Asymmetric Intramolecular Amination Catalyzed with Cp*Ir-SPDO via Nitrene Transfer for Synthesis of Spiro-Quaternary Indolinone.

An asymmetric intramolecular spiro-amination to high steric hindering α-C-H bond of 1,3-dicarbonyl via nitrene transfer using inactive aryl azides has been carried out by developing a novel Cp*Ir(III)-SPDO (spiro-pyrrolidine oxazoline) catalyst, thereby enabling the first successful construction of structurally rigid spiro-quaternary indolinone cores with moderate to high yields and excellent enantioselectivities. DFT computations support the presence of double bridging H-F bonds between [SbF6]- and both the ligand and substrate, which favors the plane-differentiation of the enol π-bond for nitrenoid attacking. These findings open up numerous opportunities for the development of new asymmetric nitrene transfer systems.

Thermally Stable and Transparent Polyimide Derived from Side-Group-Regulated Spirobifluorene Unit for Substrate Application.

Advancements in flexible electronic technology, especially the progress in foldable displays and under-display cameras (UDC), have created an urgent demand for high-performance colorless polyimide (CPI). However, current CPIs lack sufficient heat resistance for substrate applications. In this work, four kinds of rigid spirobifluorene diamines are designed, and the corresponding polyimides are prepared by their condensation with 5,5'-(perfluoropropane-2,2-diyl) bis(isobenzofuran-1,3-dione) (6FDA) or 9,9-bis(3,4-dicarboxyphenyl) fluorene dianhydride (BPAF). The rigid and conjugated spirobifluorene units endow the polyimides with higher glass transition temperature (Tg) ranging from 356 to 468 °C. Their optical properties are regulated by small side groups and spirobifluorene structure with a periodically twisted molecular conformation. Consequently, a series of CPIs with an average transmittance ranging from 75% to 88% and a yellowness index (YI) as low as 2.48 are obtained. Among these, 27SPFTFA-BPAF presents excellent comprehensive performance, with a Tg of 422 °C, a 5 wt.% loss temperature (Td5) of 562 °C, a YI of 3.53, and a tensile strength (δmax) of 140 MPa, respectively. The mechanism underlying the structure-property relationship is investigated by experimental comparison and theoretical calculation, and the proposed method provides a pathway for designing highly rigid conjugated CPIs with excellent thermal stability and transparency for photoelectric engineering.

Molecular basis for cell-wall recycling regulation by transcriptional repressor MurR in Escherichia coli.

The cell-wall recycling process is important for bacterial survival in nutrient-limited conditions and, in certain cases, is directly involved in antibiotic resistance. In the sophisticated cell-wall recycling process in Escherichia coli, the transcriptional repressor MurR controls the expression of murP and murQ, which are involved in transporting and metabolizing N-acetylmuramic acid (MurNAc), generating N-acetylmuramic acid-6-phosphate (MurNAc-6-P) and N-acetylglucosamine-6-phosphate (GlcNAc-6-P). Here, we report that both MurNAc-6-P and GlcNAc-6-P can bind to MurR and weaken the DNA binding ability of MurR. Structural characterizations of MurR in complex with MurNAc-6-P or GlcNAc-6-P as well as in the apo form revealed the detailed ligand recognition chemistries. Further studies showed that only MurNAc-6-P, but not GlcNAc-6-P, is capable of derepressing the expression of murQP controlled by MurR in cells and clarified the substrate specificity through the identification of key residues responsible for ligand binding in the complex structures. In summary, this study deciphered the molecular mechanism of the cell wall recycling process regulated by MurR in E. coli.

Total Syntheses of Polycyclic Diterpenes Phomopsene, Methyl Phomopsenonate, and iso-Phomopsene via Reorganization of C-C Single Bonds.

The first total syntheses of polycyclic diterpenes phomopsene (1), methyl phomopsenonate (2), and iso-phomopsene (3) have been accomplished through the unusual cascade reorganization of C-C single bonds. This approach features: (i) a synergistic Nazarov cyclization/double ring expansions in one-step, developed by authors, to rapid and stereospecific construction of the 5/5/5/5 tetraquinane scaffold bearing contiguous quaternary centers and (ii) a one-pot strategic ring expansion through Beckmann fragmentation/recombination to efficiently assemble the requisite 5/5/6/5 tetracyclic skeleton of the target molecules 1-3. This work enables us to determine that the correct structure of iso-phomopsene is, in fact, the C7 epimer of the originally assigned structure. Finally, the absolute configurations of three target molecules were confirmed through enantioselective synthesis.

An Axially Chiral Styrene-Phosphine Ligand for Pd-Catalyzed Asymmetric N-Alkylation of Indoles.

An efficient palladium-catalyzed enantioselective direct N-alkylation of indoles using a novel type of axially chiral styrene-phosphine ligand SJTU-PHOS-1 was developed. This reaction demonstrated good functional group compatibility and a wide range scope of substrates in mild conditions. Moreover, the DFT calculations expounded the coordination mode of the metal catalyst and the axially chiral styrene-phosphine ligand in the enantioselectivity control.

Asymmetric Intramolecular Hydroalkylation of Internal Olefin with Cycloalkanone to Directly Access Polycyclic Systems.

An asymmetric intramolecular hydroalkylation of unactivated internal olefins with tethered cyclic ketones was realized by the cooperative catalysis of a newly designed chiral amine (SPD-NH2 ) and PdII complex, providing straightforward access to either bridged or fused bicyclic systems containing three stereogenic centers with excellent enantioselectivity (up to 99 % ee) and diastereoselectivity (up to >20 : 1 dr). Notably, the bicyclic products could be conveniently transformed into a diverse range of key structures frequently found in bioactive terpenes, such as Δ6 -protoilludene, cracroson D, and vulgarisins. The steric hindrance between the Ar group of the SPD-NH2 catalyst and the branched chain of the substrate, hydrogen-bonding interactions between the N-H of the enamine motif and the C=O of the directing group MQ, and the counterion of the PdII complex were identified as key factors for excellent stereoinduction in this dual catalytic process by density functional theory calculations.

The Molecular Basis of Catalysis by SDR Family Members Ketoacyl-ACP Reductase FabG and Enoyl-ACP Reductase FabI in Type-II Fatty Acid Biosynthesis.

The short-chain dehydrogenase/reductase (SDR) superfamily members acyl-ACP reductases FabG and FabI are indispensable core enzymatic modules and catalytic orientation controllers in type-II fatty acid biosynthesis. Herein, we report their distinct substrate allosteric recognition and enantioselective reduction mechanisms. FabG achieves allosteric regulation of ACP and NADPH through ACP binding across two adjacent FabG monomers, while FabI follows an irreversible compulsory order of substrate binding in that NADH binding must precede that of ACP on a discrete FabI monomer. Moreover, FabG and FabI utilize a backdoor residue Phe187 or a "rheostat" α8 helix for acyl chain length selection, and their corresponding triad residues Ser142 or Tyr145 recognize the keto- or enoyl-acyl substrates, respectively, facilitating initiation of nucleophilic attack by NAD(P)H. The other two triad residues (Tyr and Lys) mediate subsequent proton transfer and (R)-3-hydroxyacyl- or saturated acyl-ACP production.

Bioinspired Palladium-Catalyzed Intramolecular C(sp3 )-H Activation for the Collective Synthesis of Proline Natural Products.

Bioinspired palladium-catalyzed intramolecular cyclization of amino acid derivatives containing a vinyl iodide moiety by C-H activation enabled rapid access to a wide range of functionalized proline derivatives with an exocyclic olefin. To demonstrate the practicality of this methodology, the functionalized prolines were used as intermediates for the synthesis of several natural products: lucentamycin A, oxotomaymycin, oxoprothracarcin, and barmumycin.

High brightness silicon nanocrystal white light-emitting diode with luminance of 2060 cd/m2.

High brightness Si nanocrystal white light-emitting diodes (WLED) based on differentially passivated silicon nanocrystals (SiNCs) are reported. The active layer was made by mixing freestanding SiNCs with hydrogen silsesquioxane, followed by annealing at moderately high temperatures, which finally led to a continuous spectral light emission covering red, green and blue regimes. The photoluminescence quantum yield (PLQY) of the active layer was 11.4%. The SiNC WLED was composed of a front electrode, electron transfer layer, front charge confinement layer, highly luminescent active layer, rear charge confinement layer, hole transfer layer, textured p-type Si substrate and aluminum rear electrode from top to bottom. The peak luminance of the SiNC WLED achieved was 2060 cd/m2. The turn-on voltage was 3.7 V. The chromaticity of the SiNC WLED indicated white light emission that could be adjusted by changing the annealing temperature of the active layer with color temperatures ranging from 3686 to 5291 K.

Paired Electrolysis Enabled Ni-Catalyzed Unconventional Cascade Reductive Thiolation Using Sulfinates.

Herein, we have reported a nickel-catalyzed cascade reductive thiolation of aryl halides with sulfinates driven by paired electrolysis. This protocol uses sulfinates as the sulfur source, and various thioethers could be synthesized under mild conditions. By mechanism exploration, we find that a cascade chemical step is allowed on the electrode interface and could alter the reaction pathway in paired electrolysis, whose findings could help the discovery of novel cascade reactions with unique reactivity.

Circular RNA-CDR1as is involved in lung injury induced by long-term formaldehyde inhalation.

OBJECTIVE: Formaldehyde (FA) is known to induce lung injury, but the underlying molecular mechanism remains largely unclear. CDR1as is an important member of the circular RNAs (circRNAs) family and functions as miRNA sponges with gene-regulatory potential. Our earlier circRNA microarray data showed CDR1as was highly expressed in lung tissue exposed to FA. However, the mechanism of circRNA-CDR1as mediates the FA-exposed lung injury is still unclear. This study aimed to explore the role of CDR1as in lung injury. MATERIALS AND METHODS: In this study, FA was inhaled at doses of 0.5, 2.46, and 5 mg/m3, respectively. After exposure 8 weeks, lung histopathological examination, lung injury score, and IL-1ß in bronchoalveolar lavage fluid (BALF) were determined. The expressions of CDR1as, rno-miR-7b and Atg7 were detected and the potential interaction of circRNA/miRNA/mRNA was predicted by bioinformatics analysis, including drawing circRNA/miRNA/mRNA interaction network, GO and KEGG analysis. RESULTS: Our results indicated FA inhalation upregulated the expression of CDR1as in lung tissues in a dose-dependent manner while the expression of rno-miR-7b decreased and Atg7 increased. Moreover, the alteration of CDR1as was positively correlated with lung injury. DISCUSSION AND CONCLUSIONS: CircRNA/miRNA/mRNA prediction further explained the possible effect mechanisms of CDR1as. These data implicated that CDR1as might be a critical regulator involved in lung injury induced by FA.

Mechanistic insights into staphylopine-mediated metal acquisition.

Metal acquisition is vital to pathogens for successful infection within hosts. Staphylopine (StP), a broad-spectrum metallophore biosynthesized by the major human pathogen, Staphylococcus aureus, plays a central role in transition-metal acquisition and bacterial virulence. The StP-like biosynthesis loci are present in various pathogens, and the proteins responsible for StP/metal transportation have been determined. However, the molecular mechanisms of how StP/metal complexes are recognized and transported remain unknown. We report multiple structures of the extracytoplasmic solute-binding protein CntA from the StP/metal transportation system in apo form and in complex with StP and three different metals. We elucidated a sophisticated metal-bound StP recognition mechanism and determined that StP/metal binding triggers a notable interdomain conformational change in CntA. Furthermore, CRISPR/Cas9-mediated single-base substitution mutations and biochemical analysis highlight the importance of StP/metal recognition for StP/metal acquisition. These discoveries provide critical insights into the study of novel metal-acquisition mechanisms in microbes.

[Histone ubiquitylation and its roles in DNA damage response].

Ubiquitylation is an essential type of protein post-translational modifications (PTMs) in eukaryotes, which mediates various biological processes by regulating the subcellular localization, activity, and stability of proteins. Histones, as the main protein ingredients of chromatin, are closely coupled with DNA activities such as replication, transcription and repair, and therefore are the hotspots of PTMs. After DNA damage, histone ubiquitylations are involved in DNA damage response (DDR) by regulating nucleosome structure, activating cell cycle checkpoints, remodeling the nucleosome, and the recruitment and assembly of repair factors. Meanwhile, histone ubiquitylations can also crosstalk with other types of PTMs to regulate DDR processes. In this review, we summarize how the site-specific histone ubiquitylation forms signal network and contributes to DDR, which may shed light on the further study of how histone codes formed by histone PTMs affect the entire DDR processes.

Copper-Complex-Catalyzed Asymmetric Aerobic Oxidative Cross-Coupling of 2-Naphthols: Enantioselective Synthesis of 3,3'-Substituted C1 -Symmetric BINOLs.

A novel chiral 1,5-N,N-bidentate ligand based on a spirocyclic pyrrolidine oxazoline backbone was designed and prepared, and it coordinates CuBr in situ to form an unprecedented catalyst that enables efficient oxidative cross-coupling of 2-naphthols. Air serves as an external oxidant and generates a series of C1 -symmetric chiral BINOL derivatives with high enantioselectivity (up to 99 % ee) and good yield (up to 87 %). This approach is tolerant of a broader substrates scope, particularly substrates bearing various 3- and 3'-substituents. A preliminary investigation using one of the obtained C1 -symmetric BINOL products was used as an organocatalyst, exhibiting better enantioselectivity than the previously reported organocatalyst, for the asymmetric α-alkylation of amino esters.

Lewis Base/Brønsted Acid Co-catalyzed Enantioselective Sulfenylation/Semipinacol Rearrangement of Di- and Trisubstituted Allylic Alcohols.

An enantioselective sulfenylation/semipinacol rearrangement of 1,1-disubstituted and trisubstituted allylic alcohols was accomplished with a chiral Lewis base and a chiral Brønsted acid as cocatalysts, generating various ß-arylthio ketones bearing an all-carbon quaternary center in moderate to excellent yields and excellent enantioselectivities. These chiral arylthio ketone products are common intermediates with many applications, for example, in the design of new chiral catalysts/ligands and the total synthesis of natural products. Computational studies (DFT calculations) were carried out to explain the enantioselectivity and the role of the chiral Brønsted acid. Additionally, the synthetic utility of this method was exemplified by an enantioselective total synthesis of (-)-herbertene and a one-pot synthesis of a chiral sulfoxide and sulfone.

Recent progress in the isolation, bioactivity, biosynthesis, and total synthesis of natural spiroketals.

Covering: 2011 to July 2017.Spiroketal (spiroacetal), a common moiety in numerous natural products, drugs and functional molecules, has been a central topic in organic chemistry for a long time. Owing to their structural diversity, important bioactivity and functional irreplaceability, natural spiroketals have attracted the interest of natural product chemists, medical chemists, biological chemists, agricultural chemists, synthetic chemists, and chemical biologists. In this review, we focus on the overview of the isolation, bioactivity, biosynthesis and total synthesis of spiroketals from 2011 to July 2017.

Effects of Simulated Heat Wave and Ozone on High Fat Diet ApoE Deficient Mice.

OBJECTIVE: To discuss the cardiac toxicities of a heat waves and ozone exposure on cardiovascular diseases (CVDs) and explore a possible mechanism. METHODS: The incidence of ozone exposure combined with heat wave was simulated in the Shanghai Meteorological and Environmental Animal Exposure System (Shanghai-METAS). A total of 64 ApoE-/- mice, matched by weight, were randomly divided into 8 groups and exposed to heat wave conditions or ozone. The levels of creatine kinase (CK), D-lactate dehydrogenase (D-LDH), intercellular adhesion molecule 1 (sICAM-1), tumor necrosis factor alpha (TNF-α), nitric oxide (NO), endothelin-1 (ET-1), D-dimer (D2D), plasminogen activator inhibitor-1 (PAI-1) and blood lipid in plasma and heat shock protein-60 (HSP60), hypoxia inducible factor 1 alpha (HIF-1α), interleukin-6 (IL-6), C-reactive protein (CRP), superoxide dismutase (SOD), and malondialdehyde (MDA) in hearts were measured after exposure. RESULTS: The levels of all indicators, except for SOD, increased with the ozone-only exposure. However, cardiac damage was most significant when the heat wave conditions were combined with severe ozone exposure. Moreover, the levels of CK, D-LDH, NO, PAI-1, sICAM-1, and TNF-α in plasma increased significantly (P < 0.05), and the contents of HSP60, HIF-1α, CRP, and MDA in hearts increased considerably (P < 0.05), but the activity of SOD decreased significantly. In addition, the levels of four blood lipid items remarkably increased (except the level of HDL-C which decreased significantly) with ozone exposure. CONCLUSION: A short-term exposure to a heat wave and ozone causes severe toxic effects on the heart. Cardiac damage was most significant under combined heat wave and severe ozone exposure simulations.

A Facile Approach to Oximes and Ethers by a Tandem NO+ -Initiated Semipinacol Rearrangement and H-Elimination.

An efficient oximation method has been developed on the basis of NO+ -initiated semipinacol rearrangement and subsequent proton elimination. The procedure enabled the rapid construction of a series of oximes and oxime ethers with spiro quaternary stereocenters from allylic silyl ethers. Additional features of this reaction include wide substrate tolerance as well as the commercial availability of the safe nitrosation reagent NOBF4 . The key N-heterotricyclic cores of three natural alkaloids, tuberostemoninol B, (+)-quebrachidine, and an insecticide, were also constructed efficiently by this method.

A novel RAB39B gene mutation in X-linked juvenile parkinsonism with basal ganglia calcification.

OBJECTIVES: Mutations in RAB39B have been reported as a potential cause of X-linked Parkinson's disease (PD), a rare form of familial PD. We conducted a genetic analysis on RAB39B to evaluate whether RAB39B mutations are related to PD in the Chinese population. METHODS: In this study, 2 patients from an X-linked juvenile parkinsonism pedigree were clinically characterized and underwent whole-exome sequencing. A comprehensive screening for RAB39B mutations in 505 sporadic patients with PD and 510 healthy controls in a Chinese population was also performed. RESULTS: A novel mutation, c. 536dupA (p.E179fsX48), in RAB39B was identified in the juvenile parkinsonism pedigree. Brain MRI and CT scans in the 2 patients revealed calcification within the bilateral globus pallidus. No other potentially disease-causing RAB39B mutations were found in sporadic PD patients and controls. CONCLUSIONS: X-linked juvenile parkinsonism could be caused by a RAB39B mutation, and basal ganglia calcification may be a novel clinical feature of RAB39B-related parkinsonism. © 2016 International Parkinson and Movement Disorder Society.