Régine Naejus

Nouveau procédé de synthèse de l'hexafluorophosphate de lithium

Abstract Lithium hexafluorophosphate (LiPF 6 ) has been synthesized using commercial hexafluorophosphoric acid (HPF 6 ) as starting material. The neutralization of this acid monitored by conductimetry by lithium hydroxide in aqueous, alcoholic and acetonitrile media gives LiPF 6 with yields of 42, 35 and 61% respectively. This salt may also be prepared by neutralizing similarly lithium hydroxide (LiOH) by pyridinium hexafluorophosphate (C 5 H 5 NHPF 6 ) obtained by reaction from equimolar amounts of pyridine and HPF 6 in alcoholic media (yield about 90%). From C 5 H 5 NHPF 6 a new synthesis leads to LiPF 6 in two steps. First the reaction of C 5 H 5 NHPF 6 with ROLi (R = CH 3 , C 2 H 5 ) in methyl or ethyl alcohol, acetonitrile and tetrahydrofuran media or with RLi (R = C 4 H 9 , tert -butyl) in pentane or hexane, gives lithium pyridinium hexafluorophosphate Li(C 5 H 5 N)PF 6 in about 95% yield. Heating this at 30–50 °C under vacuum gives LiPF 6 with a purity determined by lithium titration of about 99%.

Inhibition of VEGF expression in A431 and MDA-MB-231 tumour cells by cationic lipid-mediated siRNA delivery.

In order to promote siRNA transfer in tumour cells, we used an original cationic lipid, synthesized in our laboratory, dimethyl-hydroxyethyl-aminopropane-carbamoyl-cholesterol (DMHAPC-Chol). Liposomes were prepared from this lipid and dioleoylphosphatidylethanolamine (DOPE) in equimolar proportion. Its transfecting capacity was evaluated using ELISA, cell cytometry, and RT-PCR in estimating the silencing effect of VEGF siRNA. This liposome efficiently delivered VEGF siRNA in two human cancer cell lines abundantly secreting VEGF, A431 and MDA-MB-231. Results showed that 50 nM of VEGF siRNA carried by DMHAPC-Chol/DOPE liposomes already silenced more than 90% of VEGF in these cells. A comparative study with two commercial carriers indicated that the inhibition induced by VEGF siRNA transported by cationic DMHAPC-Chol/DOPE liposomes was comparable to that induced by INTERFERin and better than lipofectamine 2000. Moreover, a transfection by a GFP plasmid followed by a GFP siRNA showed that DMHAPC-Chol/DOPE liposomes compared to lipofectamine were less efficient for plasmid but better for siRNA transport. Following one of our previous works concerning cell delivery of plasmid (), the main interest of results presented here resides in the double potential of DMHAPC-Chol/DOPE liposomes to deliver little-sized siRNA as well as large nucleic acids in cells.

Aggregation of new bipolar glucosyled and cationic fluoroamphiphiles in aqueous media

A new series of N-[3-(trimethylamino)propyl]-perfluoro-N-glucosyl amide-Iodides, differing by the length of the fluorocarbon tail (7, 9, and 11), have been synthesized in three steps involving unprotected glucose, N,N-dimethyl-1,3-propane diamine, the appropriate methyl-perfluoroalcanoate, and methyl iodide. Their aggregation and surface properties were studied in aqueous solution using conductivity, surface tension, and dynamic light scattering measurements. The critical micelle concentrations (CMC), the micellar aggregation numbers, the geometric packing parameters, the area/surfactant molecule at the interface, the surface excess concentration, the micellar ionization degree β, and the free energies of micellization have been investigated. DLS results show various morphologies of aggregates such as micelles and vesicles according to the increase in the hydrophobic chain length.

A comparative study of micellization with fluorinated and hydrogenated diquaternary ammonium bolaamphiphiles

Two new N(a),N(b)-Bis[3-(trimethylamino)propyl]-perfluoroalkanes diamide-Iodide with (a=1; b=10) and (a=1; b=12), differing by the fluorocarbon tail spacer (8 or 10 CF2), and the N(1),N(12)-Bis[3-(trimethylamino)propyl]-dodecanediamide-Iodide have been synthesized in two steps involving the appropriate dimethyl perfluoro or hydrogeno alkane dicarboxylate, N,N-dimethyl-1,3-propane diamine, and methyl iodide. Their surface properties were studied at 45°C in aqueous solutions using conductivity, surface tension, and dynamic light scattering (DLS) measurements. A comparison of the micellar parameters usually obtained by these techniques has been carried out. The critical micelle concentrations (CMCs), the geometric packing parameters, the surface excess concentration, the area/surfactant molecule at the interface, the micellar ionization degree β and the free energies of micellization, the diffusion coefficient, and the hydrodynamic diameter were discussed. The effect of added KI on these parameters and on the size and on the kind of aggregates has been also investigated. The addition of 1,2-Dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) to the surfactant solutions, where the size of the complex DOPE-surfactant was determined by DLS over a wide range of concentrations, reveals a very different behavior comparing fluorinated and hydrogenated compounds.