ULTRATHIN MONOLAYER LIPID-MEMBRANES FROM A NEW FAMILY OF CROWN ETHER-BASED BOLA-AMPHIPHILES

Twelve novel alpha,OMEGA-bis(N-azacrown ether) compounds have been prepared, characterized, and converted into a previously unknown type of niosome. Four are bis(15-crown-5) derivatives having the following spacer chains: (CH2)12 (1), (CH2)16 (2), CO(CH2)20CO (3), and (CH2)22 (4). The eight bis(aza-18-crown-6) derivatives have the following spacers: (CH2)10 (5), CO(CH2)10CO (6), (CH2)12 (7), CO(CH2)14CO (8), (CH2)16 (9), (CH2)22 (10), (CH2)12O(CH2)12 (11), and CO(CH2)11S(CH2)12S(CH2)11CO (12). Aggregation studies of 1 and 7, employing transmission electron microscopy as well as dynamic and static light scattering, demonstrate that these compounds form a novel class of spherical monolayer lipid membrane vesicles when dispersed in water. Debye light-scattering profiles obtained from a suspension of large (almost-equal-to 200 nm diameter) vesicles indicate a relative refractive index near 1. Dynamic turbidimetry in acidic media on a suspension of bola-amphisomes formed from 1, suggested that the contribution of micelle-vesicle equilibria to the bolyte aggregation state is negligible. In neutral or slightly alkaline pH at 35-degrees-C, the vesicles grew irreversibly to yield large, probably multilamellar, aggregates. In acidic media at pH 2, the bola-amphisomes do not coalesce, even at 65-degrees-C. On the basis of the observations presented here, bola-amphiphiles having a hydrocarbon span of 10-12 carbon atoms aggregate in aqueous media into vesicles. When the aliphatic backbone incorporates 16 or more carbon atoms, micelles are formed.