An Enolate‐Mediated Organocatalytic Azide–Ketone [3+2]‐Cycloaddition Reaction: Regioselective High‐Yielding Synthesis of Fully Decorated 1,2,3‐Triazoles

An enolate‐mediated organocatalytic azide–ketone [3+2]‐cycloaddition (OrgAKC) reaction of a variety of enolizable arylacetones and deoxybenzoins with aryl azides was developed for the synthesis of fully decorated 1,4‐diaryl‐5‐methyl(alkyl)‐1,2,3‐triazoles in excellent yields with high regioselectivity at 25 °C for 0.5–6 h. This reaction has an excellent outcome with reference to reaction rate, yield, regioselectivity, operation simplicity, and availability of substrates and catalyst. This reaction has advantages over the previously known metal‐mediated reactions.     

Direct Synthesis of Hexagonal NaGdF4 Nanocrystals from a Single‐Source Precursor: Upconverting NaGdF4:Yb3+,Tm3+ and Its Composites with TiO2 for Near‐IR‐Driven Photocatalysis

A novel single‐source precursor NaGd(TFA)₄(diglyme) (TFA=trifluoroacetate) was synthesized, characterized thoroughly, and used to obtain the hexagonal phase of NaGdF₄ nanoparticles as an efficient matrix for lanthanide‐doped upconverting nanocrystals (NCs) that convert near‐infrared radiation into shorter‐wavelength UV/visible light. These NCs were then used to prepare well‐characterized TiO₂@NaGdF₄:Yb³⁺,Tm³⁺ nanocomposites to extend the absorption range of the TiO₂ photocatalyst from the UV to the IR region. While the visible/near IR part of the photoluminescent spectra remains almost unaffected by the presence of TiO₂, the UV part is strongly quenched due to the absorption of TiO₂ above its gap at approximately 380 nm by energy transfer or FRET. Preliminary results on the photocatalytic activity of the above obtained nanocomposites are presented.     

Investigation on major,minor and trace elements in some medicinal plants using Particle Induced X-ray Emission

Journal of Radioanalytical and Nuclear Chemistry - Elemental concentrations namely P, S, Cl, K, Ca, Sc, Ti, Mn, Fe, Cu, Zn, Rb, Br and Sr were determined using Particle Induced X-ray Emission...     

Investigation of the interface trap density and series resistance of a high-k HfO2-based MOS capacitor: before and after 50 MeV Li3+ ion irradiation

This is the first investigation on the effects of 50 MeV Li³⁺ ions on interface trap density (D _it) and series resistance (R _s), which reveal the improvement of the dielectric properties of RF-sputtered HfO₂-metal oxide semiconductor (MOS) capacitors. The samples were irradiated and characterized at room temperature. The D _it and R _s were determined from the capacitance–voltage (C–V) and conduction–voltage (G–V) characteristics at 1 MHz. The measured capacitance and conductance were corrected for series resistance. It is found that the series resistance of Al/HfO₂/p? Si MOS capacitors increases with ion fluence, calculated at a strong accumulation region before and after irradiation. The interface state density of MOS devices before and after irradiation is found to decrease with increasing ion fluence.     

Microscopic Characterization of GRP1 PH Domain Interaction with Anionic Membranes

The pleckstrin homology (PH) domain of general receptor for phosphoionositides 1 (GRP1-PHD) binds specifically to phosphatidylinositol (3,4,5)-triphosphate (PIP₃), and acts as a second messenger. Using an extensive array of molecular dynamics (MD) simulations employing highly mobile membrane mimetic (HMMM) model as well as complementary full membrane simulations, we capture differentiable binding and dynamics of GRP1-PHD in the presence of membranes containing PC, PS, and PIP₃ lipids in varying compositions. While GRP1-PHD forms only transient interactions with pure PC membranes, incorporation of anionic lipids resulted in stable membrane-bound configurations. We report the first observation of two distinct PIP₃ binding modes on GRP1-PHD, involving PIP₃ interactions at a “canonical” and at an “alternate” site, suggesting the possibility of simultaneous binding of multiple anionic lipids. The full membrane simulations confirmed the stability of the membrane bound pose of GRP1-PHD as captured from our HMMM membrane binding simulations. By performing additional steered membrane unbinding simulations and calculating nonequilibrium work associated with the process, as well as metadynamics simulations, on the protein bound to full membranes, allowing for more quantitative examination of the binding strength of the GRP1-PHD to the membrane, we demonstrate that along with the bound PIP₃, surrounding anionic PS lipids increase the energetic cost of unbinding of GRP1-PHD from the canonical mode, causing them to dissociate more slowly than the alternate mode. Our results demonstrate that concurrent binding of multiple anionic lipids by GRP1-PHD contributes to its membrane affinity, which in turn control its signaling activity. © 2019 Wiley Periodicals, Inc.     

A Comparative Synthetic Strategy Perspective on α-Amino Acid- and Non-Amino Acid-Derived Synthons towards Total Syntheses of Selected Natural Macrolides

Macrocyclic alkaloids (macrolides) and cyclopeptides have an immense range of applications in drug discovery research because of their natural abundance and potential biological and physicochemical properties. Presently, more than 100 approved drugs or clinical drug candidates contain macrocyclic scaffolds as the biologically active component. This review provides an interesting perspective about the use of amino acid-derived chiral pools versus other methods derived from miscellaneous synthons towards the total synthesis of non-peptidic macrolides. The synthetic routes and the key strategies involved in the total syntheses of ten natural macrolides have been discussed. Both the amino acid-derived and non-amino acid-derived synthetic routes have been illustrated to present a comparative study between the two approaches.     

Discovery of Novel Coumarin Derivatives as Potential Dual Inhibitors against α-Glucosidase and α-Amylase for the Management of Post-Prandial Hyperglycemia via Molecular Modelling Approaches

Coumarin derivatives are proven for their therapeutic uses in several human diseases and disorders such as inflammation, neurodegenerative disorders, cancer, fertility, and microbial infections. Coumarin derivatives and coumarin-based scaffolds gained renewed attention for treating diabetes mellitus. The current decade witnessed the inhibiting potential of coumarin derivatives and coumarin-based scaffolds against α-glucosidase and α-amylase for the management of postprandial hyperglycemia. Hyperglycemia is a condition where an excessive amount of glucose circulates in the bloodstream. It occurs when the body lacks enough insulin or is unable to correctly utilize it. With open-source and free in silico tools, we have investigated novel 80 coumarin derivatives for their inhibitory potential against α-glucosidase and α-amylase and identified a coumarin derivative, CD-59, as a potential dual inhibitor. The ligand-based 3D pharmacophore detection and search is utilized to discover diverse coumarin-like compounds and new chemical scaffolds for the dual inhibition of α-glucosidase and α-amylase. In this regard, four novel coumarin-like compounds from the ZINC database have been discovered as the potential dual inhibitors of α-glucosidase and α-amylase (ZINC02789441 and ZINC40949448 with scaffold thiophenyl chromene carboxamide, ZINC13496808 with triazino indol thio phenylacetamide, and ZINC09781623 with chromenyl thiazole). To summarize, we propose that a coumarin derivative, CD-59, and ZINC02789441 from the ZINC database will serve as potential lead molecules with dual inhibition activity against α-glucosidase and α-amylase, thereby discovering new drugs for the effective management of postprandial hyperglycemia. From the reported scaffold, the synthesis of several novel compounds can also be performed, which can be used for drug discovery.