New approach in the synthesis of M6G

Morphine-6-glucuronide (M6G) is the primarily active metabolite of morphine, produced endogenously by the UGT enzyme, which displays analgesic activity. For this reason, M6G is a promising drug candidate for the treatment of severe pain. We described herein a new, efficient and scalable synthesis of M6G using dimorphinic derivatives. This preparation of M6G could be performed on multigram scale with good yield and high purity.     

Freeze-fracture TEM imaging of robust order in swollen phases of amphiphilic diblock copolymers

We report on the structures exhibited by two different diblock poly(styrene)-b-poly(acrylic acid) (PS-b-PAA) copolymers in water, a selective solvent. Using a combination of X-ray scattering and freeze fracture-transmission electron microscopy (FF-TEM), we show that these structures can be widely swollen while retaining their initial morphology and a high degree of long-range order. The analysis of the FF-TEM pictures also evidences the presence of water crystallites of regular size and shape within the confined water domains. We relate the growth of these crystallites to the high local ionic strength of the water swelling the PAA brushes. Moreover, the confinement of the crystallites growth shows that the swollen phases have a very robust structure, potentially useful for confining colloidal particles.     

Anionic surfactants and surfactant ionic liquids with quaternary ammonium counterions

Small-angle neutron scattering and surface tension have been used to characterize a class of surfactants (SURFs), including surfactant ionic liquids (SAILs). These SURFs and SAILs are based on organic surfactant anions (single-tail dodecyl sulfate, DS, double-chain aerosol-OT, AOT, and the trichain, TC) with substituted quaternary ammonium cations. This class of surfactants can be obtained by straightforward chemistry, being cheaper and more environmentally benign than standard cationic SAILs. A surprising aspect of the results is that, broadly speaking, the physicochemical properties of these SURFs and SAILs are dominated by the nature of the surfactant anion and that the chemical structure of the added cation plays only a secondary role.     

Aqueous suspensions of natural swelling clay minerals. 2. Rheological characterization

We report in this article a comprehensive investigation of the viscoelastic behavior of different natural colloidal clay minerals in aqueous solution. Rheological experiments were carried out under both dynamic and steady-state conditions, allowing us to derive the elasticity and yield stress. Both parameters can be renormalized for all sizes, ionic strength, and type of clay using in a first approach only the volume of the particles. However, applying such a treatment to various clays of similar shapes and sizes yields differences that can be linked to the repulsion strength and charge location in the swelling clays. The stronger the repulsive interactions, the better the orientation of clay particles in flows. In addition, a master linear relationship between the elasticity and yield stress whose value corresponds to a critical deformation of 0.1 was evidenced. Such a relationship may be general for any colloidal suspension of anisometric particles as revealed by the analysis of various experimental data obtained on either disk-shaped or lath- and rod-shaped particles. The particle size dependence of the sol-gel transition was also investigated in detail. To understand why suspensions of larger particles gel at a higher volume fraction, we propose a very simplified view based on the statistical hydrodynamic trapping of a particle by an another one in its neighborhood upon translation and during a short period of time. We show that the key parameter describing this hydrodynamic trapping varies as the cube of the average diameter and captures most features of the sol-gel transition. Finally, we pointed out that in the high shear limit the suspension viscosity is still closely related to electrostatic interactions and follows the same trends as the viscoelastic properties.     

Photoreactive surfactants: a facile and clean route to oxide and metal nanoparticles in reverse micelles

A new class of photoreactive surfactants (PRSs) is presented here, consisting of amphiphiles that can also act as reagents in photochemical reactions. An example PRS is cobalt 2-ethylhexanoate (Co(EH)(2)), which forms reverse micelles (RMs) in a hydrocarbon solvent, as well as mixed reversed micelles with the standard surfactant Aerosol-OT (AOT). Small-angle neutron scattering (SANS) data show that mixed AOT/PRS RMs have a spherical structure and size similar to that of pure AOT micelles. Excitation of the ligand-to-metal charge transfer (LMCT) band in the PRSs promotes electron transfer from PRS to associated metal counterions, leading to the generation of metal and metal-oxide nanoparticles inside the RMs. This work presents proof of concept for employing PRSs as precursors to obtain nearly monodisperse inorganic nanoparticles: here both Co(3)O(4) and Bi nanoparticles have been synthesized at high metal concentration (10(-2) M) by simply irradiating the RMs. These results point toward a new approach of photoreactive self-assembly, which represents a clean and straightforward route to the generation of nanomaterials.     

DNA photo-oxidative damage hazard in transfection complexes

Complexes of DNA with various cationic vectors have been largely used for nonviral transfection, and yet the photochemical stability of DNA in such complexes has never been considered. We studied, for the first time, the influence of DNA complexation by a cationic lipid and polymers on the amount of damage induced by benzophenone photosensitization. The localization of benzophenone inside the hydrophobic domains formed by a cationic lipid, DOTAP (N-[1-(2,3-dioleoyloxy)propyl]-N,N,N-trimethylammonium chloride), and close to DNA, locally increases the photoinduced cleavage by the reactive oxygen species generated. The same effect was found in the case of DNA complexation with an amphiphilic polymer (polynorbornenemethyleneammonium chloride). However, a decrease in DNA damage was observed in the case of complexation with a hydrophilic polymer (polyethylenimine). The DNA protection in this case was because of the absence of benzophenone hydrophobic incorporation into the complex, and to DNA compaction which decreased the probability of radical attack. These results underline the importance of the chemical structure of the nonviral transfection vector in limiting the risks of photo-oxidative damage of the complexed DNA.     

Selectivity among two lectins: probing the effect of topology, multivalency and flexibility of "clicked" multivalent glycoclusters

The design of multivalent glycoconjugates has been developed over the past decades to obtain high-affinity ligands for lectin receptors. While multivalency frequently increases the affinity of a ligand for its lectin through the so-called "glycoside cluster effect", the binding profiles towards different lectins have been much less investigated. We have designed a series of multivalent galactosylated glycoconjugates and studied their binding properties towards two lectins, from plant and bacterial origins, to determine their potential selectivity. The synthesis was achieved through copper(I)-catalysed azide-alkyne cycloaddition (CuAAC) under microwave activation between propargylated multivalent scaffolds and an azido-functionalised carbohydrate derivative. The interactions of two galactose-binding lectins from Pseudomonas aeruginosa (PA-IL) and Erythrina cristagalli (ECA) with the synthesized glycoclusters were studied by hemagglutination inhibition assays (HIA), surface plasmon resonance (SPR) and isothermal titration microcalorimetry (ITC). The results obtained illustrate the influence of the scaffold's geometry on the affinity towards the lectin and also on the relative potency in comparison with a monovalent galactoside reference probe.     

Poly(ester urethane) guides for peripheral nerve regeneration

A biocompatible and elastomeric PU was synthesized from low-molecular-weight PCL as macrodiol, CMD as chain extender and HDI as chain linker for applications in the field of peripheral nerve repair. PU cast films supported in vitro attachment and proliferation of NOBEC. The in vitro adhesion and proliferation of S5Y5 neuroblastoma cells on the inner surface of uncoated, gelatin- and PL-coated PU guides were compared. Due to their superior in vitro performance, PL-coated PU guides were tested in vivo for the repair of 1.8 cm-long defects in rat sciatic nerves. The progressive regeneration was confirmed by EMG and histological analysis showing the presence of regenerating fibers in the distal stumps.     

Liquid–liquid extraction of actinides,lanthanides, and fission products by use of ionic liquids: from discovery to understanding

Liquid–liquid extraction of actinides and lanthanides by use of ionic liquids is reviewed, considering, first, phenomenological aspects, then looking more deeply at the various mechanisms. Future trends in this developing field are presented.     

Multivariate analyses for biomarkers hunting and validation through on-tissue bottom-up or in-source decay in MALDI-MSI: application to prostate cancer

The large amount of data generated using matrix-assisted laser desorption/ionization mass spectrometric imaging (MALDI-MSI) poses a challenge for data analysis. In fact, generally about 1.10⁸–1.10⁹ values (m/z, I) are stored after a single MALDI-MSI experiment. This imposes processing techniques using dedicated informatics tools to be used since manual data interpretation is excluded. This work proposes and summarizes an approach that utilizes a multivariable analysis of MSI data. The multivariate analysis, such as principal component analysis–symbolic discriminant analysis, can remove and highlight specific m/z from the spectra in a specific region of interest. This approach facilitates data processing and provides better reproducibility, and thus, broadband acquisition for MALDI-MSI should be considered an effective tool to highlight biomarkers of interest. Additionally, we demonstrate the importance of the hierarchical classification of biomarkers by analyzing studies of clusters obtained either from digested or undigested tissues and using bottom-up and in-source decay strategies for in-tissue protein identification. This provides the possibility for the rapid identification of specific markers from different histological samples and their direct localization in tissues. We present an example from a prostate cancer study using formalin-fixed paraffin-embedded tissue.