Physical and biological properties of cationic triesters of phosphatidylcholine

The properties of a new class of phospholipids, alkyl phosphocholine triest ers, are described. These compounds were prepared from phosphatidylcholines through substitution of the phosphate oxygen by reaction with alkyl triflu oromethylsulfonates. Their unusual behavior is ascribed to their net positi ve charge and absence of intermolecular hydrogen bonding. The O-ethyl, unsa turated derivatives hydrated to generate large, unilamellar liposomes. The phase transition temperature of the saturated derivatives is very similar t o that of the precursor phosphatidylcholine and quite insensitive to ionic strength. The dissociation of single molecules from bilayers is unusually f acile, as revealed by the surface activity of aqueous liposome dispersions. Vesicles of cationic phospholipids fused with vesicles of anionic lipids. Liquid crystalline cationic phospholipids such as 1,2-dioleoyl-sn-glycero-3 -ethylphosphosphocholine triflate formed normal lipid bilayers in aqueous p hases that interacted with short, linear DNA and supercoiled plasmid DNA to form a sandwich-structured complex in which bilayers were separated by str ands of DNA. DNA in a 1:1 (mol) complex with cationic lipid was shielded fr om the aqueous phase, but was released by neutralizing the cationic charge with anionic lipid. DNA-lipid complexes transfected DNA into cells very eff ectively, Transfection efficiency depended upon the form of the lipid dispe rsion used to generate DNA-lipid complexes; in the case of the O-ethyl deri vative described here, large vesicle preparations in the liquid crystalline phase were most effective.