Alkali metal cation-pi interactions observed by using a lariat ether model system.

The Na(+) or K(+) cation-pi interaction has been experimentally probed by using synthetic receptors that comprise diaza-18-crown-6 lariat ethers having ethylene sidearms attached to aromatic pi-donors. The side chains are 2-(3-indolyl)ethyl (7), 2-(3-(1-methyl)indolyl)ethyl (8), 2-(3-(5-methoxy)indolyl)ethyl (9), 2-(4-hydroxyphenyl)ethyl (10), 2-phenylethyl (11), 2-pentafluorophenylethyl (12), and 2-(1-naphthyl)ethyl (13). Solid-state structures are reported for six examples of alkali metal complexes in which the cation is pi-coordinated by phenyl, phenol, or indole. Indole-containing crown, 7, adopts a similar conformation when bound by NaI, KI, KSCN, or KPF(6). In each case, the macroring and both arenes coordinate the cation; the counteranion is excluded from the solvation sphere. NMR measurements in acetone-d(6) solution confirm the observed solid-state conformations of unbound 7 and 7.NaI. In 7.Na(+) and 7.K(+), the pyrrolo, rather than benzo, subunit of indole is the pi-donor for the alkali metal cation. Cation-pi complexes were also observed for 10.KI and11.KI. In these cases, the orientation of the cation on the aromatic ring is in accord with the binding site predicted by computational studies. In contrast to the phenyl case (11) the pentafluorophenyl group of 12 failed to coordinate K(+). Solid-state structures are also reported for 7.NaPF(6), 10.NaI, 11.NaI, 13.KI, 13.KPF(6), and 9.NaI, in which cation-pi complexation is not observed. Steric and electrostatic considerations in the pi-complexation of alkali metal cations by these lariat ethers are thought to account for the observed complexation behavior or lack thereof.

Synthetic receptors as models for alkali metal cation-pi binding sites in proteins.

The alkali metal cations Na(+) and K(+) have several important physiological roles, including modulating enzyme activity. Recent work has suggested that alkali metal cations may be coordinated by pi systems, such as the aromatic amino acid side chains. The ability of K(+) to interact with an aromatic ring has been assessed by preparing a family of synthetic receptors that incorporate the aromatic side chains of phenylalanine, tyrosine, and tryptophan. These receptors are constructed around a diaza-18-crown-6 scaffold, which serves as the primary binding site for an alkali metal cation. The ability of the aromatic rings to coordinate a cation was determined by crystallizing each of the receptors in the presence of K(+) and by solving the solid state structures. In all cases, complexation of K(+) by the pi system was observed. When possible, the structures of the unbound receptors also were determined for comparison. Further proof that the aromatic ring makes an energetically favorable interaction with the cation was obtained by preparing a receptor in which the arene was perfluorinated. Fluorination of the arene reverses the electrostatics, but the aromaticity is maintained. The fluorinated arene rings do not coordinate the cation in the solid state structure of the K(+) complex. Thus, the results of the predicted electrostatic reversal were confirmed. Finally, the biological implications of the alkali metal cation-pi interaction are addressed.

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-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.