Graphite/Nanocrystalline Zeolite Platform for Selective Electrochemical Determination of Hepatitis C Inhibitor Ledipasvir

A simple and efficient procedure is described for the electrochemical determination of ledipasvir (LDP) in presence of co‐formulated drug sofosbuvir (SOF). Herein, a highly sensitive, low‐cost electrochemical protocol was utilized to fabricate a zeolite modified carbon paste electrode (ZY/CPE) through mixing of zeolite nanostructures with graphite powder. The fabricated sensor displayed high sensitivity, allowing optimal charge transfer/electrode kinetics. Different experimental and chemical factors, including electrode composition, effect of pH, scan rate and amount of ZY were evaluated carefully to obtain the highest electrochemical response. Under optimized conditions and using square wave voltammetry (SWV), the current response of the ZY/CPE electrochemical sensing platform exhibited a detection limit of 7.5×10^?9 M and a large linear range from 5.0×10^?8 to 1.0×10^?4 M. The practical applicability of the suggested electrochemical platform was verified in the assessment of LDP in pharmaceutical formulations with excellent recoveries in the range of 99.50–98.87 %. Moreover, a biological relevance of the developed sensor was established by the analysis of LDP in human urine and plasma samples with satisfactory recoveries of 99.00 and 99.68 %, respectively. Due to the simplicity and ease of preparation of the proposed sensor, it can be used in quality control laboratories and for clinical analysis.     

Specific and Rapid Glucose Detection Using NAD‐dependent Glucose Dehydrogenase,Diaphorase, and Osmium Complex

Selective glucose measurement in serum and blood and rapid glucose measurement using nicotinamide adenine dinucleotide (NAD)‐dependent glucose dehydrogenase (NAD‐GDH) are still very challenging. Here, we report a selective and rapid glucose sensor, based on electrochemical‐enzymatic‐enzymatic (ENN) redox cycling involving bis(2,2‐bipyridyl)dichloroosmium(II) [Os(bpy)₂Cl₂], diaphorase (DI), NAD⁺, NAD‐GDH, and glucose. DI and Os(bpy)₂Cl₂ are used to obtain fast mediated oxidation of NADH that is generated as a result of glucose oxidation by NAD‐GDH. DI and NAD‐GDH are co‐immobilized via affinity binding on an avidin‐modified indium tin oxide electrode to obtain fast and stable ENN redox cycling. Two enzymes (DI and NAD‐GDH) and two electron mediators [Os(bpy)₂Cl₂ and NAD⁺] are insensitive to oxygen. The applied potential (0.0 V vs Ag/AgCl) is low enough to minimize interfering electrochemical reactions, and the redox reactions of Os(bpy)₂Cl₂ with interfering species are slow. NAD‐GDH is much less reactive to problematic monosaccharides such as xylose, fructose, galactose, and mannose than glucose. Artificial serum containing 5 % (w/v) human serum albumin shows a similar electrochemical background level in serum. All results enable us to obtain selective and reproducible glucose detection. The fast ENN redox cycling allows sensitive glucose detection with a wide range of concentrations in artificial serum with a short measuring time (5 s) without an incubation period.     

Precise molecular shape control of linear and branched strips with chirality-assisted synthesis

ABSTRACT

This account describes the latest developments in the field of chirality-assisted synthesis (CAS). CAS has emerged as a versatile method to control the shapes of π-conjugated macromolecules and supramolecular assemblies. With CAS, the sequence and chirality of the monomeric building blocks dictates the shape and functions of the resulting macromolecules in a programmable fashion. Supramolecular materials with special functions, e.g. the ability to encapsulate macrocycles, can be created with CAS. CAS has been utilized to synthesize a variety of shape-defined nanoscale structures, including polyaromatic strips, helices, molecular claws, and very large hydrogen-bonded closed-shell capsules. Applications, challenges, and future directions of the growing CAS field are discussed in light of the unique shape-control abilities CAS has to offer.     

Tunable Engineered Extracellular Matrix Materials: Polyelectrolyte Multilayers Promote Improved Neural Cell Growth and Survival

Poly‐d ‐lysine (PDL) and poly‐l ‐lysine are standard surfaces for culturing neural cells; however, both are relatively unstable, costly, and the coated surface typically must be prepared immediately before use. Here, polyelectrolyte multilayers (PEMs) are employed as highly stable, relatively inexpensive, alternative substrates to support primary neural cell culture. Initial findings identify specific silk‐based PEMs that significantly outperform the capacity of PDL to promote neuronal survival and process extension. Based on these results, a library of PEM variants, including commercial and bio‐sourced polyelectrolytes, is generated and three silk‐based PEMs that substantially outperform PDL as a substrate for primary neurons in cell culture are identified. Further, testing these PEM variants as substrates for primary oligodendrocyte progenitors demonstrates that one silk‐based PEM functions significantly better than PDL. These findings reveal specificity of cellular responses, indicating that PEMs may be tuned to optimally support different neural cell types.     

A new green method for the synthesis of silver nanoparticles and their antibacterial activities against gram‐positive and gram‐negative bacteria

This study aims to evaluate the capability of Ageratum conyzoides and Mikania micrantha extracts to synthesize silver nanoparticles (AgNPs) and their antibacterial capability against gram‐positive and gram‐negative bacteria. Several properties of the synthesized AgNPs, including plasmonic, biomolecule bonding, shape, size, and antibacterial, were investigated. Ultraviolet–visible (UV–vis) spectroscopy was employed for characterizing their plasmonic properties. Functional groups on the produced AgNPs were investigated by Fourier‐transform infrared (FT‐IR) spectroscopy. The size and shape of the AgNPs were identified using the field‐emission scanning electron microscopy (FESEM). Inhibition zone measurement was carried out for evaluating the antibacterial capability. This study showed that the extracts of A. conyzoides and M. micrantha were able reducing agents as evidenced by the formation of the spherical AgNPs. UV–vis spectroscopy, FT‐IR spectroscopy, and FESEM confirmed the physicochemical characteristics of AgNPs. AgNPs that were synthesized using M. micrantha were slightly smaller than those produced using A. conyzoides. In general, the present work establishes that the synthesized AgNPs have antibacterial capability depending on their size and synthesis procedure.     

Simple and Efficient Synthesis of Novel 3‐Substituted 2‐Thioxo‐2,3‐dihydro‐1H‐benzo[g]quinazolin‐4‐ones and Their Reactions with Alkyl Halides and α‐Glycopyranosyl Bromides

A series of 3‐substituted 2‐thioxo‐2,3‐dihydro‐1H‐benzo[g]quinazolin‐4‐ones 4a – e were synthesized from the reaction of 3‐aminonaphthalene‐2‐carboxylic acid 1 with isothiocyanate derivatives 2a – e . The alkylation of 4a – e with alkyl halides gave 3‐substituted 2‐alkylsulfanyl‐2,3‐dihydro‐1H‐benzo[g]quinazolin‐4‐ones 5a – o . S‐Glycosylation was carried out via the reaction of 4a – e with glycopyranosyl bromides 7a and 7b under anhydrous alkaline conditions. The structure of the compounds was established as S‐nucleoside and not N‐nucleoside. Conformational analysis has been studied by homonuclear and heteronuclear two‐dimensional NMR methods (2D DFQ‐COSY, heteronuclear multiple quantum coherence, and heteronuclear multiple bond correlation). The S site of alkylation and glycosylation was determined from the ¹H and ¹³C heteronuclear multiple quantum coherence experiments.     

Infrared Spectroscopic Observation of a G–C+ Hoogsteen Base Pair in the DNA:TATA‐Box Binding Protein Complex Under Solution Conditions

Hoogsteen DNA base pairs (bps) are an alternative base pairing to canonical Watson–Crick bps and are thought to play important biochemical roles. Hoogsteen bps have been reported in a handful of X‐ray structures of protein–DNA complexes. However, there are several examples of Hoogsteen bps in crystal structures that form Watson–Crick bps when examined under solution conditions. Furthermore, Hoogsteen bps can sometimes be difficult to resolve in DNA:protein complexes by X‐ray crystallography due to ambiguous electron density and by solution‐state NMR spectroscopy due to size limitations. Here, using infrared spectroscopy, we report the first direct solution‐state observation of a Hoogsteen (G–C⁺) bp in a DNA:protein complex under solution conditions with specific application to DNA‐bound TATA‐box binding protein. These results support a previous assignment of a G–C⁺ Hoogsteen bp in the complex, and indicate that Hoogsteen bps do indeed exist under solution conditions in DNA:protein complexes.     

Conformational stability of the tetrameric de novo designed hexcoil-Ala helical bundle

We have performed molecular dynamics method to investigate the conformational stability of the homotetramer form of HexCoil-Ala (PDB Code 3S0R). The previous experiments showed that the chains tend to form tetramer structures. The system was simulated in explicit water model at several temperatures by using isobaric-isothermal ensemble to better understand the behaviour of each monomer and its tetramer form. It was observed that central residues of each monomer have highly helical percentages in comparison with the termini residues. As the temperature increased, these percentages decreased, and bend-like configurations came into being due to the fact that the C-and N-terminals of the monomer were getting closer. When free energy landscapes of HexCoil-Ala were calculated by using the distance between Leu-Zipper and Ala-Coil interface, it was seen that the assemblies of monomers were very strong. What's more, the average values obtained from them were very close to the native case between 300?K and 350?K. It was also observed that the direct salt bridge forming between the residues E8 with R25 in the other chains plays a significant role for keeping tetramer structure. Consequently, our results are in better agreement with the results of experimental observations.     

Synthesis,characterisation and dosimetric evaluation of MgB4O7 glass as thermoluminescent dosimeter

This study presumably reports the dosimetric properties of MgB₄O₇ glass system. A series of MgB₄O₇ glass samples with nominal compositions XMgO-(100-X) B₂O₃, with X?=?35, 40 and 45?mol% was successfully synthesied using conventional melt quenching method. The presence of broad humps and absence of any sharp peak in typical X-ray diffraction patterns confirm the amorphous nature of the synthesised glass samples. Good glass forming ability, 0.55, of the mixture resulting in a glass with excellent glass stability, 1.4, was observed. Thermoluminescence glow curve was observed to be simple with a single well defined dosimetric peak around 200°C. The dose response was found to be linear from 6?µGy to 0.5?kGy when irradiated to Cs-137 gamma rays. Considerably satisfying thermoluminescent (TL) characteristics suggests that the MgB₄O₇ glass could be recommended as a TL dosimeter.     

The Impact of Apple Variety and the Production Methods on the Antibacterial Activity of Vinegar Samples

Apple vinegar is a natural product widely used in food and traditional medicine as it contains many bioactive compounds. The apple variety and production methods are two factors that play a major role in determining the quality of vinegar. Therefore, this study aims to determine the quality of apple vinegar samples from different varieties (Red Delicious, Gala, Golden Delicious, and Starking Delicious) prepared by three methods using small apple pieces, apple juice, and crushed apple, through determining the physicochemical properties and antibacterial activity of these samples. The antibacterial activity was studied against five pathogenic bacteria: Staphylococcus aureus, Klebsiella pneumonia, Escherichia coli (ATB: 57), Escherichia coli (ATB: 97), and Pseudomonas aeruginosa, using two methods, disk diffusion and microdilution, for determining the minimum inhibitory concentrations and the minimum bactericidal concentrations. The results of this study showed that the lowest pH value was 3.6 for Stark Delicious, obtained by liquid fermentation, and the highest acetic acid values were 4.7 and 4% for the vinegar of Red Delicious and Golden Delicious, prepared by solid fermentation, respectively. The results of the antibacterial activity showed considerable activity of apple vinegar on the tested strains. Generally, the Staphylococcus aureus strain appears less sensitive and Pseudomonas aeruginosa seems to be very sensitive against all samples, while the other strains have distinct sensitivities depending on the variety studied and the method used. A higher antibacterial activity was found in vinegar obtained by the apple pieces method and the Red Delicious variety, with a low MIC and MBC recorded, at 1.95 and 3.90 µL/mL, respectively. This study has shown that the choice of both apple variety and production method is therefore an essential step in determining and aiming for the desired quality of apple vinegar.