1-2-dioleoyloxy-3-(trimethylammonium)propane and fluoroboric-acid

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.

Topics: Adenocarcinoma; Borates; Boric Acids; Breast Neoplasms; Cations; DNA; Fatty Acids, Monounsaturated; Fluorescent Dyes; Humans; Lipids; Magnetic Resonance Spectroscopy; Phosphates; Quaternary Ammonium Compounds; Transfection; Tumor Cells, Cultured