Discovering Echinococcus granulosus thioredoxin glutathione reductase inhibitors through site-specific dynamic combinatorial chemistry

In this study, we report a strategy using dynamic combinatorial chemistry for targeting the thioredoxin (Trx)-reductase catalytic site on Trx glutathione reductase (TGR), a pyridine nucleotide thiol-disulfide oxido-reductase. We chose Echinococcus granulosus TGR since it is a bottleneck enzyme of platyhelminth parasites and a validated pharmacological target. A dynamic combinatorial library (DCL) was constructed based on thiol-disulfide reversible exchange. We demonstrate the use of 5-thio-2-nitrobenzoic acid (TNB) as a non-covalent anchor fragment in a DCL templated by E. granulosus TGR. The heterodimer of TNB and bisthiazolidine (2af) was identified, upon library analysis by HPLC (IC $_{50}$  = 24  $\upmu $ M). Furthermore, 14 analogs were synthetically prepared and evaluated against TGR. This allowed the study of a structure–activity relationship and the identification of a disulfide TNB-tricyclic bisthiazolidine (2aj) as the best enzyme inhibitor in these series, with an IC $_{50}$  = 14  $\upmu $ M. Thus, our results validate the use of DCL for targeting thiol-disulfide oxido-reductases.     

An optimization problem for nonlinear Steklov eigenvalues with a boundary potential

In this paper, we analyze an optimization problem for the first (nonlinear) Steklov eigenvalue plus a boundary potential with respect to the potential function which is assumed to be uniformly bounded and with fixed L¹$L^1$-norm.     

Sampling period,statistical complexity,and chaotic attractors

We analyze the statistical complexity measure vs. entropy plane-representation of sampled chaotic attractors as a function of the sampling period τ$\tau$ and show that, if the Bandt and Pompe procedure is used to assign a probability distribution function (PDF) to the pertinent time series, the statistical complexity measure (SCM) attains a definite maximum for a specific sampling period  _tM$t_M$. On the contrary, the usual histogram approach for assigning PDFs to a time series leads to essentially constant SCM values for any sampling period τ$\tau$. The significance of _tM$t_M$ is further investigated by comparing it with typical times found in the literature for the two main reconstruction processes: the Takens’ one in a delay-time embedding, on one hand, and the exact Nyquist–Shannon reconstruction, on the other one. It is shown that _tM$t_M$ is compatible with those times recommended as adequate delay ones in Takens’ reconstruction. The reported results correspond to three representative chaotic systems having correlation dimension 2<_D2<3$2<D_2<3$. One recent experiment confirms the analysis presented here.     

Crystallization of zeolites from organo-silicic colloids

As shown recently, the networks of mesoporous high-surface-area silicates and zeolites undergo a deep depolymerization process in glycerol, near 200 degrees C. Within 1 h, X-ray diffraction analysis amorphous gels are obtained. However, some local ordering subsists as demonstrated by a striking similarity between the silicon and aluminum high-resolution solid-state NMR spectra before and after the reaction. The residual organization could be investigated indirectly in studying the recrystallization of these gels in the presence or absence of structure-directing agents. Were this attempt successful, the way should be opened for the synthesis of molecular sieves starting from gels obtained from naturally occurring zeolites. Here, it will be shown that an amorphous gel obtained from HZSM-5 recovers the initial long-range structure of the parent material in a few hours at 85 degrees C in the presence of an aqueous solution of tetrapropyl ammonium (TPA) or NH3. The recrystallization of HY requires the presence of tetramethylammonium, but about 25% of the crystallization is obtained rapidly (approximately = 1 day) at 80 degrees C with ammonia. Hypotheses about the preorganized structural units are presented. The value of the Si-O-Si angle in the silica cluster seems to be of paramount importance.     

Dynamic thermodynamic and dynamic kinetic resolution of 2-lithiopyrrolidines

Dynamic resolution has been studied as a method for the asymmetric synthesis of 2-substituted pyrrolidines. Highly enantioselective electrophilic substitutions of racemic 2-lithiopyrrolidines in the presence of a chiral ligand have been achieved. The organolithium compounds were prepared by tin-lithium exchange from the corresponding tributylstannanes and n-butyllithium or by deprotonation of N-(tert-butyloxycarbonyl)pyrrolidine with sec-butyllithium. A range of N-substituents and chiral ligands were investigated for the dynamic resolution. Electrophilic quench of the resolved diastereomeric 2-lithiopyrrolidine-chiral ligand complexes provided the enantiomerically enriched 2-substituted pyrrolidines. With N-alkyl derivatives, the resolution occurs conveniently at (or just below) room temperature and either enantiomer of the product can be formed by appropriate choice of the chiral ligand. The asymmetric induction occurs as a result of a thermodynamic preference for one of the diastereomeric complexes. The minor complex was found to have a faster rate of reaction with the electrophile. The use of N-allylic derivatives provides a means to prepare the N-unsubstituted pyrrolidine products. Best results were obtained with the N-2,3-dimethylbut-2-enyl derivative, and this N-substituent could be cleaved using 1-chloroethyl chloroformate. With N-Boc-2-lithiopyrrolidine, the enantioselectivity arises by a kinetic resolution and high levels of asymmetric induction in the presence of excess n-butyllithium can be obtained. Dynamic kinetic resolution of the N-Boc derivative is limited in the scope of electrophile that can be used.     

A variational approach to free vibration analysis of shear deformable polygonal plates with variable thickness

This paper presents a simple and general variational approach for the study of the free vibration behaviour of polygonal isotropic plates with variable thickness. The Reissner-Mindlin plate theory is used to take into account the effects of shear deformation and rotary inertia in the analysis. Moreover, this theory allows obtaining greater accuracy of frequency coefficients corresponding to vibration higher modes, even for the thin plates.The governing eigenvalue equation is obtained employing the Ritz method. The plate geometry is approximated by using non-orthogonal triangular co-ordinates, while sets of independent polynomials, expressed in these co-ordinates, are employed to approximate the displacement and rotation fields. The developed algorithm allows obtaining approximated analytical solutions for plates with different aspect ratios, thickness variation and boundary conditions, including edges elastically restrained by both translational and rotational springs. Therefore, a unified program has been easily implemented. Convergence and comparison analyzes are carried out to verify the reliability and accuracy of the numerical solutions. Finally, sets of parametric studies are performed and the results are given in graphical and tabular form.     

Chemisorption of isocyanate (NCO) on the Pd(1 0 0) surface at different coverages

The chemisorption of isocyanate (NCO) species on Pd(1 0 0) was studied within the density functional formalism (DFT) using a periodic slab model. The NCO was adsorbed on top, bridge and hollow sites of the metal surface at different coverages. At low coverages, the adsorption energies are in the range of ?2.5/?3.0 eV, indicating an important adsorbate–substrate interaction for the three sites studied. The lateral repulsive interaction between neighboring NCO species is almost negligible or weak at lower and intermediate coverages, and very strong at complete monolayer. At low coverages, both bridge and hollow sites are energetically preferred; yet the bridge site becomes the only favoured site at intermediate and complete coverages. Work function and dipole moment calculations can be interpreted by an important charge transfer from the metal surface to NCO. Interestingly, while on hollow site the charge taken by NCO is essentially the same over all the range of coverage, an increasing depolarization is observed on bridge and top sites as the coverage increases. Symmetric and asymmetric NCO stretching modes were also calculated and compared with recent infrared spectroscopy measurements.     

Pseudomonas aeruginosa Biofilm Inactivation: Decreased Cell Culturability, Adhesiveness to Surfaces, and Biofilm Thickness Upon High-Pressure Nonthermal Plasma Treatment

Bacterial biofilms are more resilient to standard killing methods than free-living bacteria. Pseudomonas aeruginosa PAO1 biofilms grown on borosilicate coupons were treated with gas-discharge plasma for various exposure times. Almost 100% of the cells were inactivated after a 5-min plasma exposure. Atomic force microscopy was used to image the biofilms and study their micromechanical properties. Results show that the adhesiveness to borosilicate and the thickness of the Pseudomonas biofilms are reduced upon plasma treatment.     

On a certain class of nonideal clutters

In this paper we define the class of near-ideal clutters following a similar concept due to Shepherd [Near perfect matrices, Math. Programming 64 (1994) 295-323] for near-perfect graphs. We prove that near-ideal clutters give a polyhedral characterization for minimally nonideal clutters as near-perfect graphs did for minimally imperfect graphs. We characterize near-ideal blockers of graphs as blockers of near-bipartite graphs. We find necessary conditions for a clutter to be near-ideal and sufficient conditions for the clutters satisfying that every minimal vertex cover is minimum.     

Dielectric Barrier Discharge for Ammonia Production

The leading after-treatment technology for NOx removal process in Diesel engines for stationary and mobile applications is the selective catalytic reduction of oxides of nitrogen [NOx] by ammonia [NH₃]. A novel non-thermal plasma electrode with a needle array in a dielectric barrier discharge reactor, powered by a high frequency neon transformer, is used for the thermal decomposition of solid urea [(NH₂)CO(NH₂)] to produce ammonia. The thermolysis of urea produces iso-cyanic acid [HNCO] as a byproduct, besides ammonia, which can react with water in the gas phase, thus giving carbon dioxide and more ammonia. The presence of water fed before and/or after the plasma reactor was studied to assess its effect on the amount of produced ammonia. Results clearly showed that water fed to the entrance of the reactor can efficiently promote the reaction of iso-cyanic acid to produce ammonia and this result can be improved when air is used as carrier gas for 115 V of input voltage to a neon transformer and with a gas flow rate of 4 L/min.