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.     

Corrosion behaviour of AA2024 aluminium alloy in different tempers in NaCl solution and with the CeCl3 corrosion inhibitor

The paper analyses the corrosion behaviour of naturally and artificially aged AA2024 alloy in NaCl solution and in the presence of an environment-friendly corrosion inhibitor, CeCl₃. On the basis of the values of polarisation resistance and corrosion current density, the corrosion resistance of the protective inhibitor film is established as well as the general corrosion resistance of this aluminium alloy. Resistance to pit formation is determined based on the difference in pitting and corrosion potentials while resistance to pit growth is determined based on the amount of charge consumed during pit growth. A scanning electron microscope is used to examine the morphology of the pits formed during the pitting corrosion testing, as well as to determine the cerium content on intermetallic particles and the matrix AA2024 alloy. The corrosion behaviour of AA2024 alloy is investigated after different test periods in NaCl solution and in the same solution with the CeCl₃ inhibitor. The corrosion resistance of both tempers of AA2024 alloy is more than one order of magnitude higher in the presence of CeCl₃. An explanation of the observed differences in the corrosion behaviour of the naturally and artificially aged AA2024 alloy is proposed. Different corrosion behaviour of the alloy after different test periods is also explained.     

Predictive association of metal–organic systems in the solid-state: the molecular electrostatic potential based approach

Designing crystalline solids with improved properties or performances remains a challenging task, despite great strides that have been made within the field of crystal engineering since its birth several decades ago. Herein, we are bringing examples that illustrate recent successes in taking supramolecular synthetic guidelines from the organic crystal engineering and adjusting those to metal-containing systems, particularly to the lower-dimensional ones. The versatility of calculated molecular electrostatic potential (MEP) as a new crystal engineering tool is demonstrated.     

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.     

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.     

A comparative study of photocatalytically active nanocrystalline tetragonal zyrcon-type and monoclinic scheelite-type bismuth vanadate

Monoclinic scheelite-type BiVO₄ is currently considered as one of the most promising non-titania photocatalysts, wheras tetragonal zircon-type BiVO₄ is still poorly understood. Herein, a new and simple synthetic approach was applied and nanostructured single-phase zircon-type BiVO₄ was successfully prepared by a controllable ethylene-glycol colloidal route. In addition, nanostructured monoclinic scheelite-type BiVO₄ powders were also fabricated through annealing of the as-prepared samples. A comparative study of the two BiVO₄ polymorphs was conducted and it turned out that the novel synthetic approach had a significant impact on porosity and photocatalytic performance of zircon-structured BiVO₄. All the prepared materials, as-prepared and annealed, were mesoporous, while measured values of specific surface area of some zircon-structured samples (～34?m²/g) were ～7 times higher than those reported thus far for this phase. Interestingly, for the first time, zircon-type BiVO₄, previously considered to be a poor photocatalyst, exhibited a better overall performance in degradation of methyl orange compared to monoclinic scheelite-type BiVO₄. Hence, it could be expected that the here-presented synthesis and observations will both arouse interest in scarcely studied tetragonal zircon-type BiVO₄ and facilitate as well as speed up further research of its properties.     

CO2 laser-assisted preparation of transparent Eu2Ti2O7 thin films

We present a laser-assisted preparation of transparent europium-titanate Eu₂Ti₂O₇ thin films with tailored structural and optical properties. We have evaluated the effects of the irradiation time on the structural and the optical properties of the films. This approach allows the preparation of nanocrystalline crack-free films and micro patterns. The amorphous thin films were prepared by a sol-gel method. The films were annealed by a CO₂ laser beam for various time intervals. The laser irradiation induced a crystallization process that resulted in the formation of Eu₂Ti₂O₇ nanocrystals. The nanocrystals regularly grew with increasing irradiation time reaching the size from 25?nm to 45?nm. A film of a thickness 480?nm exhibited an optical transmission of 91.9% that is close to the maximal theoretical limit. The film's refractive index at 632?nm was 2.26. A micrometric pattern was prepared by a direct laser writing followed by a wet chemical etching. Feasibility of the demonstrated approach, together with the high film's quality, and europium-titanate chemical resistivity open up many opportunities for advanced applications. The approach can be used for a preparation of protective coatings and integrated photonic devices such as planar optical waveguides and couplers.     

In-situ immobilization of Sr radioactive isotope using nanocrystalline hydroxyapatite

Hydroxyapatite was used as the inert matrix for in-situ immobilization of strontium (Sr) radioactive isotopes at room temperature. A nano-emulsification method was applied to synthesize Sr-substituted calcium hydroxyapatite (Ca_1?xSr_x)₁₀(PO₄)₆(OH)₂. The concentration of incorporated Sr was in the range of 0 ≤ x ≤ 1. Immobilization of Sr was evaluated using a stable isotope instead of radioactive isotope. The effect of strontium concentration on the crystal structure was studied and the results have showed that in the whole concentration range, Sr forms solid solutions with the host hydroxyapatite crystal structure. Powders comprised of nanometre sized particles were obtained and their properties, such as crystallite and particle size, changes in lattice parameters as function of dopant content and thermal stability, were further examined. It was found that the crystal structure of obtained powders is thermally stable at high temperatures. No secondary phases were formed in as-prepared powders or during calcination. The results in this study showed that nano-emulsion strategy provides a simple pathway for synthesis of a single-phase Sr-substituted hydroxyapatite, which can be used for immobilization of Sr radioactive isotopes.