Bridged [2.2.1] bicyclic phosphine oxide facilitates catalytic γ-umpolung addition-Wittig olefination.

A novel bridged [2.2.1] bicyclic phosphine oxide, devised to circumvent the waste generation and burdens of purification that are typical of reactions driven by the generation of phosphine oxides, has been prepared in three steps from commercially available cyclopent-3-ene-1-carboxylic acid. The performance of this novel phosphine oxide was superior to those of current best-in-class counterparts, as verified experimentally through kinetic analysis of its silane-mediated reduction. It has been applied successfully in halide-/base-free catalytic γ-umpolung addition-Wittig olefinations of allenoates and 2-amidobenzaldehydes to produce 1,2-dihydroquinolines with good efficiency. One of the 1,2-dihydroquinoline products was converted to known antitubercular furanoquinolines

SAM-dependent enzyme-catalysed pericyclic reactions in natural product biosynthesis.

Pericyclic reactions-which proceed in a concerted fashion through a cyclic transition state-are among the most powerful synthetic transformations used to make multiple regioselective and stereoselective carbon-carbon bonds. They have been widely applied to the synthesis of biologically active complex natural products containing contiguous stereogenic carbon centres. Despite the prominence of pericyclic reactions in total synthesis, only three naturally existing enzymatic examples (the intramolecular Diels-Alder reaction, and the Cope and the Claisen rearrangements) have been characterized. Here we report a versatile S-adenosyl-l-methionine (SAM)-dependent enzyme, LepI, that can catalyse stereoselective dehydration followed by three pericyclic transformations: intramolecular Diels-Alder and hetero-Diels-Alder reactions via a single ambimodal transition state, and a retro-Claisen rearrangement. Together, these transformations lead to the formation of the dihydropyran core of the fungal natural product, leporin. Combined in vitro enzymatic characterization and computational studies provide insight into how LepI regulates these bifurcating biosynthetic reaction pathways by using SAM as the cofactor. These pathways converge to the desired biosynthetic end product via the (SAM-dependent) retro-Claisen rearrangement catalysed by LepI. We expect that more pericyclic biosynthetic enzymatic transformations remain to be discovered in naturally occurring enzyme 'toolboxes'. The new role of the versatile cofactor SAM is likely to be found in other examples of enzyme catalysis

Chronology of CH···O Hydrogen Bonding from Molecular Dynamics Studies of the Phosphoric Acid-Catalyzed Allylboration of Benzaldehyde

CH···O hydrogen bonds involving formyl groups have been invoked as a crucial factor controlling many asymmetric transformations. We conducted quasi-classical direct molecular dynamics simulations on the phosphoric acid-catalyzed allylboration of benzaldehyde to understand the synergy between the phosphoric acid OH···O hydrogen bond and the secondary CH···O formyl hydrogen bond as the reaction occurs. In the gas phase, both the CH···O and OH···O hydrogen bonds are enhanced from reactants to transition states. In toluene, the trend of H-bond enhancement is observed with a smaller magnitude because of solvent caging. The strength of the formyl hydrogen bond in the TS, a second CH···O interaction between the P═O oxygen and $\textit{ortho}$-hydrogen of the phenyl ring and the OH···O hydrogen bond were determined using quantum mechanical calculations (4.6, 1.0, and 14.5 kcal mol$^{-1}$, respectively).We are grateful to The English-Speaking Union (Lindemann Trust Fellowship to M.N.G.), Girton College, Cambridge (Research Fellowship to M.N.G.) and the NSF (CHE-1361104 to K.N.H.) for financial support. Computational resources were provided by the UCLA Institute for Digital Research and Education (IDRE) and the Extreme Science and Engineering Discovery Environment (XSEDE), which is supported by the NSF (OCI-1053575)

Quantifying Inactive Lithium in Lithium Metal Batteries

Inactive lithium (Li) formation is the immediate cause of capacity loss and catastrophic failure of Li metal batteries. However, the chemical component and the atomic level structure of inactive Li have rarely been studied due to the lack of effective diagnosis tools to accurately differentiate and quantify Li+ in solid electrolyte interphase (SEI) components and the electrically isolated unreacted metallic Li0, which together comprise the inactive Li. Here, by introducing a new analytical method, Titration Gas Chromatography (TGC), we can accurately quantify the contribution from metallic Li0 to the total amount of inactive Li. We uncover that the Li0, rather than the electrochemically formed SEI, dominates the inactive Li and capacity loss. Using cryogenic electron microscopies to further study the microstructure and nanostructure of inactive Li, we find that the Li0 is surrounded by insulating SEI, losing the electronic conductive pathway to the bulk electrode. Coupling the measurements of the Li0 global content to observations of its local atomic structure, we reveal the formation mechanism of inactive Li in different types of electrolytes, and identify the true underlying cause of low Coulombic efficiency in Li metal deposition and stripping. We ultimately propose strategies to enable the highly efficient Li deposition and stripping to enable Li metal anode for next generation high energy batteries

STM and RHEED study of the Si(001)-c(8x8) surface

The Si(001) surface deoxidized by short annealing at T~925C in the ultrahigh vacuum molecular beam epitaxy chamber has been in situ investigated by high resolution scanning tunnelling microscopy (STM) and reflected high energy electron diffraction (RHEED). RHEED patterns corresponding to (2x1) and (4x4) structures were observed during sample treatment. The (4x4) reconstruction arose at T<600C after annealing. The reconstruction was observed to be reversible: the (4x4) structure turned into the (2x1) one at T>600C, the (4x4) structure appeared again at recurring cooling. The c(8x8) reconstruction was revealed by STM at room temperature on the same samples. A fraction of the surface area covered by the c(8x8) structure decreased as the sample cooling rate was reduced. The (2x1) structure was observed on the surface free of the c(8x8) one. The c(8x8) structure has been evidenced to manifest itself as the (4x4) one in the RHEED patterns. A model of the c(8x8) structure formation has been built on the basis of the STM data. Origin of the high-order structure on the Si(001) surface and its connection with the epinucleation phenomenon are discussed.Comment: 26 pages, 12 figure

Antimony-doped graphene nanoplatelets

Heteroatom doping into the graphitic frameworks have been intensively studied for the development of metal-free electrocatalysts. However, the choice of heteroatoms is limited to non-metallic elements and heteroatom-doped graphitic materials do not satisfy commercial demands in terms of cost and stability. Here we realize doping semimetal antimony (Sb) at the edges of graphene nanoplatelets (GnPs) via a simple mechanochemical reaction between pristine graphite and solid Sb. The covalent bonding of the metalloid Sb with the graphitic carbon is visualized using atomic-resolution transmission electron microscopy. The Sb-doped GnPs display zero loss of electrocatalytic activity for oxygen reduction reaction even after 100,000 cycles. Density functional theory calculations indicate that the multiple oxidation states (Sb3+ and Sb5+) of Sb are responsible for the unusual electrochemical stability. Sb-doped GnPs may provide new insights and practical methods for designing stable carbon-based electrocatalystsclose0

PhySpeTree: an automated pipeline for reconstructing phylogenetic species trees

Background Phylogenetic species trees are widely used in inferring evolutionary relationships. Existing software and algorithms mainly focus on phylogenetic inference. However, less attention has been paid to intermediate steps, such as processing extremely large sequences and preparing configure files to connect multiple software. When the species number is large, the intermediate steps become a bottleneck that may seriously affect the efficiency of tree building. Results Here, we present an easy-to-use pipeline named PhySpeTree to facilitate the reconstruction of species trees across bacterial, archaeal, and eukaryotic organisms. Users need only to input the abbreviations of species names; PhySpeTree prepares complex configure files for different software, then automatically downloads genomic data, cleans sequences, and builds trees. PhySpeTree allows users to perform critical steps such as sequence alignment and tree construction by adjusting advanced options. PhySpeTree provides two parallel pipelines based on concatenated highly conserved proteins and small subunit ribosomal RNA sequences, respectively. Accessory modules, such as those for inserting new species, generating visualization configurations, and combining trees, are distributed along with PhySpeTree. Conclusions Together with accessory modules, PhySpeTree significantly simplifies tree reconstruction. PhySpeTree is implemented in Python running on modern operating systems (Linux, macOS, and Windows). The source code is freely available with detailed documentation (https://github.com/yangfangs/physpetools)

Machine-Part cell formation through visual decipherable clustering of Self Organizing Map

Machine-part cell formation is used in cellular manufacturing in order to process a large variety, quality, lower work in process levels, reducing manufacturing lead-time and customer response time while retaining flexibility for new products. This paper presents a new and novel approach for obtaining machine cells and part families. In the cellular manufacturing the fundamental problem is the formation of part families and machine cells. The present paper deals with the Self Organising Map (SOM) method an unsupervised learning algorithm in Artificial Intelligence, and has been used as a visually decipherable clustering tool of machine-part cell formation. The objective of the paper is to cluster the binary machine-part matrix through visually decipherable cluster of SOM color-coding and labelling via the SOM map nodes in such a way that the part families are processed in that machine cells. The Umatrix, component plane, principal component projection, scatter plot and histogram of SOM have been reported in the present work for the successful visualization of the machine-part cell formation. Computational result with the proposed algorithm on a set of group technology problems available in the literature is also presented. The proposed SOM approach produced solutions with a grouping efficacy that is at least as good as any results earlier reported in the literature and improved the grouping efficacy for 70% of the problems and found immensely useful to both industry practitioners and researchers.Comment: 18 pages,3 table, 4 figure

Synthesis, Biological Evaluation and Mechanism Studies of Deoxytylophorinine and Its Derivatives as Potential Anticancer Agents

Previous studies indicated that (+)-13a-(S)-Deoxytylophorinine (1) showed profound anti-cancer activities both in vitro and in vivo and could penetrate the blood brain barrier to distribute well in brain tissues. CNS toxicity, one of the main factors to hinder the development of phenanthroindolizidines, was not obviously found in 1. Based on its fascinating activities, thirty-four derivatives were designed, synthesized; their cytotoxic activities in vitro were tested to discover more excellent anticancer agents. Considering the distinctive mechanism of 1 and interesting SAR of deoxytylophorinine and its derivatives, the specific impacts of these compounds on cellular progress as cell signaling transduction pathways and cell cycle were proceeded with seven representative compounds. 1 as well as three most potent compounds, 9, 32, 33, and three less active compounds, 12, 16, 35, were selected to proform this study to have a relatively deep view of cancer cell growth-inhibitory characteristics. It was found that the expressions of phospho-Akt, Akt, phospho-ERK, and ERK in A549 cells were greater down-regulated by the potent compounds than by the less active compounds in the Western blot analysis. To the best of our knowledge, this is the first report describing phenanthroindolizidines alkaloids display influence on the crucial cell signaling proteins, ERK. Moreover, the expressions of cyclin A, cyclin D1 and CDK2 proteins depressed more dramatically when the cells were treated with 1, 9, 32, and 33. Then, these four excellent compounds were subjected to flow cytometric analysis, and an increase in S-phase was observed in A549 cells. Since the molecular level assay results of Western blot for phospho-Akt, Akt, phospho-ERK, ERK, and cyclins were relevant to the potency of compounds in cellular level, we speculated that this series of compounds exhibit anticancer activities through blocking PI3K and MAPK signaling transduction pathways and interfering with the cell cycle progression

Poly(ADP-ribose) polymerase family member 14 (PARP14) is a novel effector of the JNK2-dependent pro-survival signal in multiple myeloma

Copyright @ 2013 Macmillan Publishers Limited. This is the author's accepted manuscript. The final published article is available from the link below.Regulation of cell survival is a key part of the pathogenesis of multiple myeloma (MM). Jun N-terminal kinase (JNK) signaling has been implicated in MM pathogenesis, but its function is unclear. To elucidate the role of JNK in MM, we evaluated the specific functions of the two major JNK proteins, JNK1 and JNK2. We show here that JNK2 is constitutively activated in a panel of MM cell lines and primary tumors. Using loss-of-function studies, we demonstrate that JNK2 is required for the survival of myeloma cells and constitutively suppresses JNK1-mediated apoptosis by affecting expression of poly(ADP-ribose) polymerase (PARP)14, a key regulator of B-cell survival. Strikingly, we found that PARP14 is highly expressed in myeloma plasma cells and associated with disease progression and poor survival. Overexpression of PARP14 completely rescued myeloma cells from apoptosis induced by JNK2 knockdown, indicating that PARP14 is critically involved in JNK2-dependent survival. Mechanistically, PARP14 was found to promote the survival of myeloma cells by binding and inhibiting JNK1. Moreover, inhibition of PARP14 enhances the sensitization of MM cells to anti-myeloma agents. Our findings reveal a novel regulatory pathway in myeloma cells through which JNK2 signals cell survival via PARP14, and identify PARP14 as a potential therapeutic target in myeloma.Kay Kendall Leukemia Fund, NIH, Cancer Research UK, Italian Association for Cancer Research and the Foundation for Liver Research