Phosphane and bis(phosphane) ligands from phosphinic acids

International audienceThe Boyd-Regan methodology allowed for access to various cyclic or benzylic mono- and bis(phosphinic acids) 1-6. The reduction of monophosphinic acids to secondary phosphanes 7-9 was achieved with silanes. On the other hand, reduction of the bis(phosphinic acids) with LiAlH4 led to bis(phosphanes) 12-13. Various cyclic phosphanes and bis(phosphanes) were obtained by the alkylation of these secondary phosphanes (as their borane adducts). The Michael addition of the same borane adducts to vinylic phosphonates led to phosphane-phosphonates which could be hydrolysed to new hydrosoluble phosphanes

Phosphane and bis(phosphane) ligands from phosphinic acids

International audienceThe Boyd-Regan methodology allowed for access to various cyclic or benzylic mono- and bis(phosphinic acids) 1-6. The reduction of monophosphinic acids to secondary phosphanes 7-9 was achieved with silanes. On the other hand, reduction of the bis(phosphinic acids) with LiAlH4 led to bis(phosphanes) 12-13. Various cyclic phosphanes and bis(phosphanes) were obtained by the alkylation of these secondary phosphanes (as their borane adducts). The Michael addition of the same borane adducts to vinylic phosphonates led to phosphane-phosphonates which could be hydrolysed to new hydrosoluble phosphanes

The vibrational inelastic neutron scattering spectrum of dodecahedrane: experimental and DFT simulation

A model for red azo pigment Ca4B was characterized structurally using synchrotron radiation. This highly anisotropic ladder structure represents a new structural class in azo pigment chemistry. The picture shows that the calcium atoms coordinate in a complex manner to three azo ligands (one terdentate, one bidentate, and one monodentate) and two water molecules simultaneously

Cation substitution in cationic phosphonolipids: A new concept to improve transfection activity and decrease cellular toxicity

International audienceCationic lipids have been shown to be an interesting alternative to viral vector-mediated gene delivery into in vitro and in vivo model applications. Prior studies have demonstrated that even minor structural modifications of the lipid hydrophobic domain or of the lipid polar domain result in significant changes in gene delivery efficiency. Previously, we developed a novel class of cationic lipids called cationic phosphonolipids and described the ability of these vectors to transfer DNA into different cell lines and in vivo. Up until now, in all new cationic lipids, nitrogen atoms have always carried the cationic or polycationic charge. Recently we have developed a new series of cationic phosphonolipids characterized by a cationic charge carried by a phosphorus or arsenic atom. In a second step, we have also examined the effects of the linker length between the cation and the hydrophobic domain as regards transfection activity. Transfection activities of this library of new cationic phosphonolipids were studied in vitro in different cell lines (HeLa, CFT1, K562) and in vivo using a luciferase reporter gene. A luminescent assay was carried out to assess luciferase expression. We demonstrated that cation substitution on the polar domain of cationic phosphonolipids (N → P or As) results in significant increase in transfection activity for both in vitro and in vivo assays and decrease of cellular toxicity

Cationic lipophosphoramidates and lipophosphoguanidines are very efficient for in vivo DNA delivery

cited By 50International audienceTwo new families of cationic lipids were designed and synthesized for gene delivery, namely "lipophosphoramidates" and " lipophosphoguanidines", whose efficiency was noteworthy. The most efficient have an arsonium cation as the polar head, and the unsaturated lipidic tails (e.g. oleyl) gave the better in vivo results (mice lungs). © 2005 American Chemical Society

Phosphonolipids as non-viral vectors for gene therapy

International audienceSeveral phosphonates with two fatty chains and different polar heads were synthesized and evaluated for their potential to transfer DNA into epithelial (COS-7) and hematopoietic (K562) cell lines, and compared to commercially available references. In both cases, ammonium-phosphonates were particularly efficient

Transgene expression kinetics after transfection with cationic phosphonolipids in hematopoietic non adherent cells

International audienceCationic lipids are considered to be capable of efficiently and safely mediating DNA transfer into cells, although expression is transient. A new family of cationic lipids, called phosphonolipids, has been developed, with the relationship between the hydrophobic domain of the lipid molecules and the significant enhancement of transduction efficiency in a non-adherent cell line characterised in the present study. The kinetics of transfection efficiency were also investigated. Our results demonstrate that the peak of the transient expression of these reporter genes mediated by cationic lipids occurred within 3 to 14 days, depending on the aliphatic chain length of the complex used and on its formulation in the presence or absence of DOPE. Furthermore, the kinetics of transgene expression were found to differ in adherent and non-adherent cells. These results were obtained using three different techniques: CPRG, luminescence, and FACS-gal, and were in agreement with electron microscopy studies. We thus hypothesized that the plasma membrane composition of cells could affect the efficiency of transfection with cationic lipids. Our results suggest that phosphonolipids constitute a promising class of compounds for gene transfer protocols, and that galenic optimization should improve and modify the transfection efficiency of these DNA-lipid complexes