Persistent Organic Nanopores Amenable to Structural and Functional Tuning

Abstract

Rigid macrocycles 2, which share a hybrid backbone and the same set of side chains while having inner cavities with different inward-pointing functional groups, undergo similar nanotubular assembly as indicated by multiple techniques including (1)H NMR, fluorescence spectroscopy, and atomic force microscopy. The formation of tubular assemblies containing subnanometer pores is also attested by the different transmembrane ion-transport behavior observed for these macrocycles. Vesicle-based stopped-flow kinetic assay and single-channel electrophysiology with planar lipid bilayers show that the presence of an inward-pointing functional (X) group in the inner cavity of a macrocyclic building block exerts a major influence on the transmembrane ion-transporting preference of the corresponding self-assembling pore. Self-assembling pores with inward-pointing amino and methyl groups possess the surprising and remarkable capability of rejecting protons but are conducive to transporting larger ions. The inward-pointing groups also resulted in transmembrane pores with a different extent of positive electrostatic potentials, leading to channels having different preferences for transporting chloride ion. Results from this work demonstrate that synthetic modification at the molecular level can profoundly impact the property of otherwise structurally persistent supramolecular assemblies, with both expected tunability and suprisingly unusual behavior.

Anion transport and supramolecular medicinal chemistry

“…Recently, Gong and colleagues have extended this selfassembly strategy to form transmembrane ion channels from aromatic oligoamide macrocycles, such as 29-H and 29-NH 2 . 16 The authors hypothesized that a transmembrane pore would form if about 10 macrocycles stacked one on another to give a nanotube of ca. 34 Å, a distance matching the thickness of the hydrophobic portion of the bilayer membrane.…”

Heli(aza)cene: A Helical Molecular Tweezer with Tunable Intra‐ and Intermolecular Charge Transfer

“…In stark contrast to the emission profile, the excitation spectra (monitored at the emission maxima, Figure b) showed a continuous blueshift ( l ex decreasing from 364 to 350 nm) along with a decrease in the intensity of the ICT band at 398 nm (Figure b) as the concentration of HAC was increased (blue line in Figure c). This suggests that HAC forms H‐type aggregates and IMCT increases as its concentration was increased . However, the strong IMCT in these aggregates cause the overall emission profile to show a redshift.…”

Using Fluorescence to Enable Innovative Functions of Foldamers

“…In this complex system, the number of macrocycles in the host stack was related to the length of the guest dye. This supramolecular host built on earlier work from the same laboratory that employed fluorescence to evaluate the stacking of other macrocycles that include aromatic oligoamide and phenylene ethynylene units [58] . Although macrocycle 23 itself is not strictly considered a foldamer, macrocycles composed of common foldamer units have been commonly used to interrogate and model the interactions of more conformationally flexible foldamer analogs.…”