Fabrication of Multifunctional Filters via Online Incorporating Nano‐TiO2 into Spun‐Bonded/Melt‐Blown Nonwovens for Air Filtration and Toluene Degradation

Multifunctional air filters with high filtration efficiency for aerosol and good degradation for toluene and bacteria are fabricated via online incorporation of TiO₂/Ag nanoparticles into the composite nonwovens with spun‐bonded/melt‐blown (SM) hierarchical structure. Today, severe environmental pollution attributed to atmospheric pollutants, mainly including particulate materials, and gaseous volatile organic compounds, as well as bacterial and viral contaminants, has drawn worldwide attention. In this work, a novel online incorporation technique to fabricate a multifunctional air filter with hierarchical structure of SM nonwovens and TiO₂ based nanoparticles is proposed. The in situ incorporation technique not only enables the SM nonwovens filters with four orders increment on toluene degradation rate, but also increases filtration quality factor Q_f of the SM filters to 0.2251 Pa^?1. This research shows promising applications of the multifunctional TiO₂/SM nonwoven filters for indoor air remediation. In addition, this scale‐up fabrication method of fiber‐based filters will potentially promote engineering of macromolecular fiber materials.     

Binding Mode and Structure–Activity Relationships around Direct Inhibitors of the Nrf2–Keap1 Complex

An X‐ray crystal structure of Kelch‐like ECH‐associated protein (Keap1) co‐crystallised with (1S,2R)‐2‐[(1S)‐1‐[(1,3‐dioxo‐2,3‐dihydro‐1H‐isoindol‐2‐yl)methyl]‐1,2,3,4‐tetrahydroisoquinolin‐2‐carbonyl]cyclohexane‐1‐carboxylic acid (compound (S,R,S)‐ 1 a ) was obtained. This X‐ray crystal structure provides breakthrough experimental evidence for the true binding mode of the hit compound (S,R,S)‐ 1 a , as the ligand orientation was found to differ from that of the initial docking model, which was available at the start of the project. Crystallographic elucidation of this binding mode helped to focus and drive the drug design process more effectively and efficiently.     

Implications of melt compatibility/incompatibility on thermal and mechanical properties of metallocene and Ziegler–Natta linear low density polyethylene (LLDPE) blends with high density polyethylene (HDPE): influence of composition distribution and branch content of LLDPE

In this paper, the implications of melt compatibility on thermal and solid‐state properties of linear low density polyethylene/high density polyethylene (LLDPE/HDPE) blends were assessed with respect to the effect of composition distribution (CD) and branch content (BC). The effect of CD was studied by melt blending a metallocene (m‐LLDPE) and a Ziegler‐Natta (ZN) LLDPE with the same HDPE at 190 °C. Similarly, the effect of BC was examined. In both cases, resins were paired to study one molecular variable at a time. Thermal and solid‐state properties were measured in a differential scanning calorimeter and in an Instron mechanical testing instrument, respectively. The low‐BC m‐LLDPE (BC = 14.5 CH₃/1000 C) blends with HDPE were compatible at all compositions: rheological, thermal and some mechanical properties followed additivity rules. For incompatible high‐BC (42.0 CH₃/1000 C) m‐LLDPE‐rich blends, elongation at break and work of rupture showed synergistic effects, while modulus was lower than predictions of linear additivity. The CD of LLDPE showed no significant effect on thermal properties, elongation at break or work of rupture; however, it resulted in low moduli for ZN‐LLDPE blends with HDPE. For miscible blends, no effect for BC or CD of LLDPE was observed. The BC of LLDPE has, in general, a stronger influence on melt and solid‐state properties of blends than the CD. Copyright © 2004 Society of Chemical Industry     

A Parallel Semisynthetic Approach for Structure–Activity Relationship Studies of Peptide YY

The gut hormone peptide YY (PYY) is postprandially secreted from enteroendocrine L cells and is involved in the regulation of energy homeostasis. The N‐terminal truncated version PYY(3–36) decreases food intake and has potential as an anti‐obesity agent. The anorectic effect of PYY(3–36) is mediated through Y₂ receptors in the hypothalamus, vagus, and brainstem regions, and it is well known that the C‐terminal tetrapeptide sequence of PYY(3–36) is crucial for Y₂ receptor activation. The aim of this work was to develop a semisynthetic methodology for the generation of a library of C‐terminally modified PYY(3–36) analogues. By using an intein‐based expression system, PYY(3–29) was generated as a C‐terminal peptide α‐thioester. Heptapeptides bearing an N‐terminal cysteine and modifications at one of the four C‐terminal positions were synthesized in a 96‐well plate by parallel solid‐phase synthesis. In the plate format, an array of [Ala30]PYY(3–36) analogues were generated by ligation, desulfurization, and subsequent solid‐phase extraction. The generated analogues, in which either Arg33, Gln34, Arg35, or Tyr36 had been substituted with proteinogenic or non‐proteinogenic amino acids, were tested in a functional Y₂ receptor assay. Generally, substitutions of Tyr36 were better tolerated than modifications of Arg33, Gln34, and Arg35. Two analogues showed significantly improved Y₂ receptor selectivity; therefore, these results could be used to design new drug candidates for the treatment of obesity.     

Mechanical properties and structure of high‐density polyethylene samples prepared by injection molding with low‐frequency vibration

To better understand the formation of different crystal structures and improve the mechanical properties of high‐density polyethylene samples, melt vibration technology, which generally includes shear vibration and hydrostatic pressure vibration, was used to prepare injection samples. Through melt vibration, the crystal structure changed from typical spherulites of the traditional injection sample to obviously orientated lamellae of vibration samples. Sizes and orientation degrees of lamellae were different according to different vibration conditions. Crystallinity degrees of vibration samples increased notably. Therefore, the tensile strength of vibration samples increased with increasing vibration frequency and vibration pressure, whereas elongation of vibration samples decreased during the first stage and then continued to increase as the vibration frequency increased. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 96: 818–823, 2005     

Total Synthesis of (−)‐Doliculide,Structure–Activity Relationship Studies and Its Binding to F‐Actin

Actin, an abundant protein in most eukaryotic cells, is one of the targets in cancer research. Recently, a great deal of attention has been paid to the synthesis and function of actin‐targeting compounds and their use as effective molecular probes in chemical biology. In this study, we have developed an efficient synthesis of (?)‐doliculide, a very potent actin binder with a higher cell‐membrane permeability than phalloidin. Actin polymerization assays with (?)‐doliculide and two analogues on HeLa and BSC‐1 cells, together with a prediction of their binding mode to F‐actin by unbiased computational docking, show that doliculide stabilizes F‐actin in a similar way to jasplakinolide and chondramide C.     

Time‐Dependent Diaryl Ether Inhibitors of InhA: Structure–Activity Relationship Studies of Enzyme Inhibition,Antibacterial Activity,and in vivo Efficacy

The diaryl ethers are a novel class of antituberculosis drug candidates that inhibit InhA, the enoyl‐ACP reductase involved in the fatty acid biosynthesis (FASII) pathway, and have antibacterial activity against both drug‐sensitive and drug‐resistant strains of Mycobacterium tuberculosis. In the present work, we demonstrate that two time‐dependent B‐ring modified diaryl ether InhA inhibitors have antibacterial activity in a mouse model of TB infection when delivered by intraperitoneal injection. We propose that the efficacy of these compounds is related to their residence time on the enzyme, and to identify structural features that modulate drug–target residence time in this system, we have explored the inhibition of InhA by a series of B‐ring modified analogues. Seven ortho‐substituted compounds were found to be time‐dependent inhibitors of InhA, where the slow step leading to the final enzyme–inhibitor complex (EI*) is thought to correlate with closure and ordering of the InhA substrate binding loop. A detailed mechanistic understanding of the molecular basis for residence time in this system will facilitate the development of InhA inhibitors with improved in vivo activity.     

Structure–property relationship of polyimides based on pyromellitic dianhydride and short‐chain aliphatic diamines for dielectric material applications

Most polyolefins that are used for dielectric materials exhibit a low dielectric constant and operating temperatures up to 70°C. Polyimides offer a means to a higher dielectric constant material by the introduction of a polar group in the polymer backbone and are thermally stable at temperatures exceeding 250°C. A common dianhydride, pyromellitic dianhydride (PMDA), is reacted with various short‐chain diamines to produce polymers with high imide density. Homopolymers and copolymers synthesized had dielectric constants ranging from 3.96 to 6.57. These materials exhibit a dielectric constant twice that of biaxially oriented polypropylene and therefore a twofold increase in capacitance as well as maintaining low dissipation factors that are acceptable for this application. The experimental dielectric constants of these materials are also compared to density functional theory calculations and exhibit a close relationship. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 130: 1276‐1280, 2013     

Cinnamamide Derivatives for Central and Peripheral Nervous System Disorders—A Review of Structure–Activity Relationships

The cinnamamide scaffold has been incorporated in to the structure of numerous organic compounds with therapeutic potential. The scaffold enables multiple interactions, such as hydrophobic, dipolar, and hydrogen bonding, with important molecular targets. Additionally, the scaffold has multiple substitution options providing the opportunity to optimize and modify the pharmacological activity of the derivatives. In particular, cinnamamide derivatives have exhibited therapeutic potential in animal models of both central and peripheral nervous system disorders. Some have undergone clinical trials and were introduced on to the pharmaceutical market. The diverse activities observed in the nervous system included anticonvulsant, antidepressant, neuroprotective, analgesic, anti‐inflammatory, muscle relaxant, and sedative properties. Over the last decade, research has focused on the molecular mechanisms of action of these derivatives, and the data reported in the literature include targeting the γ‐aminobutyric acid type A (GABA_A) receptors, N‐methyl‐D ‐aspartate (NMDA) receptors, transient receptor potential (TRP) cation channels, voltage‐gated potassium channels, histone deacetylases (HDACs), prostanoid receptors, opioid receptors, and histamine H₃ receptors. Here, the literature data from reports evaluating cinnamic acid amide derivatives for activity in target‐based or phenotypic assays, both in vivo and in vitro, relevant to disorders of the central and peripheral nervous systems are analyzed and structure–activity relationships discussed.     

Synthesis of clay–TiO2 nanocomposite thin films with barrier and photocatalytic properties for food packaging application

In this study, low‐density polyethylene (LDPE) nanocomposite films with two types of nanoparticles, TiO₂ (3 wt %) and Closite 20A (3 and 5 wt %), were prepared using a melt blow extrusion as an industrial method and their properties such as mechanical properties, water vapor, oxygen and carbon dioxide gas barrier, and antimicrobial activity were tested. Transmission electron microscopy (TEM) and X‐ray diffraction (XRD) were also performed to determine the degree of dispersion and exfoliation of nanoparticles. Mechanical test indicated that the reinforcement in the presence of the nanocomposites was more than that with their conventional counterparts, and the highest stiffness was achieved in a sample containing 5 wt % clay and 3 wt % TiO₂. Exfoliation of silicate layers and a good dispersion of TiO₂ nanoparticles in LDPE were achieved as confirmed by XRD and TEM. The gas barrier properties were improved after formation of the nanocomposites especially by insertion of 5 wt % of clay nanoparticles as a filler in the LDPE matrix. The photocatalytic effect of the nanocomposite film was carried out by antimicrobial evaluation against Pseudomonas spp. and Rhodotorula mucilaginosa and by ethylene removal test using 8 W ultraviolet (UV) lamps with a constant relative intensity of 1 mW cm^?2. The greatest effects were recorded by combining UVA illumination and active film. It was also proven that the photocatalyst thin film with improved barrier properties prepared by extrusion could be used in horticultural product packaging applications. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 41764.     

Characterization of polypropylene and ethylene–propylene copolymer blends for industrial applications

The crystalline structure and physico‐mechanical properties of polypropylene (PP) blended with ethylene–propylene copolymer (EPM) were investigated. WAXS diffractograms showed that the addition of EPM did not affect the crystalline structure of PP. DSC curves revealed the presence of two T_g peaks indicating the amorphous phases of EPM and PP. As EPM increased, the elastomeric domains cavitated from PP matrix increased while the tensile stress and modulus of elasticity decreased. Impact strength, on the other hand, increased, and showed a remarkable effect at 30% EPM/PP. The properties of the blended polymers were compared with the commercial PP impact copolymer, and it was found that polyblends containing 30% EPM was suited for applications on products requiring very high impact strength. Further addition of EPM from 40 to 50% produced very high impact strength, but the tensile stress and modulus of elasticity were very low. © 2000 John Wiley & Sons, Inc. J Appl Polym Sci 78: 1200–1208, 2000     

The Structure of Glycerol Trinitrate Reductase NerA from Agrobacterium radiobacter Reveals the Molecular Reason for Nitro‐ and Ene‐Reductase Activity in OYE Homologues

In recent years, Old Yellow Enzymes (OYEs) and their homologues have found broad application in the efficient asymmetric hydrogenation of activated C?C bonds with high selectivities and yields. Members of this class of enzymes have been found in many different organisms and are rather diverse on the sequence level, with pairwise identities as low as 20 %, but they exhibit significant structural similarities with the adoption of a conserved (αβ)₈‐barrel fold. Some OYEs have been shown not only to reduce C?C double bonds, but also to be capable of reducing nitro groups in both saturated and unsaturated substrates. In order to understand this dual activity we determined and analyzed X‐ray crystal structures of NerA from Agrobacterium radiobacter, both in its apo form and in complex with 4‐hydroxybenzaldehyde and with 1‐nitro‐2‐phenylpropene. These structures, together with spectroscopic studies of substrate binding to several OYEs, indicate that nitro‐containing substrates can bind to OYEs in different binding modes, one of which leads to C?C double bond reduction and the other to nitro group reduction.     

Structure–Activity Relationship,Biological, and Pharmacological Characterization of the Proline Sulfonamide ACT‐462206: a Potent,Brain‐Penetrant Dual Orexin 1/Orexin 2 Receptor Antagonist

The orexin system consists of two G‐protein‐coupled receptors, the orexin 1 and orexin 2 receptors, widely expressed in diverse regions of the brain, and two peptide agonists, orexin A and orexin B, which are produced in a small assembly of neurons in the lateral hypothalamus. The orexin system plays an important role in the maintenance of wakefulness. Several compounds (almorexant, SB‐649868, suvorexant) have been in advanced clinical trials for treating primary insomnia. ACT‐462206 is a new, potent, and selective dual orexin receptor antagonist (DORA) that inhibits the stimulating effects of the orexin peptides at both the orexin 1 and 2 receptors. It decreases wakefulness and increases non‐rapid eye movement (non‐REM) and REM sleep while maintaining natural sleep architectures in rat and dog electroencephalography/electromyography (EEG/EMG) experiments. ACT‐462206 shows anxiolytic‐like properties in rats without affecting cognition and motor function. It is therefore a potential candidate for the treatment of insomnia.     

Methylene Homologues of Artemisone: An Unexpected Structure–Activity Relationship and a Possible Implication for the Design of C10‐Substituted Artemisinins

We sought to establish if methylene homologues of artemisone are biologically more active and more stable than artemisone. The analogy is drawn with the conversion of natural O‐ and N‐glycosides into more stable C‐glycosides that may possess enhanced biological activities and stabilities. Dihydroartemisinin was converted into 10β‐cyano‐10‐deoxyartemisinin that was hydrolyzed to the α‐primary amide. Reduction of the β‐cyanide and the α‐amide provided the respective methylamine epimers that upon treatment with divinyl sulfone gave the β‐ and α‐methylene homologues, respectively, of artemisone. Surprisingly, the compounds were less active in vitro than artemisone against P. falciparum and displayed no appreciable activity against A549, HCT116, and MCF7 tumor cell lines. This loss in activity may be rationalized in terms of one model for the mechanism of action of artemisinins, namely the cofactor model, wherein the presence of a leaving group at C10 assists in driving hydride transfer from reduced flavin cofactors to the peroxide during perturbation of intracellular redox homeostasis by artemisinins. It is noted that the carba analogue of artemether is less active in vitro than the O‐glycoside parent toward P. falciparum, although extrapolation of such activity differences to other artemisinins at this stage is not possible. However, literature data coupled with the leaving group rationale suggest that artemisinins bearing an amino group attached directly to C10 are optimal compounds.     

Synthesis and Structure–Activity Relationship Studies of 2‐(1,3,4‐Oxadiazole‐2(3H)‐thione)‐3‐amino‐5‐arylthieno[2,3‐b]pyridines as Inhibitors of DRAK2

In recent years, DAPK‐related apoptosis‐inducing protein kinase 2 (DRAK2) has emerged as a promising target for the treatment of a variety of autoimmune diseases and for the prevention of graft rejection after organ transplantation. However, medicinal chemistry optimization campaigns for the discovery of novel small‐molecule inhibitors of DRAK2 have not yet been published. Screening of a proprietary compound library led to the discovery of a benzothiophene analogue that displays an affinity constant (K_d) value of 0.25 μM . Variation of the core scaffold and of the substitution pattern afforded a series of 5‐arylthieno[2,3‐b]pyridines with strong binding affinity (K_d=0.008 μM for the most potent representative). These compounds also show promising activity in a functional biochemical DRAK2 enzyme assay, with an IC₅₀ value of 0.029 μM for the most potent congener. Selectivity profiling of the most potent compounds revealed that they lack selectivity within the DAPK family of kinases. However, one of the less potent analogues is a selective ligand for DRAK2 and can be used as starting point for the synthesis of selective and potent DRAK2 inhibitors.