title: Inductive electron-withdrawal from ammonium ion headgroups of cationic lipids and the influence on DNA transfection.
abstract: We have prepared a panel of lipidic ammonium tetrafluoroborate salts that contain trifluoromethyl, trichloromethyl, and methyl groups attached to the headgroup. 19F-NMR analyses of the cationic lipid panel revealed that the differences in electron-withdrawal from the ammonium ion headgroup accounted for differences in ion-pairing. Exchange of the tetrafluoroborate counterion by complexation to DNA-phosphate of a reporter gene enabled us to probe the influence of inductive electron-withdrawal in cationic lipid-mediated DNA transfection. We tested the lipid panel for transfection activity in two cell lines. The results indicate that the inductive effects of electron-withdrawing functionality diminish transfection activity in modest (2-4-fold) increments. The present study suggests that the mechanism whereby poly(alcohol)- or poly(ether)-substituted headgroups improve DNA transfection is not based on electronic activation of the ammonium ion.
authors.affiliation: Department of Chemistry, University of California, Davis, CA 95616, USA.
authors.forename: M H
authors.initials: MH
authors.lastname: Nantz
authors.forename: L
authors.initials: L
authors.lastname: Li
authors.forename: J
authors.initials: J
authors.lastname: Zhu
authors.forename: K L
authors.initials: KL
authors.lastname: Aho-Sharon
authors.forename: D
authors.initials: D
authors.lastname: Lim
authors.forename: K L
authors.initials: KL
authors.lastname: Erickson
mesh_terms: D000230:Adenocarcinoma; D001881:Borates; D001888:Boric Acids / Q000737:chemistry; D001943:Breast Neoplasms; D002412:Cations; D004247:DNA / Q000737:chemistry*; D005229:Fatty Acids, Monounsaturated; D005456:Fluorescent Dyes; D006801:Humans; D008055:Lipids / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D010710:Phosphates / Q000737:chemistry; D000644:Quaternary Ammonium Compounds / Q000737:chemistry*; D014162:Transfection; D014407:Tumor Cells, Cultured
chemical_list: D001881:Borates; D001888:Boric Acids; D002412:Cations; D005229:Fatty Acids, Monounsaturated; D005456:Fluorescent Dyes; D008055:Lipids; D010710:Phosphates; D000644:Quaternary Ammonium Compounds; D004247:DNA; C098759:fluoroboric acid; C070046:1,2-dioleoyloxy-3-(trimethylammonium)propane