Quinazoline Derivatives Designed as Efflux Pump Inhibitors: Molecular Modeling and Spectroscopic Studies

Multidrug resistance of bacteria is a worrying concern in the therapeutic field and an alternative method to combat it is designing new efflux pump inhibitors (EPIs). This article presents a molecular study of two quinazoline derivatives, labelled BG1189 and BG1190, proposed as EPIs. In silico approach investigates the pharmacodynamic and pharmacokinetic profile of BG1189 and BG1190 quinazolines. Molecular docking and predicted ADMET features suggest that BG1189 and BG1190 may represent attractive candidates as antimicrobial drugs. UV-Vis absorption spectroscopy was employed to study the time stability of quinazoline solutions in water or in dimethyl sulfoxide (DMSO), in constant environmental conditions, and to determine the influence of usual storage temperature, normal room lighting and laser radiation (photostability) on samples stability. The effects of irradiation on BG1189 and BG1190 molecules were also assessed through Fourier-transform infrared (FTIR) spectroscopy. FTIR spectra showed that laser radiation breaks some chemical bonds affecting the substituents and the quinazoline radical of the compounds.     

Adding Value in Production of Multifunctional Polylactide (PLA)–ZnO Nanocomposite Films through Alternative Manufacturing Methods

Due to the added value conferred by zinc oxide (ZnO) nanofiller, e.g., UV protection, antibacterial action, gas-barrier properties, poly(lactic acid) (PLA)–ZnO nanocomposites show increased interest for utilization as films, textile fibers, and injection molding items. The study highlights the beneficial effects of premixing ZnO in PLA under given conditions and its use as masterbatch (MB), a very promising alternative manufacturing technique. This approach allows reducing the residence time at high processing temperature of the thermo-sensitive PLA matrix in contact of ZnO nanoparticles known for their aptitude to promote degradation effects onto the polyester chains. Various PLA–ZnO MBs containing high contents of silane-treated ZnO nanoparticles (up to 40 wt.% nanofiller specifically treated with triethoxycaprylylsilane) were produced by melt-compounding using twin-screw extruders. Subsequently, the selected MBs were melt blended with pristine PLA to produce nanocomposite films containing 1–3 wt.% ZnO. By comparison to the more traditional multi-step process, the MB approach allowed the production of nanocomposites (films) having improved processing and enhanced properties: PLA chains displaying higher molecular weights, improved thermal stability, fine nanofiller distribution, and thermo-mechanical characteristic features, while the UV protection was confirmed by UV-vis spectroscopy measurements. The MB alternative is viewed as a promising flexible technique able to open new perspectives to produce more competitive multifunctional PLA–ZnO nanocomposites.     

Variance of the virtual displacement

We show that the affine structure of the 3-dimensional space is deeply enmeshed with the static laws expression. The relevance of tensorial rules for calculus in mechanics is thus enhanced. The virtual work principle is stated precisely but a little twist is given to the usual statements: the tensorial nature of the so-called virtual displacement vector is asserted to be covariant. To cite this article: C. Vallée et al., C. R. Mecanique 332 (2004).

Résumé

Nous montrons que la structure affine de l'espace tridimensionnel est fortement imbriquée avec l'expression des lois de la statique. La pertinence de l'application des règles du calcul tensoriel à la mécanique est ainsi renforcée. Le principe des travaux virtuels est établi précisément avec une seule entorse aux exposés classiques : la nature tensorielle de l'habituel vecteur déplacement virtuel est affirmée covariante. Pour citer cet article : C. Vallée et al., C. R. Mecanique 332 (2004).     

Triple Self-Sorting in Constitutional Dynamic Networks: Parallel Generation of Imine-Based CuI,FeII, and ZnII Complexes

Three imine-based metal complexes, having no overlap in terms of their compositions, have been simultaneously generated from the self-sorting of a constitutional dynamic library (CDL) containing three amines, three aldehydes, and three metal salts. The hierarchical ordering of the stability of the three metal complexes assembled and the leveraging of the antagonistic and agonistic relationships existing between the constituents within the constitutional dynamic network corresponding to the CDL were pivotal in achieving the sorting. Examination of the process by NMR spectroscopy showed that the self-sorting of the Fe^II and Zn^II complexes depended on an interplay between the thermodynamic driving forces and a kinetic trap involved in their assembly. These results also exemplify the concept of “simplexity”—the fact that the output of a self-assembling system may be simplified by increasing its initial compositional complexity—as the two complexes could self-sort only in the presence of the third pair of organic components, those of the Cu^I complex.     

Shape distortions induced by convective effect on hot object in visible, near infrared and infrared bands

The goal of this study is to examine the perturbation induced by the convective effect (or mirage effect) on shape measurement and to give an estimation of the error induced. This work explores the mirage effect in different spectral bands and single wavelengths. A numerical approach is adopted and an original setup has been developed in order to investigate easily all the spectral bands of interest with the help of a CCD camera (Si, 0.35–1.1 μm), a near infrared camera (VisGaAs, 0.8–1.7 μm) or infrared cameras (8–12 μm). Displacements due to the perturbation for each spectral band are measured and finally some hints about how to correct them are given.     

METHYLTHIODITHIOLYLIUM REACTIONS WITH 2-BUTENE NITRILES DERIVATIVES

Abstract

The 3-methylthio-1. 2-dithiolylium including at 5 position a donor substituent, in acetic acid in the presence of pyridine, the 2-methylthio-1. 3-dithiolylium ions in methylene chloride-triethylamine, react with the 2-butene nitrile derivatives and lead to the (A) and (B) corresponding 4-dithiolylidene-2-butene nitriles. In contrast ring opening reaction of the 1, 2-dithiole is observed when 2-cyano-3-phenyl-2-butene nitrile reacts with the 3-methylthio-4-aryl-1. 2-dithiolylium ions in 3 and 5 positions, in methylene chloride-triethylamine. The nucleophilic attack on the 5 position of the dithiolylium ion leads to a 2-cyano-3-phenyl-3 (4-aryl-5-methylthio-2-thienyl) propene nitrile (C), meanwhile the attack on the 3 position leads to a 2-cyano-3-phenyl-3-(4-aryl-3-mercapto-2-thienyl) propene nitrile (D). The proposed structures are established by means of physical methods (IR, NMR, and Mass Spectrometry) and by non ambiguous synthesis. The reactivities of the various sites are explained in function of the electronic and steric effects, furthermore the reaction conditions and the intermediary isolation allow to propose the mecanisms of these reactions.     

1,1-Bis(Methylthio)-2-Nitroethene,a Versatile Synthon for the Synthesis of Oximinoorthothioesters

Abstract

1,1-bis(methylthio)-2-nitroethene gives a stable hydro-xynitrilium ion in trifluoromethanesulfonic acid. This cation can be trapped by various nucleophiles to yield a-oximinoorthothioesters.