SYNTHETIC TRANSMEMBRANE CHANNELS - FUNCTIONAL-CHARACTERIZATION USING SOLUBILITY CALCULATIONS, TRANSPORT STUDIES, AND SUBSTITUENT EFFECTS

Dibenzyldiaza-18-crown-6 (PhCH2[N18N]CH2Ph, 1), di(dodecyldiaza-18-cro wn-6 (C12H25[N18N]C12H25, 2), HOOC(CH2)(11)[N18N](CH2)(11)COOH (3), (1 8N)(CH2)(12)[N18N](CH2)(12)[N18] (4), [N18N](CH2)(12)[N18N](CH2)(12)[N 18N] (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]C-1 2)(2)[N18N] (8), (p-NO2C6H4CH2[N18N]C-12)(2)[N18N] (9), and [chol-O-(C H2)(2)[N18N]C-12](2)[N18N] (10) were studied. Octanol-water partition coefficients were determined for 1, 6, 7, 8, 10, and (CH2)(12)[N18N](C H2)(12)[N18N]COCH2O-3-cholestanyl (11). All were found to favor octano l, and by implication the phospholipid bilayer membrane, by at least 1 0(4)-fold. Transport of Na+ was assessed in both a phospholipid bilaye r and in a bulk CHCl3 membrane phase. Addition of ionophores to the la tter was found in some cases to strongly enhance CHCl3 phase hydration . An attempt to correlate transport rates determined in the two system s failed, suggesting that the carrier mechanism, required in the CHCl3 phase, does not apply to the tris(macrocyclic) compounds in the bilay er. Sodium transport rates were also assessed for these compounds by u sing the bilayer clamp technique. Although Na+ flux rates thus determi ned for 7-9 in the phospholipid bilayer did not correlate with results obtained by the Na-23-NMR technique, the traces are similar to those obtained with protein channels, further supporting the function of tri s(macrocycle)s as channel formers.