Partitioning of ionizing molecules between aqueous buffers and phospholipid vesicles

Abstract

The distribution of four ionizing molecules between small unilamellar vesicles of dimyristoylphosphatidylcholine (DMPC) and aqueous buffers has been studied as a function of pH using an ultrafiltration method. The results show that pH-distribution behavior observed in the standard 1-octanol-water system does not always apply in model membrane systems, since the charged form of some molecules are able to partition into a phospholipid bilayer. It was further shown that the partitioning of these charged species into the bilayer is not as a consequence of ion pairing. The results clarify reports suggesting that protonated amines have a surprisingly high membrane affinity, and the implications of these findings for drug design are discussed.