Reduced percolation concentration in polypropylene/expanded graphite composites: Effect of viscosity and polypyrrole

With the goal to obtain material combining electrical and thermal conductivity at low filler loadings, composites based on polypropylenes (PP) and expanded graphite (EG) have been prepared. The effects of matrix viscosity and of coating the EG particles with polypyrrole (PPy, EG/PPy = 37.5/62.5 by weight) on the EG dispersibility and formation of percolation structures have been analyzed. When increasing the EG amount from 6 to 8 wt %, the electrical conductivity of PP/EG composites increased by 7–9 orders of magnitude, independent of matrix viscosity. When EG‐PPy is added, percolation was observed between 8 and 12 wt % EG‐PPy (3 and 4.5 wt % EG) in case of PP with higher viscosity and 6 wt % EG (2.25 wt % EG) in case of PP with lower viscosity, exhibiting a strong synergistic effect of EG and PPy in the latter case. In contrast, PPy does not contribute to reduction of thermal percolation concentration. Thermal percolation is observed at 8 wt % EG in PP/EG composites, but no percolation was found in PP/EG‐PPy composites with EG‐PPy contents of up to 20 wt %, corresponding to 7.5 wt % EG. Analyzing the melt rheology it becomes clear that the contribution of PPy to the formation of a filler network is strongly dependent on the matrix viscosity. The comparison of thermal, electrical and rheological percolation reveals that PPy participates in electron transport reducing the electrical percolation but not to heat transport. Overall, we found a good correlation between electrical, thermal, and melt rheological percolation concentrations. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 41994.     

Peculiar crystallization kinetics of biodegradable poly(lactic acid)/poly(propylene carbonate) blends

Binary blends of poly(lactic acid) (PLA) and poly(propylene carbonate) (PPC) were found to display a peculiar crystallization kinetics. The two biodegradable polymers were blended by melt mixing, to obtain binary blends at various compositions. Temperature‐modulated calorimetry and dynamic‐mechanical analysis indicated that the blend components are partially miscible, and display two separate glass transitions, at temperatures intermediate to those of the plain polymers. Electron microscopy analysis disclosed the morphology of PLA/PPC blends, made of PPC‐rich particles finely dispersed within the PLA‐rich matrix. The possible establishment of interactions between the functional groups of the two polymers upon melt mixing has been hypothesized as the reason for partial miscibility and compatibility of the two biodegradable polymers. The PLA/PPC blends display good mechanical properties, with enhanced performance at rupture compared with plain PLA. Most importantly, the addition of PPC affects also the crystallization kinetics of PLA, since the more mobile PPC chains favor diffusion of the stiffer PLA chain segments towards the growing crystals, which fastens the spherulite growth rate of PLA. Such positive influence of an amorphous polymer on crystal growth rate has been demonstrated here for the first time in blends that display phase‐separation in the melt. POLYM. ENG. SCI., 55:2698–2705, 2015. © 2015 Society of Plastics Engineers     

Disinfection of Dental Instruments Contaminated with Streptococcus mutans Using Ozonated Water Alone or Combined with Ultrasound

Ozone gas diluted in water has been shown to produce significant results in terms of the elimination of microorganisms. Streptococcus mutans is the etiologic agent of dental caries. Methods using water containing ozone and an ultrasonic cleaner were employed for the disinfection of a curette. Streptococcus mutans was grown in a selective medium. The curette was submitted to disinfection by water containing ozone, by ultrasound, and then both techniques were combined. The results show that either method produced a significant microbial reduction, but the efficacy of both methods combined was greater. This method of disinfection proved to be both viable and cheap.     

Bleaching of Knitted Cotton Fabric Applying Ozone

Several samples of knitted cotton fabric in raw state were impregnated with a solution of industrial wetting detergent and treated directly with ozone gas in a closed chamber. Working conditions for the variables: time, pH of the impregnation solution, residual pickup and feed flow rate of oxygen (for ozone generation) were investigated to identify the effects on whiteness degree and fabric strength. The application of ozone proved to be an efficient and promising technology with low water usage.     

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.     

Identification of Aminoimidazole and Aminothiazole Derivatives as Src Family Kinase Inhibitors

Src family kinases (SFKs) are a family of non‐receptor tyrosine kinases (TKs) implicated in the regulation of many cellular processes. The aberrant activity of these TKs has been associated with the growth and progression of cancer. In particular, c‐Src is overexpressed or hyperactivated in a variety of solid tumors and is most likely a strong promoting factor for the development of metastasis. Herein, the synthesis of new 4‐aminoimidazole and 2‐aminothiazole derivatives and their in vitro biological evaluation are described for their potential use as SFK inhibitors. Initially, 2‐aminothiazole analogues of dasatinib and 4‐aminoimidazole derivatives were synthesized and tested against the SFKs Src, Fyn, Lyn, and Yes. Five hits were identified as the most promising compounds, with K_i values in the range of 90–480 nm . A combination of molecular docking, homology modeling, and molecular dynamics were then used to investigate the possible binding mode of such compounds within the ATP binding site of the SFKs. Finally, the antiproliferative activities of the best candidates were evaluated against SH‐SY5Y and K562 cell lines. Compound 3 b [2‐(4‐{2‐methyl‐6‐[(5‐phenylthiazol‐2‐yl)amino]pyrimidin‐4‐yl}piperazin‐1‐yl)ethanol] was found to be the most active inhibitor.     

Antitumor Activity of Ionic Liquids Based on Ampicillin

Significant antiproliferative effects against various tumor cell lines were observed with novel ampicillin salts as ionic liquids. The combination of anionic ampicillin with appropriate ammonium, imidazolium, phosphonium, and pyridinium cations yielded active pharmaceutical ingredient ionic liquids (API‐ILs) that show potent antiproliferative activities against five different human cancer cell lines: T47D (breast), PC3 (prostate), HepG2 (liver), MG63 (osteosarcoma), and RKO (colon). Some API‐ILs showed IC₅₀ values between 5 and 42 nM , activities that stand in dramatic contrast to the negligible cytotoxic activity level shown by the ampicillin sodium salt. Moreover, very low cytotoxicity against two primary cell lines—skin (SF) and gingival fibroblasts (GF)—indicates that the majority of these API‐ILs are nontoxic to normal human cell lines. The most promising combination of antitumor activity and low toxicity toward healthy cells was observed for the 1‐hydroxyethyl‐3‐methylimidazolium–ampicillin pair ([C₂OHMIM][Amp]), making this the most suitable lead API‐IL for future studies.     

Potent,Metabolically Stable 2‐Alkyl‐8‐(2H‐1,2,3‐triazol‐2‐yl)‐9H‐adenines as Adenosine A2A Receptor Ligands

Inhibition of adenosine A_2A receptors has been shown to elicit a therapeutic response in preclinical animal models of Parkinson’s disease (PD). We previously identified the triazolo‐9H‐purine, ST1535, as a potent A_2AR antagonist. Studies revealed that ST1535 is extensively hydroxylated at the ω‐1 position of the butyl side chain. Here, we describe the synthesis and evaluation of derivatives in which the ω‐1 position has been substituted (F, Me, OH) in order to block metabolism. The stability of the compounds was evaluated in human liver microsomes (HLM), and the affinity for A_2AR was determined. Two compounds, (2‐(3,3‐dimethylbutyl)‐9‐methyl‐8‐(2H‐1,2,3‐triazol‐2‐yl)‐9H‐purin‐6‐amine ( 3 b ) and 4‐(6‐amino‐9‐methyl‐8‐(2H‐1,2,3‐triazol‐2‐yl)‐9H‐purin‐2‐yl)‐2‐methylbutan‐2‐ol ( 3 c ), exhibited good affinity against A_2AR (K_i=0.4 nM and 2 nM , respectively) and high in vitro metabolic stability (89.5 % and 95.3 % recovery, respectively, after incubation with HLM for two hours).     

A Pharmacogenetics Study in Mozambican Patients Treated with Nevirapine: Full Resequencing of TRAF3IP2 Gene Shows a Novel Association with SJS/TEN Susceptibility

Steven–Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) are severe adverse drug reactions, characterized by extensive epidermal detachment and erosions of mucous membrane. SJS/TEN is one of the most serious adverse reactions to Nevirapine (NVP) treatment, commonly used in developing countries as first-line treatment of human immunodeficiency virus infection. In the last years TRAF3IP2 gene variants had been described as associated with susceptibility to several diseases such as psoriasis and psoriatic arthritis. We hypothesized that this gene, involved in immune response and in NF-κB activation, could also be implicated in the SJS/TEN susceptibility. We performed a full resequencing of TRAF3IP2 gene in a population of patients treated with NVP. Twenty-seven patients with NVP-induced SJS/TEN and 78 controls, all from Mozambique, were enrolled. We identified eight exonic and three intronic already described variants. The case/control association analysis highlighted an association between the rs76228616 SNP in exon 2 and the SJS/TEN susceptibility. In particular, the variant allele (C) resulted significantly associated with a higher risk to develop SJS/TEN (p = 0.012 and OR = 3.65 (95% CI 1.33–10.01)). A multivariate analysis by logistic regression confirmed its significant contribution (p = 0.027, OR = 4.39 (95% CI 1.19–16.23)). In conclusion, our study suggests that a variant in TRAF3IP2 gene could be involved in susceptibility to SJS/TEN.