title: 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.
authors.affiliation: Department of Physical Chemistry, Astra Charnwood, Loughborough, Leicestershire, United Kingdom.
authors.forename: R P
authors.initials: RP
authors.lastname: Austin
authors.forename: A M
authors.initials: AM
authors.lastname: Davis
authors.forename: C N
authors.initials: CN
authors.lastname: Manners
mesh_terms: D017311:Amlodipine / Q000737:chemistry / Q000493:pharmacokinetics; D002021:Buffers; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004134:Dimyristoylphosphatidylcholine / Q000737:chemistry* / Q000378:metabolism; D007477:Ions; D007700:Kinetics; D008051:Lipid Bilayers / Q000737:chemistry / Q000378:metabolism; D008567:Membranes, Artificial; D014867:Water / Q000737:chemistry* / Q000378:metabolism
chemical_list: D002021:Buffers; D007477:Ions; D008051:Lipid Bilayers; D008567:Membranes, Artificial; D014867:Water; D017311:Amlodipine; D004134:Dimyristoylphosphatidylcholine