The Se–S Bond Formation in the Covalent Inhibition Mechanism of SARS-CoV-2 Main Protease by Ebselen-like Inhibitors: A Computational Study

The inhibition mechanism of the main protease (M^pro) of SARS-CoV-2 by ebselen (EBS) and its analog with a hydroxyl group at position 2 of the benzisoselenazol-3(2H)-one ring (EBS-OH) was studied by using a density functional level of theory. Preliminary molecular dynamics simulations on the apo form of M^pro were performed taking into account both the hydrogen donor and acceptor natures of the Nδ and Nε of His41, a member of the catalytic dyad. The potential energy surfaces for the formation of the Se–S covalent bond mediated by EBS and EBS-OH on M^pro are discussed in detail. The EBS-OH shows a distinctive behavior with respect to EBS in the formation of the noncovalent complex. Due to the presence of canonical H-bonds and noncanonical ones involving less electronegative atoms, such as sulfur and selenium, the influence on the energy barriers and reaction energy of the Minnesota hybrid meta-GGA functionals M06, M06-2X and M08HX, and the more recent range-separated hybrid functional wB97X were also considered. The knowledge of the inhibition mechanism of M^pro by the small protease inhibitors EBS or EBS-OH can enlarge the possibilities for designing more potent and selective inhibitor-based drugs to be used in combination with other antiviral therapies.     

Dynamics of Stress Bearing Particle Networks in Poly(propylene)/Alumina Nanohybrids

In this work, we report about the relationships between the linear rheology and the microstructure of a polymer‐nanoparticle model system (i‐PP/Al₂O₃ nanospheres). Over a critical particle volume fraction, rheological evolutions during a quasi‐quiescent thermal annealing indicate the formation of a whole‐space‐spanning transient network of Al₂O₃ nanospheres, as confirmed by transmission electron microscopy. The dynamics of this network, responsible for the liquid‐like to solid‐like transition of the nanohybrid, have been investigated by means of rheological measurements. Once the network had formed, the application of large amplitude oscillatory shear progressively and irreversibly destroyed it, leading to a flow‐induced structure unable to contribute to the elasticity of the nanohybrid. Conversely, if the large deformation is applied to an unstructured sample, a solid‐like feature still emerges by ageing the sample. The resulting strength of such a nanohybrid, however, was lower than that obtainable without the application of large deformations. Energetic considerations may explain the transient nanoparticle network dynamics, strictly related to the bulk rheological properties.

     

A comparative study on comb electrodes devices made of MWPECVD diamond films grown on p-doped and intrinsic silicon substrate

Diamond is considered as a very promising material for the development of devices for radiation detection. Unlike other conventional photoconductive detectors diamond-based devices should provide high discrimination between UV and visible radiation. In this work we present the electro-optical properties of devices based on randomly oriented diamond films, synthesized in a microwave plasma enhanced chemical vapor deposition reactor. A comparative study on devices with coplanar interdigitated Cr/Au electrodes (with different interelectrode pitches) made of films grown simultaneously on intrinsic and p-doped silicon (100) substrates has been performed. The chemical-structural, morphological, electrical and optical properties of ROD films have been studied. In particular, the optical response has been measured in air using a Xe flash lamp coupled with an optical quartz fiber and a properly tailored front-end electronics based on a charge sensitive amplifier. Experimental results gave indications on how the device performances are dependent on the two types of employed substrates.     

Synthesis and antitumor molecular mechanism of agents based on amino 2-(3',4',5'-trimethoxybenzoyl)benzo[b]furan: inhibition of tubulin and induction of apoptosis

Induction of apoptosis is a promising strategy that could lead to the discovery of new molecules active in cancer chemotherapy. This property is generally observed when cells are treated with agents that target microtubules, dynamic structures that play a crucial role in cell division. Small molecules such as benzo[b]furans are attractive as inhibitors of tubulin polymerization. A new class of inhibitors of tubulin polymerization based on the 2-(3',4',5'-trimethoxybenzoyl)benzo[b]furan molecular skeleton, with the amino group placed at different positions on the benzene ring, were synthesized and evaluated for antiproliferative activity, inhibition of tubulin polymerization, and cell-cycle effects. The methoxy substitution pattern on the benzene portion of the benzo[b]furan moiety played an important role in affecting antiproliferative activity. In the series of 5-amino derivatives, the greatest inhibition of cell growth occurred if the methoxy substituent is placed at the C6 position, whereas C7 substitution decreases potency. The most promising compound in this series is 2-(3',4',5'-trimethoxybenzoyl)-3-methyl-5-amino-6-methoxybenzo[b]furan (3 h), which inhibits cancer cell growth at nanomolar concentrations (IC(50) =16-24 nM), and interacts strongly with tubulin by binding to the colchicine site. Sub-G(1) apoptotic cells in cultures of HL-60 and U937 cells were observed by flow cytometric analysis after treatment with 3 h in a concentration-dependent manner. We also show that compound 3 h induces apoptosis by activation of caspase-3, -8, and -9, and this is associated with cytochrome c release from mitochondria. The introduction of an α-bromoacryloyl group increased antiproliferative activity with respect to the parent amino derivatives.     

ST6GALNAC5 Expression Decreases the Interactions between Breast Cancer Cells and the Human Blood-Brain Barrier

The ST6GALNAC5 gene that encodes an α2,6-sialyltransferase involved in the biosynthesis of α-series gangliosides, was previously identified as one of the genes that mediate breast cancer metastasis to the brain. We have shown that the expression of ST6GALNAC5 in MDA-MB-231 breast cancer cells resulted in the expression of G_D1α ganglioside at the cell surface. By using a human blood-brain barrier in vitro model recently developed, consisting in CD34⁺ derived endothelial cells co-cultivated with pericytes, we show that ST6GALNAC5 expression decreased the interactions between the breast cancer cells and the human blood-brain barrier.     

Thermal and electrical behaviour of some hybrid polyimide films containing barium and titanium oxides

Aromatic polyimides are high‐performance polymers used in applications demanding service at enhanced temperature while maintaining their structural integrity and excellent combination of chemical, physical and mechanical properties. The incorporation of various metallic additives into a polyimide matrix improves its properties, leading to materials required by specific applications. Hybrid polyimide films containing barium and titanium oxides having thicknesses in the range of tens of micrometres were prepared. These films were obtained using the sol–gel technique starting from a poly(amic acid) and a soluble precursor of metal oxides. They exhibited good thermal stability having an initial decomposition temperature above 460 °C, and a glass transition temperature in the range 217–238 °C. Two subglass transitions, γ and β, were evident from dynamic mechanical analysis and dielectric spectroscopy. A study of the thermal and electrical behaviour of some hybrid polyimide films containing barium and titanium oxides is presented. On increasing the concentration of metal oxides, an increase of dielectric constant and a decrease of thermal stability of the hybrid films were observed. The presence of metal oxides shifted the glass transition temperature and the temperature of the β transition to higher values. Copyright © 2009 Society of Chemical Industry     

Effects of post-fermentation processing on the stabilisation of naturally fermented green table olives (cv Nocellara etnea)

The effects of thermal treatment on green table olives were evaluated as a method to control enzymatic browning, to minimise the microorganism presence and to extend their shelf-life. However this treatment is often responsible for colour alterations, development of off-flavours and unfavourable texture changes. Moreover, the effect of different re-use of the natural brine of fermentation with or without different treatments was investigated. Calcium treatment was suggested to maintain firmness. Firming effects obtained from heat treatment combined with calcium treatment have been attributed to heat-activated pectin methylesterase and/or to increased calcium diffusion into tissues at higher temperatures. The results derived from this study will help in designing new processes which can be applied in table olive industry.     

Volatile compounds and capsaicinoid content of fresh hot peppers (Capsicum annuum L.) of different Calabrian varieties

BACKGROUND: Because of the great variability in size, shape, colour, pungency and aroma of Calabrian Capsicum annuum(hot pepper), this study was carried out to furnish producers with information on volatile compounds and capsaicinoid content useful for the genetic improvement of this species. Fully ripened fresh peppers of the most widely cultivated varieties were studied. Capsaicinoid content was determined by reverse phase high‐performance liquid chromatography/diode array detection (RP‐HPLC/DAD). Volatile compounds were determined by headspace solid phase microextraction/gas chromatography/mass spectrometry (HS‐SPME/GC/MS). RESULTS: Sixty‐four volatile compounds were identified, the main classes being alcohols, aldehydes, terpenes and aliphatic branched‐chain hydrocarbons. The ‘Naso di cane’ (C. annuumvar. abbreviatum) variety contained the lowest amount of volatiles, especially alcohols and aldehydes, while the highest levels of capsaicin and dihydrocapsaicin were found in ‘Vulcan’ and ‘Corno di capra’ varieties. CONCLUSION: From statistical evaluation of the data obtained, each variety showed a typical composition of capsaicinoids and volatiles determining the taste and odour of the hot peppers. These results should be useful in the context of research aimed at selecting varieties with the best sensory characteristics. Copyright © 2009 Society of Chemical Industry     

Optimization of intercooling compression in CO2 capture systems

Compression of CO₂ is an essential process in the development of carbon capture and storage (CCS) technologies. In spite of power requirements for CO₂ compression could be as much as 100 kWe per tonne CO₂, the minimization of energy requirements has received little attention in the literature. Although intercooling compression reduces power requirements, it introduces important cooling necessities that could be minimized.The aim of this paper is the integration of intercooling compression into the low-pressure part of a steam cycle to take advantage of the intercooling heat and analyse the energetic and economical results under different assumptions. Simulation and optimization have been performed in order to evaluate the intercooling configuration, energy requirements and the most cost-effective integration. Results have shown reduction in compression power requirement around 40% and reduction of the incremental COE around 23%. Proposed integration could be used to increase the efficiency of CO₂ capture processes and, therefore, to reduce the CO₂ capture cost.