Novel synthetic ion transporters that function in bilayer membranes

In the studies reported here, we probed interactions between synthetic ion transporters and bilayer membranes. This was done by varying structural and electronic parameters and assayed by measuring the rates of ion flux mediated by synthetic ion transporters through bilayer membranes. Several families of novel ion transporters were designed, synthesized and fully characterized by chemical methods. Transporter activity was tested by various analytical methods that rely on ion selective electrodes, fluorescent dyes, and planar bilayer conductance techniques.;The presence of amides in synthetic "hydraphile" ion channels influences channel activity. Incorporating amides into synthetic ion transporters alters the donor group type and strength, and the conformation of the structural unit in which it occurs (chapter 2). The final outcome of amide residue incorporation depends on the number of amides in the structure, the positions of amides, and the basic structures of parent transporters.;The first asymmetric synthetic ion channel in the hydraphile family was prepared and characterized (chapter 3). Diminished transport activity was observed in the asymmetric channel compared to parent (control) compounds. This suggests the possibility of different and conflicting interactions of the different side arms with the membrane. Planar bilayer conductance data showed that the asymmetric transporter forms a unimolecular channel in the membrane. Although the asymmetric transporter is not a rectifier, its activity varied as a function of the applied membrane potential.;A family of synthetic ion transporters containing rigid aromatic rings, that we refer to as "protochannels," were investigated (chapter 4). The release of ions from vesicles was monitored and a correlation was observed between the rigidity of channel structure and the magnitude of the channel activity. Planar bilayer experiments suggested that the protochannel forms a conductance pathway by aggregation within the membrane.;These data provide insight into the relationship between structure and ion transport activity. In principle, such information is extensible to natural protein transporters, which are much more complex entities.