A di-walled molecular umbrella (1a) has been synthesized by acylation of the terminal amino groups of spermidine with cholic acid, followed by condensation with bis(3-O-[N-1,2,3-benzotriazin-4(3H)-one]yl)-5,5'-dithiobis-2-nitrobenzoate (BDTNB), and displacement with glutathione (gamma-Glu-Cys-Gly, GSH). Replacement of the sterol hydroxyls with sulfate groups, prior to displacement with GSH, afforded a hexasulfate analogue 1b. Both conjugates have been found to enter large unilamellar vesicles (200 nm diameter, extrusion) of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), and to react with entrapped GSH to form oxidized glutathione (GSSG). Evidence for vesicular entry has come from the formation of oxidized glutathione (GSSG) within the interior of the vesicle, the appearance of the thiol form of the umbrella (USH), and the absence of release of GSH into the external aqueous phase. Results that have been obtained from monolayer experiments, together with the fact that the heavily sulfated conjugate is able to cross the phospholipid bilayer, have yielded strong inferential evidence for an "umbrella-like" action of these molecules as they cross the lipid bilayer.

A series of ion conductors have been synthesized in which the degree of facial hydrophilicity has been systematically varied. Specifically, conjugates have been prepared from cholic acid and spermine in which the hydrophilic face of each sterol bears methoxy (1), hydroxy (2), carbamate (3), or sulfate groups (4). The ability of these conjugates to promote the transport of Na(+) across phosphatidylcholine membranes of varying thickness has been investigated by (23)Na NMR spectroscopy. Examination of observed activities in three different phosphatidylcholine membranes has provided evidence for membrane-spanning dimers as the transport-active species. In the thinnest membranes investigated, made from 1,2-dimyristoleoyl-sn-glycero-3-phosphocholine (C14), Na(+)-transport activity was found to increase, substantially, with increasing facial hydrophilicity. In thicker membranes, made from 1,2-dioleoyl-sn-glycero-3-phosphocholine (C18), observed activities were found to decrease with increasing facial hydrophilicity; with a membrane of intermediate thickness, prepared from 1,2-dipalmitoleoyl-sn-glycero-3-phosphocholine (C16), ion-conducting activity increased and then decreased, with continuous increases in facial hydrophilicity. The possible origins for these variations in activity are briefly discussed.