INDUCTIVE ELECTRON-WITHDRAWAL FROM AMMONIUM ION HEADGROUPS OF CATIONIC LIPIDS AND THE INFLUENCE ON DNA TRANSFECTION

We have prepared a panel of lipidic ammonium tetrafluoroborate salts t hat contain trifluoromethyl, trichloromethyl, and methyl groups attach ed to the headgroup. F-19-NMR analyses of the cationic lipid panel rev ealed that the differences in electron-withdrawal from the ammonium io n headgroup accounted for differences in ion-pairing. Exchange of the tetrafluoroborate counterion by complexation to DNA-phosphate of a rep orter gene enabled us to probe the influence of inductive electron-wit hdrawal in cationic lipid-mediated DNA transfection. We tested the lip id panel for transfection activity in two cell lines. The results indi cate that the inductive effects of electron-withdrawing functionality diminish transfection activity in modest (2-4-fold) increments. The pr esent study suggests that the mechanism whereby poly(alcohol)- or poly (ether)-substituted headgroups improve DNA transfection is not based o n electronic activation of the ammonium ion. (C) 1998 Published by Els evier Science B.V. All rights reserved.