3D-QSAR,molecular dynamics simulations,and molecular docking studies on pyridoaminotropanes and tetrahydroquinazoline as mTOR inhibitors

Cancer is a second major disease after metabolic disorders where the number of cases of death is increasing gradually. Mammalian target of rapamycin (mTOR) is one of the most important targets for treatment of cancer, specifically for breast and lung cancer. In the present research work, Comparative Molecular Field Analysis (CoMFA) and Comparative Molecular Similarity Indices Analysis (CoMSIA) studies were performed on 50 compounds reported as mTOR inhibitors. Three different alignment methods were used, and among them, distill method was found to be the best method. In CoMFA, leave-one-out cross-validated coefficients \((q^{2})\), conventional coefficient \((r^{2})\), and predicted correlation coefficient \((r^{2}_{\mathrm{pred}})\) values were found to be 0.664, 0.992, and 0.652, respectively. CoMSIA study was performed in 25 different combinations of features, such as steric, electrostatic, hydrogen bond donor, hydrogen bond acceptor, and hydrophobic. From this, a combination of steric, electrostatic, hydrophobic (SEH), and a combination of steric, electrostatic, hydrophobic, donor, and acceptor (SEHDA) were found as best combinations. In CoMSIA (SEHDA), \(q^{2}\), \(r^{2}\) and \(r^{2}_{\mathrm{pred}}\) were found to be 0.646, 0.977, and 0.682, respectively, while in the case of CoMSIA (SEH), the values were 0.739, 0.976, and 0.779, respectively. Contour maps were generated and validated by molecular dynamics simulation-assisted molecular docking study. Highest active compound 19, moderate active compound 15, and lowest active compound 42 were docked on mTOR protein to validate the results of our molecular docking study. The result of the molecular docking study of highest active compound 19 is in line with the outcomes generated by contour maps. Based on the features obtained through this study, six novel mTOR inhibitors were designed and docked. This study could be useful for designing novel molecules with increased anticancer activity.     

Testing of holographic optical elements for holographic gun-sight

Conventional methods of measuring the various parameters of holographic optical elements are tedious for mass production. A novel approach is described for the holographic elements used in the holographic sight, in which the parameters are defined and measured as per their intended final application. Since the holographic sight is used for accurate target acquisition along with the other features, parallax in the sight becomes a critical parameter. Besides, the maximum brightness of the reticle is another parameter of the device, which is important for the use of sight in the strong sunlight in summers. There are two holographic elements, namely holographic reticle and holographic lens in the sight. Both can be tested in a simple set-up in terms of the parallax of the sight and the brightness of the reticle. The masters for both elements are required to be benchmarked once and rest of the elements in a mass production can be tested with the reference of masters.     

Melt processing of alumina in graphite ambient for dosimetric applications

Carbon-doped alumina samples were prepared by a simple process involving melting of polycrystalline alumina powder in graphite environment. The melting was carried out using an electron gun of a vacuum deposition system meant for deposition of thin films. The samples showed excellent thermoluminescence (TL) and optically stimulated luminescence (OSL) response in the dose range 3 mGy to 1 Gy. Defect centers in the prepared material, as determined by excitation spectra, were found to be similar to those of commercial α-Al₂O₃:C single crystals. Samples were found to be suitable for radiation dosimetry, with a detection threshold of 50-μGy. Fading in the dark has been found to be<2% for a period of 2 months at room temperature. The variation in OSL response among the samples processed under similar conditions was found to be within ±14%.     

Synthesis of a Novel Thyrotropin Releasing Hormone (TRH) Analog Incorporating a Piperazin‐2‐one Ring

The synthesis of a Thyrotropin Releasing Hormone (TRH) analog incorporating a piperazin‐2‐one ring is described. This conformationally restricted peptidomimetic attempts to retain the key recognition elements of the interaction between TRH and its receptor. The synthesis started from the protected dipeptide 2 and proceeded via the 4‐nitrobenzenesulfonyl‐activated intermediate 3 , which was then cyclized, N‐acylated, and deprotected to yield the target compound 1 .     

Transient Metallo-Lipidoid Assemblies Amplify Covalent Catalysis of Aqueous and Non-Aqueous Reactions

Dissipative supramolecular assemblies are hallmarks of living systems, contributing to their complex, dynamic structures and emerging functions. Living cells can spatiotemporally control diverse biochemical reactions in membrane compartments and condensates, regulating metabolite levels, signal transduction or remodeling of the cytoskeleton. Herein, we constructed membranous compartments using self-assembly of lipid-like amphiphiles (lipidoid) in aqueous medium. The new double-tailed lipidoid features Cu(II) coordinated with a tetravalent chelator that dictates the binding of two amphiphilic ligands in cis-orientation. Hydrophobic interactions between the lipidoids coupled with intermolecular hydrogen bonding led to a well-defined bilayer vesicle structure. Oil-soluble S_NAr reaction is efficiently upregulated in the hydrophobic cavity, acting as a catalytic crucible. The modular system allows easy incorporation of exposed primary amine groups, which augments the catalysis of retro aldol and C−N bond formation reactions. Moreover, a higher-affinity chelator enables consumption of the Cu(II) template leveraging the differential thermodynamic stability, which allows a controllable lifetime of the vesicular assemblies. Concomitant temporal upregulation of the catalytic reactions could be tuned by the metal ion concentration. This work offers new possibilities for metal ion-mediated dynamic supramolecular systems, opening up a massive repertoire of functionally active dynamic “life-like” materials.     

High Energy Density Supercapacitors: An Overview of Efficient Electrode Materials,Electrolytes, Design,and Fabrication

Supercapacitors (SCs) are potentially trustworthy energy storage devices, therefore getting huge attention from researchers. However, due to limited capacitance and low energy density, there is still scope for improvement. The race to develop novel methods for enhancing their electrochemical characteristics is still going strong, where the goal of improving their energy density to match that of batteries by increasing their specific capacitance and raising their working voltage while maintaining high power capability and cutting the cost of production. In this light, this paper offers a succinct summary of current developments and fresh insights into the construction of SCs with high energy density which might help new researchers in the field of supercapacitor research. From electrolytes, electrodes, and device modification perspectives, novel applicable methodologies were emphasized and explored. When compared to conventional SCs, the special combination of electrode material/composites and electrolytes along with their fabrication design considerably enhances the electrochemical performance and energy density of the SCs. Emphasis is placed on the dynamic and mechanical variables connected to SCs′ energy storage process. To point the way toward a positive future for the design of high-energy SCs, the potential and difficulties are finally highlighted. Further, we explore a few important topics for enhancing the energy densities of supercapacitors, as well as some links between major impacting factors. The review also covers the obstacles and prospects in this fascinating subject. This gives a fundamental understanding of supercapacitors as well as a crucial design principle for the next generation of improved supercapacitors being developed for commercial and consumer use.     

Slow flow past a heterogeneous porous sphere

Stokes’ flow past a heterogeneous porous sphere has been studied, adopting the boundary conditions modified by Jones (1973) for curved surfaces at the interface of the free fluid region and porous material. The porous sphere is made up ofn + 1 concentric spheres of different permeability. The results for drag experienced by the sphere has been discussed and the following cases of interest are deduced:

1. WhenK ₁=K ₂=...=K _n+1=K.
2. WhenK _i is very small for eachi.

     

Oxidation of aromatic substrates with hydrogen peroxide and hydrochloric acid

Chloroquinones are prepared conveniently from phenol, naphthols and aromatic amines.     

Weak convergence to a Markov process: The martingale approach

Summary In this article, we obtain some sufficient conditions for weak convergence of a sequence of processes {X _n } toX, whenX arises as a solution to a well posed martingale problem. These conditions are tailored for application to the case when the state space for the processesX _n ,X is infinite dimensional. The usefulness of these conditions is illustrated by deriving Donsker's invariance principle for Hilbert space valued random variables. Also, continuous dependence of Hilbert space valued diffusions on diffusion and drift coefficients is proved.Research supported by National Board for Higher Mathematics, Bombay, IndiaPart of the work was done at University of California, Santa Barbara, USA     

A.c. conductivity in AsF5 doped polyphenylacetylene (PPA)

The a.c. conductivity of semiconducting cis-cisoid polyphenylacetylene (PPA) pellets has been studied at temperatures between 230 and 290 K and frequencies, ?, from 37 to 10⁵ Hz. The a.c. conductivity (σ_a.c.) is found to be strongly temperature dependent. σ_a.c. is proportional to ?^s with s varying from 0.45 to 0.75 as temperature is raised from 230 to 290 K. Both frequency dispersion and strong temperature dependence of σ_a.c. are best explained by the mechanism of hopping conduction in the band-tails.