title: Novel fluorescent cationic phospholipid, O-4-napthylimido-1-butyl-DOPC, exhibits unusual foam morphology, forms hexagonal and cubic phases in mixtures, and transfects DNA.
abstract: The novel cationic triester of phosphatidylcholine, O-4-napthylimido-1-butyl-dioleoylphosphatidylcholine (NB-DOPC), has been synthesized: 1-amino-4-butanol was reacted with napthylic anhydride to form 4-hydroxybutyl-1-napthylamide, which was then reacted with triflic anhydride; the resultant triflate was reacted with dioleoylphosphatidylcholine so as to transfer the napthylimido-butyl group to the unsubstituted phosphate oxygen. The resultant compound is thus not only positively charged, but also has a bulky hydrophobic moiety attached to the headgroup. This novel cationic phospholipid exhibits a peculiar long-living foam-like morphology upon hydration, which could have applications in encapsulation and delivery. It is characterized by high adhesiveness to hydrophobic surfaces. X-ray diffraction showed that it forms a lamellar structure of rather short repeat period, indicative of an unusually small interlamellar separation and low hydration level. It readily incorporates DNA and organizes into lamellar lipoplexes. These DNA-lipid complexes effectively transfect DNA into cells. In an equimolar mixture of this lipid with the anionic dioleoylphosphatidylglycerol lamellar arrays coexist with disordered uncorrelated structures, however, these transform into a bicontinuous cubic phase, Pn3m, upon addition of DNA. When mixed with another anionic lipid, cardiolipin, at a NB-DOPC/ cardiolipin 2:1 molar ratio, it forms the inverted hexagonal phase which is of potential interest for nanotechnology applications.
authors.affiliation: Department of Biochemistry, Molecular Biology & Cell Biology, Northwestern University, 2205 Tech Drive, Evanston, IL 60208, USA. r-tenchova@northwestern.edu
authors.forename: Rumiana
authors.initials: R
authors.lastname: Koynova
authors.forename: Howard S
authors.initials: HS
authors.lastname: Rosenzweig
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.forename: Michael
authors.initials: M
authors.lastname: Wasielewski
authors.forename: Robert C
authors.initials: RC
authors.lastname: MacDonald
mesh_terms: D004247:DNA / Q000737:chemistry*; D007094:Imides / Q000138:chemical synthesis / Q000737:chemistry*; D008081:Liposomes / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D008823:Micelles; D008968:Molecular Conformation; D010713:Phosphatidylcholines / Q000138:chemical synthesis / Q000737:chemistry*; D010743:Phospholipids / Q000138:chemical synthesis / Q000737:chemistry*; D014162:Transfection; D014961:X-Ray Diffraction
chemical_list: D007094:Imides; D008081:Liposomes; D008823:Micelles; C493897:O-4-naphthylimido-1-butyl-dioleoylphosphatidylcholine; D010713:Phosphatidylcholines; D010743:Phospholipids; D004247:DNA