Impact on thermomechanical behaviour of a maleic anhydride grafted ABS on ABS/PC multi-layered blends

The significant increase of Waste Electric and Electronic Equipment (WEEE) has led to an important research in upgrading recycled engineering plastics by means of a blending technique. In particular, there is an interest in studying the properties of ABS/PC blends, the two most important components of WEEE, at ABS rich compositions, according to the generation ratio of waste [1]. Since ABS and PC are immiscible, the final properties depend to a large extent on the flow-induced morphology [2]. In order to better control the final blend morphology of injection molded samples, we propose a two-step approach: the first step consists in producing pellets with multilayered structure, using a multilayer coextrusion device. During the second subsequent step, the pellets are injection molded, with temperature conditions chosen to minimize the deformation of the created structures. The effect of a compatibilizer, namely, an ABS grafted with maleic anhydride (ABS-g-MA) [3] on the thermomechanical properties and morphology has been investigated

Chemoenzymatically synthesized ganglioside GM3 analogues with inhibitory effects on tumor cell growth and migration

Ganglioside GM3, belonging to glycosphingolipid family, has been known as tumor-associated carbohydrate antigen on several types of tumor. Many studies have revealed that GM3 plays a role in cell proliferation, adhesion and differentiation, which is crucial in the process of cancer development. In the present study, we firstly synthesized novel mannose-containing GM3 analogues by enzymatic hydrolysis and chemical procedures. Then the antiproliferative activity of the novel analogues along with galactose-containing analogues we prepared previously was investigated and the data demonstrated that these analogues exhibited antiproliferative effect on K562 and HCT116 cells. Finally, the influence of these analogues on tumor cell migration was studied on B16, B16-F10 and HCCLM3 cells by wound healing test, because the migration of tumor cells represents one of the relevant factors in assessing the malignancy of cancer. This study could lay the foundation for optimizing leading compounds and provide valuable information for finding new antitumor drugs for cancer therapy

From 1,4-Disaccharide to 1,3-Glycosyl Carbasugar : Synthesis of a Bespoke Inhibitor of Family GH99 Endo-α-mannosidase

Understanding the enzyme reaction mechanism can lead to the design of enzyme inhibitors. A Claisen rearrangement was used to allow conversion of an α-1,4-disaccharide into an α-1,3-linked glycosyl carbasugar to target the endo-α-mannosidase from the GH99 glycosidase family, which, unusually, is believed to act through a 1,2-anhydrosugar "epoxide" intermediate. Using NMR and X-ray crystallography, it is shown that glucosyl carbasugar α-aziridines can act as reasonably potent endo-α-mannosidase inhibitors, likely by virtue of their shape mimicry and the interactions of the aziridine nitrogen with the conserved catalytic acid/base of the enzyme active site

Crystallization behavior and morphological features of ethylene-vinyl alcohol 44 copolymer

This work is a first attempt to study the crystallization behavior of ethylene-vinyl alcohol copolymer with 44 mol% of ethylene units (EVOH44) and to observe the supermolecular structures developed during its crystallization. Thermal analysis has evidenced a very fast crystallization and the formation of different crystal populations during isothermal crys-tallization. In-situ wide-angle X-ray scattering experiments using a synchrotron radiation source have shown a unique or-thorhombic morphology, independently of the crystallization conditions. Small spherulites (with an average radius of about 1 µm) were observed using polarized optical microscopy and confirmed by typical four-leaf patterns obtained by small-angle light scattering. In-situ atomic force microscopy has revealed stacked lamellae growing from common centers to form small spherulitic entities. Finally, studies of isothermal crystallization have evidenced the existence of partial crystallization (especially at high crystallization temperatures) and the need for higher undercooling to complete crystallization. © BME-PT

An alternative radiolytic route for synthesizing conducting polymers in an organic solvent

A new and simple promising method for synthesizing conducting polymers in organic solvents was successfully achieved for the first time thanks to the oxidative polymerization of 3,4-ethylenedioxythiophene (EDOT) monomers dissolved in dichloromethane by means of gamma-radiolysis. The EDOT polymerization was controlled and optimized thanks to the study of the dose effect under an inert atmosphere. UV-Vis absorption spectroscopy was used to follow the polymerization process and to estimate both the radiolytic yield of EDOT oxidation and the required irradiation dose for quantitative poly(3,4-ethylenedioxythiophene) (PEDOT) preparation. Size exclusion chromatography (SEC) was used to determine the molar mass of the PEDOT polymers and thus their degree of polymerization. Polymers containing up to 20 EDOT units were detected. After deposition, ATR-FTIR spectroscopy and Energy-Dispersive X-ray (EDX) analysis highlighted the in situ doping of PEDOT polymers with chloride ions generated during dichloromethane radiolysis, while XRD analysis demonstrated the amorphous structure of the polymers. The morphology of the radiosynthesized PEDOT polymers was characterized in solution by Cryo-TEM microscopy and after deposition by SEM microscopy as well as by high-resolution AFM-IR microscopy coupled with infrared nanospectroscopy. In all cases, aggregated and packed spheroidal PEDOT particles with diameters comprising between 100 nm and 1.5 μm were observed. Besides, cyclic voltammetry (CV), four-point probe measurements and thermogravimetric analysis (TGA) showed that the PEDOT polymers radiosynthesized in dichloromethane are characterized by interesting electrical properties and good thermal stability. The present study bears witness to the tremendous potential of our radiation-based methodology and gives us a glimpse of future promising syntheses of different kinds of conducting polymers in organic solvents and even in complex matrices

Contribution of shape and charge to the inhibition of a family GH99 endo-α-1,2-mannanase

[Image: see text] Inhibitor design incorporating features of the reaction coordinate and transition-state structure has emerged as a powerful approach for the development of enzyme inhibitors. Such inhibitors find use as mechanistic probes, chemical biology tools, and therapeutics. Endo-α-1,2-mannosidases and endo-α-1,2-mannanases, members of glycoside hydrolase family 99 (GH99), are interesting targets for inhibitor development as they play key roles in N-glycan maturation and microbiotal yeast mannan degradation, respectively. These enzymes are proposed to act via a 1,2-anhydrosugar “epoxide” mechanism that proceeds through an unusual conformational itinerary. Here, we explore how shape and charge contribute to binding of diverse inhibitors of these enzymes. We report the synthesis of neutral dideoxy, glucal and cyclohexenyl disaccharide inhibitors, their binding to GH99 endo-α-1,2-mannanases, and their structural analysis by X-ray crystallography. Quantum mechanical calculations of the free energy landscapes reveal how the neutral inhibitors provide shape but not charge mimicry of the proposed intermediate and transition state structures. Building upon the knowledge of shape and charge contributions to inhibition of family GH99 enzymes, we design and synthesize α-Man-1,3-noeuromycin, which is revealed to be the most potent inhibitor (K(D) 13 nM for Bacteroides xylanisolvens GH99 enzyme) of these enzymes yet reported. This work reveals how shape and charge mimicry of transition state features can enable the rational design of potent inhibitors

Molecular Basis for Inhibition of GH84 Glycoside Hydrolases by Substituted Azepanes: Conformational Flexibility Enables Probing of Substrate Distortion

Here we report the synthesis of a series of polyhydroxylated 3- and 5-acetamido azepanes and detail the molecular basis of their inhibition of family 84 glycoside hydrolases. These family 84 enzymes include human O-GlcNAcase, an enzyme involved in post-translational processing of intracellular proteins modified by O-linked β-N-acetylglucosamine residues. Detailed structural analysis of the binding of these azepanes to BtGH84, a bacterial homologue of O-GlcNAcase, highlights their conformational flexibility. Molecular mechanics and molecular dynamics calculations reveal that binding to the enzyme involves significant conformational distortion of these inhibitors from their preferred solution conformations. The binding of these azepanes provides structural insight into substrate distortion that likely occurs along the reaction coordinate followed by O-GlcNAcase during glycoside hydrolysis. This class of inhibitors may prove to be useful probes for evaluating the conformational itineraries of glycosidases and aid the development of more potent and specific glycosidase inhibitors

An epoxide intermediate in glycosidase catalysis

Retaining glycoside hydrolases cleave their substrates through stereochemical retention at the anomeric position. Typically, this involves two-step mechanisms using either an enzymatic nucleophile via a covalent glycosyl enzyme intermediate or neighboring-group participation by a substrate-borne 2-acetamido neighboring group via an oxazoline intermediate; no enzymatic mechanism with participation of the sugar 2-hydroxyl has been reported. Here, we detail structural, computational, and kinetic evidence for neighboring-group participation by a mannose 2-hydroxyl in glycoside hydrolase family 99 endo-α-1,2-mannanases. We present a series of crystallographic snapshots of key species along the reaction coordinate: a Michaelis complex with a tetrasaccharide substrate; complexes with intermediate mimics, a sugar-shaped cyclitol β-1,2-aziridine and β-1,2-epoxide; and a product complex. The 1,2-epoxide intermediate mimic displayed hydrolytic and transfer reactivity analogous to that expected for the 1,2-anhydro sugar intermediate supporting its catalytic equivalence. Quantum mechanics/molecular mechanics modeling of the reaction coordinate predicted a reaction pathway through a 1,2-anhydro sugar via a transition state in an unusual flattened, envelope (E 3) conformation. Kinetic isotope effects (k cat/K M) for anomeric-2H and anomeric-13C support an oxocarbenium ion-like transition state, and that for C2-18O (1.052 ± 0.006) directly implicates nucleophilic participation by the C2-hydroxyl. Collectively, these data substantiate this unprecedented and long-imagined enzymatic mechanism

Synthèse de cyclodextrines multidifférenciées et mise en évidence de la chiralité de plateforme par la catalyse

Nous avons utilisé la méthode de déprotection sélective des éthers benzyliques au DIBAl-H pour synthétiser de nouvelles cyclodextrines possédant plusieurs groupements protecteurs différents sur leur couronne primaire, et notamment des motifs tétradifférenciés inaccessibles jusqu à présent. Ces molécules ont servi à la synthèse d alpha- et béta-cyclodextrines amino-acides hydrosolubles, ainsi qu à l élaboration de chromophores contraints. Nous avons ensuite étudié la relation entre deux motifs régioisomères présentant des plateformes énantiomères l une de l autre. Pour cela, nous avons synthétisé des ligands diphosphine à partir de ces motifs régioisomères, et les avons engagés en catalyse asymétrique. Les résultats ont permis de valider le concept de plateforme chirale, et d élucider la relation de pseudo-énantiomérie entre les deux motifs. Enfin, nous avons synthétisé un ligand alpha-cyclodextrine-tétraphosphine qui a été engagé dans des tests catalytiques préliminaires.PARIS-BIUSJ-Thèses (751052125) / SudocPARIS-BIUSJ-Physique recherche (751052113) / SudocSudocFranceF

Fonctionnalisation des cols primaire et secondaire de l alpha-cyclodextrine et études de complexes NHC-cyclodextrines-métaux

Deux aspects de la chimie des cyclodextrines (CDs) sont abordés dans cette thèse. D une part deux nouvelles méthodes de fonctionnalisation ont été développées. Tout d abord l utilisation d iode et de triethylsilane a permis de déprotéger les alcools en position 3 de CDs polybenzylées. Ensuite, en se basant sur l action du DIBAL-H précédemment découverte au laboratoire et en empêchant la réactivité connue en AD, un nouveau motif de triol ACE inédit a été obtenu. Une étude cinétique a été conduite afin d éclairer le mécanisme de la réaction montrant la formation intermédiaire de deux diols convergent vers le triol. Enfin cette stratégie a pu être combinée à la réaction tandem de débenzylation/réduction d azoture pour fournir CDs des amino-diols déoxy. D autre part, des complexes hybrides CD-NHC-métaux (NHC= N-Heterocyclic Carbene ) ont été synthétisés. L introduction de deux NHCs en AD sur le col primaire de l a-CD a permis de préparer les complexes de PdII correspondant sur des CDs perbenzylées et perméthylées et ces complexes ont été utilisés en couplage croisé de Suzuki dans l ethanol et dans l eau. Par ailleurs, à partir d une CD ponté en AD par un unique NHC, les complexes AgI, CuI et AuI ont été obtenus. Une étude structurale a mis en évidence la position intra-cavitaire du métal, induisant des interactions C-H M, C-H X et p X originales et celles-ci ont été confirmées par des études d échange de ligand. Enfin, le complexe d or s est montré efficace en réaction de cycloisomérisation d ényne permettant même d induire de l énantiosélectivitéTwo aspects of the cyclodextrins (CDs) chemistry were studied. On one hand two new methods of functionalization were developed. First using iodine and triethylsilane the 3 position of polybenzylated CDs could be selectively deprotected. Second, based on the known DIBAL-H reactivity in the lab and preventing the AD reactivity, an unprecedented ACE triol was obtained. A kinetic study enlightened the mechanism, showing the existence of two intermediate diols converging to the triol. Furthermore, this strategy was combined to the known tandem debenzylation/azido reduction to afford deoxy amino-diols CDs. On the other hand, CD-NHC-Metals (NHC=N-Heterocyclic Carbene) hybrid complexes were synthesized. Two NHCs were introduced on A and D positions of the primary rim of perbenzylated and permethylated a-CDs and the corresponding PdII complexes prepared. These complexes were used in Suzuki cross-coupling. Then, after capping the CD in AD with a NHC, the AgI, CuI and AuI complexes were obtainded. A structural study evidenced the position of the metal inside the cavity, inducing original C-H M, C-H X et p X interactions, confirmed by ligand exchange experiments. Finally, the gold complex show good activity in cycloisomerisation, even affording enantioselectivityPARIS-BIUSJ-Biologie recherche (751052107) / SudocSudocFranceF