Tacrines as Therapeutic Agents for Alzheimer's Disease. V. Recent Developments

Herein we have reviewed our recent developments for the identification of new tacrine analogues for Alzheimer's disease (AD) therapy. Tacrine, the first cholinesterase inhibitor approved for AD treatment, did not stop the progression of AD, producing only some cognitive improvements, but exhibited secondary effects mainly due to its hepatotoxicity. Thus, the drug was withdrawn from the clinics administration. Since then, many publications have described non‐hepatotoxic tacrines, and in addition, important efforts have been made to design multitarget tacrines by combining their cholinesterase inhibition profile with the modulation of other biological targets involved in AD.     

Divergent synthetic routes to biologically relevant types of compounds: chiral polyfunctional γ-lactams and amino acids

Divergent and versatile synthetic routes leading to the title compounds are described. They start from a common chiral precursor derived from (−)-(S)-verbenone and afford polyfunctional γ-lactams and γ- and ε-amino acids. The cyclobutane moiety in these molecules acts as a chiral and polyfunctional platform providing stereogenic centres with unambiguous absolute configuration that control the chirality of the newly produced asymmetric carbons. Furthermore, it affords functional groups and carbon chains suitable not only to create the basic skeleton of the desired products but additional functional groups. These features confer on these derivatives a great versatility for further uses in the development of new drugs and as synthetic building blocks.     

The Shapley value for arbitrary families of coalitions

We address the problem of finding a suitable definition of a value similar to that of Shapley’s, when the games are defined on a subfamily of coalitions with no structure. We present two frameworks: one based on the familiar efficiency, linearity and null player axioms, and the other on linearity and the behavior on unanimity games. We give several properties and examples in each case, and give necessary and sufficient conditions on the family of coalitions for the approaches to coincide.     

Interaction between a Novel Oligopeptide Fragment of the Human Neurotrophin Receptor TrkB Ectodomain D5 and the C-Terminal Fragment of Tetanus Neurotoxin

This article presents experimental evidence and computed molecular models of a potential interaction between receptor domain D5 of TrkB with the carboxyl-terminal domain of tetanus neurotoxin (Hc-TeNT). Computational simulations of a novel small cyclic oligopeptide are designed, synthesized, and tested for possible tetanus neurotoxin-D5 interaction. A hot spot of this protein-protein interaction is identified in analogy to the hitherto known crystal structures of the complex between neurotrophin and D5. Hc-TeNT activates the neurotrophin receptors, as well as its downstream signaling pathways, inducing neuroprotection in different stress cellular models. Based on these premises, we propose the Trk receptor family as potential proteic affinity receptors for TeNT. In vitro, Hc-TeNT binds to a synthetic TrkB-derived peptide and acts similar to an agonist ligand for TrkB, resulting in phosphorylation of the receptor. These properties are weakened by the mutagenesis of three residues of the predicted interaction region in Hc-TeNT. It also competes with Brain-derived neurotrophic factor, a native binder to human TrkB, for the binding to neural membranes, and for uptake in TrkB-positive vesicles. In addition, both molecules are located together in vivo at neuromuscular junctions and in motor neurons.     

Fractionation of nitrogen stable isotopes by ion exchange chromatography

The ion exchange chromatography displacement technique was used for the enrichment of ¹⁵N. The runs were conducted in laboratory and bench scales using two systems of columns filled with Wofatit KPS ion exchange resin (medium porosity type). Ammonia NH₄ ⁺/NH₃ aq. was chosen as the isotopic exchange system. The ammonium bands formed in the columns were eluted by means of sodium hydroxide solution. Hydrodynamic patterns in the column beds was evaluated in terms of dimensionless Reynolds number. The results show that separation process can be performed in the turbulent or laminar flow regime.     

Synthesis of Na<Subscript>2</Subscript>Ti<Subscript>3</Subscript>O<Subscript>7</Subscript> nanoparticles by sonochemical method for solid state electrolyte applications

Na₂Ti₃O₇ ceramic materials have been widely used in sodium-ion battery applications with relative good results; however, there are still several studies that might be carried out in the improvement of the Na₂Ti₃O₇ properties and the overall batteries’ performance. In this direction, we used sonochemical method following a thermal treatment in order to synthetized pure phase Na₂Ti₃O₇ nanopowders. X-ray diffraction characterization revealed that Na₂Ti₃O₇ is the primary phase in nanopowders and ceramic sample; although, a high level of amorphization was observed in the sonicated nanopowder without heat treatment process. Nanopowder-prepared ceramic sample showed a crystallite size of 50 nm after sintering at 900 °C for 1 h. The specific surface area, pore volume, and pore size were obtained from the B.E.T. measurements, being 51 m² g^?1, 0.07 cm³ g^?1, and 55 Å, respectively. The capacitance values of the nanopowder-prepared ceramic sample were in the order of microfarad. The total energy of the system was used to determine relaxation time of the sample (τ ₀ = 31 ms).     

Morphology and performance of CoOOH films synthesized via electrochemical oxidation: substrate effects

In the present work, CoOOH films are synthesized from the electrochemical oxidation of α-Co(OH)₂ as precursor. The substrate influences on the material electrochemical properties are studied. The samples are structural and morphologically characterized using techniques of X-ray diffraction (XRD) and scanning electronic microscopy (SEM). The cyclic voltammetry, galvanostatic charge-discharge, and electrochemical impedance spectroscopy techniques are used for the electrochemical characterization. The films deposited on steel substrate grew in the vertical hexagonal platelet form. Meanwhile, films on Ti plate presented morphology in agglomerated sphere form. After electrochemical oxidation, the film initial morphology is maintained. The films deposited on steel plate have a structure which favors charge storage showing a high specific capacity value (110.92 mA h g^?1) and cyclic stability of 92% after 1000 cycles. Finally, the relaxation time constant value calculated was 5.6 s. This fact is making this material as a possible good candidate for application as electrode material or additive for other materials, in energy storage devices.     

A novel class of metal-directed supramolecular DNA-delivery systems

The bis-complexes [Cu(L(dt))(2)](OTf)(2) (1) and [Cu(L(ot))(2)](OTf)(2) (2), where L(dt) = 1-dodecyl-1,4,7-triazacyclononane, L(ot) = 1-octadecyl-1,4,7-triazacyclononane and OTf = trifluoromethanesulfonate, formed a novel class of metallo-liposomes in water that transfect pEGFP-N1 plasmids into HEK 293-T cells at 38% and 4% efficiency, respectively.     

Multi-element Saha–Boltzmann and Boltzmann plots in laser-induced plasmas

A multi-element Saha–Boltzmann plot method is proposed for the determination of the temperature and the relative number density in laser-induced plasmas, assuming local thermodynamic equilibrium and stoichiometry conservation. The method has been applied to the characterization of a plasma generated with a Cu–Fe–Ni–Mn alloy, using a Nd:YAG laser in air at atmospheric pressure. Spectra of the local emissivity have been obtained by spatial deconvolution of the intensity spectra, obtained with spatial resolution. Saha–Boltzmann plots obtained from the emissivities of 58 spectral lines of Fe I, Fe II, Ni I, Ni II, Mn I and Mn II have been fitted to linear behavior with high correlation, which shows the validity of the equation proposed. Radial distributions of the temperature and number densities of neutral atoms and ions have been determined. The results obtained reinforce the initial considerations of local thermodynamic equilibrium and conservation of stoichiometry. The proposed equation can also be applied to only one ionization species (multi-element Boltzmann plot). Spatially-integrated measurements of the plasma emission have also been performed to show that, in this case, the application of the method to the line intensities provides the two different apparent temperatures for neutral atoms and ions.