4-Oxobenzo[d]1,2,3-triazin-pyridinium-phenylacetamide derivatives as new anti-Alzheimer agents: design,synthesis, in vitro evaluation,molecular modeling,and molecular dynamic study

Structural Chemistry - A new series of 4-oxobenzo[d]1,2,3-triazin-pyridinium-phenylacetamide hybrids 8a–p was designed, synthesized, and screened as the potential cholinesterase inhibitors...     

Adsorptive Stripping Voltammetric Determination of Imipramine and Amitriptiline at a Nanoclay Composite Carbon Ionic Liquid Electrode

A new carbon nanocomposite electrode has been designed by incorporation of montmorillonite nanoclay into a carbon ionic liquid electrode for the electrochemical determination of imipramine (IMP) and amitriptyline (AMT). They are expected to accumulate on the electrode surface through the cooperative interaction of ionic liquid and clay with the drugs. The proposed electrode also possesses attractive electrocatalytic effects towards the drugs especially AMT. Low detection limits of 19 nM for IMP and 24 nM for AMT were achieved. The proposed nanocomposite electrode exhibits good applicability for monitoring IMP and AMT in pharmaceutical formulations and blood serum samples.     

Polyvinylimidazole/sol–gel composite as a novel solid‐phase microextraction coating for the determination of halogenated benzenes from aqueous solutions

A polyvinylimidazole/sol–gel composite is proposed as a novel solid‐phase microextraction fiber to extract five halobenzenes from the headspace of aqueous solutions in combination with gas chromatography with mass spectrometry. The prepared fiber was characterized by scanning electron microscopy and Fourier transform infrared spectroscopy. The obtained results showed that porous polyvinylimidazole/sol–gel composite was chemically deposited on fused silica fiber. The effect of important extraction parameters including extraction temperature, extraction time, and salt content were investigated. The optimum conditions were as follows: extraction temperature 25°C, extraction time 20 min, and salt concentration 30 w/v%. Detection limits and relative standard deviations of the developed method for halogenated benzenes were below 0.1 pg/mL and 15%, respectively. Repeatability of the proposed method, explained by relative standard deviation, varied between 5.48 and 9.15% (n = 5). The limits of detection (S/N = 3) ranged between 0.01 and 0.10 ng/L using gas chromatography with mass spectrometry with selected ion monitoring mode. For real sample analysis, three types of water samples with different matrices (ground, surface, and tap water) were studied. The optimized procedure was applied to extraction and method validation of halogenated benzenes in spiked water samples.     

Synthesis and reactivity of alkenyl- and alkynyl-substituted β,β-dihalo-and β,β,β-trichloroamines

β,β-Dihalo- and β,β,β-trichloroamines, obtained by Lewis acid-promoted Petasis-type reaction of α,α-dichlorinated and α,α,α-trichlorinated imines or reduction of α,α-dihaloaldimines, were subjected to a reactivity study and turned out to be remarkably stable compounds. In general, only the bases KO^tBu and NaOMe cause a 1,2-dehydrochlorination with formation of unsaturated α-chloroimines or unsaturated α,α-dichloroimines. Hydrolysis of the α-chloroimines with aqueous oxalic acid resulted in the formation of the corresponding unsaturated α-chloroketones. The reaction of simple β,β-dihaloamines with NaOMe and KO^tBu generated 2-haloprop-2-enylmines and 2,2-dimethoxypropylamines.     

Intensification of gadolinium(III) separation by effective utilization of nanoliquids in supported liquid membrane using Aliquat 336 as carrier

A supported nanoliquid membrane was developed to improve the separation of rare metal ion gadolinium (Gd) from nitrate solution medium. The nanoliquid membrane was prepared by dispersion of nanoparticles in organic phase and Aliquat 336 was applied as the carrier. TiO₂ and SiO₂ as hydrophobic and hydrophilic nanoparticles were effectively incorporated in the supported liquid membrane (SLM) system and the effect of size, concentration, and type of nanoparticle in the SLM were evaluated. A membrane phase of 0.015 M Aliquat-336 in kerosene and 0.04 wt% of SiO₂ with the size of 15 nm was found to have the highest permeability coefficient of 12.57?×?10^?5 m/s and enhanced the permeability coefficient by 28.2%. Hydrophobicity and hydrophilicity of the nanoparticles were observed to have remarkable effects on the permeation of the SLM system and concluded that the hydrophobic nanoparticle was more desirable. Results showed that the solid supported pore’s blockage and aggregation of nanoparticles could bring adverse effects at a high nanoparticle concentration at this SLM configuration. The stability tests were conducted over ten cycles of separation and the supported nanoliquid membrane had slight reduction of permeation during the test.     

Beyond Chemoselectivity: Catalytic Site‐Selective Aldolization of Diketones and Exploitation for Enantioselective Alzheimer's Drug Candidate Synthesis

Site selectivity, differentiating instances of the same functional group type on one substrate, represents a forward‐looking theme within chemistry: reduced dependence on protection/deprotection protocols for increased overall yield and step‐efficiency. Despite these potential benefits and the expanded tactical advantages afforded to synthetic design, site selectivity remains elusive and especially so for ketone‐based substrates. Herein, site‐selective intermolecular mono‐aldolization has been demonstrated for an array of prochiral 4‐keto‐substituted cyclohexanones with concomitant regio‐, diastereo‐, and enantiocontrol. Importantly, the aldol products allow rapid access to molecularly complex ketolactones or keto‐1,3‐diols, respectively containing three and four stereogenic centers. The reaction conditions are of immediate practical value and general enough to be applicable to other reaction types. These findings are applied in the first enantioselective, formal, synthesis of a leading Alzheimer's research drug, a γ‐secretase modulator (GSM), in the highest known yield.