Hervé des Abbayes

Cationic Phosphonolipids Containing Quaternary Phosphonium and Arsonium Groups for DNA Transfection with Good Efficiency and Low Cellular Toxicity

Replacing the ammonium polar head in cationic lipids 1 (A=N) by a phosphonium or an arsonium group (A=P, As) improves their properties as synthetic vectors for DNA transfection. The increased volume of the cationic head is supposed to modify the interactions of the vector with the solvent and DNA.

COMPLEXATION ON RHODIUM OF BIDENTATE AND POTENTIALLY HEMILABILE PHOSPHOROUS LIGANDS

Abstract Various bifunctional potentially hemilabile ligands bearing phosphorous groups have been prepared and their coordination to rhodium has been studied. Their effect on the hydroformylation of styrene has been assessed.

Phosphonolipids as non-viral vectors for gene therapy

Several 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.

Cationic phosphonolipids as non viral vectors for DNA transfection

Abstract The Mannich reaction from fatty phosphites followed by quaternarisation of the resulting aminophosphonates led to new cationic phosphonolipids which showed promising DNA transfection properties.

A CONVENIENT ACCESS TO NEW PHOSPHINE AND DIPHOSPHINE LIGANDS FROM PHOSPHINIC ACIDS

Abstract Phosphinic acids are convenient starting materials for a two-steps route to a large variety of phosphines and polyphosphines.

Mono N-functionalization of cyclic and linear tetraamines via their tridentate tricarbonylchromium complexes

The fac-LCr(CO)3 tridentate complexes of 1,4,7,10-tetraazacyclododecane 1, 1,4,8,11-tetraazacyclotetradecane 2, 1,4,7,10-tetraazadecane 3 and 1,5,8,12-tetraazadodecane 4 have been selectively alkylated in high yield at the uncomplexed nitrogen atom, giving rise to mono N-functionalized tetraamines and bis-macrocyclic compounds.

CFTR transgene expression in primary ΔF508 epithelial cell cultures from human nasal polyps following gene transfer with cationic phosphonolipids

Cystic fibrosis (CF) is the most common autosomal lethal recessive disorder in the Caucasian population. The major cause of mortality is lung disease, owing to the failure of a functional protein from the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Today, even though the knowledge about the CFTR genomic is extensive, no efficient treatment has been developed yet.In this context, gene therapy represents a potential important advance on condition that it could develop efficient and safe transfection agents. Even though viral vectors have been used in most clinical trials owing to their high transfection efficiency, random integration and immunogenicity are still critical side effects. Consequently, all of these drawbacks brought forth the development of nonviral transfection systems. Although they engender few toxicity and immunogenicity problems, their low transfection efficiency is a hurdle that must be overcome. Over the past decade, we have developed an original family of monocationic lipids, cationic phosphonolipids, whose efficiency has been previously demonstrated both in vitro and in vivo.In this report, we observe that a new cationic phosphonolipid (KLN 30) can lead to the restoration of the CFTR protein following the ex vivo transfection of epithelial cells issuing from a ΔF508 homozygous patient. The transgene expression and the cytotoxicity correlate with the charge ratio of the lipoplex. A kinetic study was performed, and a luminescent signal was detected until 35 d after transfection.

Rhodium-catalyzed hydroformylation of styrene at low temperature using potentially hemilabile phosphite–phosphonate ligands

Abstract The synthesis and the effect of phosphite–phosphonate ligands in rhodium-catalyzed hydroformylation of styrene are described. Activity and selectivity of the catalyst are improved, at low temperature, by increasing bulkiness of both phosphite and phosphonate moieties.

One pot symmetrical and dissymmetrical regiospecific ω,ω′-bis mono N-alkylation of linear tetraamines via their chromium, molybdenum or tungsten tricarbonyl complexes

Abstract Dissymmetric ω, ω′-N-dialkylated linear tetraamines have been obtained after the successive reactions of two aldehydes and subsequent reduction and removal of the M(CO) 3 protection.

Synthesis, reactivity of the [(CO)3(L)Fe(CO2R)2] dialkoxycarbonyl carbonyl iron complexes (L = CO or PPh3; R CH3, C2H5), and an easy access to [(CO)5Fe(CO2Me)]+

Abstract The cis -dialkylcarboxytetracarbonyliron complexes [(CO) 4 Fe(CO 2 R) 2 ] were readily obtained from reaction of oxalyl chloride with the corresponding tetracarbonylcarboxyiron anion [(CO) 4 Fe(CO 2 R)] − (R  Me, 1a ; R  Et, 1b ). 1a underwent a clean ligand exchange with triphenylphosphine to give [Fe(CO) 3 (PPh 3 )(CO 2 Me) 2 ] ( 2 ). Neither 1a nor 2 yielded dimethyl oxalate after thermolysis; rather, a mixture of methanol and methyl carbonate was obtained. The mobility of the alkoxy groups on 1 was shown by several exchange experiments. A clean reaction of the tetrafluoroboric acid ether with 1a gave [(CO) 5 Fe(CO 2 Me)] + which was isolated and characterized by IR, 1 H, and 13 C NMR spectroscopy.