Synthesis and properties of peptoads: A group of amphiphilic long-chain tri-amides

ORGN 17

Hailing Zhang, hzhan22@emory.edu and Fredric M. Menger, menger@emory.edu. Department of Chemistry, Emory University, 1515 Dickey Drive, Atlanta, GA 30322
A new class of amphiphilic compounds (dubbed “peptoad”) has been synthesized. The properties of these molecules have been investigated by X-ray analysis, solubility studies, light and electron microscopy, surface tensiometry, light scattering, and drug dissolution. In the solid state the peptoads assemble in layers with both intra- and inter-layer hydrogen-bonding coupled to side-by-side proximity of the hydrocarbon chains. Peptoads with a terminal primary amide, and a total of three amide NH sites, are water-insoluble owing presumably to attractive forces in the solid state. However, peptoads with terminal –CONMe2 groups, and two internal amide NH sites, are water-soluble at room temperature. This solubility is critically dependent upon the chain-length. Water-soluble peptoads can lower water's surface tension as effectively as a soap with a much longer chain. A peptoad solubilizes a water-insoluble drug, albendazole, seven times more effectively than does Cremophor EL, a commercial excipient widely used with taxol and other non-polar drugs.