2-Amino-3-cyano-4H-chromene-4-ylphosphonates as potential antiviral agents: Synthesis,in ovo and in silico approach

A simplistic synthetic procedure for the synthesis of structurally diversified 2-amino-3-cyano-4H-chromene-4-ylphosphonates ( 4a-j ) were developed by the treatment of substituted salicylaldehydes, malononitrile, and dialkyl phosphite in presence of Cu(OAc)₂ catalyst at room temperature and neat conditions. The synthesized compounds were tested for their antiviral assay. Among all, the compounds 4a , 4d and 4h have shown good in ovo antiviral activity against New castle disease virus (NDV) at a concentration of 150 μg/mL. The remarkable reduction in NDV virus population in embryos treated with title compounds ( 4a-j ) in a dose dependent manner, indicated that the synthesized compounds are extreme by toxic to the NDV virus. The title compounds were also docked against hemagglutinin neuraminidase enzyme and the more bioactive compound 4a showed highest docking score than the standard antiviral drug taribavirin while the compounds 4d and 4h has the same docking score as that of the standard.     

Thiazole–Chalcone Hybrids as Prospective Antitubercular and Antiproliferative Agents: Design,Synthesis, Biological,Molecular Docking Studies and In Silico ADME Evaluation

Compounds bearing thiazole and chalcone pharmacophores have been reported to possess excellent antitubercular and anticancer activities. In view of this, we designed, synthesized and characterized a novel series of thiazole–chalcone hybrids (1–20) and further evaluated them for antitubercular and antiproliferative activities by employing standard protocols. Among the twenty compounds, chalcones 12 and 7, containing 2,4-difluorophenyl and 2,4-dichlorophenyl groups, showed potential antitubercular activity higher than the standard pyrazinamide (MIC = 25.34 µM) with MICs of 2.43 and 4.41 µM, respectively. Chalcone 20 containing heteroaryl 2-thiazolyl moiety exhibited promising antiproliferative activity against the prostate cancer cell line (DU-145), higher than the standard methotrexate (IC₅₀ = 11 ± 1 µM) with an IC₅₀ value of 6.86 ± 1 µM. Furthermore, cytotoxicity studies of these compounds against normal human liver cell lines (L02) revealed that the target molecules were comparatively less selective against L02. Additional computational studies using AutoDock predicted the key binding interactions responsible for the activity and the SwissADME tool computed the in silico drug likeliness properties. The lead compounds generated through this study, create a way for the optimization and development of novel drugs against tuberculosis infections and prostate cancer.     

Polymer wiring of insulating electrode materials: An approach to improve energy density of lithium-ion batteries

The poor electronic conductivity of LiFePO₄ has been one of the major issues impeding it from achieving high power and energy density lithium-ion batteries. In this communication, a novel polymer-wiring concept was proposed to improve the conduction of the insulating electrode material. By using a polymer with tethered “swing” redox active molecules (S) attached on a polymer chain, as the standard redox potential of S matches closely the Fermi level of LiFePO₄, electronic communication between the redox molecule and LiFePO₄ is established. Upon charging, S is oxidized at the current collector to S⁺, which then delivers the charge (holes) to the LiFePO₄ particles by intermolecular hopping assisted by a “swing” – type motion of the shuttle molecule. And Li⁺ is extracted. Upon discharging, the above process is just reversed. Preliminary studies with redox polymer consisting of poly (4-vinylpyridine) and phenoxazine moiety tethered with a C₁₂ alkyl chain have shown promising result with carbon-free LiFePO₄, where effective electron exchange between the shuttle molecule and LiFePO₄ has been observed. In addition, as the redox polymer itself could act as binder, we anticipate that the polymer-wiring concept would provide a viable approach to conducting-additive and binder free electrode for high energy density batteries.     

CdSe quantum dot (QD) and molecular dye hybrid sensitizers for TiO2 mesoporous solar cells: working together with a common hole carrier of cobalt complexes

Redox couples based on cobalt complexes were found to be effective in regenerating both inorganic CdSe quantum dot- and organic dye-sensitizers. The hybrid sensitizer composed of CdSe QD and ruthenium sensitizer (Z907Na) dye showed a maximum power conversion efficiency of 4.76% on using cobalt(o-phen)(3)(2+/3+) as a common redox mediator.     

Fundamental frequency analysis of microtubules under different boundary conditions using differential quadrature method

Microtubules (MTs) are a central part of the cytoskeleton in eukaryotic cells. The dynamic behaviors of MTs are of great interest in biomechanics. Many researchers have studied the vibration analysis of MTs by modeling them as an orthotropic cylindrical elastic shell and the exact solution to its displacements is investigated under simply supported boundary conditions. Other boundary conditions lead to some coupled equations, which there are no exact solution to them. Considering various boundary conditions requires implementing semi-analytic or numerical methods. In this study, the differential quadrature method (DQM) has been used to solve the nonlinear problem of seeking fundamental frequency. At first to verify the DQM results, this method has been applied to the equations of MTs under simply supported boundary condition. The coincidence of the exact solution results and the results of DQM shows the effectiveness and precision of this method. After verification, DQM has been used for the other boundary conditions. These boundary conditions are including clamped–clamped (CC), clamped–simply (CS), clamped–free (CF) and free–free (FF) constraints. Finally, the effect of edges boundary condition, radius of MTs and half wave numbers on the vibration behavior of MTs is considered.     

A single transition state serves two mechanisms. The branching ratio for CH2O*- + CH3Cl on improved potential energy surfaces

The reaction of formaldehyde radical anion with methyl chloride, CH2O*- + CH3Cl, is an example in which a single transition state leads to two products: substitution at carbon (Sub(C), CH3CH2O* + Cl-) and electron transfer (ET, CH2O + CH3* + Cl-). The branching ratio for this reaction has been studied by ab initio molecular dynamics (AIMD). The energies of transition states and intermediates were computed at a variety of levels of theory and compared to accurate energetics calculated by the G3 and CBS-QB3 methods. A bond additivity correction has been constructed to improve the Hartree-Fock potential energy surface (BAC-UHF). A satisfactory balance between good energetics and affordable AIMD calculations can be achieved with BH&HLYP/6-31G(d) and BAC-UHF/6-31G(d) calculations. Approximately 200 ab initio classical trajectories were calculated for each level of theory with initial conditions sampled from a thermal distribution at 298 K at the transition state. Three types of trajectories were distinguished: trajectories that go directly to ET product, trajectories that go to Sub(C) product, and trajectories that initially go into the Sub(C) valley and then dissociate to ET products. The BH&HLYP/6-31G(d) calculations overestimate the number of nonreactive and direct ET trajectories because the transition state is too early. For the BH&HLYP and BAC-UHF methods, about one-third of the trajectories that initially go into the Sub(C) valley dissociate to ET products, compared to just over half with UHF/6-31G(d) in the earlier study. This difference can be attributed to a better value for the calculated energy release from the initial transition state and to an improved Sub(C) --> ET barrier height with the BH&HLYP and BAC-UHF methods.     

A single-site mutation (F429H) converts the enzyme CYP 2B4 into a heme oxygenase: a QM/MM study

The intriguing deactivation of the cytochrome P450 (CYP) 2B4 enzyme induced by mutation of a single residue, Phe429 to His, is explored by quantum mechanical/molecular mechanical calculations of the O-OH bond activation of the (Fe(3+)OOH)(-) intermediate. It is found that the F429H mutant of CYP 2B4 undergoes homolytic instead of heterolytic O-OH bond cleavage. Thus, the mutant acquires the following characteristics of a heme oxygenase enzyme: (a) donation by His429 of an additional NH---S H-bond to the cysteine ligand combined with the presence of the substrate retards the heterolytic cleavage and gives rise to homolytic O-OH cleavage, and (b) the Thr302/water cluster orients nascent OH(?) and ensures efficient meso hydroxylation.     

Two-Way Catalysis in a Diels–Alder Reaction Limits Inhibition Induced by an External Electric Field

Oriented external electric fields (EEFs) act as catalysts that can induce selectivity in chemical reactions. The responses of the Diels–Alder (DA) reaction between butadiene and ethylene (BDE-DA) as well as cyclopentadiene and ethylene (CPDE-DA) towards EEF stimuli are investigated here using density functional theory (B3LYP) calculations. EEF is a vector that catalyzes the reaction in one direction while inhibiting it in the opposite direction. Here we report that the inhibitive direction becomes rate-enhancing after some increase in the EEF. The EEF value that brings about the maximum possible inhibition for the reaction is defined as the electrostatic resistance point (ERP). The possibility of both normal and inverse electron-demand DA reactions causes catalytic activity in both directions of the EEF starting at a unique ERP value. The C5 substituents of cyclopentadiene control the ERP values depending upon the resistance power that the functional group provides against the EEF. The endo and exo diastereomeric transition states of the DA reaction have distinct ERP values and the difference (ΔERP) provides the through-space electrostatic contribution to the stereoselectivity on a relative scale. Thus, the ERP values can be used as a gauge for the electrostatic interactions between substituent groups and external stimuli.