Monofluoroalkene-Isostere as a 19F NMR Label for the Peptide Backbone: Synthesis and Evaluation in Membrane-Bound PGLa and (KIGAKI)3

Solid-state ¹⁹F NMR is a powerful method to study the interactions of biologically active peptides with membranes. So far, in labelled peptides, the ¹⁹F-reporter group has always been installed on the side chain of an amino acid. Given the fact that monofluoroalkenes are non-hydrolyzable peptide bond mimics, we have synthesized a monofluoroalkene-based dipeptide isostere, Val-Ψ[(Z)-CF=CH]-Gly, and inserted it in the sequence of two well-studied antimicrobial peptides: PGLa and (KIGAKI)₃ are representatives of an α-helix and a β-sheet. The conformations and biological activities of these labeled peptides were studied to assess the suitability of monofluoroalkenes for ¹⁹F NMR structure analysis.     

Online large volume sample staking preconcentration and separation of enantiomeric GHRH analogs by capillary electrophoresis

A capillary electrophoresis method is proposed to analyze the four most well-known growth hormone–releasing hormone (GHRH) analogs that are misused by athletes. Dimethyl-β-cyclodextrin used as a chiral selector allowed, for the first time, the separation of those basic peptide analogs, including enantiopeptides (sermorelin and CJC-1293) that differ by the chirality of only one amino acid. To increase the method sensitivity, electrokinetic preconcentration methods have been investigated. The large volume sample stacking with polarity switching (PS-LVSS) method with an injected sample volume corresponding to 80% of the capillary one was found superior to the sweeping in terms of signal enhancement factor (SEF). Acid and organic solvent addition to the sample (0.1 mM phosphoric acid with 30% methanol) led to a twofold signal improvement, when compared to water as a matrix. We increased capillary dimensions to provide a signal enhancement through the injection of a larger sample volume. Finally, using a combination of the optimized PS-LVSS preconcentration with the chiral capillary zone electrophoresis (CZE), the GHRH analogs were separated and limits of detection between 75 and 200 ng/mL were reached. This method was successfully applied to urine after a desalting step. An optimized C18 SPE was used for that purpose in order to provide low sample conductivity (<130 µS/cm) and preserve the efficiency of LVSS preconcentration. SEF of 640 was obtained with desalted urine spiked with sermorelin by comparison to the CZE (without preconcentration) method.     

Capillary electrophoresis for rapid identification of monoclonal antibodies for routine application in hospital

mAbs are widely used in cancer therapy. Their compounding, performed just before their administration to patients, is executed in a production unit of the hospital. Identification of these drugs, individually prepared in bags for infusion before patient administration, is of paramount importance to detect potential mistakes during compounding stage. A fast and reliable analytical method based on CZE combined to a cationic capillary coating (hexadimethrine bromide) was developed for identification of the most widely used compounded therapeutic for cancer therapy (bevacizumab, cetuximab, rituximab, and trastuzumab). Considering the high structural and physico‐chemical similarities of these mAbs, an extensive optimization of the BGE composition has been performed. The addition of perchlorate ions and polysorbate in the BGE greatly increased the resolution. To validate the method, an internal standard was used and the relative migration times (RTm) were estimated. Very satisfactory RSDs of the RTm for rituximab (0.76%), cetuximab (0.46%), bevacizumab (0.31%), and trastuzumab (0.60%) were obtained. The intraday and interday RSD of the method were less than 0.32 and 1.3%, respectively for RTm. Significant differences between theses RTms have been demonstrated allowing mAbs identification. Finally, accurate mAbs identification has been demonstrated by a blind test.     

Evidence for the flexo-electric effect in a nematic liquid crystal cell

Abstract

We present evidence for the flexo-electric effect in a hybrid aligned nematic cell containing 4-methoxybenzylidene-4'-n-butylaniline (MBBA) subject to d.c. excitation, by comparing the theoretical curve derived by including the flexo-electric term in the free energy with the experimental points. The agreement appears to be very good for MBBA doped with a small amount of an additive which shows reversible electrochemical reactions at very low redox potential; this allows us to determine the sum of the flexo-electric coefficients and the anchoring energy on the planar wall. For undoped MBBA the experimental results can be justified only by assuming a low voltage screening of the electric field, due to the presence of ionic impurities in the material.     

Structural and morphological studies on the deformation behavior of polypropylene/multi‐walled carbon nanotubes nanocomposites prepared through ultrasound‐assisted melt extrusion process

Structural and morphological behavior under stress–strain of polypropylene/multi‐walled carbon nanotubes (PP/MWCNTs) nanocomposites prepared through ultrasound‐assisted melt extrusion process was studied by means of optical microscopy, scanning electron microscopy, transmission electron microscopy, Raman spectroscopy, small angle X‐ray scattering (SAXS), and wide angle X‐ray scattering (WAXS). A high ductile behavior was observed in the PP/MWCNT nanocomposites with low concentration of MWCNTs. This was related to an energy‐dissipating mechanism, achieved by the formation of an ordered PP‐CNTs interphase zone and crystal oriented structure in the undeformed samples. Different strain‐induced‐phase transformations were observed by ex situ SAXS/WAXS, characterizing the different stages of structure development during the deformation of PP and PP/MWCNTs nanocomposites. The high concentration of CNTs reduced the strain behavior of PP due to the agglomeration of nanoparticles. A structural pathway relating the deformation‐induced phase transitions and the dissipation energy mechanism in the PP/MWCNTs nanocomposites at low concentration of nanoparticles was proposed. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2015 , 53, 475–491     

Role of interfacial chemistry on the rheology and thermo-mechanical properties of clay-polymer nanocomposites for building applications

This study is directed towards investigating the role of the surface treatment of clay particles on the rheological and thermomechanical behaviour of clay-epoxy blends. Nanocomposites were prepared by mixing small amounts (5–10 mass %) of commercial organoclays or raw clays with an epoxy system commonly used in civil engineering. Rheological characterisations in the liquid state revealed a pronounced thixotropic character of the organoclay-based systems, which all exhibited a shear-thinning behaviour above a critical stress threshold (yield stress), depending on both the intensity of interfacial interactions and the degree of filler dispersion. On the other hand, systems based on raw clay particles behaved like Newtonian fluids, in the same way as the unreinforced polymer matrix. Complementary dynamic mechanical analyses (DMA) performed on the cured cross-linked nanocomposites also showed significant changes in the viscoelastic behaviour of the epoxy matrix due to the introduction of organoclays, whereas only minor variations were observed following the introduction of raw fillers. These results were consistent with nanoscale morphological characterisations performed by conventional X-ray diffraction (XRD) on the various hybrid systems. In this context, rheology and DMA appear as attractive alternative methods for assessing the filler dispersion at a macroscopic (and possibly more relevant) scale. This research is of practical interest for civil engineers, since clay reinforced-epoxies could in the future be used as coating materials with enhanced barrier performances, in order to protect infrastructures against environmental ageing or corrosion.