Studies with enaminones: Formation of a N,O‐cyclicacetal on coupling of 3‐dimethylamino‐1‐hydroxyphenyl‐2‐propenone with arenediazonium salts

Coupling the title compound 3 with arenediazonium salts affords the arylhydrazonochromones 6 . The latter compounds react with hydrazine hydrate to yield novel pyrazoles 11 .     

1,1-dioxonaphtho[1,2-b]thiophene-2-methyloxycarbonyl (alpha-Nsmoc) and 3,3-dioxonaphtho[2,1-b]thiophene-2-methyloxycarbonyl (beta-Nsmoc) amino-protecting groups

Of the three theoretically possible, Bsmoc-related, naphthothiophene sulfone-based amino-protecting groups, the two most readily available derivatives, the alpha- and beta-Nsmoc analogues, have been examined as substitutes for the Bsmoc residue in cases where the latter lead to oily protected amino acids or amino acid fluorides. All of the naphtho systems gave easily handled solid amino acid derivatives. The intermediate sulfone alcohol 11 used as the key reagent for introduction of the alpha-Nsmoc protecting group was readily made from alpha-tetralone (Scheme 1). The corresponding beta-analogue 17 was made similarly on a small scale, but due to the high cost of beta-tetralone, an alternate route involving reaction of rhodanine with alpha-naphthaldehyde was used for large-scale work (Scheme 2). All proteinogenic amino acids were converted to their alpha- and beta-Nsmoc derivatives. Deblocking studies showed that the reactivity toward deblocking by piperidine followed the order alpha-Nsmoc > Bsmoc > beta-Nsmoc. 1H NMR experiments showed that deblocking of the two new systems was mechanistically similar to that previously established for the Bsmoc derivative in that the reaction is initiated by Michael addition to the beta-carbon atom of the alpha,beta-unsaturated sulfone system. Application of alpha- and beta-Nsmoc amino acids to the solid-phase synthesis of two model peptides was examined. An advantage of the alpha-Nsmoc system over the long-known Bsmoc system proved to be the milder conditions needed for the deblocking step relative to the Bsmoc case, which is itself more readily deblocked than the classic Fmoc analogue.     

Thermodynamic properties of the ternary system {yNH4Cl + (1 − y)MgCl2} (aq) at 298.15 K

The mixture {yNH₄Cl + (1 − y)MgCl₂} (aq) has been studied using the hygrometric method at the temperature 298.15 K. The water activities are measured at total molalities from 0.30 mol kg⁻¹ up to saturation for different ionic strength fractions y of NH₄Cl with y = 0.20, 0.50 and 0.80. The obtained data allow the deduction of osmotic coefficients. Experimental results are compared with the calculations using the models of Zdanovskii–Stokes–Robinson, Kusik and Meissner, Robinson and Stokes, Lietzke and Stoughton, Reilly–Wood and Robinson and Pitzer. Thermodynamic properties have been modeled using the Pitzer ion-interaction model with inclusion of an ionic strength dependence of the third virial coefficient for the binary systems. From these measurements and the obtained binary parameters β⁽⁰⁾, β⁽¹⁾, C⁽⁰⁾ and C⁽¹⁾, the mixing ionic parameters θNH₄Mg${\theta }_{\text{N}{\text{H}}_4\text{Mg}}$ and ψNH₄MgCl${\psi }_{\text{N}{\text{H}}_4\text{MgCl}}$ are determined by the standard Pitzer model. The results show that a good accuracy is obtained with the standard Pitzer model using extended binary parameters. The parameters θNH₄Mg${\theta }_{\text{N}{\text{H}}_4\text{Mg}}$ and ψNH₄MgCl${\psi }_{\text{N}{\text{H}}_4\text{MgCl}}$ were used for evaluation of activity coefficients in the mixture. The excess Gibbs energy is also determined.     

Studies of interactions between silane coupling agents and cellulose fibers with liquid and solid-state NMR

The hydrolysis of three alkoxy-silane coupling agents, gamma-methacryloxypropyl trimethoxy silane (MPS), gamma-aminopropyl triethoxy silane (APS), and gamma-diethylenetriaminopropyl trimethoxy silane (TAS), was carried out in ethanol/water solutions (80/20 w/w) at different pH values and followed by 1H, 13C and 29Si NMR spectroscopy. Acidic media were found to stabilize the hydrolyzed forms. As expected, the formation of silanol groups was followed by their self-condensation to generate oligomeric structures, yielding, ultimately, solid homopolycondensated structures, as analyzed by 29Si and 13C high-resolution solid-state NMR. Hydrolyzed MPS in acidic media was then successfully adsorbed onto a cellulose surface and the ensuing substrates submitted to thermal treatment at 110-120 degrees C under reduced pressure, in order to create covalent bonds between cellulose and the coupling agent.     

Development of Antibacterial,Degradable and pH-Responsive Chitosan/Guar Gum/Polyvinyl Alcohol Blended Hydrogels for Wound Dressing

The present research is based on the fabrication preparation of CS/PVA/GG blended hydrogel with nontoxic tetra orthosilicate (TEOS) for sustained paracetamol release. Different TEOS percentages were used because of their nontoxic behavior to study newly designed hydrogels’ crosslinking and physicochemical properties. These hydrogels were characterized using Fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and wetting to determine the functional, surface morphology, hydrophilic, or hydrophobic properties. The swelling analysis in different media, degradation in PBS, and drug release kinetics were conducted to observe their response against corresponding media. The FTIR analysis confirmed the components added and crosslinking between them, and surface morphology confirmed different surface and wetting behavior due to different crosslinking. In various solvents, including water, buffer, and electrolyte solutions, the swelling behaviour of hydrogel was investigated and observed that TEOS amount caused less hydrogel swelling. In acidic pH, hydrogels swell the most, while they swell the least at pH 7 or higher. These hydrogels are pH-sensitive and appropriate for controlled drug release. These hydrogels demonstrated that, as the ionic concentration was increased, swelling decreased due to decreased osmotic pressure in various electrolyte solutions. The antimicrobial analysis revealed that these hydrogels are highly antibacterial against Gram-positive (Staphylococcus aureus and Bacillus cereus) and Gram negative (Pseudomonas aeruginosa and Escherichia coli) bacterial strains. The drug release mechanism was 98% in phosphate buffer saline (PBS) media at pH 7.4 in 140 min. To analyze drug release behaviour, the drug release kinetics was assessed against different mathematical models (such as zero and first order, Higuchi, Baker–Lonsdale, Hixson, and Peppas). It was found that hydrogel (CPG2) follows the Peppas model with the highest value of regression (R² = 0.98509). Hence, from the results, these hydrogels could be a potential biomaterial for wound dressing in biomedical applications.     

Computational Approaches for the Design of Novel Anticancer Compounds Based on Pyrazolo[3,4-d]pyrimidine Derivatives as TRAP1 Inhibitor

In the present in-silico study, various computational techniques were applied to determine potent compounds against TRAP1 kinase. The pharmacophore hypothesis DHHRR_1 consists of important features required for activity. The 3D QSAR study showed a statistically significant model with R² = 0.96 and Q² = 0.57. Leave one out (LOO) cross-validation (R² CV = 0.58) was used to validate the QSAR model. The molecular docking study showed maximum XP docking scores (−11.265, −10.532, −10.422, −10.827, −10.753 kcal/mol) for potent pyrazole analogs (42, 46, 49, 56, 43), respectively, with significant interactions with amino acid residues (ASP 594, CYS 532, PHE 583, SER 536) against TRAP1 kinase receptors (PDB ID: 5Y3N). Furthermore, the docking results were validated using the 100 ns MD simulations performed for the selected five docked complexes. The selected inhibitors showed relatively higher binding affinities than the TRAP1 inhibitor molecules present in the literature. The ZINC database was used for a virtual screening study that screened ZINC05297837, ZINC05434822, and ZINC72286418, which showed similar binding interactions to those shown by potent ligands. Absorption, distribution, metabolism, and excretion (ADME) analysis showed noticeable results. The results of the study may be helpful for the further development of potent TRAP1 inhibitors     

Sage,Salvia officinalis L., Constituents,Hepatoprotective Activity,and Cytotoxicity Evaluations of the Essential Oils Obtained from Fresh and Differently Timed Dried Herbs: A Comparative Analysis

Sage, Salvia officinalis L., is used worldwide as an aromatic herb for culinary purposes as well as a traditional medicinal agent for various ailments. Current investigations exhibited the effects of extended dryings of the herb on the yields, composition, oil quality, and hepatoprotective as well as anti-cancer biological activities of the hydrodistillation-obtained essential oils from the aerial parts of the plant. The essential oils’ yields, compositions, and biological activities levels of the fresh and differently timed and room-temperature dried herbs differed significantly. The lowest yields of the essential oil were obtained from the fresh herbs (FH, 631 mg, 0.16%), while the highest yield was obtained from the two-week dried herbs (2WDH, 1102 mg, 0.28%). A notable decrease in monoterpenes, with increment in the sesquiterpene constituents, was observed for the FH-based essential oil as compared to all the other batches of the essential oils obtained from the different-timed dried herbs. Additionally, characteristic chemotypic constituents of sage, i.e., α-pinene, camphene, β-pinene, myrcene, 1, 8-cineole, α-thujone, and camphor, were present in significantly higher proportions in all the dried herbs’ essential oils as compared to the FH-based essential oil. The in vivo hepatoprotective activity demonstrated significant reductions in the levels of AST, ALT, and ALP, as well as a significant increase in the total protein (p < 0.05) contents level, as compared to the acetaminophen (AAP) administered experimental group of rats. A significant reduction (p < 0.05) in the ALT level was demonstrated by the 4WDH-based essential oil in comparison to the FH-based essential oil. The levels of creatinine, cholesterol, and triglycerides were reduced (p < 0.05) in the pre-treated rats by the essential oil batches, with non-significant differences found among them as a result of the herbs dryings based oils. A notable increase in the viability of the cells, and total antioxidant capacity (TAOxC) levels, together with the reduction in malondialdehyde (MDA) levels were observed by the essential oils obtained from all the batches as compared with the AAP-treated cell-lines, HepG-2, HeLa, and MCF-7, that indicated the in vitro hepatoprotective effects of the sage essential oils. However, significant improvements in the in vivo and in vitro hepatoprotective activities with the 4WDH-based oil, as compared to all other essential oil-batches and silymarin standard demonstrated the beneficial effects of the drying protocol for the herb for its medicinal purposes.     

Predicting Homoclinic Bifurcations in Planar Autonomous Systems

An analytical method to predict the homoclinic bifurcation in a planar autonomous self-excited weakly nonlinear oscillator is presented. The method is mainly based on the collision between the periodic orbit undergoing the homoclinic bifurcation and the saddle fixed point. To illustrate the analytical predictive criteria, two typical examples are investigated. The results obtained in this work are then compared to Melnikov's technique and to a previous criterion based on the vanishing of the frequency. Numerical simulations are also provided.     

The electrochemical behaviour of polycrystalline silver electrodes in Na2CO3 solution and the effect of ClO− 4 ions

The electrochemical behaviour of polycrystalline silver electrodes in Na₂CO₃ solutions was studied under potentiodynamic and potentiostatic conditions and complemented with X-ray diffraction analysis. Potentiodynamic E/i anodic curves exhibit active passive transition prior to an oxygen evolution reaction. The active region involves a small peak AI followed by a major peak AII before the passive region. Peak AI is assigned to the formation of an Ag₂O layer while peak AII is due to the formation of an Ag₂CO₃ layer. The height of the anodic peaks increases with increasing Na₂CO₃ concentration, scan rate and temperature. The effect of increasing additions of NaClO₄ on the electrochemical behaviour of Ag in Na₂CO₃ solutions was investigated. The perchlorate ions stimulate the active dissolution of Ag, presumably as a result of the formation of soluble AgClO₄ salt. In the passive region, ClO⁻ ₄ ions tend to break down the dual passive film, leading to pitting corrosion at a certain critical pitting potential. The pitting potential decreases with ClO⁻ ₄ concentration. Potentiostatic current/time transients showed that the formation of Ag₂O and Ag₂CO₃ layers involves a nucleation and growth mechanism under diffusion control. However, in the presence of ClO⁻ ₄ ions, the incubation time for pit initiation decreases on increasing the anodic potential step. Received: 3 July 1998 / Accepted: 10 March 1999     

Synthesis of 4‐amino‐3‐cyano‐2‐ methylsulfanyl‐1H‐[1,5]benzodiazepine,benzo[1,3]azole,and pyrazolobenzo[1,3]azole derivatives via a new utility of bis(methylsulfanyl)methylene derivatives

Novel polysubstituted 1,5‐benzodiazepine 5 , 2,2‐bis(methylthio)benzoxazoles 8a–d , 2,2‐bis‐ (acetyl)benzoxazole 8e , 2‐(3‐methyl‐1‐phenylpyrazolo‐ 4‐yl)benzoazole derivatives 16a–c , as well as the previously reported 2‐di[cyano(acetyl)‐methylene]benzothiazoles 7a,b have been obtained via a new utility of ketene dithioacetals 1a,b and 12 with aniline derivatives 2 . Rationales for the reactions pathways are presented. © 2004 Wiley Periodicals, Inc. Heteroatom Chem 15:407–412, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.20031