Aging effects of nanoscale ceria in ceria–platinum composite electrodes for direct alcohol electro-oxidation

Nanocrystalline Pt/CeO₂ composite electrodes were fabricated to study the electrochemical oxidation of methanol and ethanol. The performance of the electrodes was tested as the ceria solutions aged over time. It was observed that the performance oscillated with time, suggesting that the catalytic behavior towards alcohol oxidation was greatly dependent on the aging of the particles. These results point to a great dependence of the catalytic effect on the redox state of the ceria particles.     

Brain‐Penetrant Triazolopyrimidine and Phenylpyrimidine Microtubule Stabilizers as Potential Leads to Treat Human African Trypanosomiasis

In vitro whole‐organism screens of Trypanosoma brucei with representative examples of brain‐penetrant microtubule (MT)‐stabilizing agents identified lethal triazolopyrimidines and phenylpyrimidines with sub‐micromolar potency. In mammalian cells, these antiproliferative compounds disrupt MT integrity and decrease total tubulin levels. Their parasiticidal potency, combined with their generally favorable pharmacokinetic properties, which include oral bioavailability and brain penetration, suggest that these compounds are potential leads against human African trypanosomiasis.     

Vitamin E acetate addition to poly(d,l)lactic acid modifies its mechanical behavior without affecting biocompatibility

Mechanical properties of poly(d,l )lactic acid films enriched with Vitamin E and Vitamin E Acetate (5–40% w/w) were investigated. The addition of both formulations resulted in increased polymer Young's modulus and tensile strength. Human foreskin fibroblasts and murine pre‐osteoblasts were used to assess the biocompatibility of polymers. Pre‐osteoblasts adhesion and proliferation were strongly decreased by Vitamin E, whereas Vitamin E Acetate did not alter cell proliferation. Collagen deposition was lower onto Vitamin E blended polymers than onto native and Vitamin E Acetate blended ones. Fibroblasts adhesion and proliferation were increased by both Vitamin E and Vitamin E Acetate addition. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2014 , 131, 39970.     

Novel Tacrine‐Grafted Ugi Adducts as Multipotent Anti‐Alzheimer Drugs: A Synthetic Renewal in Tacrine–Ferulic Acid Hybrids

Herein we describe the design, multicomponent synthesis, and biological, molecular modeling and ADMET studies, as well as in vitro PAMPA‐blood–brain barrier (BBB) analysis of new tacrine–ferulic acid hybrids (TFAHs). We identified (E)‐3‐(hydroxy‐3‐methoxyphenyl)‐N‐{8[(7‐methoxy‐1,2,3,4‐tetrahydroacridin‐9‐yl)amino]octyl}‐N‐[2‐(naphthalen‐2‐ylamino)2‐oxoethyl]acrylamide (TFAH 10 n ) as a particularly interesting multipotent compound that shows moderate and completely selective inhibition of human butyrylcholinesterase (IC₅₀=68.2 nM ), strong antioxidant activity (4.29 equiv trolox in an oxygen radical absorbance capacity (ORAC) assay), and good β‐amyloid (Aβ) anti‐aggregation properties (65.6 % at 1:1 ratio); moreover, it is able to permeate central nervous system (CNS) tissues, as determined by PAMPA‐BBB assay. Notably, even when tested at very high concentrations, TFAH 10 n easily surpasses the other TFAHs in hepatotoxicity profiling (59.4 % cell viability at 1000 μM ), affording good neuroprotection against toxic insults such as Aβ_1–40, Aβ_1–42, H₂O₂, and oligomycin A/rotenone on SH‐SY5Y cells, at 1 μM . The results reported herein support the development of new multipotent TFAH derivatives as potential drugs for the treatment of Alzheimer′s disease.     

Optical and Structural Properties of ZnO and ZnO:Cd Particles Grown by the Hydrothermal Method

Here, we examine the structural, vibrational, optical, and morphological properties of ZnO particles synthesized by the hydrothermal method, incorporating cadmium at different concentrations through the molar ratio R_m = Cd⁺²/Zn⁺² and a thermal treatment at 500°C. The X‐ray diffraction results demonstrated the high crystallinity of the ZnO compound with a wurtzite‐type hexagonal structure. The Raman scattering spectra demonstrated that the ZnO vibrational modes occur in the region between 200 and 1300 cm^?1, which is associated with different vibrational configurations characteristic of the ZnO molecule: E₂(Low), E₂(M), A₁(TO) E₁(TO), 2B₁(High), E₂(High), and TA + LO. The modes that were most affected by the incorporation of Cd²⁺ were those assigned to 2E₂(Low), E₂(M), and 2B₁(High), and this effect was associated with a greater displacement of Zn²⁺ ions. The optical study showed a reduction in the band gap and a decrease in the crystalline quality due to the substitution of Cd²⁺ in the ZnO lattice. Cadmium incorporation affected the morphology of the ZnO:Cd particles, changing the lengths and diameters of the ZnO rods; when the Cd concentration was increased, the ZnO rods shortened, forming coin‐type hexagonal structures.     

Synergistic effect of graphite nanoplatelets and glass fibers in polypropylene composites

In this study, polypropylene (PP) composites reinforced with short glass fibers (GF) and exfoliated graphite nanoplatelets were obtained by melt compounding followed by injection molding. Morphological observations and quasi‐static tensile tests were carried out in order to investigate how the morphology and the mechanical properties of the composites were affected by the combined effect of two fillers of rather different size scales (i.e., micro‐ and nanoscale). The results indicate that the dispersion of the nanofiller in the PP matrix promoted the formation of a stronger interface between the matrix and GF, as indicated by the increase of the interfacial shear strength determined by the single‐fiber microdebonding test. Concurrently, a significant improvement of the tensile modulus and impact strength of the composites was observed, with small changes in the processability of hybrid composites compared to that of GF composites, as confirmed by rheological measurements. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 41682.     

Recent Advances in Lipase-Mediated Preparation of Pharmaceuticals and Their Intermediates

Biocatalysis offers an alternative approach to conventional chemical processes for the production of single-isomer chiral drugs. Lipases are one of the most used enzymes in the synthesis of enantiomerically pure intermediates. The use of this type of enzyme is mainly due to the characteristics of their regio-, chemo- and enantioselectivity in the resolution process of racemates, without the use of cofactors. Moreover, this class of enzymes has generally excellent stability in the presence of organic solvents, facilitating the solubility of the organic substrate to be modified. Further improvements and new applications have been achieved in the syntheses of biologically active compounds catalyzed by lipases. This review critically reports and discusses examples from recent literature (2007 to mid-2015), concerning the synthesis of enantiomerically pure active pharmaceutical ingredients (APIs) and their intermediates in which the key step involves the action of a lipase.     

Relation between the adsorbed quantity and the immersion enthalpy in catechol aqueous solutions on activated carbons

An activated carbon, Carbochem(TM)-PS230, was modified by chemical and thermal treatment in flow of H(2), in order to evaluate the influence of the activated carbon chemical characteristics in the adsorption of the catechol. The catechol adsorption in aqueous solution was studied along with the effect of the pH solution in the adsorption process of modified activated carbons and the variation of immersion enthalpy of activated carbons in the aqueous solutions of catechol. The interaction solid-solution is characterized by adsorption isotherms analysis, at 298 K and pH 7, 9 and 11 in order to evaluate the adsorption value above and below that of the catechol pK(a). The adsorption capacity of carbons increases when the solution pH decreases. The retained amount increases slightly in the reduced carbon to maximum adsorption pH and diminishes in the oxidized carbon. Similar conclusions are obtained from the immersion enthalpies, whose values increase with the solute quantity retained. In granular activated carbon (CAG), the immersion enthalpies obtained are between 21.5 and 45.7 J·g(-1) for catechol aqueous solutions in a range of 20 at 1500 mg·L(-1).     

Interactions between Artemisinins and other Antimalarial Drugs in Relation to the Cofactor Model—A Unifying Proposal for Drug Action

Artemisinins are proposed to act in the malaria parasite cytosol by oxidizing dihydroflavin cofactors of redox‐active flavoenzymes, and under aerobic conditions by inducing their autoxidation. Perturbation of redox homeostasis coupled with the generation of reactive oxygen species (ROS) ensues. Ascorbic acid–methylene blue (MB), N‐benzyl‐1,4‐dihydronicotinamide (BNAH)–MB, BNAH–lumiflavine, BNAH–riboflavin (RF), and NADPH–FAD–E. coli flavin reductase (Fre) systems at pH 7.4 generate leucomethylene blue (LMB) and reduced flavins that are rapidly oxidized in situ by artemisinins. These oxidations are inhibited by the 4‐aminoquinolines piperaquine (PPQ), chloroquine (CQ), and others. In contrast, the arylmethanols lumefantrine, mefloquine (MFQ), and quinine (QN) have little or no effect. Inhibition correlates with the antagonism exerted by 4‐aminoquinolines on the antimalarial activities of MB, RF, and artemisinins. Lack of inhibition correlates with the additivity/synergism between the arylmethanols and artemisinins. We propose association via π complex formation between the 4‐aminoquinolines and LMB or the dihydroflavins; this hinders hydride transfer from the reduced conjugates to the artemisinins. The arylmethanols have a decreased tendency to form π complexes, and so exert no effect. The parallel between chemical reactivity and antagonism or additivity/synergism draws attention to the mechanism of action of all drugs described herein. CQ and QN inhibit the formation of hemozoin in the parasite digestive vacuole (DV). The buildup of heme–Fe^III results in an enhanced efflux from the DV into the cytosol. In addition, the lipophilic heme–Fe^III complexes of CQ and QN that form in the DV are proposed to diffuse across the DV membrane. At the higher pH of the cytosol, the complexes decompose to liberate heme–Fe^III. The quinoline or arylmethanol reenters the DV, and so transfers more heme–Fe^III out of the DV. In this way, the 4‐aminoquinolines and arylmethanols exert antimalarial activities by enhancing heme–Fe^III and thence free Fe^III concentrations in the cytosol. The iron species enter into redox cycles through reduction of Fe^III to Fe^II largely mediated by reduced flavin cofactors and likely also by NAD(P)H–Fre. Generation of ROS through oxidation of Fe^II by oxygen will also result. The cytotoxicities of artemisinins are thereby reinforced by the iron. Other aspects of drug action are emphasized. In the cytosol or DV, association by π complex formation between pairs of lipophilic drugs must adversely influence the pharmacokinetics of each drug. This explains the antagonism between PPQ and MFQ, for example. The basis for the antimalarial activity of RF mirrors that of MB, wherein it participates in redox cycling that involves flavoenzymes or Fre, resulting in attrition of NAD(P)H. The generation of ROS by artemisinins and ensuing Fenton chemistry accommodate the ability of artemisinins to induce membrane damage and to affect the parasite SERCA PfATP6 Ca²⁺ transporter. Thus, the effect exerted by artemisinins is more likely a downstream event involving ROS that will also be modulated by mutations in PfATP6. Such mutations attenuate, but cannot abrogate, antimalarial activities of artemisinins. Overall, parasite resistance to artemisinins arises through enhancement of antioxidant defense mechanisms.     

On the Viscoelastic Properties of Collagen‐Gel‐Based Lattices under Cyclic Loading: Applications for Vascular Tissue Engineering

Reconstituted collagen gels are widely used as scaffolds even though their low strength and poor elasticity limit their applications in VTE. Here, two approaches are adopted to modify their mechanical behavior: in the first, gels prepared under physiologic conditions are remodeled by cell‐mediated contraction; in the second, gels prepared in non‐physiologic conditions are chemically crosslinked. Samples are tested under cyclic loading and their viscoelastic behavior is assessed. The results show that both approaches result in lattices with adequate strength, and crosslinking significantly reduces hysteresis and permanent deformation. SEM shows that SMCs are capable of contracting and remodeling all the lattices, confirming that these are suitable supports for tissue regeneration.