Ion exchange chromatographic separation and isolation of oligosaccharides of intact low-molecular-weight heparin for the determination of their anticoagulant and anti-inflammatory properties

It is well known that enoxaparin, a widely used anticoagulant and low-molecular-weight heparin containing a large number of oligosaccharides, possesses anti-inflammatory activity. Whilst enoxaparin has shown promising results in various inflammatory disorders, some of its oligosaccharides have anti-inflammatory properties and others increase the risk of bleeding due to their anticoagulant effects. The aim of this study was to develop an effective ion exchange chromatographic (IC) technique which allows the separation, isolation and, consequently, the identification of different oligosaccharides of enoxaparin with or without anticoagulant activity. The developed method utilises a semi-preparative CarboPac PA100 (9?×?250 mm) ion exchange column with sodium chloride gradient elution and UV detection at 232 nm. The method successfully resolved enoxaparin into more than 30 different peaks. IC-derived oligosaccharides with high, moderate, low or no anticoagulant activity were identified using an anti-factor Xa assay. The anti-inflammatory activity of selected oligosaccharides was investigated using the Griess assay. Using this technique, the oligosaccharides of enoxaparin with low or no anticoagulant activity, whilst exhibiting significant anti-inflammatory activity, could be fractionated. This technique can provide a platform to identify the oligosaccharides which are devoid of significant anticoagulant activity and are responsible for the therapeutic effects of enoxaparin that have been observed in various inflammatory conditions.

Improved total synthesis of the potent HDAC inhibitor FK228 (FR-901228)

A scaleable synthesis of the potent histone deacetylase (HDAC) inhibitor FK228 is described. A reliable strategy for preparing the key beta-hydroxy mercapto heptenoic acid partner was accomplished in nine steps and 13% overall yield. A Noyori asymmetric hydrogen-transfer reaction established the hydroxyl stereochemistry in >99:1 er via the reduction of a propargylic ketone.     

Probing the Structure and Chemistry of Perylenetetracarboxylic Dianhydride on Graphene Before and After Atomic Layer Deposition of Alumina

The superlative electronic properties of graphene suggest its use as the foundation of next generation integrated circuits. However, this application requires precise control of the interface between graphene and other materials, especially the metal oxides that are commonly used as gate dielectrics. Towards that end, organic seeding layers have been empirically shown to seed ultrathin dielectric growth on graphene via atomic layer deposition (ALD), although the underlying chemical mechanisms and structural details of the molecule/dielectric interface remain unknown. Here, confocal resonance Raman spectroscopy is employed to quantify the structure and chemistry of monolayers of 3,4,9,10-perylenetetracarboxylic dianhydride (PTCDA) on graphene before and after deposition of alumina with the ALD precursors trimethyl aluminum (TMA) and water. Photoluminescence measurements provide further insight into the details of the growth mechanism, including the transition between layer-by-layer growth and island formation. Overall, these results reveal that PTCDA is not consumed during ALD, thereby preserving a well-defined and passivating organic interface between graphene and deposited dielectric thin films.     

Dielectric properties and AC conductivity studies of novel NR/PVA full-interpenetrating polymer networks

Fully interpenetrating polymer networks (IPN) based on natural rubber (NR) and polyvinyl alcohol (PVA) were prepared by using Glutaraldehyde as the common crosslinking agent. Crosslinking reactions were confirmed by Fourier Transform Infra-red Spectroscopy. The electrical properties of full-IPN have been studied in the frequency range of 10²–10⁶ Hz. The dielectric constant, dielectric loss and ac conductivity were analyzed as a function of frequency, temperature and blend composition. It was found that the dielectric constant and dielectric loss increased with the addition of PVA into NR. Interpenetrated system showed a significant reduction in dielectric constant and dielectric loss and almost frequency independent. The dielectric constant and dielectric loss were increased with increase in temperature. The change in these parameters with temperature in the IPN system was found too low as compared to the pure blends. The ac conductivity study revealed that the IPN materials exhibited a considerable reduction in conductivity.     

Distribution of surfactants in latex films: a Rutherford Backscattering study

Uneven distribution of surfactant in dried latex films can affect the final film properties such as its water-resistance, gloss, and adhesiveness. Therefore, it is important to understand the driving force for surfactant transport during drying. In this paper, the accumulation of surfactant on the surface of poly(styrene-co-butyl acrylate) latex is studied using Rutherford Backscattering (RBS) and compared with results from a model that is based on the diffusive transport of particles and surfactant. Experimentally, a 30-50 nm thick surface layer, rich in surfactant, is seen and the concentration in the bulk of the film, obtained from RBS, agrees, at least qualitatively, with the model predictions for two of the surfactants tested.     

The Role of Cytochrome P450 AbyV in the Final Stages of Abyssomicin C Biosynthesis

Abyssomicin C and its atropisomer are potent inhibitors of bacterial folate metabolism. They possess complex polycyclic structures, and their biosynthesis has been shown to involve several unusual enzymatic transformations. Using a combination of synthesis and in vitro assays we reveal that AbyV, a cytochrome P450 enzyme from the aby gene cluster, catalyses a key late-stage epoxidation required for the installation of the characteristic ether-bridged core of abyssomicin C. The X-ray crystal structure of AbyV has been determined, which in combination with molecular dynamics simulations provides a structural framework for our functional data. This work demonstrates the power of combining selective carbon-13 labelling with NMR spectroscopy as a sensitive tool to interrogate enzyme-catalysed reactions in vitro with no need for purification.