Network-analysis-guided synthesis of weisaconitine D and liljestrandinine.

General strategies for the chemical synthesis of organic compounds, especially of architecturally complex natural products, are not easily identified. Here we present a method to establish a strategy for such syntheses, which uses network analysis. This approach has led to the identification of a versatile synthetic intermediate that facilitated syntheses of the diterpenoid alkaloids weisaconitine D and liljestrandinine, and the core of gomandonine. We also developed a web-based graphing program that allows network analysis to be easily performed on molecules with complex frameworks. The diterpenoid alkaloids comprise some of the most architecturally complex and functional-group-dense secondary metabolites isolated. Consequently, they present a substantial challenge for chemical synthesis. The synthesis approach described here is a notable departure from other single-target-focused strategies adopted for the syntheses of related structures. Specifically, it affords not only the targeted natural products, but also intermediates and derivatives in the three families of diterpenoid alkaloids (C-18, C-19 and C-20), and so provides a unified synthetic strategy for these natural products. This work validates the utility of network analysis as a starting point for identifying strategies for the syntheses of architecturally complex secondary metabolites

A mechanophysical phase transition provides a dramatic example of colour polymorphism: the tribochromism of a substituted tri(methylene)tetrahydrofuran-2-one

BACKGROUND: Derivatives of fulgides have been shown to have interesting photochromic properties. We have synthesised a number of such derivatives and have found, in some cases, that crystals can be made to change colour on crushing, a phenomenon we have termed "tribochromism". We have studied a number of derivatives by X-ray crystallography, to see if the colour is linked to molecular structure or crystal packing, or both, and our structural results have been supported by calculation of molecular and lattice energies. RESULTS: A number of 5-dicyanomethylene-4-diphenylmethylene-3-disubstitutedmethylene-tetrahydrofuran-2-one compounds have been prepared and structurally characterised. The compounds are obtained as yellow or dark red crystals, or, in one case, both. In two cases where yellow crystals were obtained, we found that crushing the crystals gave a deep red powder. Structure determinations, including those of the one compound which gave both coloured forms, depending on crystallisation conditions, showed that the yellow crystals contained molecules in which the structure comprised a folded conformation at the diphenylmethylene site, whilst the red crystals contained molecules in a twisted conformation at this site. Lattice energy and molecular conformation energies were calculated for all molecules, and showed that the conformational energy of the molecule in structure IIIa (yellow) is marginally higher, and the conformation thus less stable, than that of the molecule in structure IIIb (red). However, the van der Waals energy for crystal structure IIIa, is slightly stronger than that of structure IIIb - which may be viewed as a hint of a metastable packing preference for IIIa, overcome by the contribution of a more stabilising Coulomb energy to the overall more favourable lattice energy of structure IIIb. CONCLUSIONS: Our studies have shown that the crystal colour is correlated with one of two molecular conformations which are different in energy, but that the less stable conformation can be stabilised by its host crystal lattice. Graphical abstractGraphical representation of the structural and colour change in the tribochromic compound (III)

Insights into antibody catalysis: Structure of an oxygenation catalyst at 1.9-Å resolution

The x-ray crystal structures of the sulfide oxidase antibody 28B4 and of antibody 28B4 complexed with hapten have been solved at 2.2-Å and 1.9-Å resolution, respectively. To our knowledge, these structures are the highest resolution catalytic antibody structures to date and provide insight into the molecular mechanism of this antibody-catalyzed monooxygenation reaction. Specifically, the data suggest that entropic restriction plays a fundamental role in catalysis through the precise alignment of the thioether substrate and oxidant. The antibody active site also stabilizes developing charge on both sulfur and periodate in the transition state via cation-pi and electrostatic interactions, respectively. In addition to demonstrating that the active site of antibody 28B4 does indeed reflect the mechanistic information programmed in the aminophosphonic acid hapten, these high-resolution structures provide a basis for enhancing turnover rates through mutagenesis and improved hapten design

Humidity control in different building applications; restaurant and operation theatre

Air conditioning (AC) in tropical climate required dehumidification of air at a low dew point temperature to meet humidity standard. This increase the required cooling energy and heating energy is needed to raise the supply air temperature to meet the room’s design temperature. This research was carried out to study energy efficiency and indoor environment factor in two different applications that is restaurant and operation theatre (OT). A method was proposed to enhance the humidity control and energy efficiency in the AC system by applying psychrometric analysis based on actual measurement. Three (3) different systems were used in this study that consists of economizer damper, desiccant wheel and heat pipe heat exchanger (HPHX).The economizer damper analysed base on fresh air intake requirement for ventilation purposes on standard ASHRAE 55 (2010). Manufacturing software by Novelaire and HPC were used to perform the psychorometric analysis for desiccant wheel and HPHX. At the restaurant, the grand total loads (Qt) of the existing AC system were 296.1 kW as to meet temperature and humidity level requirement. The Qt was reduced to 153.8 kW for economizer damper, 170 kW with heating 60.38 kW for desiccant wheel and 178.3 kW with heating 4.1 kW for HPHX. In actual measurement for the OT, the existing AC system had a grand total load Qt of 90.1 kW with heating 5.6 kW and it did not meet the humidity level requirement. However, the AC system required Qt 95.9 kW with heating 12.2 kW as to meet the humidity level requirement for an OT. By using the HPHX in the system, a reduced Qt of 81.6 kW with heating 17.7 kW was achieved, where as a Qt of 100.8 kW with heating 39.9 kW was attained by utilizing the desiccant wheel, whilst maintaining the humidity level requirement. The economizer damper was not applicable for the OT because the OT requires 100% fresh air intake. As a conclusion, damper economizer was beneficial for energy efficiency in restaurants with reducing of 48% energy used and HPHX was beneficial for energy efficiency with reduced 9.4% in OT compared with existing AC system

Double Carbon−Hydrogen Activation of 2-Vinylpyridine: Synthesis of Tri- and Pentanuclear Clusters Containing the μ-NC\u3csub\u3e5\u3c/sub\u3eH\u3csub\u3e4\u3c/sub\u3eCH═C Ligand

Reactions of 2-vinylpyridine with the triruthenium complexes [Ru3(CO)12] and [Ru3(CO)10(μ-dppm)] leads to a previously unknown double carbon−hydrogen bond activation of the β-carbon of the vinyl group to afford the pentaruthenium and triruthenium complexes [Ru5(CO)14(μ4-C5H4CH═C)(μ-H)2] (1) and [Ru3Cl(CO)5(μ-CO)(μ-dppm)(μ3-NC5H4CH═C)(μ-H)] (2), respectively. Crystal structures reveal two different forms of bridging of the dimetalated 2-vinylpyridyl ligand, capping a square face in 1 and a triangular face in 2

Desirable properties for XML update mechanisms

The adoption of XML as the default data interchange format and the standardisation of the XPath and XQuery languages has resulted in significant research in the development and implementation of XML databases capable of processing queries efficiently. The ever-increasing deployment of XML in industry and the real-world requirement to support efficient updates to XML documents has more recently prompted research in dynamic XML labelling schemes. In this paper, we provide an overview of the recent research in dynamic XML labelling schemes. Our motivation is to define a set of properties that represent a more holistic dynamic labelling scheme and present our findings through an evaluation matrix for most of the existing schemes that provide update functionality

A computer graphics program for general finite element analyses

Documentation for a computer graphics program for displays from general finite element analyses is presented. A general description of display options and detailed user instructions are given. Several plots made in structural, thermal and fluid finite element analyses are included to illustrate program options. Sample data files are given to illustrate use of the program

Selective engagement of FcγRIV by a M2e-specific single domain antibody construct protects against influenza A virus infection

Lower respiratory tract infections, such as infections caused by influenza A viruses, are a constant threat for public health. Antivirals are indispensable to control disease caused by epidemic as well as pandemic influenza A. We developed a novel anti-influenza A virus approach based on an engineered single-domain antibody (VHH) construct that can selectively recruit innate immune cells to the sites of virus replication. This protective construct comprises two VHHs. One VHH binds with nanomolar affinity to the conserved influenza A matrix protein 2 (M2) ectodomain (M2e). Co-crystal structure analysis revealed that the complementarity determining regions 2 and 3 of this VHH embrace M2e. The second selected VHH specifically binds to the mouse Fc gamma Receptor IV (Fc gamma RIV) and was genetically fused to the M2e-specific VHH, which resulted in a bi-specific VHH-based construct that could be efficiently expressed in Pichia pastoris. In the presence of M2 expressing or influenza A virus-infected target cells, this single domain antibody construct selectively activated the mouse Fc gamma RIV. Moreover, intranasal delivery of this bispecific Fc gamma RIV-engaging VHH construct protected wild type but not Fc gamma RIV-/- mice against challenge with an H3N2 influenza virus. These results provide proof of concept that VHHs directed against a surface exposed viral antigen can be readily armed with effector functions that trigger protective antiviral activity beyond direct virus neutralization

Issues in designing transport layer multicast facilities

Multicasting denotes a facility in a communications system for providing efficient delivery from a message's source to some well-defined set of locations using a single logical address. While modem network hardware supports multidestination delivery, first generation Transport Layer protocols (e.g., the DoD Transmission Control Protocol (TCP) (15) and ISO TP-4 (41)) did not anticipate the changes over the past decade in underlying network hardware, transmission speeds, and communication patterns that have enabled and driven the interest in reliable multicast. Much recent research has focused on integrating the underlying hardware multicast capability with the reliable services of Transport Layer protocols. Here, we explore the communication issues surrounding the design of such a reliable multicast mechanism. Approaches and solutions from the literature are discussed, and four experimental Transport Layer protocols that incorporate reliable multicast are examined