MT1‐Selective Melatonin Receptor Ligands: Synthesis,Pharmacological Evaluation,and Molecular Dynamics Investigation of N‐{[(3‐O‐Substituted)anilino]alkyl}amides

The design of compounds selective for the MT₁ melatonin receptor is still a challenging task owing to the limited knowledge of the structural features conferring selectivity for the MT₁ subtype, and only few selective compounds have been reported so far. N‐(Anilinoalkyl)amides are a versatile class of melatonin receptor ligands that include nonselective MT₁/MT₂ agonists and MT₂‐selective antagonists. We synthesized a new series of N‐(anilinoalkyl)amides bearing 3‐arylalkyloxy or 3‐alkyloxy substituents at the aniline ring, looking for new potent and MT₁‐selective ligands. To evaluate the effect of substituent size and shape on binding affinity and intrinsic activity, both flexible and conformationally constrained derivatives were prepared. The phenylbutyloxy substituent gave the best result, providing the partial agonist 4 a , which was endowed with high MT₁ binding affinity (pK_i=8.93) and 78‐fold selectivity for the MT₁ receptor. To investigate the molecular basis for agonist recognition, and to explain the role of the 3‐arylalkyloxy substituent, we built a homology model of the MT₁ receptor based on the β₂ adrenergic receptor crystal structure in its activated state. A binding mode for MT₁ agonists is proposed, as well as a hypothesis regarding the receptor structural features responsible for MT₁ selectivity of compounds with lipophilic arylalkyloxy substituents.     

IR-change and colour changes of long-oil air drying alkyd paints as a result of UV irradiation

In this study the formation of photo-oxidative species was studied by monitoring the changes in the FT-IR spectra and colour changes. To stabilize long-oil air drying alkyd paint, separate and synergistic influence of two stabilizers were used Uvasorb^®S28 as the UV-absorber and Uvasorb^®HA29 as the stabilizer which inhibits the degradation of some groups. In the presence of UV radiation (450 h, λ > 300 nm), the alkyd paint undergoes photodegradation with gradual change of its colour. The photochemical degradation of the alkyd paint is associated with an increase in the hydroxyl content and broadening of the absorption in the carbonyl region. Analysis of the colour changes in alkyd surface during photodegradation was carried out by measuring CIEL*a*b* colour components (L*, a*, b* and ΔE*). Overall, ΔE* colour change correlates well with photodegradation of alkyd paint by relative increase of the concentration of carbonyl and hydroxyl groups determinated by FT-IR measurements.     

Effect of amine-terminated butadiene-acrylonitrile/clay combinations on the structure and properties of epoxy nanocomposites

The effect of the clay content and the method of its combination with amine-terminated butadiene-acrylonitrile (ATBN) on the structure and behavior of epoxy was studied. In the case of the simultaneous addition of both components, the increasing clay content had a very small effect on the size of the reaction-induced phase separation-formed particles at 5% rubber content due to predominant elimination of two major clay effects, i.e., the nucleation due to phase separation and the kinetics. As a result, both the time window between the onset of phase separation and vitrification and the viscosity at the cloud point did not change significantly. The minor change in the particle size/clay content dependences with different curing temperatures indicates that the balance between the two clay effects shifted. The corresponding study of the mechanical behavior indicated that the best balanced mechanical properties were obtained at certain clay/ATBN ratios, and thus, there was synergy between the components. Similar mechanical parameters were obtained for the application of both components in the form of ATBN/montmorillonite intercalate. © 2012 Wiley Periodicals, Inc. J Appl Polym Sci, 2012     

Refractory Alkali-Free Cristobalite Glass-Ceramics: Activated Reaction Sinter-Crystallization Synthesis and Properties

A new approach for the synthesis of chemically stabilized β-cristobalite-like glass-ceramic materials is developed. It is based on an activated reaction sinter-crystallization process of compacted powder mixtures at relatively low temperatures (1400–1450°C) and short heat treatment times. To facilitate homogeneous dopant distribution and thus the formation of a high content of β_x-cristobalite-like phases, possessing a very low thermal expansion coefficient, the batch components are introduced in a chemically, mechanically, or thermally preactivated form. In this way, the high-temperature glass premelting usually employed in the “classical” synthesis of glass-ceramics is avoided. Using different, mutually complementary techniques of analysis it is revealed that optimal refractory properties are achieved with glass-ceramics containing α_x- and β_x-cristobalite solid solutions with close values of the lattice parameters. In this case, the transformation between these two cristobalite-like solid solutions proceeds instead by a first-order displacive transition, by a process exhibiting features characteristic for both a suppressed first-order phase change and a second-order λ-type phase transitions. The refractory properties of the glass-ceramic materials thus synthesized and the possibility to use various forming techniques open many fields for their application.     

Fluidization of spherical versus elongated particles: Experimental investigation using magnetic particle tracking

In biomass processing fluidized beds are used to process granular materials where particles typically possess elongated shapes. However, for simplicity, in computer simulations particles are often considered spherical, even though elongated particles experience more complex particle– particle interactions as well as different hydrodynamic forces. The exact effect of these more complex interactions in dense fluidized suspensions is still not well understood. In this study we use the magnetic particle tracking technique to compare the fluidization behavior of spherical particles to that of elongated particles. We found a considerable difference between fluidization behavior of spherical versus elongated particles in the time-averaged particle velocity field as well as in the time-averaged particle rotational velocity profile. Moreover, we studied the effect of fluid velocity and the particle's aspect ratio on the particle's preferred orientation in different parts of the bed, which provides new insight in the fluidization behavior of elongated particles.     

Multiple Chemical Features Impact Biological Performance Diversity of a Highly Active Natural Product-Inspired Library

A systematic, diversity-oriented synthesis approach was employed to access a natural product-inspired flavonoid library with diverse chemical features, including chemical properties, scaffold, stereochemistry, and appendages. Using Cell Painting, the effects of these diversity elements were evaluated, and multiple chemical features that predict biological performance diversity were identified. Scaffold identity appears to be the dominant predictor of performance diversity, but stereochemistry and appendages also contribute to a lesser degree. In addition, the diversity of chemical properties contributed to performance diversity, and the driving chemical property was dependent on the scaffold. These results highlight the importance of key chemical features that may inform the creation of small-molecule, performance-diverse libraries to improve the efficiency and success of high-throughput screening campaigns.     

Manipulation of Chemically Mediated Interactions in Agricultural Soils to Enhance the Control of Crop Pests and to Improve Crop Yield

In most agro-ecosystems the organisms that feed on plant roots have an important impact on crop yield and can impose tremendous costs to farmers. Similar to aboveground pests, they rely on a broad range of chemical cues to locate their host plant. In their turn, plants have co-evolved a large arsenal of direct and indirect defense to face these attacks. For instance, insect herbivory induces the synthesis and release of specific volatile compounds in plants. These volatiles have been shown to be highly attractive to natural enemies of the herbivores, such as parasitoids, predators, or entomopathogenic nematodes. So far few of the key compounds mediating these so-called tritrophic interactions have been identified and only few genes and biochemical pathways responsible for the production of the emitted volatiles have been elucidated and described. Roots also exude chemicals that directly impact belowground herbivores by altering their behavior or development. Many of these compounds remain unknown, but the identification of, for instance, a key compound that triggers nematode egg hatching to some plant parasitic nematodes has great potential for application in crop protection. These advances in understanding the chemical emissions and their role in ecological signaling open novel ways to manipulate plant exudates in order to enhance their natural defense properties. The potential of this approach is discussed, and we identify several gaps in our knowledge and steps that need to be taken to arrive at ecologically sound strategies for belowground pest management.     

Reorganization of perylene bisimide J-aggregates: from delocalized collective to localized individual excitations

Water-induced reorganization of individual one-dimensional J-aggregates of perylene bisimide (PBI) dyes was observed by fluorescence microscopy. Fluorescence spectra and decay kinetics of individual J-aggregates immobilized on glass surfaces were measured under a dry nitrogen atmosphere and under humid conditions. The fluorescence properties of PBI J-aggregates arisen from collective excitons under dry nitrogen atmosphere were changed to those of non-interacting dye monomers when water vapor was introduced into the environment (sample chamber). Time-dependent changes of the fluorescence spectra and lifetimes upon exposure to water vapor suggest an initial coordination of water molecules at defect sites leading to the formation of H-type dimer units that act as exciton quenchers, and a subsequent slower disintegration of the hydrogen-bonded J-aggregate into monomers that lack resonance coupling. Our present studies resulted in a direct demonstration of how drastically the optical properties of molecular ensembles and characteristics of their excited states can be changed by delicate reorganization of dye molecules at nanometre scales.     

Metabolism of Storage Lipids and the Role of Lipid Droplets in the Yeast Schizosaccharomyces pombe

Storage lipids, triacylglycerols (TAG), and steryl esters (SE), are predominant constituents of lipid droplets (LD) in fungi. In several yeast species, metabolism of TAG and SE is linked to various cellular processes, including cell division, sporulation, apoptosis, response to stress, and lipotoxicity. In addition, TAG are an important source for the generation of value-added lipids for industrial and biomedical applications. The fission yeast Schizosaccharomyces pombe is a widely used unicellular eukaryotic model organism. It is a powerful tractable system used to study various aspects of eukaryotic cellular and molecular biology. However, the knowledge of S. pombe neutral lipids metabolism is quite limited. In this review, we summarize and discuss the current knowledge of the homeostasis of storage lipids and of the role of LD in the fission yeast S. pombe with the aim to stimulate research of lipid metabolism and its connection with other essential cellular processes. We also discuss the advantages and disadvantages of fission yeast in lipid biotechnology and recent achievements in the use of S. pombe in the biotechnological production of valuable lipid compounds.     

Synthetic Peroxides Promote Apoptosis of Cancer Cells by Inhibiting P-Glycoprotein ABCB5

This article discloses a new horizon for the application of peroxides in medical chemistry. Stable cyclic peroxides are demonstrated to have cytotoxic activity against cancer cells; in addition a mechanism of cytotoxic action is proposed. Synthetic bridged 1,2,4,5-tetraoxanes and ozonides were effective against HepG2 cancer cells and some ozonides selectively targeted liver cancer cells (the selectivity indexes for compounds 11 b and 12 a are 8 and 5, respectively). In some cases, tetraoxanes and ozonides were more selective than paclitaxel, artemisinin, and artesunic acid. Annexin V flow-cytometry analysis revealed that the active ozonides 22 a and 23 a induced cell death of HepG2 by apoptosis. Further study showed that compounds 22 a and 23 a exhibited a strong inhibitory effect on P-glycoprotein (P-gp/ABCB5)-overexpressing HepG2 cancer cells. ABCB5 is a key player in the multidrug-resistant phenotype of liver cancer. Peroxides failed to demonstrate a direct correlation between oxidative potential and their biological activity. To our knowledge this is the first time that peroxide diastereoisomers have been found to show stereospecific antimalarial action against the chloroquine-sensitive 3D7 strain of Plasmodium falciparum. Stereoisomeric ozonide 12 b is 11 times more active than stereoisomeric ozonide 12 a (IC₅₀=5.81 vs 65.18 μm ). Current findings mean that ozonides merit further investigation as potential therapeutic agents for drug-resistant hepatocellular carcinoma.