Selectfluor and NFSI exo‐Glycal Fluorination Strategies Applied to the Enhancement of the Binding Affinity of Galactofuranosyltransferase GlfT2 Inhibitors

Two complementary methods for the synthesis of fluorinated exo‐glycals have been developed, for which previously no general reaction had been available. First, a Selectfluor‐mediated fluorination was optimized after detailed analysis of all the reaction parameters. A dramatic effect of molecular sieves on the course of the reaction was observed. The reaction was generalized with a set of biologically relevant furanosides and pyranosides. A second direct approach involving carbanionic chemistry and the use of N‐fluorobenzenesulfonimide (NFSI) was performed and this method gave better diastereoselectivities. Assignment of the Z/E configuration of all the fluorinated exo‐glycals was achieved based on the results of HOESY experiments. Furthermore, fluorinated exo‐glycal analogues of UDP‐galactofuranose were prepared and assayed against GlfT2, which is a key enzyme involved in the cell‐wall biosynthesis of major pathogens. The fluorinated exo‐glycals proved to be potent inhibitors as compared with a series of C‐glycosidic analogues of UDP‐Galf, thus demonstrating the double beneficial effect of the exocyclic enol ether functionality and the fluorine atom.     

Intercalation is not required for DNA light-switch behavior

The DNA light-switch complex [Ru(bpy)2(tpphz)]2+ (1, bpy = 2,2'-bipyridine, tpphz = tetrapyrido[3,2-a:2',3'-c:3',2'-h:2',3'-j]phenazine) is luminescent when bound to DNA and in organic solvents and weakly emissive in water. To date, light-switch behavior by transition metal complexes has generally been regarded as confirmation of DNA intercalation. In contrast, the present work demonstrates that the nonintercalating bimetallic complex [(bpy)2Ru(tpphz)Ru(bpy)2]4+ (2) behaves as a DNA light-switch. Weak emission from the 3MLCT excited state of 2 is observed in water with lambda(em) = 623 nm (phi(em) = 1.4 x 10(-4)), and a red shift (lambda(em) = 702 nm) and 40-fold increase in intensity are observed upon addition of 100 microM calf thymus DNA (ct-DNA). Addition of increasing concentrations of 2 to 1 mM herring sperm DNA does not result in an increase in the viscosity of the solution, indicating that the complex is not an intercalator. Additionally, experiments were conducted to ensure that the emission enhancement did not arise from threading intercalation of the complex. The in situ generation of 2 intercalated between the base pairs of ct-DNA in a threading fashion, however, exhibits emission maximum at 685 nm, which is blue-shifted from that of surface-bound 2. DFT calculations show low-lying orbitals in 2 that are expected to exhibit nonemissive character when contributing to the MLCT state, in accord with the lower emission intensity observed for 2 relative to that for 1. To our knowledge, the present work is the first example of a nonintercalating light-switch metal complex, thus showing that light-switch behavior cannot be used exclusively as confirmation of intercalation.     

Electrochemical Sensing of Paracetamol Using 3D Porous Laser Scribed Graphene Platform

This work presents a novel disposable electrochemical sensor for paracetamol (PCM). The sensing platform is based on graphene, manufactured via laser-scribing technology (LSG) to produce a 3D-porous structure that offers a large surface area. The analytical performances of LSG electrodes were greatly enhanced due to the high catalytic activity of graphene produced by LSG technology compared to conventional carbon electrodes. Moreover, the results showed an outstanding adsorption feature towards PCM, allowing its detection at nanomolar level from 5 nM to 100 nM through pre-concentration. The proposed sensing strategy was successfully applied for the determination of PCM in human urine samples.     

Synthesis of new 1‐[4‐methane(amino)sulfonylphenyl)]‐5‐[4‐(aminophenyl)]‐3‐trifluoromethyl‐1H‐pyrazoles

A regiospecific cyclization‐dehydration reaction of a 1‐[(4‐(N‐alkyl‐N‐(tert‐butyloxycarbony)amino)‐phenyl]‐4,4,4‐trifluorobutane‐1,3‐done with a 4‐aminosulfonyl‐, or 4‐methylsulfonyl‐, phenylhydrazine hydrochloride in refluxing ethanol proceeded with simultaneous loss of the N‐tert‐butyloxycarbonyl protecting group to afford a group of 1‐(4‐methanesulfonylphenyl or 4‐aminosulfonylphenyl)‐5‐[4‐(N‐alkylaminophenyl)]‐3‐(trifluoromethyl)‐11H‐pyrazoles(6). Subsequent reaction of the pyrazole 6 (R¹ = R² = Me) with nitric oxide (40 psi) proceeded via a N‐methylamino‐N‐diazen‐1‐ium‐1,2‐diolate intermediate that undergoes protonation of the more basic diazen‐1‐ium‐1,2‐diolate N²‐nitrogen and then loss of a nitroxyl (HNO) species to furnish the N‐nitroso product 7.     

Local atomic structures of single-component metallic glasses

In this study we examine the structural properties of single-component metallic glasses of aluminum. We use a molecular dynamics simulation based on semi-empirical many-body potential, derived from the embedded atom method (EAM). The radial distribution function (RDF), common neighbors analysis method (CNA), coordination number analysis (CN) and Voronoi tessellation are used to characterize the metal’s local structure during the heating and cooling (quenching). The simulation results reveal that the melting temperature depends on the heating rate. In addition, atomic visualization shows that the structure of aluminum after fast quenching is in a glassy state, confirmed quantitatively by the splitting of the second peak of the radial distribution function, and by the appearance of icosahedral clusters observed via CNA technique. On the other hand, the Wendt-Abraham parameters are calculated to determine the glass transition temperature (T_g), which depends strongly on the cooling rate; it increases while the cooling rate increases. On the basis of CN analysis and Voronoi tessellation, we demonstrate that the transition from the Al liquid to glassy state is mainly due to the formation of distorted and perfect icosahedral clusters.     

Electrochemical Characterization of Carbon Solidlike Paste Electrode Assembled Using Different Carbon Nanoparticles

Solid like carbon paste electrodes (SCPEs) are built using different carbon materials namely carbon black N110, N220, N375, N772 and acetylene black. The electrochemical behavior of these electrodes and the influence of carbon black/paraffin ratio were studied and the results were discussed and compared to other electrodes prepared with graphite, mesoporous carbon and nanopowder carbon. Cyclic voltammetry, amperometry and electrochemical impedance spectroscopy were employed for their electrochemical and analytical characterizations. Amperometric measurements using N110, N220, N375 SCPEs with solid paraffin, showed a linear response of benzoquinone concentration with a detection limit of 75, 32 and 171 nM respectively.     

The Anti-Inflammatory Effect of a γ-Lactone Isolated from Ostrich Oil of Struthio camelus (Ratite) and Its Formulated Nano-Emulsion in Formalin-Induced Paw Edema

The ostrich oil of Struthio camelus (Ratite) found uses in folk medicine as an anti-inflammatory in eczema and contact dermatitis. The anti-inflammatory effect of a γ-lactone (5-hexyl-3H-furan-2-one) isolated from ostrich oil and its formulated nano-emulsion in formalin-induced paw edema was investigated in this study. Ostrich oil was saponified using a standard procedure; the aqueous residue was fractionated, purified, and characterized as γ-lactone (5-hexyl-3H-furan-2-one) through the interpretation of IR, NMR, and MS analyses. The γ-lactone was formulated as nano-emulsion using methylcellulose (MC) for oral solubilized form. The γ-lactone methylcellulose nanoparticles (γ-lactone-MC-NPs) were characterized for their size, shape, and encapsulation efficiency with a uniform size of 300 nm and 59.9% drug content. The γ-lactone was applied topically, while the formulated nanoparticles (NPs) were administered orally to rats. A non-steroidal anti-inflammatory drug (diclofenac gel) was used as a reference drug for topical use and ibuprofen suspension for oral administration. Edema was measured using the plethysmograph method. Both γ-lactone and γ-lactone-MC-NPs showed reduction of formalin-induced paw edema in rats and proved to be better than the reference drugs; diclofenac gel and ibuprofen emulsion. Histological examination of the skin tissue revealed increased skin thickness with subepidermal edema and mixed inflammatory cellular infiltration, which were significantly reduced by the γ-lactone compared to the positive control (p-value = 0.00013). Diuretic and toxicity studies of oral γ-lactone-MC-NPs were performed. No diuretic activity was observed. However, lethargy, drowsiness, and refusal to feeding observed may limit its oral administration.     

Abdellatif Ghendir Aoun

In this paper, we study a fractional differential equation $$^{c}D^{\alpha}_{0^{+}}u(t)+f(t,u(t))=0,\quad t\in(0, +\infty)$$ satisfying the boundary conditions: $$u^{\prime}(0)=0,\quad \lim_{t\rightarrow +\infty}\,^{c}D^{\alpha-1}_{0^{+}}u(t)=g(u),$$ where $1<\alpha\leqslant2$, $^{c}D^{\alpha}_{0^{+}}$ is the standard Caputo fractional derivative of order $\alpha$. The main tools used in the paper is contraction principle in the Banach space and the fixed point theorem due to D. O''Regan. Some the compactness criterion and existence of solutions are established.