Synthetic transmembrane channels: Functional characterization using solubility calculations, transport studies, and substituent effects

Article abstract of DOI:10.1021/ja962694a

Dibenzyldiaza- 18-crown-6 (PhCH₂CH₂Ph, 1), di(dodecyldiaza-18- crown-6(C₁₂H₂₅C₁₂H₂₅, 2), HOOC(CH₂)₁₁(CH₂)₁₁COOH (3), <18N>(CH₂)₁₂(CH₂)₁₂ (4), (CH₂)₁₂(CH₂)₁₂ (5), C₁₂H₂₅(CH₂)₁₂(CH₂)₁₂C₁₂H₂₅ (6), PhCH₂(CH₂)₁₂(CH₂)₁₂CH₂Ph(7), 4-(p- MeOC₆H₄CH₂C₁₂)₂ (8), (p-NO₂C₆H₄CH₂C₁₂)₂ (9), and [chol-O-(CH₂)₂C₁₂]₂(N18N) (10) were studied. Octanol- water partition coefficients were determined for 1, 6, 7, 8, 10, and 3- cholestanyl-OCOCH₂(CH₂)₁₂(CH₂)₁₂COCH₂O-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.