A synthetic approach to the modification of the drug “riluzole” with pharmacologically active fragments such as carbazole, tetrahydrocarbazole, phenothiazine, and aminothiophene, based on the copper-catalyzed alkyne-azide 1,3-dipolar cycloaddition of azide-containing pharmacophores with “riluzole” decorated with 5-trifluoromethylhydantoin, has been suggested.
Background The World Health Organization has warned that cigarette smoking is an avoidable risk factor for endothelial injury. Myogenin might play a role in muscle metabolism and energy utilization. Electrolytes and minerals are involved in most cellular activities. The objective of this study was to compare myogenin and electrolyte levels between adult male cigarette smokers (CS) and non-smokers (NS). Methods A cross-sectional study was conducted involving 90 subjects, consisting of 55 CS and 35 NS. The sandwich enzyme-linked immunosorbent assay was used to determine myogenin levels while the ion-selective electrode method was used to determine electrolyte levels. The levels of sodium, potassium, and chloride and the body mass index (BMI) were measured. Mann-Whitney and independent t-test were used to analyse the data. Results The BMI of CS was significantly lower than that of NS (p
The detection of ~20 ppb of phosphine in Venus clouds by observations in the millimetre-wavelength range from JCMT and ALMA is puzzling, because according to our knowledge of Venus, no phosphine should be there. As the most plausible formation paths do not work, the source could be unknown chemical processes—maybe even life?
With a sharp increase in the cases of multi-drug resistant (MDR) bacteria all over the world, there is a huge demand to develop a new generation of antibiotic agents to fight against them. As an alternative to the traditional drug discovery route, we have designed an effective antibacterial agent by modifying an existing commercial antibiotic, kanamycin, conjugated on the surface of gold nanoparticles (AuNPs). In this study, we report a single-step synthesis of kanamycin-capped AuNPs (Kan-AuNPs) utilizing the combined reducing and capping properties of kanamycin. While Kan-AuNPs have increased toxicity to a primate cell line (Vero 76), antibacterial assays showed dose-dependent broad spectrum activity of Kan-AuNPs against both Gram-positive and Gram-negative bacteria including Kanamycin resistant bacteria. Further, a significant reduction in the minimum inhibitory concentration (MIC100) of Kan-AuNPs was observed when compared to free kanamycin against all the bacterial strains tested. Mechanistic studies using transmission electron microscopy and fluorescence microscopy indicated that at least part of Kan-AuNPs increased efficacy may be through disrupting the bacterial envelope, resulting in the leakage of cytoplasmic content and the death of bacterial cells. Results of this study provide critical information about a novel method for the development of antibiotic capped AuNPs as potent next-generation antibacterial agents.
Microporous polymers feature shape-persistent free volume elements (FVEs), which are permeated by small molecules and ions when used as membranes for chemical separations, water purification, fuel cells and batteries1–3. Identifying FVEs that have analyte specificity remains a challenge, owing to difficulties in generating polymers with sufficient diversity to enable screening of their properties. Here we describe a diversity-oriented synthetic strategy for microporous polymer membranes to identify candidates featuring FVEs that serve as solvation cages for lithium ions (Li+). This strategy includes diversification of bis(catechol) monomers by Mannich reactions to introduce Li+-coordinating functionality within FVEs, topology-enforcing polymerizations for networking FVEs into different pore architectures, and several on-polymer reactions for diversifying pore geometries and dielectric properties. The most promising candidate membranes featuring ion solvation cages exhibited both higher ionic conductivity and higher cation transference number than control membranes, in which FVEs were aspecific, indicating that conventional bounds for membrane permeability and selectivity for ion transport can be overcome4. These advantages are associated with enhanced Li+ partitioning from the electrolyte when cages are present, higher diffusion barriers for anions within pores, and network-enforced restrictions on Li+ coordination number compared to the bulk electrolyte, which reduces the effective mass of the working ion. Such membranes show promise as anode-stabilizing interlayers in high-voltage lithium metal batteries.
We have developed a new methodology for protein–ligand docking and scoring, WScore, incorporating a flexible description of explicit water molecules. The locations and thermodynamics of the waters are derived from a WaterMap molecular dynamics simulation. The water structure is employed to provide an atomic level description of ligand and protein desolvation. WScore also contains a detailed model for localized ligand and protein strain energy and integrates an MM-GBSA scoring component with these terms to assess delocalized strain of the complex. Ensemble docking is used to take into account induced fit effects on the receptor conformation, and protein reorganization free energies are assigned via fitting to experimental data. The performance of the method is evaluated for pose prediction, rank ordering of self-docked complexes, and enrichment in virtual screening, using a large data set of PDB complexes and compared with the Glide SP and Glide XP models; significant improvements are obtained.
The coarse-grained Martini force field is widely used in biomolecular simulations. Here we present the refined model, Martini 3 (http://cgmartini.nl), with an improved interaction balance, new bead types and expanded ability to include specific interactions representing, for example, hydrogen bonding and electronic polarizability. The updated model allows more accurate predictions of molecular packing and interactions in general, which is exemplified with a vast and diverse set of applications, ranging from oil/water partitioning and miscibility data to complex molecular systems, involving protein–protein and protein–lipid interactions and material science applications as ionic liquids and aedamers.
A series of hybrid compounds was designed to target histone deacetylases and ds-/G-quadruplex DNAs by merging structural features deriving from Scriptaid and compound 1. Compound 6 binds different DNA arrangements, inhibits HDACs both in vitro and in cells, and is able to induce a reduction of cell proliferation. Moreover, compound 6 displays cell phenotype-reprogramming properties since it prevents the epithelial to mesenchymal transition in cancer cells, inducing a less aggressive and migratory phenotype, which is one of the goals of present innovative strategies in cancer therapies.
Abstract. Alkenes are oxidized rapidly in the atmosphere by addition of OH and subsequently O 2 leading to the formation of β-hydroxy peroxy radicals. These peroxy radicals react with NO to form β-hydroxy nitrates with a branching ratio α. We quantify α for C 2 –C 8 alkenes at 295 K ± 3 and 993 hPa. The branching ratio can be expressed as α = (0.045 ± 0.016) × N − (0.11 ± 0.05) where N is the number of heavy atoms (excluding the peroxy moiety), and listed errors are 2σ. These branching ratios are larger than previously reported and are similar to those for peroxy radicals formed from H abstraction from alkanes. We find the isomer distributions of β-hydroxy nitrates formed under NO-dominated peroxy radical chemistry to be different than the isomer distribution of hydroxy hydroperoxides produced under HO 2 -dominated peroxy radical chemistry. Assuming unity yield for the hydroperoxides implies that the branching ratio to form β-hydroxy nitrates increases with substitution of RO 2 . Deuterium substitution enhances the branching ratio to form hydroxy nitrates in both propene and isoprene by a factor of ~ 1.5. The role of alkene chemistry in the Houston region is re-evaluated using the RONO 2 branching ratios reported here. Small alkenes are found to play a significant role in present-day oxidant formation more than a decade (2013) after the 2000 Texas Air Quality Study identified these compounds as major contributors to photochemical smog in Houston.