MaxPHOS is an active and robust P-stereogenic ligand for asymmetric catalysis. The presence of an À NH À bridge between the two phosphine moieties allows the NH/PH tautomerism to take place. The neutral ligand, in which the NH form predominates, is an air-sensitive compound. However, protonation of MaxPHOS leads to the stable PH form of the ligand, in which the overall positive charge is distributed on both P centers. This protonation turns the MaxPHOS·HBF 4 salt 3 into an airstable compound both in the solid state and in solution.The salt 3 is also a convenient precursor for the preparation of rhodium(I) complexes by direct ligand exchange with the complexFinally, the corresponding rhodium(I)-MaxPHOS complex was tested in the asymmetric hydrogenation of a wide range of substrates. The complex proved to be a highly selective and robust system in these reactions.

The synthesis and properties of gemini surfactants of the type (R(1)(CO)-Lys(H)-NH)2(CH2)n are reported. For a spacer length of n = 6, the hydrophobic acyl tail was varied in length (R(1) = C8, C10, C12, C14, C16, and C18) and, for R(1) = C18, the degree of unsaturation. For R(1)(CO) = oleoyl (C18:1 Z) the spacer length (n = 2-8) and the stereochemistry of the lysine building block were varied; a 'half-gemini' derivative with a single oleoyl tail and head group was also prepared. The potential of the gemini surfactants to transfer polynucleotides across a cell membrane was investigated by transfection of HeLa cells with beta-galactosidase, both in the presence and absence of the helper lipid DOPE. Oleoyl was found to be by far the best hydrophobic tail for this biological activity, whereas the effect of the lysine stereochemistry was less pronounced. The effect of an optimum spacer length (n = 6) was observed only in the absence of helper lipid. The most active surfactant, i.e. the one with oleoyl chains and n = 6, formed liposomes with sizes in the range of 60-350 nm, and its lipoplex underwent a transition from a lamellar to a hexagonal morphology upon lowering the pH from 7 to 3.

Highlights Robust preparation of liposomal formulation by DELOS-susp method. Implementation of Quality by Design methodology to liposomes preparation. Influence of critical parameters on quality was studied through DoE analysis. Design Space was obtained for GLA-loaded liposomes formulation.

Supporting Information. This material is available free of charge via the Internet at http://pubs.acs.org. Equipment configuration and DELOS-susp methodology; Separation of free GLA by diafiltration; Concentration of the sample for in vivo testing; Stability of the sample in human serum; Composition of nanovesicles; Theoretical number of GLA per vesicle; Morphology of liposomes using SAXS; Enzymatic activity assay conditions; In vitro cell viability in endothelial HMEC-1; Plasma coagulation times (PDF).