Synthesis and in vitro evaluation of N-(Bromobut-3-en-2-yl)-7-methoxy-1,2,3,4-tetrahydroacridin-9-amine as a cholinesterase inhibitor with regard to Alzheimer's disease treatment

A new tacrine based cholinesterase inhibitor, N-(bromobut-3-en-2-yl)-7-methoxy-1,2,3,4-tetrahydroacridin-9-amine (1), was designed and synthesized to interact with specific regions of human acetylcholinesterase and human butyrylcholinesterase. Its inhibitory ability towards cholinesterases was determined and compared to tacrine (THA) and 9-amino-7-methoxy-1,2,3,4-tetrahydroacridine (7-MEOTA). The assessment of IC50 values revealed 1 as a weak inhibitor of both tested enzymes.     

Synthesis, antimycobacterial, antifungal and photosynthesis-inhibiting activity of chlorinated N-phenylpyrazine-2-carboxamides

A series of sixteen pyrazinamide analogues with the -CONH- linker connecting the pyrazine and benzene rings was synthesized by the condensation of chlorides of substituted pyrazinecarboxylic acids with ring-substituted (chlorine) anilines. The prepared compounds were characterized and evaluated for their antimycobacterial and antifungal activity, and for their ability to inhibit photosynthetic electron transport (PET). 6-Chloro-N-(4-chlorophenyl)pyrazine-2-carboxamide manifested the highest activity against Mycobacterium tuberculosis strain H37Rv (65% inhibition at 6.25 μg/mL). The highest antifungal effect against Trichophyton mentagrophytes, the most susceptible fungal strain tested, was found for 6-chloro-5-tert-butyl-N-(3,4-dichlorophenyl)pyrazine-2-carboxamide (MIC=62.5 μmol/L). 6-chloro-5-tert-butyl-N-(4-chlorophenyl)pyrazine-2-carboxamide showed the highest PET inhibition in spinach chloroplasts (Spinacia oleracea L.) chloroplasts (IC50=43.0 μmol/L). For all the compounds, the relationships between the lipophilicity and the chemical structure of the studied compounds as well as their structure-activity relationships are discussed.     

Synthesis and characterization of non-aggregating octa-substituted azaphthalocyanines bearing bulky phenoxy substituents

The synthesis and characterization of two novel series of octaazaphthalocyanines (AzaPc) bearing bulky phenoxy substituents are described. Target precursors to AzaPcs derivatives were prepared by using a nucleophilic aromatic substitution reaction between sterically hindered phenols (2,6-di-iso-propylphenol and 2,6-diphenylphenol) and 5,6-dichloropyrazine-2,3-dicarbonitrile. UV-vis and ¹H NMR analyses confirm that steric isolation of the AzaPcs cores enforced both in the solution and in the solid state. This study explores the effectiveness of the steric factor imposed by the applied bulky phenoxy substituents on the packing behaviour of azaphthalocyanines and thereby improving their solubility and photo-physical properties.     

A Phase-Field Model of Ductile Fracture at Finite Strains

This work outlines a variational-based framework for the phase field modeling of ductile fracture in elastic-plastic solids at large strains. The phase field approach regularizes sharp crack discontinuities within a pure continuum setting by a specific gradient damage model with geometric features rooted in fracture mechanics. Based on the recent works [1, 2], the phase field model of ductile fracture is linked to a formulation of gradient plasticity at finite strains in order to ensure the crack to evolve inside the plastic zones. The thermodynamic formulation is based on the definition of a constitutive work density function including the stored elastic energy and the dissipated work due to plasticity and fracture. The proposed canonical theory is shown to be governed by a rate-type minimization principle, which determines the coupled multi-field evolution problem. Another aspect is the regularization towards a micromorphic gradient plasticity-damage setting which enhances the robustness of the finite element formulation. (© 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim)     

Ductile failure with gradient plasticity coupled to the phase-field fracture at finite strains

Most metals fail in a ductile fashion, i.e, fracture is preceded by significant plastic deformation. The modeling of failure in ductile metals must account for complex phenomena at micro-scale, such as nucleation, growth and coalescence of micro-voids. In this work, we start with von-Mises plasticity model without considering void generation. The modeling of macroscopic cracks can be achieved in a convenient way by the continuum phase field approaches to fracture, which are based on the regularization of sharp crack discontinuities [1]. This avoids the use of complex discretization methods for crack discontinuities and can account for complex crack patterns. The key aspect of this work is the extension of the energetic and the stress-based phase field driving force function in brittle fracture to account for a coupled elasto-plastic response in line with our recent work [3]. We develop a new theoretical and computational framework for the phase field modeling of ductile fracture in elastic-plastic solids. To account for large strains, the constitutive model is constructed in the logarithmic strain space, which simplify the model equations and results in a formulation similar to small strains. We demonstrate the modeling capabilities and algorithmic performance of the proposed formulation by representative simulations of ductile failure mechanisms in metals. (© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim)     

Exploring the Symmetry,Structure, and Self‐Assembly Mechanism of a Gigantic Seven‐Fold Symmetric {Pd84} Wheel

The symmetry, structure and formation mechanism of the structurally self‐complementary { Pd₈₄ } = [Pd₈₄O₄₂(PO₄)₄₂(CH₃CO₂)₂₈]⁷⁰⁻ wheel is explored. Not only does the symmetry give rise to a non‐closest packed structure, the mechanism of the wheel formation is proposed to depend on the delicate balance between reaction conditions. We achieve the resolution of gigantic polyoxopalladate species through electrophoresis and size‐exclusion chromatography, the latter has been used in conjunction with electrospray mass spectrometry to probe the formation of the ring, which was found to proceed by the stepwise aggregation of {Pd₆}⁻ = [Pd₆O₄(CH₃CO₂)₂(PO₄)₃Na_6−nH_n]⁻ building blocks. Furthermore, the higher‐order assembly of these clusters into hollow blackberry structures of around 50 nm has been observed using dynamic and static light scattering.     

Short-pulse, high-peak-power Q-switched Tm–silica fibre laser at 1.9 m

High-performance Tm–silica fibre lasers operating at 1.9 μm when pumped at 1319 or 1064 nm have been Q-switched using a rotating mirror mounted at an asymmetric angle. Pumping by 1319 nm gives better performance compared with 1064 nm pumping due to greater excited state absorption (ESA) at 1064 nm. A short Q-switched pulse duration of 25 ns and a peak pulse power of about 2.7 kW has been obtained from a 1.8 m fibre for 3.5 W launched pump power at 1.3 μm. The Q-switch performance has been studied for variation of fibre length and shown that the optimum length under these pumping conditions is around 2 m.     

A fully consistent experimental and molecular simulation study of methane adsorption on activated carbon

The adsorption of pure methane in activated carbon Ecosorb was studied by combining grand canonical ensemble Monte Carlo molecular simulations and an experimental approach based on a gravimetric device. Experimental and calculated adsorption isotherms of methane were determined in supercritical conditions at 303.15 and 353.15 K and pressures up to 10 MPa. The comparison between both experimental and estimated data proves the consistency of the methodology used in this work, starting from the characterization of the porous media in terms of pore size distribution, the determination of the experimental adsorption isotherms, and the final estimation of computational results through estimated isotherms determination. Moreover, additional differential enthalpy of adsorption calculations were compared with experimental values obtained by means of a manometric/calorimetric technique. The good agreement shows the strength and the originality of this paper by combining experimental and computational homemade results allowing a complete characterization of the activated carbon substrate and its methane storage capacity.     

The response of clamped-clamped microbeams under mechanical shock

We present modeling, simulation, and characterization for the dynamic response of clamped-clamped microbeams under mechanical shock. A Galerkin-based reduced-order model is utilized and its results are verified by comparing to finite-element results. The results indicate that the response of a microbeam to mechanical shock is inherently non-linear because of the dominating effect of mid-plane stretching. The effect of the shock pulse shape is investigated. It is concluded that the shape of the shock pulse can result in significant dynamic amplification in the response of the microbeam even in cases where the shock load is considered quasi-static.The combined effect of the electrostatic force and mechanical shock is investigated. The results show that this combined effect can lead to early instability in microelectromechanical systems (MEMS) devices through dynamic pull-in. This could explain some of the reported experimental evidences for the existence of strange modes of failure of MEMS devices under mechanical shock and impact. These failures are characterized by overlaps between moving microstructures and stationary electrodes, which cause electrical shorts. The shock-electrostatic interaction is shown to be promising to design smart MEMS switches triggered at predetermined level of shock and acceleration. Finally, the mechanical shock combined with the packaging effect of MEMS devices is analyzed. A single-degree-of-freedom model representing the motion of the package, which is mounted over a printed circuit board, coupled with the continuous beam model is utilized. Our results reveal that neglecting the effect of the package motion on the response of microbeams can overestimate or underestimate their response. It is concluded that a poor design of the package may result in severe amplification of the shock effect leading to a device failure.