Chemical Switching of Vesicle Bilayer Membrane Disruption by Bis(crown ether) Bolaamphiphiles

Abstract

Bis(crown ether) bolaamphiphiles derived from 18-crown-6 dicarboxylic acid were prepared, and their ability to release vesicle encapsulated 5[6]-carboxyfluorescein was determined. Bolaamphiphiles with a linear central spacer are poor membrane disrupting agents except in the presence of alkaline earth metal cations or ethylenediammonium cation. Divalent ion enhancement of membrane disruption is cation selective and can be used to determine the apparent association constant of the bolaamphiphile crown ether with the added cation. The cis-isomer of a thioindigo bis(crown ether) bolaamphiphile is an active membrane disrupting agent, but the trans-isomer is significantly less active. In homogeneous solution, cis-to-trans thermal and photochemical isomerization is retarded by added alkaline earth metal salts, indicating that cooperative ditopic binding of the cations occurs despite the inherent flexibility of the bolaamphiphile. The membrane disruption mechanism occurs via U-shaped conformations of the bolaamphiphile. All available data indicate that divalent cations accelerate membrane disruption by stabilization of the U-shaped conformation via cooperative interaction of the crown ethers with the dication. Thus the membrane disruption process is switched "on" by molecular recognition.Semiochemistry is the chemistry of the generation, propagation, conversion, and detection of molecular signals. 1 Much of the current effort to develop chemical model systems which illustrate semiochemical principles is focused on switching phenomena, typically involving photochemical or redox processes. 2 Less attention has been paid to direct molecular or ionic switching, whereby a molecular recognition event controls another supramolecular process. 3 The potential of ionic switching is amply illustrated by the stunning array of biological signaling phenomena, from "simple" receptor-mediated cellular processes to the complex neurophysiological processes of thought and memory. 4 These processes are intimately associated with membranes: ionic signals are propagated along membranes, are transduced through membranes, and are amplified by release of vesicle encapsulated (ionic) signal molecules. Model systems which explore these phenomena must therefore be membrane-based and must be switched by the recognition of molecular signals near the membrane surface.Interfacial molecular recognition has been demonstrated for a variety of systems (guanidinium-phosphate, 5a melamine-barbiturate, 5b,c other hydrogen bonding recognition 5d ) at a variety of interfaces (air-water, 5e supported monolayer-water, 5f vesicle bilayer 5g ). The selectivities and energetics of the molecular recognition are generally those expected from related recognition processes in homogeneous solutions. 5 However, the organization and structure of the interface imposed by the intermolecular organization of the amphiphiles can also play a role. In some cases this effect is reciprocal (binding influences organization 5d ) implying that the interfacial environment can be used t...

Supramolecular nano-architectures and two-dimensional/three-dimensional aggregation of a bolaamphiphilic diacid at the air/water interface

“…Typical amphiphiles, in which one headgroup and one hydrophobic chain are simultaneously contained, play an important role in forming these organized architectures. Recently, bolaamphiphiles, consisting of two polar functional headgroups linked covalently by one or more hydrophobic hydrocarbon chains [15][16][17], are attracting considerable attention due to the unique physiological properties and self-assemble properties [18][19][20][21][22][23][24][25][26][27][28]. Compared with conventional amphiphiles, bolaamphiphiles have potential fascinating properties both in solution and at interface.…”

A membrane-spanning macrocyclic bolaamphiphile lipid mimic of archaeal lipids

“…Early work focussed on macrocyclic bolaamphiphiles bearing short (C 12 -C 18 ) spans that produced much thinner monolayer membranes where it is clear that the macrocycles must be membrane-spanning 16 . An alternative approach involves bolaamphiphiles with a single long hydrophobic strand (ca 3 nm) separating two headgroups 14,17,18 . It is not clear in these cases that the bolaamphiphile is membrane-spanning when mixed with bilayer-forming phospholipids, and U-shaped insertion is common 18,19 .…”

Design and interfacial behavior of two series of gemini amphiphiles with different charge positions based on imidazole moiety

“…Gemini amphiphiles can also be regarded as derived from the bolaamphiphiles by adding two alkyl chains to the headgroups. Compared with the conventional amphiphile (single chain, single headgroup), these special amphiphiles have particularly interesting properties both in solution and at the air/water interface [1][2][3][4][5][6][7][8][9][10][11]. For example, bolaamphiphiles can form various kinds of nanostructures in solution systems and show different kinds of conformations at the air/water interface [7][8][9][10][11].…”

“…Bolaamphiphiles molecules in which two polar functional headgroups are linked covalently by one or more hydrophobic hydrocarbon chains [1][2][3][4][5][6][7][8][9][10][11]. Gemini amphiphiles are molecules containing two headgroups and two aliphatic chains linked by a rigid or flexible spacer.…”