Inclusion complex of n-octyl beta-D-glucopyranoside and alpha-cyclodextrin in aqueous solutions: thermodynamic and structural characterization

Complex formation between octyl beta-D-glucopyranoside (OG) and alpha-cyclodextrin (alphaCD) was investigated on the basis of three highly accurate and appropriate experimental techniques. First, surface tension measurements showed that alphaCD directly acts on the surfactant monomers in the aqueous phase, leading to progressive depletion of the air-water interface with increasing cyclodextrin contents. Significant shift of OG critical micelle concentration (cmc) was consequently observed: the higher alphaCD concentration, the higher the cmc value. Experiments performed at surfactant and cyclodextrin concentrations in the Gibbs regime of surface tension versus OG content were performed on one hand to establish Job's plot that showed 1:1 stoichiometry of the OG-alphaCD complex and on the other hand to calculate the association constant found equal to (1.85 +/- 0.35) x 10(3) L mol(-1). An inclusion process of the surfactant alkyl residue within the cyclodextrin cavity was confirmed by one-dimensional (1)H NMR, and the structure of the mixed assembly was extensively characterized by two-dimensional NOESY (1)H NMR. OG penetrates alphaCD so that its hydrocarbon chain is embedded inside the cyclodextrin cavity, and its polar head as well as the alpha-methylene group emerges outside the alphaCD secondary face. Solubility behavior of the OG-alphaCD complex in a wide range of host-guest ratios and concentrations was finally examined by turbidity recording and optical microscopy. At very low free cyclodextrin levels in the solution, the complex presented high solubility behavior up to more than 70 mM. By increasing nonassociated alphaCD in the mixture, propensity of the cyclodextrin molecules to crystallize was observed at concentrations far below the 100 mM aqueous solubility of the pure cyclodextrin. The hexagonal shape of the crystals seen in the optical microscopy images suggested they were, partially at least, composed of the solid complex.     

Dehydrogenation processes via C-H activation within alkylphosphines

Phosphines are commonly used in organometallic chemistry and are present in a wide variety of catalytic systems. This feature article highlights the advances made in dehydrogenation processes occurring within alkylphosphines, with the aim of further developing catalytic processes involving C-H activation together with potential applications in the field of hydrogen storage.     

Detailed structure of diamond-type lipid cubic nanoparticles

Supramolecular three-dimensional self-assembly of nonlamellar lipids with fragments of the protein immunoglobulin results in a bicontinuous cubic phase fragmented into nanoparticles with open water channels (cubosomes). The structure of the diamond-type cubic nanoparticles is characterized experimentally by freeze-fracture electron microscopy, and it is mathematically modeled with nodal surfaces emphasizing the fluid-like undulations of the cubosomic interfaces. Based on scaling-up and scaling-down approaches, we present stable and intermediate-kind nanoparticles resulting from the cubosomic growth. Our results reveal the smallest stable diamond-type cubosomic entity that can serve as a building block of more complex nanostructured fluid drug delivery vehicles of therapeutic proteins. The evidence presented for lipid-bilayer undulations in the surface region of the protein/lipid cubosomes could have important consequences for possible applications of these hierarchically organized porous nanoparticles.     

Generation of superparamagnetic liposomes revealed as highly efficient MRI contrast agents for in vivo imaging

Maghemite (gamma-Fe2O3) nanocrystals stable at neutral pH and in isotonic aqueous media were synthesized and encapsulated within large unilamellar vesicles of egg phosphatidylcholine (EPC) and distearoyl-SN-glycero-3-phosphoethanolamine-N-[methoxy(poly(ethylene glycol))-2000] (DSPE-PEG(2000), 5 mol %), formed by film hydration coupled with sequential extrusion. The nonentrapped particles were removed by flash gel exclusion chromatography. The magnetic-fluid-loaded liposomes (MFLs) were homogeneous in size (195 +/- 33 hydrodynamic diameters from quasi-elastic light scattering). Iron loading was varied from 35 up to 167 Fe(III)/lipid mol %. Physical and superparamagnetic characteristics of the iron oxide particles were preserved after liposome encapsulation as shown by cryogenic transmission electron microscopy and magnetization curve recording. In biological media, MFLs were highly stable and avoided ferrofluid flocculation while being nontoxic toward the J774 macrophage cell line. Moreover, steric stabilization ensured by PEG-surface-grafting significantly reduced liposome association with the macrophages. The ratios of the transversal (r2) and longitudinal (r1) magnetic resonance (MR) relaxivities of water protons in MFL dispersions (6 < r2/r1 < 18) ranked them among the best T2 contrast agents, the higher iron loading the better the T2 contrast enhancement. Magnetophoresis demonstrated the possible guidance of MFLs by applying a magnetic field gradient. Mouse MR imaging assessed MFLs efficiency as contrast agents in vivo: MR angiography performed 24 h after intravenous injection of the contrast agent provided the first direct evidence of the stealthiness of PEG-ylated magnetic-fluid-loaded liposomes.     

Development of immobilization technique for liver microsomes

In the present report, physically adsorbed rat liver microsomes were used in order to optimize the immobilization of membrane proteins on solid surfaces for use in biosensing and microreactor applications. Physical adsorption was used to form thin films on solid supports (gold, mica, macroporous aluminum oxide membrane). The characterization of the films was performed by surface plasmon resonance (SPR), atomic force microscopy (AFM) and environmental scanning electron microscopy (ESEM). Commercially available macroporous aluminium oxide membranes with a high surface area, allow the retention of a high amount of microsomal membranes in the form of a thin film. Microsomal film functionality was tested by monitoring the activities of several enzymes of phases I and II. Microsomal modified supports can be re-utilized for the same or different substrate after washing with appropriate buffer.     

A new synthetic approach to functionalize pyrimido[4,5-<Emphasis Type="Italic">b</Emphasis>]quinoline-2,4(1<Emphasis Type="Italic">H</Emphasis>,3<Emphasis Type="Italic">H</Emphasis>)-diones via a three-component one-pot reaction

Functionalized pyrimido[4,5-b]quinoline-2,4 (1H,3H)-diones were synthesized by a three-component one-pot reaction involving barbituric acid, aldehydes, and anilines. The use of commercially available anilines allowed the facile syntheses of pyrimido[4,5-b]quinolinediones substituted in all the positions on the benzene ring with electron donor or electron withdrawing groups. This straightforward method circumvents the preparation of unstable substituted 2-aminobenzaldehydes that limits the scope of previously described syntheses. Furthermore, access to the 5-substituted derivatives is now also possible starting from aliphatic or aromatic aldehydes. Our strategy and methodology offer significant and practical improvements over other methodologies.     

Unfolding the long-term pathophysiological processes following an acute inflammatory demyelinating lesion of multiple sclerosis

Background

Acute symptomatic inflammation is a main feature of multiple sclerosis but pathophysiological processes underlying total or partial recovery are poorly understood.

Objective

To characterize in vivo these processes at molecular, structural and functional levels using multimodal MR methods.

Methods

A neuroimaging 3-year follow-up (Weeks 0, 3, 11, 29, 59 and 169) was conducted on a 41-year-old woman presenting at baseline with a large acute demyelinating lesion of multiple sclerosis. Conventional magnetic resonance imaging (MRI), magnetization transfer imaging, diffusion-weighted imaging, functional MRI and magnetic resonance spectroscopy were conducted at 1.5 T.

Results

Patient presenting with subacute left hemiplegia recovered progressively (expended disability status scale 7 to 5.5). The MR exploration demonstrated structural functional and metabolic impairments at baseline. Despite restoration of the blood brain barrier integrity, high lactate levels persisted for several weeks concomitant with glial activation. Slow and progressive structural and metabolic restorations occurred from baseline to W169 (lesion volume −64%; apparent diffusion coefficient −14.7%, magnetization transfer ratio +14%, choline −51%, lipids −78%, N-acetylaspartate +77%) while functionality of the motor system recovered.

Conclusions

Multimodal MRI/MRS evidenced long-term dynamics recovery processes involving tissue repair, glial activation, recovery of neuronal function and functional systems. This may impact on customized rehabilitation strategies generally focused on the first months following the onset of symptoms.     

Numerical simulation of 3D free surface flows,with multiple incompressible immiscible phases. Applications to impulse waves

A numerical method for the solution to the density‐dependent incompressible Navier–Stokes equations modeling the flow of N immiscible incompressible liquid phases with a free surface is proposed. It allows to model the flow of an arbitrary number of liquid phases together with an additional vacuum phase separated with a free surface. It is based on a volume‐of‐fluid approach involving N indicator functions (one per phase, identified by its density) that guarantees mass conservation within each phase. An additional indicator function for the whole liquid domain allows to treat boundary conditions at the interface between the liquid domain and a vacuum. The system of partial differential equations is solved by implicit operator splitting at each time step: first, transport equations are solved by a forward characteristics method on a fine Cartesian grid to predict the new location of each liquid phase; second, a generalized Stokes problem with a density‐dependent viscosity is solved with a FEM on a coarser mesh of the liquid domain. A novel algorithm ensuring the maximum principle and limiting the numerical diffusion for the transport of the N phases is validated on benchmark flows. Then, we focus on a novel application and compare the numerical and physical simulations of impulse waves, that is, waves generated at the free surface of a water basin initially at rest after the impact of a denser phase. A particularly useful application in hydraulic engineering is to predict the effects of a landslide‐generated impulse wave in a reservoir. Copyright © 2014 John Wiley & Sons, Ltd.     

New measurement of (g−2) of the Muon

The g-factor anomaly, a≡(g?2)/2, has been measured for μ⁺ in the new Muon Storage Ring at CERN. The result is a = (1 165 895 ± 27) × 10^?9. This is (13 ± 29) × 10^?9 below the theoretical value which includes sixth-order QED terms and a hadronic contribution of (73 ± 10) × 10^?9.