Direct Regio‐, Diastereo‐, and Enantioselective Vinylogous Michael Addition of Prochiral 3‐Alkylideneoxindoles to Nitroolefins

3‐Alkylidene‐2‐oxindoles represent a simple, yet enabling subfamily of indole alkaloids, and their ability to react as electron‐poor acceptors has largely been investigated. In contrast, their utility as pronucleophilic synthons remains elusive. In this context, the present article describes the successful execution of the direct, organocatalytic asymmetric Michael addition of prochiral 3‐alkylideneoxindoles to nitroolefins. A variety of γ‐substituted alkylideneoxindoles carrying two stereocenters at both the γ‐ and δ‐carbon sites was assembled with excellent stereoselectivity and without olefin isomerization or stereochemical ablation.     

Alder ene functionalization of polyisobutene oligomer and styrene-butadiene-styrene triblock copolymer

The Alder ene functionalization reaction of double bonds containing macromolecules such as polyisobutene oligomer (PIB) and a styrene-butadiene-styrene triblock copolymer (SBS) samples with maleic anhydride (MAH) or diethyl maleate (DEM) as enophiles is described. The analysis of the products by means of different techniques assesses the addition of the polar molecules to the reactive vinylidene units of the polymer with functional degrees (FD) depending on the type of enophile and polymer reactivity. The role of the reaction conditions and the use as Lewis acids as catalysts are discussed in terms of their influence on the addition reaction extent and on the polymer molecular weight.     

Reactively Modified Poly(lactic acid): Properties and Foam Processing

Summary: In order to produce modified poly(lactic acid) (PLA) resins for applications requiring high melt viscosity and elasticity (e.g., low‐density foaming, thermoforming), a commercial PLA product has been reactively modified in melt by sequentially adding 1,4‐butanediol and 1,4‐butane diisocyanate as low‐molecular‐weight chain extenders. By varying amounts of the two chain extenders associated to the end group contents of PLA, three resulted samples were obtained. They were then structurally characterized by FTIR spectroscopy and molecular structure analysis. Their thermal, dynamic mechanical thermal properties and melt viscoelastic properties were investigated and compared along with unmodified PLA. The results indicated that chemical modification may be characterized as chain scission, extension, crosslinking, or any combination of the three depending on the chain extender amounts. The increase of PLA molecular weight could be obtained by properly controlling amounts of two chain extenders. The samples with increased molecular weights showed enhanced melt viscosity and elasticity. Such property improvements promised a successful application for modified PLA in a batch foam processing by producing foams with reduced cell size, increased cell density and lowered bulk foam density in comparison with plain PLA foam.

Cellular morphology of a modified PLA foam.     

Application of the dry‐spinning method to produce poly(ε‐caprolactone) fibers containing bovine serum albumin laden gelatin nanoparticles

We designed and manufactured a polymeric system with combined hydrophilic–hydrophobic properties by loading gelatin nanoparticles (GNPs) containing bovine serum albumin (BSA) into poly(ε‐caprolactone) (PCL) fibers. Our ultimate goal was to create a device capable of carrying and releasing protein drugs. Such a system could find several biomedical applications, such as those in controlled release systems, surgical sutures, and bioactive scaffolds for tissue engineering. A two‐step desolvation method was used to produce GNPs, whereas PCL fibers were produced by a dry‐spinning method. The morphological, mechanical, and thermal properties of the produced system were investigated, and the distribution of nanoparticles both inside and on the surface of the fibers was examined. The effect of the particles on the biodegradability of the fibers was also evaluated. In vitro preliminary tests were performed to study the release of BSA from nanoparticle‐laden fibers and to compare this with its release from free nanoparticles. Our results indicate that the distribution of particles inside the fibers was quite homogeneous and only a few of them were present on the surface. The presence of the particles in the fibers did not affect the thermal properties of the PCL polymer matrix, although it created voids that affected the degradation characteristics so the PCL fibers favored faster erosion compared to the plain fibers. Preliminary results indicate that the release from GNP‐laden fibers occurred much more slowly compared to that in the free GNPs. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 44233.     

Application of the Shvo catalyst in homogeneous hydrogenation of bio-oil obtained from pyrolysis of white poplar: New mild upgrading conditions

Upgrading of bio-oils obtained from the fast pyrolysis of biomasses requires the development of efficient catalysts able to work under mild conditions and to cope with the complex chemical nature of the reactant. The present work focuses on the use of the ruthenium based Shvo homogeneous catalyst for the hydrogenation of model mixtures (vanillin, cinnamaldehyde, methylacetophenone, glycolaldehyde, acetol, acetic acid) and of a real bio-oil. The hydrogenation of model compounds has been investigated both in mono- and biphasic mixtures under a P(H₂) = 10 atm in the temperature range of 90-145 °C varying the substrate to catalyst molar ratio from 2000:1 to 200:1. Employing the most active reaction conditions (substrate/catalyst 200:1, T = 145 °C, P(H₂) = 10 atm) the Shvo catalyst maintains its performances under acidic “bio-oil conditions” leading to the almost quantitative conversion of the polar double bonds within 1 h. The activity of the Shvo catalyst was also investigated for the hydrogenation of a bio-oil from poplar in solvent free conditions. Hydrogenation deeply changed the chemical nature of the pyrolysis oil. Aldehydes, ketones and non-aromatic double bonds were almost totally hydrogenated. The catalytic system also promoted the hydrolysis of sugar oligomers into monomers.     

Hybrid MCM-41 grafted by a general microwave-assisted procedure: a characterization study

Hybrid materials obtained through a Microwave-assisted grafting of organic functional groups on mesoporous silica (MCM-41 type) have been characterized by X-ray powder diffraction, TG-DSC, N₂ adsorption, solid state ¹³C- and ²⁹Si-NMR, TEM and SEM. The studied grafting procedure is effective in the preparation of hybrid organosilicas under solvent-free conditions. Microwaves allows an ultra-fast and clean functionalization of the mesoporous materials and the method has been applied to produce a wide series of functional materials. The hybrid materials maintain the original mesoporous structure when the loading of linked organic groups does not exceed 10 %. In this cases, the slight pore volume reduction is linearly correlated to the organic amount in the product. If functional groups able to interact among them through hydrogen bond are used, hybrid materials exhibit high Organic/SiO₂ ratios and low pore volumes due to the formation of a network occluding the pores, where functional groups of free organosilane molecules interacts with the functional groups of molecules linked to the matrix. NMR data confirm that the network is composed by organosilane molecules linked or not to the framework. Acid washing is able to labilize hydrogen bond and open the network. In the case of bulky but chemically inert functionalising agents the network is not produced.     

Unpatterned Bioactive Poly(Butylene 1,4-Cyclohexanedicarboxylate)-Based Film Fast Induced Neuronal-Like Differentiation of Human Bone Marrow-Mesenchymal Stem Cells

Herein, we present poly(butylene 1,4-cyclohexanedicarboxylate) (PBCE) films characterized by an unpatterned microstructure and a specific hydrophobicity, capable of boosting a drastic cytoskeleton architecture remodeling, culminating with the neuronal-like differentiation of human bone marrow-mesenchymal stem cells (hBM-MSCs). We have used two different filming procedures to prepare the films, solvent casting (PBCE) and compression-moulding (PBCE*). PBCE film had a rough and porous surface with spherulite-like aggregations (Ø = 10–20 μm) and was characterized by a water contact angle = 100°. PBCE* showed a smooth and continuous surface without voids and visible spherulite-like aggregations and was more hydrophobic (WCA = 110°). Both surface characteristics were modulated through the copolymerization of different amounts of ether-oxygen-containing co-units into PBCE chemical structure. We showed that only the surface characteristics of PBCE-solvent-casted films steered hBM-MSCs toward a neuronal-like differentiation. hBM-MSCs lost their canonical mesenchymal morphology, acquired a neuronal polarized shape with a long cell protrusion (≥150 μm), expressed neuron-specific class III β-tubulin and microtubule-associated protein 2 neuronal markers, while nestin, a marker of uncommitted stem cells, was drastically silenced. These events were observed as early as 2-days after cell seeding. Of note, the phenomenon was totally absent on PBCE* film, as hBM-MSCs maintained the mesenchymal shape and behavior and did not express neuronal/glial markers.     

BET-Inhibitor I-BET762 and PARP-Inhibitor Talazoparib Synergy in Small Cell Lung Cancer Cells

Small cell lung cancer (SCLC) is an aggressive type of lung cancer with high mortality that is caused by frequent relapses and acquired resistance. Despite that several target-based approaches with potential therapeutic impact on SCLC have been identified, numerous targeted drugs have not been successful in providing improvements in cancer patients when used as single agents. A combination of targeted therapies could be a strategy to induce maximum lethal effects on cancer cells. As a starting point in the development of new drug combination strategies for the treatment of SCLC, we performed a mid-throughput screening assay by treating a panel of SCLC cell lines with BETi or AKi in combination with PARPi or EZH2i. We observed drug synergy between I-BET762 and Talazoparib, BETi and PARPi, respectively, in SCLC cells. Combinatorial efficacy was observed in MYCs-amplified and MYCs-wt SCLC cells over SCLC cells with impaired MYC signaling pathway or non-tumor cells. We indicate that drug synergy between I-BET762 and Talazoparib is associated with the attenuation HR-DSBR process and the downregulation of various players of DNA damage response by BET inhibition, such as CHEK2, PTEN, NBN, and FANCC. Our results provide a rationale for the development of new combinatorial strategies for the treatment of SCLC.     

Evaluation of Antioxidant,Antidiabetic and Anticholinesterase Activities of Smallanthus sonchifolius Landraces and Correlation with Their Phytochemical Profiles

The present study aimed to investigate the phytochemical profile of leaf methanol extracts of fourteen Smallanthus sonchifolius (yacon) landraces and their antioxidant, anticholinesterase and antidiabetic activities that could lead to the finding of more effective agents for the treatment and management of Alzheimer’s disease and diabetes. For this purpose, antioxidant activity was assessed using different tests: ferric reducing ability power (FRAP), 2,2-diphenyl-1-picryl hydrazyl (DPPH), nitric oxide (˙NO) and superoxide (O₂˙⁻) scavenging and lipid peroxidation inhibition assays. Anticholinesterase activity was investigated by quantifying the acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities, whereas antidiabetic activity was investigated by α-amylase and α-glucosidase inhibition tests. To understand the contribution of metabolites, phytochemical screening was also performed by high performance liquid chromatography-diode array detector (HPLC-DAD) system. Among all, methanol extract of PER09, PER04 and ECU44 landraces exhibited the highest relative antioxidant capacity index (RACI). ECU44 was found to be rich in 4,5-di-O-caffeoylquinic acid (CQA) and 3,5-di-O-CQA and displayed a good α-amylase and α-glucosidase inhibition, showing the lowest IC₅₀ values. Flavonoids, instead, seem to be involved in the AChE and BChE inhibition. The results of this study revealed that the bioactive compound content differences could be determinant for the medicinal properties of this plant especially for antioxidant and antidiabetic activities.