Effect of antimicrobial peptide (AMP)–tethered stainless steel surfaces on the bacterial membrane

Bacterial colonization leading to biofilm formation on surfaces induces industry-related as well as health care–associated infections worldwide. Emerging antibiotic-resistant microbes and related persistent infections due to adherent biofilm formation on surfaces have urged the need of effective alternative solutions to eradicate prevailing problems. Antimicrobial peptides are considered as potential candidates with distinguished characteristics, namely, broad-spectrum antimicrobial activity, low propensity toward pathogen resistance, and low immune response. In this study, we immobilize an in-house–designed peptide, KLLLRLRKLLRR (KLR), using a 2-step functionalization strategy onto stainless steel (SS) surfaces. SS is amino-silanized using (3-aminopropyl) triethoxysilane followed by tethering of KLR on it via formation of the amide bond. KLR-coated SS surfaces show nearly 95–100% reduction in bacterial colonization in vitro as obtained from antibacterial susceptibility testing while being non-toxic to mammalian cells. The coating strategy does not affect the microstructure of the SS surfaces. These findings demonstrate that this tethering process is able to produce excellent antibacterial surfaces.     

An Improved Process for the Enantioselective Synthesis of HCV NS5A Inhibitor Elbasvir (MK-8742) Chiral Amine Intermediate

Russian Journal of General Chemistry - Large-scale enantioselective synthesis of the chiral amine unit of HCV NS5A inhibitor Elbasvir has been accomplished in six steps, with 55% overall yield. The...     

Coinage Metal Complexes with Di-tertiary-butyl Sulfide as Precursors with Ultra-Low Decomposition Temperature

We report here the synthesis of [Cu₂(TFA)₄(^tBu₂S)₂] ( 1 ), [Ag₄(TFA)₄(^tBu₂S)₄] ( 2 ) and [AuCl(^tBu₂S)] ( 3 ) (TFA=trifluoroacetate), which decompose in solution medium at ultra-low temperature (e. g., in boiling toluene) to afford phase-pure and highly crystalline Cu₉S₅, Ag₂S and metallic Au nanoparticles, respectively. The low decomposition temperature of these precursors is attributed to the facile decomposition mechanism in the di-tertiary-butyl sulfide ligand. These results are a significant step in the direction of establishing a general low-temperature strategy spanning a range of systems including thermodynamically metastable materials and incorporate them in technologies that are sensitive to the harsh conditions.     

An Effective MM/GBSA Protocol for Absolute Binding Free Energy Calculations: A Case Study on SARS-CoV-2 Spike Protein and the Human ACE2 Receptor

The binding free energy calculation of protein–ligand complexes is necessary for research into virus–host interactions and the relevant applications in drug discovery. However, many current computational methods of such calculations are either inefficient or inaccurate in practice. Utilizing implicit solvent models in the molecular mechanics generalized Born surface area (MM/GBSA) framework allows for efficient calculations without significant loss of accuracy. Here, GBNSR6, a new flavor of the generalized Born model, is employed in the MM/GBSA framework for measuring the binding affinity between SARS-CoV-2 spike protein and the human ACE2 receptor. A computational protocol is developed based on the widely studied Ras–Raf complex, which has similar binding free energy to SARS-CoV-2/ACE2. Two options for representing the dielectric boundary of the complexes are evaluated: one based on the standard Bondi radii and the other based on a newly developed set of atomic radii (OPT1), optimized specifically for protein–ligand binding. Predictions based on the two radii sets provide upper and lower bounds on the experimental references: −14.7(ΔGbindBondi)<−10.6(ΔGbindExp.)<−4.1(ΔGbindOPT1) kcal/mol. The consensus estimates of the two bounds show quantitative agreement with the experiment values. This work also presents a novel truncation method and computational strategies for efficient entropy calculations with normal mode analysis. Interestingly, it is observed that a significant decrease in the number of snapshots does not affect the accuracy of entropy calculation, while it does lower computation time appreciably. The proposed MM/GBSA protocol can be used to study the binding mechanism of new variants of SARS-CoV-2, as well as other relevant structures.     

Determination of Pentacyclic Triterpenes from Betula utilis by High-Performance Liquid Chromatography and High-Resolution Magic Angle Spinning Nuclear Magnetic Resonance Spectroscopy

A rapid and reliable method was developed and validated for determining betulin and betulinic acid in bark in Betula utilis by high-resolution magic angle spinning ¹H nuclear magnetic resonance (HR-MAS NMR) spectroscopy. HR-MAS NMR spectroscopy clearly distinguished the resonances of betulin and betulinic acid in the bark of all accessions of B. utilis. The concentrations of betulin and betulinic acid were calculated and added to the spectra. The determination of the targeted metabolites in chloroform extract of bark of each accession of B. utilis was performed by high-performance liquid chromatography (HPLC). Quantitatively, betulin was present at higher concentrations than betulinic acid in all accessions. The HR-MAS NMR and HPLC results showed that betulin and betulinic acid varied significantly among accessions of B. utilis. Principal component analysis of the NMR and HPLC results provided classification into three metabolic groups in which the betulin concentration was high, moderate, or low. The results show that HR-MAS NMR is rapid for fingerprinting of betulin and betulinic acid in the bark of B. utilis, while minimizing the drawbacks associated with solvent extraction.     

Enhanced mechanical properties of MWCNT reinforced ABS nanocomposites fabricated through additive manufacturing process

Multiwall carbon nanotubes (MWCNTs) can be spread out in acrylonitrile butadiene styrene (ABS) using a twin-screw micro-compounding extruder. It can significantly improve the mechanical properties of 3D-printed objects. Dispersed MWCNTs in pure ABS to develop the nanocomposites through a two-time micro compounding extruding process. 3D printed filaments with a diameter of 1.75 mm have been prepared by processing the acquired composite structure through a filament extruder. The mechanical and other properties of 3D printed pure ABS and 1, 2, and 3 wt.% of the fused deposition modeling (FDM) process were studied for MWCNTs/ABS composites. Compared with pure ABS, the tensile and thermal properties were significant for 1, 2, and 3 wt.% of MWCNTs/ABS composites. Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), thermogravimetric analysis (TGA), and scanning electron microscopy (SEM) were also analyzed for 0, 1, 2, and 3 wt.% MWCNTs/ABS composites. Additive manufacturing (AM) processes have recently been emphasized for their applications in electronics, aerospace, biomedical, and automobile engineering.     

Stereospecific Conversion of Boronic Esters into Enones using Methoxyallene: Application in the Total Synthesis of 10-Deoxymethynolide

Enones are widely utilized linchpin functional groups in chemical synthesis and molecular biology. We herein report the direct conversion of boronic esters into enones using commercially available methoxyallene as a three-carbon building block. Following boronate complex formation by reaction of the boronic ester with lithiated-methoxyallene, protonation triggers a stereospecific 1,2-migration before oxidation generates the enone. The protocol shows broad substrate scope and complete enantiospecificity is observed with chiral migrating groups. In addition, various electrophiles could be used to induce 1,2-migration and give a much broader range of α-functionalized enones. Finally, the methodology was applied to a 14-step synthesis of the enone-containing polyketide 10-deoxymethynolide.     

Catalytic kinetic determination of ultratrace amounts of ruthenium(III) based on the oxidation of benzylamine by alkaline hexacyanoferrate(III)

A kinetic method is proposed for the determination of ruthenium(III) by means of its catalytic effect on the oxidation of benzylamine by hexacyanoferrate(III) in alkaline medium. The reaction is followed spectrophotometrically by measuring the decrease in the absorbance of hexacyanoferrate(III) at 420 nm. Under the optimum experimental conditions ruthenium(III) can be determined in the range 10-121 ng/ml with an average error of 1.7% and maximum relative standard deviation of 1.3%. The influence of many potential interferents has been examined and the method has been tested for determination of ruthenium(III) in synthetic mixtures. The method is convenient, reliable and rapid.     

Novel Electrochemical Biosensing for Detection of Neglected Tropical Parasites of Animal Origin: Recent Advances

Parasitic diseases are among neglected disease of human and animals, especially in tropical and sub tropical regions. In the era of artificial intelligence, the novel biosensing diagnostic platform is needed for an early control measure implementation. This goal can be successfully achieved by onsite application of electrochemical biosensors. They are being developed towards point of care diagnostics; however commercial availability is scanty. The recent developments during last one decade in terms of the electrode surface modification for rapid diagnosis of important emerging/re-emerging parasites is presented. The information would help future improvement in the electrochemical biosensing of parasites.     

A validated high-performance thin-layer chromatography method for the simultaneous quantification of 6-gingerol,guggulsterone E and guggulsterone Z in coded formulation AYUSH SG-5 prepared for rheumatoid arthritis

JPC – Journal of Planar Chromatography – Modern TLC - A new, simple, selective, sensitive, precise, and robust high-performance thin-layer chromatography (HPTLC) method for the...