Physicochemical properties of cationic lipophosphoramidates with an arsonium head group and various lipid chains: A structure–activity approach Damien Loizeau a , Tony Le Gall b , Sélim Mahfoudhi a , Mathieu Berchel a , Alicia Maroto a , Jean-Jacques Yaouanc a , Paul-Alain Jaffrès a , Pierre Lehn b , Laure Deschamps a , Tristan Montier b , Philippe Giamarchi a, ⁎ a Laboratoire CEMCA, CNRS UMR 6521, IFR 148 ScInBIoS, Faculté des sciences, Université de Bretagne Occidentale, 6 Avenue Le Gorgeu, 29238 Brest Cedex, France b INSERM U613, IFR 148 ScInBIoS, Faculté de médecine, Université de Bretagne Occidentale, Avenue Camille Desmoulins, 46 rue Félix Le Dantec, CS 51819, 29218 Brest Cedex 2, France HIGHLIGHTS ► New series of cationic lipophosphorami- dates liposomes used as gene vectors ► Influence of chain length and insatu- ration numbers on physico-chemical properties ► Study of membranes viscosity and fu- sion, DNA condensation and in vitro transfection ► Comparison of physico-chemical prop- erties and in vitro transfection efficiency ► Best compound for transfection is fluid and efficient for fusion and DNA condensation GRAPHICAL ABSTRACT abstract article info Article history: Received 24 August 2012 Received in revised form 12 October 2012 Accepted 13 October 2012 Available online 22 October 2012 Keywords: Liposomes Phospholipids Fluorescence Anisotropy FRET Transfection We studied the physicochemical properties of some cationic lipophosphoramidates used as gene vectors in an attempt to better understand the link between the nature of the hydrophobic chain and both physico- chemical properties and transfection efficiency. These compounds have an arsonium head group and various chain lengths and unsaturation numbers. The synthesis of cationic phospholipids with oleic (Guenin et al., 2000 [1]; Floch et al., 2000 [2]) or linoleic (Fraix et al., 2011 [3]; Le Gall et al., 2010 [4]) chains has already been reported by our group and their efficiency as gene carriers has been demonstrated. Four new compounds were synthesized which incorporated either C14:0, C18:0, C20:4 or C20:5 chains. The membrane fluidity was studied by fluorescence anisotropy measurements. The fusion of liposomes and lipoplexes with membrane models was studied by Förster Resonant Energy Transfer. Finally, DNA condensation was studied and the lipoplexes were tested in vitro to quantify their transfection efficiency. From the results obtained on these cation- ic lipophosphoramidates series, we show that aliphatic chain length and unsaturation number have an important influence on liposomes physicochemical properties and transfection efficiency. However there is no direct link between fluidity and fusion efficiency or between fluidity and DNA condensation. Nevertheless, it seems that for best transfection efficiency the compounds need to combine the properties of fluidity, fusion efficiency and DNA condensation efficiency. This was the case for the C18:1 and C18:2 compounds. © 2012 Elsevier B.V. All rights reserved. Biophysical Chemistry 171 (2013) 46–53 ⁎ Corresponding author. E-mail address: philippe.giamarchi@univ-brest.fr (P. Giamarchi). 0301-4622/$ – see front matter © 2012 Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.bpc.2012.10.003 Contents lists available at SciVerse ScienceDirect Biophysical Chemistry journal homepage: http://www.elsevier.com/locate/biophyschem