Some novel layered-silicate nanocomposites based on a biodegradable hydroxybutyrate copolymer

This paper describes the preparation, characterization, mechanical properties and thermal stability of layered silicate nanocomposites based on poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHB-co-PHH, known as Nodax^TM). The dispersed phases were organically modified montmorillonites (clay 20A and clay 25A), mica, and talc, and they were introduced by solution mixing. Wide-angle X-ray scattering results and transmission electron microscopy (TEM) images confirmed that these two clays were intercalated and finely distributed in the Nodax^TM matrix. This type of layered filler led to remarkable improvements in mechanical properties even at very low loadings. Minimizing aggregation was more of a problem in the case of the mica and the talc, at least in this particular matrix. In some cases, these layered fillers slightly decreased the thermal stability of the Nodax^TM.     

Design,Synthesis, Docking,DFT, MD Simulation Studies of a New Nicotinamide-Based Derivative: In Vitro Anticancer and VEGFR-2 Inhibitory Effects

A nicotinamide-based derivative was designed as an antiproliferative VEGFR-2 inhibitor with the key pharmacophoric features needed to interact with the VEGFR-2 catalytic pocket. The ability of the designed congener ((E)-N-(4-(1-(2-(4-benzamidobenzoyl)hydrazono)ethyl)phenyl)nicotinamide), compound 10, to bind with the VEGFR-2 enzyme was demonstrated by molecular docking studies. Furthermore, six various MD simulations studies established the excellent binding of compound 10 with VEGFR-2 over 100 ns, exhibiting optimum dynamics. MM-GBSA confirmed the proper binding with a total exact binding energy of −38.36 Kcal/Mol. MM-GBSA studies also revealed the crucial amino acids in the binding through the free binding energy decomposition and declared the interactions variation of compound 10 inside VEGFR-2 via the Protein–Ligand Interaction Profiler (PLIP). Being new, its molecular structure was optimized by DFT. The DFT studies also confirmed the binding mode of compound 10 with the VEGFR-2. ADMET (in silico) profiling indicated the examined compound’s acceptable range of drug-likeness. The designed compound was synthesized through the condensation of N-(4-(hydrazinecarbonyl)phenyl)benzamide with N-(4-acetylphenyl)nicotinamide, where the carbonyl group has been replaced by an imine group. The in-vitro studies were consonant with the obtained in silico results as compound 10 prohibited VEGFR-2 with an IC₅₀ value of 51 nM. Compound 10 also showed antiproliferative effects against MCF-7 and HCT 116 cancer cell lines with IC₅₀ values of 8.25 and 6.48 μM, revealing magnificent selectivity indexes of 12.89 and 16.41, respectively.     

Microwave-assisted synthesis of double-headed derivatives of (4-amino-5-mercapto-4H-1,2,4-triazol-3-yl)-ethan-1-ol and study of their biological activity

Research on Chemical Intermediates - The present investigation involves rapid and efficient synthesis of a series of some novel derivatives for...     

Ab Initio and DFT Studies on CO2 Interacting with Znq+–Imidazole (q=0, 1, 2) Complexes: Prediction of Charge Transfer through σ‐ or π‐Type Models

Using first‐principles methodologies, the equilibrium structures and the relative stability of CO₂@[Zn^q+Im] (where q=0, 1, 2; Im=imidazole) complexes are studied to understand the nature of the interactions between the CO₂ and Zn^q+–imidazole entities. These complexes are considered as prototype models mimicking the interactions of CO₂ with these subunits of zeolitic imidazolate frameworks or Zn enzymes. These computations are performed using both ab initio calculations and density functional theory. Dispersion effects accounting for long‐range interactions are considered. Solvent (water) effects were also considered using a polarizable continuum model approach. Natural bond orbital, charge, frontier orbital and vibrational analyses clearly reveal the occurrence of charge transfer through covalent and noncovalent interactions. Moreover, it is found that CO₂ can adsorb through more favorable π‐type stacking as well as σ‐type hydrogen‐bonding interactions. The inter‐monomer interaction potentials show a significant anisotropy that might induce CO₂ orientation and site‐selectivity effects in porous materials and in active sites of Zn enzymes. Hence, this study provides valuable information about how CO₂ adsorption takes place at the microscopic level within zeolitic imidazolate frameworks and biomolecules. These findings might help in understanding the role of such complexes in chemistry, biology and material science for further development of new materials and industrial applications.     

Design and synthesis of new series of 3-cyanopyridine and pyrazolopyridine derivatives

Reaction of 3-cyano-4,6-dimethyl-2-pyridone with ethyl chloroacetate afforded ethyl 2-([3-cyano-4,6-dimethylpyridin-2-yl]oxy)acetate 2 and ethyl 2-(3-cyano-4,6-dimethyl-2-oxopyridin-1[2H]-yl)acetate 3 , the reaction product yield depend on the reaction condition (potassium carbonate concentration and reaction time). These compounds used as precursors to synthesize pyridine derivatives 4 , 6-10 , 15, 17-20 , furopyridines 5, 16 , pyrazolopyridine 12 , pyridopyrazolopyrimidines 14a,b . The structure of the newly synthesized compounds was confirmed by spectral data (IR, NMR, and mass spectra) and elemental analysis.     

Enhanced Photocatalytic Activity of MIL‐125 by Post‐Synthetic Modification with CrIII and Ag Nanoparticles

NH₂‐MIL‐125, [Ti₈O₈(OH)₄(bdc‐NH₂)₆] (bdc^2?=1,4‐benzene dicarboxylate) is a highly porous metal–organic framework (MOF) that has a band gap lying within the ultraviolet region at about 2.6 eV. The band gap may be reduced by a suitable post‐synthetic modification of the nanochannels using conventional organic chemistry methods. Here, it is shown that the photocatalytic activity of NH₂‐MIL‐125 in the degradation of methylene blue under visible light is remarkably augmented by post‐synthetic modification with acetylacetone followed by Cr^III complexation. The latter metal ion extends the absorption from the ultraviolet to the visible light region (band gap 2.21 eV). The photogenerated holes migrate from the MOF’s valence band to the Cr^III valence band, promoting the separation of holes and electrons and increasing the recombination time. Moreover, it is shown that the MOF’s photocatalytic activity is also much improved by doping with Ag nanoparticles, formed in situ by the reduction of Ag⁺ with the acetylacetonate pendant groups (the resulting MOF band gap is 2.09 eV). Presumably, the Ag nanoparticles are able to accept the MOF’s photogenerated electrons, thus avoiding electron–hole recombination. Both, the Cr‐ and Ag‐bearing materials are stable under photocatalytic conditions. These findings open new avenues for improving the photocatalytic activity of MOFs.     

Identification of Potential SARS-CoV-2 Main Protease and Spike Protein Inhibitors from the Genus Aloe: An In Silico Study for Drug Development

Severe acute respiratory syndrome coronavirus (SARS-CoV-2) disease is a global rapidly spreading virus showing very high rates of complications and mortality. Till now, there is no effective specific treatment for the disease. Aloe is a rich source of isolated phytoconstituents that have an enormous range of biological activities. Since there are no available experimental techniques to examine these compounds for antiviral activity against SARS-CoV-2, we employed an in silico approach involving molecular docking, dynamics simulation, and binding free energy calculation using SARS-CoV-2 essential proteins as main protease and spike protein to identify lead compounds from Aloe that may help in novel drug discovery. Results retrieved from docking and molecular dynamics simulation suggested a number of promising inhibitors from Aloe. Root mean square deviation (RMSD) and root mean square fluctuation (RMSF) calculations indicated that compounds 132, 134, and 159 were the best scoring compounds against main protease, while compounds 115, 120, and 131 were the best scoring ones against spike glycoprotein. Compounds 120 and 131 were able to achieve significant stability and binding free energies during molecular dynamics simulation. In addition, the highest scoring compounds were investigated for their pharmacokinetic properties and drug-likeness. The Aloe compounds are promising active phytoconstituents for drug development for SARS-CoV-2.     

HETEROCYCLIZATION OF AMINOTHIAZOLES

Several new 2-arylidinoamino-4-(3-coumaryl)thiazole derivatives were synthesized via the reaction of 2-amino-4-(coumaryl)thiazole with aromatic aldehydes and other reagents. Structural elucidations were based on elementary analysis and spectral data studies.     

CHEMISTRY OF UNCONDENSED 1,2,4-TRIAZINES: PART II-SULFUR CONTAINING 5-OXo-1,2,4-TRIAZIN-3-yl MOIETY AN OVERVIEW

Abstract

Studies on the chemical constituents of sulfur containing the 5-oxo-1,2,4-triazin-3-yl moiety are reviewed. The synthesis. unique features of the structures and biological significance of these constituents are discussed.