Formation of Stable Vesicles from N- or 3-Alkylindoles: Possible Evidence for Tryptophan as a Membrane Anchor in Proteins

Twelve indole derivatives have been prepared and studied. Five were 1-substituted: 1, methyl; 2, n-hexyl; 3, n-octyl; 4, n-octadecyl; and 5, cholestanyloxycarbonylmethyl. Four were 3-substituted: 6, methyl; 7, n-hexyl; 8, n-octyl; and 9, n-octadecyl. Three were disubstituted as follows: 10, 1-ndecyl- 3- n-decyl; 11, 1-methyl-3-n-decyl; and 12, 1,3-bis(n-octadecyl)indole. Sonication of aqueous suspensions afforded stable aggregates from 3-5 and 8-12. Laser light scattering, dye entrapment, and electron microscopy were used to characterize the aggregates. Aggregates formed from N-substituted indoles proved to be more robust than those formed from 3-alkylindoles. A stable monolayer formed from 3-n-octadecylindole but not from N- or 1,3-disubstituted analogues by using a Langmuir-Blodgett trough. The formation of aggregates was explained in terms of stacking by the relatively polar indole headgroup. In the monolayer experiment, this force was apparently overwhelmed by H-bonding interactions with the aqueous phase.