivatives. By adjusting the number and the arrangement of conjugated rings, the identity of heteroatoms, lengths of fluorinated alkyl chains, and other interaction parameters, we create a library of glassformers with a wide range of properties. Measurements of the glass transition temperature (Tg) show a power-law relationship between Tg and molecular weight (MW), with of the molecules, with an exponent of 0.3 ± 0.1, for Tg values spanning a range of 300-450 K. The trends in indices of refraction and expansion coefficients indicate a general increase in the glass density with MW, consistent with the trends observed in Tg variations. A notable exception to these trends was observed with the addition of alkyl and fluorinated alkyl groups, which significantly reduced Tg and increased the dynamical fragility (which is otherwise insensitive to MW). This is an indication of reduced density and increased packing frustrations in these systems, which is also corroborated by the observations of the decreasing index of refraction with increasing length of these groups. These data were used to launch a new database for glassforming materials, glass.apps.sas.upenn.edu.

The transcription factor IbNAC29 positively regulates the carotenoid accumulation in sweet potato.

Carotenoid is a tetraterpene pigment beneficial for human health. Although the carotenoid biosynthesis pathway has been extensively studied in plants, relatively little is known about their regulation in sweet potato. Previously, we conducted the transcriptome database of differentially expressed genes between the sweet potato (Ipomoea batatas) cultivar 'Weiduoli' and its high-carotenoid mutant 'HVB-3'. In this study, we selected one of these candidate genes, IbNAC29, for subsequent analyses. IbNAC29 belongs to the plant-specific NAC (NAM, ATAF1/2, and CUC2) transcription factor family. Relative IbNAC29 mRNA level in the HVB-3 storage roots was ~1.71-fold higher than Weiduoli. Additional experiments showed that the contents of α-carotene, lutein, ß-carotene, zeaxanthin, and capsanthin are obviously increased in the storage roots of transgenic sweet potato plants overexpressing IbNAC29. Moreover, the levels of carotenoid biosynthesis genes in transgenic plants were also up-regulated. Nevertheless, yeast one-hybrid assays indicated that IbNAC29 could not directly bind to the promoters of these carotenoid biosynthesis genes. Furthermore, the level of IbSGR1 was down-regulated, whose homologous genes in tomato can negatively regulate carotene accumulation. Yeast three-hybrid analysis revealed that the IbNAC29-IbMYB1R1-IbAITR5 could form a regulatory module. Yeast one-hybrid, electrophoretic mobility shift assay, quantitative PCR analysis of chromatin immunoprecipitation and dual-luciferase reporter assay showed that IbAITR5 directly binds to and inhibits the promoter activity of IbSGR1, up-regulating carotenoid biosynthesis gene IbPSY. Taken together, IbNAC29 is a potential candidate gene for the genetic improvement of nutritive value in sweet potato.

Role of Molecular Layering in the Enhanced Mechanical Properties of Stable Glasses.

The density, degree of molecular orientation, and molecular layering of vapor-deposited stable glasses (SGs) vary with substrate temperature (Tdep) below the glass-transition temperature (Tg). Density and orientation have been suggested to be factors influencing the mechanical properties of SGs. We perform nanoindentation on two molecules which differ by only a single substituent, allowing one molecule to adopt an in-plane orientation at low Tdep. The reduced elastic modulus and hardness of both molecules show similar Tdep dependences, with enhancements of 15-20% in reduced modulus and 30-45% in hardness at Tdep ≈ 0.8Tg, where the density of vapor-deposited films is enhanced by ∼1.4% compared to that of the liquid-quenched glass. At Tdep < 0.8Tg, one of the molecules produces highly unstable glasses with in-plane orientation. However, both systems show enhanced mechanics. Both the modulus and hardness correlate with the degree of layering, which is similar in both systems despite their variable stability. We suggest that nanoindentation performed normal to the film's surface is influenced by the tighter packing of the molecules in this direction.

Three-phase extraction of polysaccharide from Stropharia rugosoannulata: Process optimization, structural characterization and bioactivities.

The isolation of Stropharia rugosoannulata polysaccharide (SRP) by three-phase extraction was optimized, and its structure and biological activities were identified. The optimal extraction conditions were: mass fraction of ammonium sulfate, 20%; volume ratio of sample solution to t-butanol, 1:1.5; extraction temperature, 35°C. Under these conditions, the yield of SRP was 6.85% ± 0.13%. SRP was found to be composed of glucose (35.79%), galactose (26.80%), glucuronic acid (9.92%), fructose (8.65%), xylose (7.92%), fucose (4.19%), arabinose (3.46%) and rhamnose (3.26%), with the molecular weight of 27.52 kDa. The results of DPPH, hydroxyl, ABTS+ radical scavenging and reducing power tests showed that SRP had good antioxidant capacities. SRP had no cytotoxic effect on RAW264.7 macrophages at the concentrations of 25-200 µg/mL, and could significantly promote phagocytosis activity and cell migration according to CCK-8 assay, phagocytosis assay and cell scratch experiment. SRP can significantly stimulate the transcript expression levels of TNF-α, IL-1ß and IL-6, as determined by RT-PCR and Western blot assays. SRP activated the TLR4/NF-κB signaling pathway, and autophagy also occurred. These results suggest that SRP is a safe antioxidant and immunomodulator, and that it can be used in the development of functional foods and/or pharmaceuticals.

Expression of the Sweet Potato MYB Transcription Factor IbMYB48 Confers Salt and Drought Tolerance in Arabidopsis.

Sweet potato (Ipomoea batatas (L.) Lam) is one of the most crucial food crops widely cultivated worldwide. In plants, MYB transcription factors play crucial roles in plant growth, defense regulation, and stress resistance. However, the regulatory mechanism of MYBs in salt and drought response remain poorly studied in sweet potato. By screening a transcriptome database for differentially expressed genes between the sweet potato variety Jingshu 6 and its mutant JS6-5 with high anthocyanin and increased tolerance to salt and drought stresses, we identified a R2R3-MYB gene IbMYB48, for which expression was induced by PEG6000, NaCl, abscisic acid (ABA), methyl jasmonic acid (MeJA), salicylic acid (SA) and H2O2. Particle-mediated transient transformation of onion epidermal cells showed IbMYB48 is localized in the nucleus. Transactivation activity assay in yeast cells revealed that IbMYB48 has transactivation activity, and its active domain is located in the carboxyl (C)-terminal region. Furthermore, expression of IbMYB48 confers enhanced tolerance to salt and drought stresses in transgenic Arabidopsis. The contents of endogenous ABA, JA, and proline in transgenic lines were higher than control, and the activity of superoxide dismutase (SOD) was significantly increased under salt and drought stress conditions. By contrast, the accumulation of malondialdehyde (MDA) and H2O2 were lower. Moreover, genes encoding enzymes involved in ABA biosynthetic pathway, JA biosynthesis and signaling pathway, and reactive oxygen species (ROS) scavenging system were significantly up-regulated in transgenic Arabidopsis under salt or drought stress. Altogether, these results suggest IbMYB48 may be a candidate gene for improvement of abiotic stress tolerance.

Palladium-catalyzed benzylic C(sp3)-H carbonylative arylation of azaarylmethyl amines with aryl bromides.

A highly selective palladium-catalyzed carbonylative arylation of weakly acidic benzylic C(sp3)-H bonds of azaarylmethylamines with aryl bromides under 1 atm of CO gas has been achieved. This work represents the first examples of use of such weakly acidic pronucleophiles in this class of transformations. In the presence of a NIXANTPHOS-based palladium catalyst, this one-pot cascade process allows a range of azaarylmethylamines containing pyridyl, quinolinyl and pyrimidyl moieties and acyclic and cyclic amines to undergo efficient reactions with aryl bromides and CO to provide α-amino aryl-azaarylmethyl ketones in moderate to high yields with a broad substrate scope and good tolerance of functional groups. This reaction proceeds via in situ reversible deprotonation of the benzylic C-H bonds to give the active carbanions, thereby avoiding prefunctionalized organometallic reagents and generation of additional waste. Importantly, the operational simplicity, scalability and diversity of the products highlight the potential applicability of this protocol.

Betulinic Acid Alleviates Spleen Oxidative Damage Induced by Acute Intraperitoneal Exposure to T-2 Toxin by Activating Nrf2 and Inhibiting MAPK Signaling Pathways.

T-2 toxin, which is mainly produced by specific strains of Fusarium in nature, can induce immunotoxicity and oxidative stress, resulting in immune organ dysfunction and apoptosis. Betulinic acid (BA), a pentacyclic triterpenoids from nature plants, has been demonstrated to possess immunomodulating and antioxidative bioactivities. The purpose of the study was to explore the effect of BA on T-2 toxin-challenged spleen oxidative damage and further elucidate the underlying mechanism. We found that BA not only ameliorated the contents of serum total cholesterol (TC) and triglyceride (TG) but also restored the number of lymphocytes in T-2 toxin-induced mice. BA dose-dependently reduced the accumulation of reactive oxygen species (ROS), enhanced superoxide dismutase (SOD) activity, and decreased malondialdehyde (MDA) content, as well as increased the total antioxidant capacity (T-AOC) in the spleen of T-2-toxin-exposed mice. Moreover, BA reduced inflammatory cell infiltration in the spleen, improved the morphology of mitochondria and enriched the number of organelles in splenocytes, and dramatically attenuated T-2 toxin-triggered splenocyte apoptosis. Furthermore, administration of BA alleviated the protein phosphorylation of p38, c-Jun N-terminal kinase (JNK), and extracellular signal-regulated kinases (ERK); decreased the protein expression of kelch-like erythroid cell-derived protein with CNC homology [ECH]-associated protein1 (Keap1); and increased the protein expression of nuclear factor erythroid 2 [NF-E2]-related factor (Nrf2) and heme oxygenase-1 (HO-1) in the spleen. These findings demonstrate that BA defends against spleen oxidative damage associated with T-2 toxin injection by decreasing ROS accumulation and activating the Nrf2 signaling pathway, as well as inhibiting the mitogen-activated protein kinase (MAPK) signaling pathway.

Cobalt(III)-Catalyzed Regioselective C6 Olefination of 2-Pyridones Using Alkynes: Olefination/Directing Group Migration and Olefination.

Co(III)-catalyzed highly regio- and stereoselective direct C6 olefination of 2-pyridones with alkynes has been developed with the assistance of chelation. Upon variation of the reaction conditions, 2-pyridones react well with diaryl alkynes via a C6 olefination/directing group migration pathway to give the tetrasubstituted 6-vinyl-2-pyridones, but the C6-H olefination with terminal alkynes works effectively to afford only the C6-olefinated 2-pyridones. A judicious choice of a solvent and an additive is crucial for catalysis. The protocols feature 100% atom economy, excellent site selectivity, high stereoselectivity, an ample substrate scope, and good compatibility of functional groups. Synthetic applications are demonstrated, and experimental studies and density functional theory calculations are conducted to gain mechanistic insight into the two transformations.

Betulinic acid protects against renal damage by attenuation of oxidative stress and inflammation via Nrf2 signaling pathway in T-2 toxin-induced mice.

Betulinic acid (BA) is a pentacyclic triterpenoid compound with potential antioxidant and anti-inflammatory effects. In this study, T-2 toxin was injected intraperitoneally in mice to establish kidney damage model and to evaluate the protective effects of BA and further reveal the molecular mechanism. BA pretreatment inhibited the T-2 toxin-stimulated increase in serum Crea, but showed no significant effect on serum Urea. BA pretreatment alleviated excessive glomerular hemorrhage and inflammatory cell infiltration in kidneys caused by T-2 toxin. Moreover, pretreatment with BA mitigated T-2 toxin-induced renal oxidative damage by up-regulating the activities of SOD and CAT, and the content of GSH, while down-regulating the accumulation of ROS and MDA. Meanwhile, BA pretreatment markedly attenuated T-2 toxin-induced renal inflammatory response by decreasing the mRNA expression of IL-1ß, TNF-α and IL-10, and increasing IL-6 mRNA expression. Furthermore, mechanism research found that pretreatment with BA could activate Nrf2 signaling pathway. It was suggested that BA ameliorated the oxidative stress and inflammatory response of T-2 toxin-triggered renal damage by activating the Nrf2 signaling pathway.