Computational studies on G-quadruplex DNA-stabilizing property of novel Wittig-based Schiff-Base ligands and their copper(II) complexes

A series of mono imine (C=N) group that contained Wittig-based Schiff-Base ligands was optimized using the DFT-based computational method and Gaussian 09 program package. These optimized molecules were docked with Quadruplex DNA (PDB ID: 1KF1) and duplex DNA (PDB ID: 1BNA) using AutoDock Vina program along with the reference molecules. Schiff-Base ligands derived from fused aromatic rings contained amines and precursor aldehyde (PA-5 both Z and E isomers) showed lower binding energy for G-quadruplex DNA among all and N-5 category both Z and E isomer Schiff-Base ligands have shown high selectivity for G-quadruplex DNA over duplex DNA which is a very important phenomenon to develop the G-quadruplex DNA stabilizers. For a few Schiff-Base molecules like Ligand-6 (1-{[2-Hydroxy-5-(2-pyren-1-yl-vinyl)-benzylidene]-amino}-naphthalen-2-ol) of N-5 category both Z and E isomers with groove binding and end stacking modes, molecular dynamic calculations were carried out. The study revealed that Ligand-6 of N-5 category E isomer with groove binding mode has higher stabilizing effect on G-quadruplex DNA in spite of having the higher binding energy value. Among Schiff-Base copper(II) complexes, Complex-3 (E-(1-{[2-Hydroxy-5-(2-pyren-1-yl-vinyl)-benzylidene]-amino}-naphthalen-2-ol)Cu) is having high binding affinity for G-quadruplex DNA as compared to others.

     

Indium(III) Triflate: A Highly Efficient Catalyst for Reactions of Sugars[1]

Indium(III) trifluoromethanesulfonate has been found to be extremely efficient in catalyzing acyl transfer reactions of various carbohydrates and their derivatives. Selective acetolyses of certain benzyl ethers/isopropylidene acetals of sugars have been possible using In(OTf)₃ in Ac₂O (neat). Reaction of the per-O-acetate of 2-deoxy-2-phthalimido-D-glucose with benzyl mercaptan in the presence of In(OTf)₃ led to the formation of the corresponding thioglycoside in high yield. Facile formation and hydrolysis of the isopropylidene and benzylidene acetals of various carbohydrates have also been achieved very efficiently in the presence of In(OTf)₃. The results show great promise for In(OTf)₃ in synthetic carbohydrate chemistry.     

Nickel-Catalyzed Regioselective Intermolecular Dialkylation of Alkenylarenes: Generation of Two Vicinal C(sp3)−C(sp3) Bonds Across Alkenes**

We disclose a Ni-catalyzed regioselective dialkylation reaction of alkenylarenes with α-halocarbonyls and alkylzinc reagents. The reaction produces γ-arylated alkanecarbonyl compounds with the generation of two new C(sp³)−C(sp³) bonds at the vicinal carbons of alkenes. This reaction is effective for the use of primary, secondary and tertiary α-halocarboxylic esters, amides and ketones in conjunction with primary and secondary alkylzinc reagents as the sources of two C(sp³) carbons for the dialkylation of terminal and cyclic internal alkenes.     

Virtual Screening for Potential Phytobioactives as Therapeutic Leads to Inhibit NQO1 for Selective Anticancer Therapy

NAD(P)H:quinone acceptor oxidoreductase-1 (NQO1) is a ubiquitous flavin adenine dinucleotide-dependent flavoprotein that promotes obligatory two-electron reductions of quinones, quinonimines, nitroaromatics, and azo dyes. NQO1 is a multifunctional antioxidant enzyme whose expression and deletion are linked to reduced and increased oxidative stress susceptibilities. NQO1 acts as both a tumor suppressor and tumor promoter; thus, the inhibition of NQO1 results in less tumor burden. In addition, the high expression of NQO1 is associated with a shorter survival time of cancer patients. Inhibiting NQO1 also enables certain anticancer agents to evade the detoxification process. In this study, a series of phytobioactives were screened based on their chemical classes such as coumarins, flavonoids, and triterpenoids for their action on NQO1. The in silico evaluations were conducted using PyRx virtual screening tools, where the flavone compound, Orientin showed a better binding affinity score of −8.18 when compared with standard inhibitor Dicumarol with favorable ADME properties. An MD simulation study found that the Orientin binding to NQO1 away from the substrate-binding site induces a potential conformational change in the substrate-binding site, thereby inhibiting substrate accessibility towards the FAD-binding domain. Furthermore, with this computational approach we are offering a scope for validation of the new therapeutic components for their in vitro and in vivo efficacy against NQO1.     

An Improved Process for the Enantioselective Synthesis of HCV NS5A Inhibitor Elbasvir (MK-8742) Chiral Amine Intermediate

Russian Journal of General Chemistry - Large-scale enantioselective synthesis of the chiral amine unit of HCV NS5A inhibitor Elbasvir has been accomplished in six steps, with 55% overall yield. The...     

Converting gem-dimethyl groups into cyclopropanes via Pd-catalyzed sequential C-H activation and radical cyclization

A novel route to the synthesis of cyclopropane derivatives is described. 1,1-Dimethyls in 2-(1,1-dimethylalkyl)dimethyloxazolines are first converted into 1,3-diiodide derivatives via Pd-catalyzed sequential C-H activation and then radically cyclized to provide 2-(1-alkylcylclopropyl)dimethyloxazolines. The use of EtOAc as a solvent is crucial for the diiodination of the functionalized substrates. [reaction: see text]     

Ultra fast magic angle spinning solid – state NMR spectroscopy of intact bone

Ultra fast magic angle spinning (MAS) has been a potent method to significantly average out homogeneous/inhomogeneous line broadening in solid‐state nuclear magnetic resonance (ssNMR) spectroscopy. It has given a new direction to ssNMR spectroscopy with its different applications. We present here the first and foremost application of ultra fast MAS (~60 kHz) for ssNMR spectroscopy of intact bone. This methodology helps to comprehend and elucidate the organic content in the intact bone matrix with resolution and sensitivity enhancement. At this MAS speed, amino protons from organic part of intact bone start to appear in ¹H NMR spectra. The experimental protocol of ultra‐high speed MAS for intact bone has been entailed with an additional insight achieved at 60 kHz. Copyright © 2015 John Wiley & Sons, Ltd.     

Oxidation of propane to acrylic acid and acetic acid over alkaline earth-doped Mo-V-Sb-Ox catalysts

Alkaline earth metal (Mg, Ca, Sr and Ba)-doped Mo-V-Sb-Ox catalysts, prepared by a dry-up method, have been investigated for their catalytic performance in the oxidation of propane under different reaction conditions. The catalysts have been characterized by N2 adsorption-desorption, temperature-programmed desorption (TPD) of NH3, SEM and XRD. Influence of water vapor on the catalytic performance, particularly on the selectivities to acetic acid and acrylic acid, has also been studied. The selectivity to acrylic acid was improved significantly by the doping of alkaline earth metals to Mo-V-Sb-Ox catalysts. The surface acidic sites of the catalyst decreased with the doping of the catalyst with alkaline earth metals, which ultimately was found to be beneficial for obtaining high selectivity to acrylic acid. The catalytic activity and product selectivities were found to be influenced by the reaction temperature, C3H8/O2 ratio and space velocity. A significant improvement in the selectivity to acrylic acid has also been observed by the addition of water vapor in the feed of propane and oxygen in the oxidation of propane.     

Existence of Extremizers for a Model Convolution Operator

The operator T, defined by convolution with the affine arc length measure on the moment curve parametrized by \(h(t)=(t,t^{2},\ldots ,t^{d})\) is a bounded operator from \(L^{p}\) to \(L^{q}\) if \((\frac{1}{p}, \frac{1}{q})\) lies on a line segment. In this article we prove that at non-end points there exist functions which extremize the associated inequality and any extremizing sequence is pre compact modulo the action of the symmetry of T. We also establish a relation between extremizers for T at the end points and the extremizers of an X-ray transform restricted to directions along the moment curve. Our proof is based on the ideas of Michael Christ on convolution with the surface measure on the paraboloid.

     

Surface adsorption and collapse transition of linear polymer chains

The critical behaviour of surface adsorption and collapse transition of a flexible self-attracting self-avoiding polymer chain is examined. Depending upon the underlying lattice and space dimensionality, phase diagrams that exhibit many different universality domains of critical behavior are found. We discuss these phase diagrams and the values of the critical exponents found from different theoretical methods.