Novel cationic amphiphilic derivatives from vernonia oil: synthesis and self-aggregation into bilayer vesicles, nanoparticles, and DNA complexants.
Self-assembling nanostructures were prepared from novel cationic amphiphilic compounds synthesized from vernonia oil, a natural epoxydized triglyceride. The presence of a 12,13-epoxy group on the C18 unsaturated fatty acid, vernolic acid, which is the main constituent of vernonia oil, permitted the synthesis of novel amphiphilic derivatives with a hydrogen-bonding hydroxyl and a cationic headgroup moiety on adjacent carbon atoms. The amphiphiles were prepared in a two-stage synthesis that comprised opening of the epoxy groups with a haloacetic acid, followed by quaternization of the halo group with a tertiary amine containing a C12 aliphatic chain. Intact vernonia oil as the starting material gave a triple-headed cationic amphiphile, containing three vernolic acid derived moieties connected through a glycerol backbone. A single-headed amphiphile with two alkyl chains and a single quaternary ammonium headgroup was synthesized from the methyl ester of vernolic acid as the starting material. The triple-headed derivative could form nonencapsulating structures. Cholesterol was required in the formulation (1:1) to make spherical vesicles that could encapsulate a water-soluble marker. The single-headed derivative, however, formed spherical encapsulating vesicles without cholesterol. TEM, NMR, and FT-IR were used to characterize the vesicles, and molecular structure vs morphology relationships were postulated on the basis of these data. The triple-headed amphiphile also formed a DNA complex that was highly resistant to hydrolysis by DNase. This amphiphile-DNA complex was used as vector for gene transfer in cell culture demonstrating efficient DNA transfection.
Grinberg
S
S
The Institutes for Applied Research, and The Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel. sarina@bgumail.bgu.ac.il
Linder
C
C
Kolot
V
V
Waner
T
T
Wiesman
Z
Z
Shaubi
E
E
Heldman
E
E
D000818:Animals; D019556:COS Cells; D002412:Cations / Q000737:chemistry; D002522:Chlorocebus aethiops; D004247:DNA / Q000737:chemistry* / Q000235:genetics; D049452:Green Fluorescent Proteins / Q000737:chemistry / Q000235:genetics; D008051:Lipid Bilayers / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D015394:Molecular Structure; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D010938:Plant Oils / Q000737:chemistry*; D012680:Sensitivity and Specificity; D017550:Spectroscopy, Fourier Transform Infrared / Q000379:methods; D013501:Surface-Active Agents / Q000138:chemical synthesis / Q000737:chemistry*; D035741:Vernonia / Q000737:chemistry*
D002412:Cations; D008051:Lipid Bilayers; D010938:Plant Oils; D013501:Surface-Active Agents; D049452:Green Fluorescent Proteins; D004247:DNA