Thermal Raman study of Li4Ti5O12 and discussion about the number of its characteristic bands

Lithium battery industry is booming, and this fast growth should be supported by developing industry friendly tools to control the quality of positive and negative electrode materials. Raman spectroscopy was shown to be a cost effective and sensitive instrument to study defects and heterogeneities in lithium titanate, popular negative electrode material for high power applications, but there are still some points to be clarified. This work presents a detailed thermal Raman study for lithium titanate and discusses the difference of the number of predicted and experimentally observed Raman-active bands. The low temperature study and the analysis of thermal shifts of bands positions during heating let us to conclude about advantages of the proposed approach with surplus bands and recommend using shifts of major band to estimate the sample heating

Discovery of a novel non-narcotic analgesic derived from the CL-20 explosive: Synthesis, pharmacology, and target identification of thiowurtzine, a potent inhibitor of the opioid receptors and the ion channels

The number of candidate molecules for new non-narcotic analgesics is extremely limited. Here, we report the identification of thiowurtzine, a new potent analgesic molecule with promising application in chronic pain treatment. We describe the chemical synthesis of this unique compound derived from the hexaazaisowurtzitane (CL-20) explosive molecule. Then, we use animal experiments to assess its analgesic activity in vivo upon chemical, thermal, and mechanical exposures, compared to the effect of several reference drugs. Finally, we investigate the potential receptors of thiowurtzine in order to better understand its complex mechanism of action. We use docking, molecular modeling, and molecular dynamics simulations to identify and characterize the potential targets of the drug and confirm the results of the animal experiments. Our findings finally indicate that thiowurtzine may have a complex mechanism of action by essentially targeting the mu opioid receptor, the TRPA1 ion channel, and the Cav voltage-gated calcium channel

Soft modes condensation in Raman spectra of (Pb–La)(Zr–Sn–Ti)O3 ceramics

Текст статьи не публикуется в открытом доступе в соответствии с политикой журнала.Исследованы низкочастотные спектры комбинационного рассеяния керамики (Pb0:97La0:02)Zr0:864Sn0:04Ti0:096O3 в области фазового перехода из кубической в антисегнетоэлектрическую фазу при 200 С. В дополнение к ранее известной моде при 100 см-1, обнаружена группа низкочастотных мягких мод, восстанавливающихся ниже точки перехода. У этих мод в точке перехода наблюдаются резкие аномалии, что позволяет предположить существенное межмодовое взаимодействие через затухание

Bulk affinity Manuscript supporting file

   The excel file contains modeled distributions of Kd values for progressive rounds of aptamer selection and proposed bulk affinity workflow.  The origin file includes the construction of gaussian distribution figure, theoretical bulk affinity workflow, experimental bulk  affinity workflow and electropherograms.  </p

Label-Free Solution-Based Kinetic Study of Aptamer–Small Molecule Interactions by Kinetic Capillary Electrophoresis with UV Detection Revealing How Kinetics Control Equilibrium

Here we demonstrate a label-free solution-based approach for studying the kinetics of biopolymer–small molecule interactions. The approach utilizes kinetic capillary electrophoresis (KCE) separation and UV light absorption detection of the unlabeled small molecule. In this proof-of-concept work, we applied KCE-UV to study kinetics of interaction between a small molecule and a DNA aptamer. From the kinetic analysis of a series of aptamers, we found that dissociation rather than binding controls the stability of the complex. Because of its label-free features and generic nature, KCE-UV promises to become a practical tool for challenging kinetic studies of biopolymer–small molecule interactions

Using Nonequilibrium Capillary Electrophoresis of Equilibrium Mixtures (NECEEM) for Simultaneous Determination of Concentration and Equilibrium Constant

Nonequilibrium capillary electrophoresis of equilibrium mixtures (NECEEM) is a versatile tool for studying affinity binding. Here we describe a NECEEM-based approach for simultaneous determination of both the equilibrium constant, <i>K</i>_d, and the unknown concentration of a binder that we call a target, T. In essence, NECEEM is used to measure the unbound equilibrium fraction, <i>R</i>, for the binder with a known concentration that we call a ligand, L. The first set of experiments is performed at varying concentrations of T, prepared by serial dilution of the stock solution, but at a constant concentration of L, which is as low as its reliable quantitation allows. The value of <i>R</i> is plotted as a function of the dilution coefficient, and dilution corresponding to <i>R</i> = 0.5 is determined. This dilution of T is used in the second set of experiments in which the concentration of T is fixed but the concentration of L is varied. The experimental dependence of <i>R</i> on the concentration of L is fitted with a function describing their theoretical dependence. Both <i>K</i>_d and the concentration of T are used as fitting parameters, and their sought values are determined as the ones that generate the best fit. We have fully validated this approach <i>in silico</i> by using computer-simulated NECEEM electropherograms and then applied it to experimental determination of the unknown concentration of MutS protein and <i>K</i>_d of its interactions with a DNA aptamer. The general approach described here is applicable not only to NECEEM but also to any other method that can determine a fraction of unbound molecules at equilibrium

Predicting Electrophoretic Mobility of Protein–Ligand Complexes for Ligands from DNA-Encoded Libraries of Small Molecules

Selection of target-binding ligands from DNA-encoded libraries of small molecules (DELSMs) is a rapidly developing approach in drug-lead discovery. Methods of kinetic capillary electrophoresis (KCE) may facilitate highly efficient homogeneous selection of ligands from DELSMs. However, KCE methods require accurate prediction of electrophoretic mobilities of protein–ligand complexes. Such prediction, in turn, requires a theory that would be applicable to DNA tags of different structures used in different DELSMs. Here we present such a theory. It utilizes a model of a globular protein connected, through a single point (small molecule), to a linear DNA tag containing a combination of alternating double-stranded and single-stranded DNA (dsDNA and ssDNA) regions of varying lengths. The theory links the unknown electrophoretic mobility of protein–DNA complex with experimentally determined electrophoretic mobilities of the protein and DNA. Mobility prediction was initially tested by using a protein interacting with 18 ligands of various combinations of dsDNA and ssDNA regions, which mimicked different DELSMs. For all studied ligands, deviation of the predicted mobility from the experimentally determined value was within 11%. Finally, the prediction was tested for two proteins and two ligands with a DNA tag identical to those of DELSM manufactured by GlaxoSmithKline. Deviation between the predicted and experimentally determined mobilities did not exceed 5%. These results confirm the accuracy and robustness of our model, which makes KCE methods one step closer to their practical use in selection of drug leads, and diagnostic probes from DELSMs