Although lithium-sulfur (Li-S) batteries offer a high theoretical energy density, shuttling of dissolved sulfur and polysulfides is a major factor limiting the specific capacity, energy density, and cyclability of Li-S batteries with a liquid electrolyte. Cathode host materials with a microstructure to restrict the migration of active material may not totally eliminate the shuttling effect or may create additional problems that limit the full dissolution and redox conversion of all active cathode materials. Selecting a cathode coating binder with a multifunctional role offers a universal solution suitable for various cathode hosts.
View Article and Find Full Text PDFThe crystal structure of orthorhombic Bovine Pancreatic Ribonuclease A has been determined to 0.85 Å resolution using low temperature, 100 K, synchrotron X-ray data collected at 16000 keV (λ = 0.77 Å).
View Article and Find Full Text PDFA variety of two-dimensional (2D) nanomaterials, including graphene oxide and clays, are known to stabilize Pickering emulsions to fabricate structures for functions in sensors, catalysts, and encapsulation. We introduce here a novel Pickering emulsion using self-assembled amphiphilic triblock oligoglycine as the emulsifier. Peptide amphiphiles are more responsive to environmental changes (e.
View Article and Find Full Text PDFPhys Chem Chem Phys
June 2022
Acid Sensing Ion Channels (ASICs) are one of the most studied channels of the Epithelial Sodium Channel/Degenerin (ENaC/DEG) superfamily. They are responsible for excitatory responses following acidification of the extracellular medium and are involved in several important physiological roles. The ASIC1 subunit can form a functional homotrimeric channel and its structure is currently the most characterised of the whole ENaC/DEG family.
View Article and Find Full Text PDFThe Epithelial Sodium Channel/Degenerin (ENaC/DEG) family is a superfamily of sodium-selective channels that play diverse and important physiological roles in a wide variety of animal species. Despite their differences, they share a high homology in the pore region in which the ion discrimination takes place. Although ion selectivity has been studied for decades, the mechanisms underlying this selectivity for trimeric channels, and particularly for the ENaC/DEG family, are still poorly understood.
View Article and Find Full Text PDFAgeing is a major risk factor for many conditions including cancer, cardiovascular and neurodegenerative diseases. Pharmaceutical interventions that slow down ageing and delay the onset of age-related diseases are a growing research area. The aim of this study was to build a machine learning model based on the data of the DrugAge database to predict whether a chemical compound will extend the lifespan of Caenorhabditis elegans.
View Article and Find Full Text PDFThe DNA repair enzyme AAG has been shown in mice to promote tissue necrosis in response to ischaemic reperfusion or treatment with alkylating agents. A chemical probe inhibitor is required for investigations of the biological mechanism causing this phenomenon and as a lead for drugs that are potentially protective against tissue damage from organ failure and transplantation, and alkylative chemotherapy. Herein, we describe the rationale behind the choice of arylmethylpyrrolidines as appropriate aza-nucleoside mimics for an inhibitor followed by their synthesis and the first use of a microplate-based assay for quantification of their inhibition of AAG.
View Article and Find Full Text PDFMaterials science is beginning to adopt computational simulation to eliminate laboratory trial and error campaigns-much like the pharmaceutical industry of 40 years ago. To further computational materials discovery, new methodology must be developed that enables rapid and accurate testing on accessible computational hardware. To this end, the authors utilise a novel methodology concept of intermediate molecules as a starting point, for which they propose the term 'symthon'[a] rather than conventional monomers.
View Article and Find Full Text PDFA recyclable mercury(ii) selective dimer based on a calix[4]pyrrole derivative has been synthesised and characterised by mass and FT-IR spectrometry, Scanning Electron Microscopy (SEM) and Energy Dispersive X-ray (EDX). Information regarding the ability of the dimer to interact with metal cations was obtained from FTIR and SEM-EDX analyses. A striking feature of micrographs of the loaded dimer is the change of morphology with the cation.
View Article and Find Full Text PDFJ Mol Graph Model
September 2019
Medicinal chemistry has in the past been dominated by learned insights from experienced organic chemists. However, with the advent of computer based methods, computer aided drug design has become prominent. We have compared here the ability of locally sourced expert medicinal chemists to purely automated methods and found that the automated method produces a better potential candidate drug than the expert input.
View Article and Find Full Text PDFThe reaction of phenyl glycidyl ether (PGE) with 1-ethyl-3-methylimidazolium acetateand 1-ethyl-3-methylimidazolium thiocyanate to initiate the polyetherification reaction wasexamined using thermal and spectral analysis techniques. The influence of the nucleophilicity of theanions on the deprotonation of the 1-ethyl-3-methylimidazolium cation determined the reactionpathway. The thermal degradation of the ionic liquid liberated the acetate ion and led, subsequently,to the deprotonation of the acidic proton in the imidazole ring.
View Article and Find Full Text PDFA series of commercial difunctional benzoxazine monomers are characterized using thermal and thermo-mechanical techniques before constructing representative polymer networks using molecular simulation techniques. Good agreement is obtained between replicate analyses and for the kinetic parameters obtained from differential scanning calorimetry data (and determined using the methods of Kissinger and Ozawa). Activation energies range from 85 to 108 kJ/mol (Kissinger) and 89 to 110 kJ/mol (Ozawa) for the uncatalyzed thermal polymerization reactions, which achieve conversions of between 85% and 97%.
View Article and Find Full Text PDFWet processes of phosphoric acids produce untreated wastewater containing large amounts of fluoride leading to serious environmental problems. This paper reports fundamental studies on two lower rim functionalised calix[4]arene based receptors namely 5, 11, 17, 23 tetra-tert-butyl, 25, 27 bis [diethylphenylurea]ethoxy, 26, 28 dihydroxycalix[4]arene, 1 and 25, 27 bis[diethylphenylurea]ethoxy, 26, 28 dihydroxycalix[4]arene, 2 and their ionic interactions. It is shown that these receptors only interact with fluoride and phosphate in acetonitrile.
View Article and Find Full Text PDFFor the first time we present nanoindentation analysis of charred, cured aromatic cyanate esters, which exhibit outstanding mechanical properties when analysed under applied loads of 0.1-300 mN. Following charring (900 °C for 10 minutes to achieve graphitised structures), the samples display a remarkable combination of a modulus of elasticity of around 25 GPa and nanohardness of 300 kgf mm, making them some 30-40% stiffer than bone and practically as hard as tooth enamel.
View Article and Find Full Text PDFThe crystal structure of a commercially available form of human recombinant (HR) insulin, Insugen (I), used in the treatment of diabetes has been determined to 0.92 Å resolution using low temperature, 100 K, synchrotron X-ray data collected at 16,000 keV (λ = 0.77 Å).
View Article and Find Full Text PDFThe synthesis and characterisation of a partially substituted calix[4]arene, namely, 5,11,17,23-tetra-tert-butyl,25,27-bis[aminoethoxy] 26,28-dihydroxycalix[4]arene are reported. Its interaction with commonly used pharmaceuticals (clofibric acid, diclofenac and aspirin) was investigated by spectroscopic (H NMR and UV), electrochemical (conductance measurements) and thermal (titration calorimetry) techniques. It is concluded on the basis of the experimental work and molecular simulation studies that the receptor interacts selectively with these drugs.
View Article and Find Full Text PDFBackground: The NADPH oxidase, by generating reactive oxygen species, is involved in the pathophysiology of many cardiovascular diseases and represents a therapeutic target for the development of novel drugs. A single-nucleotide polymorphism, C242T of the p22(phox) subunit of NADPH oxidase, has been reported to be negatively associated with coronary heart disease and may predict disease prevalence. However, the underlying mechanisms remain unknown.
View Article and Find Full Text PDFThis study uses the Molecular Operating Environment software (MOE) to generate models to calculate the char yield of polybenzoxazines (PBz). A series of benzoxazine (Bz) monomers were constructed to which a variety of parameters relating to the structure (e.g.
View Article and Find Full Text PDFJ Biomol Struct Dyn
November 2016
Simple molecular docking calculations on quercetin, kojic acid and diethylcarbamatodithoic acid using the software package MOE are shown to be close to the geometries reported in the X-ray crystal structures of the protein co-crystallized with the respective ligands. Furthermore, DFT optimization of the docked conformations is shown to reproduce the essential features of previous studies on quercetin, showing that docking can be used to provide good starting structures for mechanistic study. The flavone ligand, lacking the hydroxyl group of the quercetin is shown by docking to be unable to approach closely the copper atom, indicating the necessity of the presence of the hydroxyl group and providing a prediction of the likely binding environment of this ligand.
View Article and Find Full Text PDFBinding to bovine serum albumin of monomeric (vescalagin and pedunculagin) and dimeric ellagitannins (roburin A, oenothein B, and gemin A) was investigated by isothermal titration calorimetry and fluorescence spectroscopy, which indicated two types of binding sites. Stronger and more specific sites exhibited affinity constants, K1, of 10(4)-10(6) M(-1) and stoichiometries, n1, of 2-13 and dominated at low tannin concentrations. Weaker and less-specific binding sites had K2 constants of 10(3)-10(5) M(-1) and stoichiometries, n2, of 16-30 and dominated at higher tannin concentrations.
View Article and Find Full Text PDFPhagocyte superoxide production by a multicomponent NADPH oxidase is important in host defense against microbial invasion. However inappropriate NADPH oxidase activation causes inflammation. Endothelial cells express NADPH oxidase and endothelial oxidative stress due to prolonged NADPH oxidase activation predisposes many diseases.
View Article and Find Full Text PDFBackground: A new algorithm has been developed to enable the interpretation of black box models. The developed algorithm is agnostic to learning algorithm and open to all structural based descriptors such as fragments, keys and hashed fingerprints. The algorithm has provided meaningful interpretation of Ames mutagenicity predictions from both random forest and support vector machine models built on a variety of structural fingerprints.
View Article and Find Full Text PDFThree bis-benzoxazine monomers based on the aniline derivatives of bisphenol A (BA-a), bisphenol F (BF-a), and 3,3'-thiodiphenol (BT-a) are examined using a variety of spectroscopic, chromatographic, and thermomechanical techniques. The effect on the polymerization of the monomers is compared using two common compounds, 3,3'-thiodiphenol (TDP) and 3,3'-thiodipropionic acid (TDA), at a variety of loadings. It is found that the diacid has a greater effect on reducing the onset of polymerization and increasing cross-link density and for a given benzoxazine.
View Article and Find Full Text PDFUpdated models of the Rat Cytochrome P450 2D enzymes are produced based on the recent x-ray structures of the Human P450 2D6 enzyme both with and without a ligand bound. The differences in species selectivity between the epimers quinine and quinidine are rationalised using these models and the results are discussed with regard to previous studies. A close approach to the heme is not observed in this study.
View Article and Find Full Text PDFBackground: Corrections to the chemical and x-ray structures of two forms of the antibiotic oligomycin A are presented: the original and best known, form (E), from Streptomyces diastatochromogenes, and a new form (C) from Streptomyces diastaticus.
Method: The crystal structures are isomorphous, crystallizing in space group P212121, with Z = 4[C45H73O11.CH3OH] per unit cell.