1.D.77.  The acyclic bolaamphiphile (ACBA) Family 

 Bolaform surfactants, bolaphiles, alpha-omega-type surfactants or bolaampiphiles are amphiphilic molecules that have hydrophilic groups at both ends of a sufficiently long central hydrophobic carbon chain. Compared to single-headed amphiphiles, the introduction of a second head-group generally gives rise to higher solubility in water, an increase in the critcal micellar concentration (cmc), and a decrease in aggregation number. The aggregate morphologies of bolaamphiphiles include spheres, cylinders, disks, and vesicles. Bolaamphiphiles are also known to form helical structures, that can form monolayer microtubular self-assemblies. Acyclic bolaamphiphiles form ion channels in vesicles and planar bilayer membranes that resemble channels formed by related bismacrocyclic compounds. The functions of these ion channels do not depend on synthetically difficult macrocyclic subunits (Fyles et al. 2001).

The synthesis of macrocyclic tetraesters from 5-substituted isophthalic acids and 1,8-octane diol gave macrocylic metacyclophanes with the axially symmetric positions differentially protected. Dimer bis(metacyclophane)bolaamphiphiles is largely insoluble, but one derivative had membrane activity with high continuous conductance and the formation of discrete single-ion channels. This depended on how the compound was incorporated into the bilayer membrane (Cameron et al. 2002).

Ion channel activities of three bola-amphiphiles, derived from a bis-cyclophane bola-amphiphile through opening of the cyclophanes to acyclic structures, were found to form ion channels in planar bilayer membranes. All three compounds behaved similarly: the dominant channels formed by all three are Ohmic with specific conductance of 10 +/- 1 pS (NaCl electrolyte) and 39 +/- 1 pS (CsCl electrolyte). Single-ion permeability ratios, determined from dissymmetric electrolyte experiments, showed the selectivity P(Cs+) > P(Na+) > P(Cl-). Lower conductance channels were observed to act independently of the dominant channels. The lifetimes of the dominant channels range from 70 to 280 ms for the three compounds with some very long-lived openings (20-40 s) observed for two of the three. The lower conductance states have shorter lifetimes. Thus, bis-macrocyclic compounds are not essential for channel formation by bola-amphiphiles (Eggers et al. 2003).



Cameron, L.M., T.M. Fyles, and C.W. Hu. (2002). Synthesis and membrane activity of a bis(metacyclophane)bolaamphiphile. J Org Chem 67: 1548-1553.

Eggers, P.K., T.M. Fyles, K.D. Mitchell, and T. Sutherland. (2003). Ion channels from linear and branched bola-amphiphiles. J Org Chem 68: 1050-1058.

Fyles, T.M., Hu Cw, and R. Knoy. (2001). Transmembrane ion conductance by an acyclic bolaamphiphile. Org Lett 3: 1335-1337.