Three novel tris(macrocycle)s having fluorescent residues at their distal termini have been prepared and studied. The compounds are of the form 2), and dansyl (3). Compounds 2 and 3 were found to transport Na + at rates similar to those of other tris(macrocyclic)s but 1 was not an ionophore in the bilayer as assessed by 23 Na NMR analysis. The latter failure may be due to a hydrogen-bond blockade leading to a globular conformation adopted by the hydraphile. The fluorescence maximum of 3 was determined in a variety of solvents and in a phospholipid bilayer. The polarity experienced by the dansyl group in the bilayer was intermediate between that observed in methanol and ethanol. Fluorescence depth quenching using doxylsubstituted lipids showed that the dansyl headgroups of 3 were 14 Å from the bilayer's midplane or separated by about 28 Å. Fluorescence energy transfer between 2 and 3 showed that these two hydraphiles were not appreciably aggregated in the bilayer.

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Previously unreported indoles having hexyl (2), decyl (3), octadecyl (4), and cholestanylacetoxy (5) groups attached to nitrogen have been prepared. A-Methylindole (1) and 2 did not form aggregates detectable by laser light scattering but compounds 3-5 did so. Formation of vesicles was confirmed by size-exclusion chromatography, dye entrapment, and freeze-fracture electron microscopy. The surprising ability of indole to serve as a head group in single-chain, amphiphilic molecules is discussed relative to the indole residue of tryptophan and its role in the anchoring of membrane proteins.

Dibenzyldiaza-18-crown-6 (PhCH2〈N18N〉CH2Ph, 1), di(dodecyldiaza-18-crown-6 (C12H25〈N18N〉C12H25, 2), HOOC(CH2)11〈N18N〉(CH2)11COOH (3), 〈18N〉(CH2)12〈N18N〉(CH2)12〈N18〉 (4), 〈N18N〉(CH2)12〈N18N〉(CH2)12〈N18N〉 (5), C12H25〈N18N〉(CH2)12〈N18N〉(CH2)12〈N18N〉C12H25 (6), PhCH2〈N18N〉(CH2)12〈N18N〉(CH2)12〈N18N〉CH2Ph (7), 4-(p-MeOC6H4CH2〈N18N〉C12)2〈N18N〉 (8), (p-NO2C6H4CH2〈N18N〉C12)2〈N18N〉 (9), and [chol-O-(CH2)2〈N18N〉C12]2〈N18N〉 (10) were studied. Octanol−water partition coefficients were determined for 1, 6, 7, 8, 10, and 3-cholestanyl-OCOCH2〈N18N〉(CH2)12〈N18N〉(CH2)12〈N18N〉COCH2O-3-cholestanyl (11). All were found to favor octanol, and by implication the phospholipid bilayer membrane, by at least 104-fold. Transport of Na+ was assessed in both a phospholipid bilayer and in a bulk CHCl3 membrane phase. Addition of ionophores to the latter was found in some cases to strongly enhance CHCl3 phase hydration. An attempt to correlate transport rates determined in the two systems failed, suggesting that the carrier mechanism, required in the CHCl3 phase, does not apply to the tris(macrocyclic) compounds in the bilayer. Sodium transport rates were also assessed for these compounds by using the bilayer clamp technique. Although Na+ flux rates thus determined for 7−9 in the phospholipid bilayer did not correlate with results obtained by the 23Na-NMR technique, the traces are similar to those obtained with protein channels, further supporting the function of tris(macrocycle)s as channel formers.

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-n-decyl-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.