A Fine Line Between Molecular Umbrella Transport and Ionophoric Activity

Abstract

A persulfated molecular umbrella derived from one spermine, four lysine and eight deoxycholic acid molecules was found to exhibit ionophoric activity, as shown by pH discharge, and Na + and Cl − transport experiments. In sharp contrast, a moderately more hydrophilic analog derived from cholic acid showed no such ionophoric activity. Both molecular umbrellas crossed liposomal membranes by passive transport with experimental rates that were similar. These findings show how the interactions between such amphomorphic molecules and phospholipid bilayers are a sensitive function of the umbrella's hydrophilic/lipophilic balance (HLB). They also raise the possibility of exploiting molecular umbrellas in fundamentally new ways.

Synthesis, Anion Recognition, and Transmembrane Anionophoric Activity of Tripodal Diaminocholoyl Conjugates

“…The strong and selective anion recognition properties of compounds 1 and 2 encouraged us to evaluate their ion transport activity on liposomal models. First, we assess the pH discharge activity of compounds 1 and 2 across vesicular membranes formed from egg-yolk l -α-phosphatidylcholine (EYPC) . In these experiments, large unilamellar vesicles (100 nm diameter, extrusion) were prepared with pyranine encapsulated.…”

“…First, we assess the pH discharge activity of compounds 1 and 2 across vesicular membranes formed from egg-yolk L-α-phosphatidylcholine (EYPC). 31 In these experiments, large unilamellar vesicles (100 nm diameter, extrusion) were prepared with pyranine encapsulated. Here pyranine (pK a = 7.2), a pH-sensitive dye, was used to report the pH changes within the vesicle interior.…”

Recent synthetic transport systems

“…The subtle balance between transport and uptake known from polyion-counterion systems 1,2,[17][18][19] was explored with umbrellas 99-101. 73 The sulfonated umbrella 101 was active in pH discharge and Na + and Cltransport experiments, 645 whereas the slightly more hydrophilic analogues 100 and 99 were not. However, under similar conditions, both umbrellas could cross bilayer membranes and enter into intact vesicles.…”

“…9). [70][71][72][73][74] Because of their amphomorphic nature, these synthetic transport systems are also referred to as molecular umbrellas. 70 Whereas polyion-counterion systems achieve solubility in both hydrophilic and lipophilic environments by dynamic counterion exchange, [17][18][19] umbrellas 94-104 achieve this important adaptability to changing environments on the molecular level by means of rationally designed of 615 amphomorphism.…”

Toward transmembrane anionophores based on rigid bis(choloyl) conjugates: reversal of the ion selectivity by appended polyamines

“…If there is proton or hydroxide transport across the EYPC bilayers, this will lead to a variation in the internal pH of the vesicles and is detected by a change in the uorescence intensity (FI) of pyranine. 10,14 Thus, liposomes were prepared in a buffer containing an anion under study and then a pH gradient was applied. If the transport process is dependent of the anions, this suggests that anion transport is a dominant or rate-determining step and that compound 1 is anion-selective.…”