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.     

Ruthenium dihydrogen complexes with wide bite angle diphosphines

The wide bite angle diphosphines homoxantphos (10,11-dihydro-4,5,-bis(diphenylphosphino)dibenzo[b,f]oxepine), sixantphos (4,6-bis(diphenylphosphino)-10,10-dimethylphenoxasilin), and thixantphos (2,8-dimethyl-4,6-bis(diphenylphosphino)phenoxathiin) were used to prepare cis[MH(2)(diphosphine)(2)] complexes (1a-f) by reaction of [Ru(cod)(cot)] (cod = cyclo-octa-1,5-diene, cot = cyclo-octa-1,3,5-triene) with 2 equiv of the diphosphine under dihydrogen pressure. The electronic properties of the thixantphos ligand were varied. Complexes 1a-f can be protonated with HBF(4) or CF(3)COOH to yield hydrido(dihydrogen) complexes cis[MH(H(2))(diphosphine)(2)](+) (2a-f), which were characterized by VT (variable temperature) NMR and T(1) measurements. These complexes show fast hydrogen atom exchange between the eta(2)-H(2) and the terminal hydride at all temperatures studied. They are thermally unstable toward dihydrogen loss yielding the cationic monohydride complexes cis[MH(diphosphine)(2)](+) (3a-f). Coordination of the eta(2)-H(2) is dominated by sigma --> d donation, and hence, the H-H distance is hardly influenced by the electronic properties of the ligands.     

Heterometallic Werner complexes as energetic materials

New heterometallic Werner complexes have been synthesized by combining the cobalt cationic [Co(NH3)6]3+ species with a nitrato metal fragment [M(NO3)4](x-) (M = Fe, Mn, Cu, Zn) or with metal oxides X2MO4 (M = Mo, W and X = Na, NH4). Depending on the metals, an organic and/or a water synthetic route was developed. X-Ray data on Mn and Cu precursors have shown the versatility of nitrate ligand coordination. TDA-TGA studies have been performed to demonstrate the energetic material character. The [Co(NH3)6]x[M(NO3)4]3 complexes display a good oxygen balance and, as shown by standard sensitivity tests, are suitable for automotive applications.     

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.     

Design and effective synthesis of the first 4-aza-2,3-didehydropodophyllotoxin rigid aminologue: a N-methyl-4-[(3,4,5-trimethoxyphenyl)amino)]-1,2-dihydroquinoline-lactone

The first N1-alkyl-4-amino-1,2-dihydroquinoline-lactone has been prepared by a five-step sequence in a 51% overall yield via the corresponding furo[3,4-b]quinolin-1(3H)-one. A new practical synthesis of this intermediate was carried out using versatile, commercially available starting materials and constitutes the shortest and highest yielding route. These synthetic pathways could be widened with a view toward the preparation of different substituted derivatives, which could be considered as rigid aminologues of 4-aza-2,3-didehydropodophyllotoxins.     

Bonding mode of a bifunctional P approximately Si-H ligand in the ruthenium complex "Ru(PPh2CH2OSiMe2H)3"

The phosphinosilane compound PPh 2CH 2OSiMe 2H is potentially a bifunctional P approximately Si-H ligand. By treatment with the Ru (II) precursor RuH 2(H 2) 2(PCy 3) 2, the complex Ru(PPh 2CH 2OSiMe 2H) 3 ( 2), resulting from the coordination of three ligands and the displacement of two PCy 3 and two dihydrogen ligands, was formed. The different bonding modes for each of the three bifunctional P approximately Si-H ligands are discussed on the basis of multinuclear NMR, X-ray diffraction, and density functional theory studies. One ligand acts as a monodentate phosphine ligand with a pendant Si-H group, whereas the two others act as bidentate ligands with different Si-H bond activations. Indeed, an intermediate structure between two arrested forms 2a and 2b can be proposed: a dihydrido(disilyl)ruthenium(IV) species (form 2a) resulting from two Si-H oxidative additions or a hydrido(silyl)ruthenium(II) species (form 2b) presenting an agostic Si-H bond and only one oxidative addition.     

Cationic carbon nanotubes bind to CpG oligodeoxynucleotides and enhance their immunostimulatory properties

Functionalized cationic carbon nanotubes are able to form a stable complex with CpG ODN based on charge interaction and to increase the immunostimulatory activity of CpG motifs.     

The influence of structure and composition of a reverse SDS microemulsion on enzymatic activities and electrical conductivities

The activity of the enzyme horse radish peroxidase (HRP) is studied in a series of reverse microemulsions composed of dodecane, aqueous buffer, sodium dodecylsufate (SDS) and alcohols of the homologous series 1-butanol to 1-octanol. The HRP catalyzed reaction is the oxidation of a classical water soluble substrate, the 2,2-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS) by hydrogen peroxide. In parallel electrical conductivity measurements are performed on the same solutions. The structural changes in the microemulsions, as inferred by the conductivity measurements, correlate remarkably well with the changes in the enzymatic activities. In particular it is found that (a) the maximum activity of the enzyme is always related to its optimum hydration and that this hydration can be related to the microemulsion structures, (b) the enzyme inhibition caused by the alcohols in microemulsions is a consequence of both the solubility of the alcohols in the buffer and the rigidity of the interfacial film. Consequently, it can be concluded that enzymatic activity measurements are a valuable tool to study confined systems such as microemulsions and, in particular, the amount of available hydration water. Enzymatic activities can be finely tuned by small changes in microemulsion structures, probably in a predictive way.     

Hemoglobin,horseradish peroxidase,and heme-bovine serum albumin as biocatalyst for the oxidation of dibenzothiophene

Hemoglobin, horseradish peroxidase, and bovine serum albumin incubated heme-catalyzed the oxidation of dibenzothiophene into sulfoxide in the presence of hydrogen peroxide. This reaction was carried out in an aqueous buffer containing 25% of water-miscible organic solvents. The observation of this transient state of hemoproteins during sulfoxidation showed heme degradation. None of the compounds usually involved in a classical peroxidative activity mechanism were detected. Furthermore, this activity did not appear to be based on a Fenton-type reaction. The highest degrees of sulfoxidation were obtained with hemoglobin. Under the best conditions of reaction, 100% of dibenzothiophene were converted into dibenzothiophene sulfoxide by hemoglobin. Heat-denatured hemoproteins did keep their sulfoxidation activity. With hemoglobin, a k_cat of 0.22 min^-1 was determined. Nearly the same values were obtained with heat-denatured hemoglobin and bovine serum albumin-adsorbed heme. With horseradish peroxidase, only 4% of conversion was attained. This percentage could be slightly increased by using a less pure peroxidase or heat-denatured peroxidase.