Calixarene‐Mediated Liquid‐Membrane Transport of Choline Conjugates

Abstract

A series of supramolecular calixarenes efficiently transport distinct molecular species through a liquid membrane when attached to a receptor-complementary choline handle. Calix-[6]arene hexacarboxylic acid was highly effective at transporting different target molecules against a pH gradient. Both carboxylic- and phosphonic-acid-functionalized calix[4]arenes effect transport without requiring a pH or ion gradient. NMR binding studies, two-phase solvent extraction, and three-phase transport experiments reveal the necessary and subtle parameters to effect the transport of molecules attached to a choline “handle”. On the other hand, rescorin[4]arene cavitands, which have similar guest recognition profiles, did not transport guest molecules. These developments reveal new approaches towards attempting synthetic-receptor-mediated selective small-molecule transport in vesicular and cellular systems.

Paramagnetic Molecular Grippers: The Elements of Six-State Redox Switches

“…This behavior renders them promising for applications as transporters, 7,8 sensors, 9−15 nanoreactors, 14,16−21 or elements in nanorobotics. 4,7,8,22,23 Resorcin [4]arenes are suitable platforms for the development of molecular grippers, owing to their capability to adopt bistable, open (kite) and closed (vase) conformations.…”

Calixarene‐Mediated Liquid Membrane Transport of Choline Conjugates 2: Transport of Drug‐Choline Conjugates and Neurotransmitters

“…Indeed, our original work on transport unveiled very different behaviors with carboxyfluorescein (no transport) versus FITC–choline (transport). [1] We observed some transport in vesicle systems for calcein. Lacking a trimethylammonium, or ammonium group we carried out three-phase transport experiments as described above and found amplified guest molecule transport in response to the use of host 1 .…”

“…We have previously demonstrated the significance and selectivity of the choline handle. [1] However, given the number of ionizable groups on 10 , we decided to confirm that the choline handle is required for transport for this polyfunctional molecule. Parent compound bentiromide [21] presented some challenges associated with its poor solubility.…”

“…Previously, we had shown that choline-fluorescein and choline-NBD dye conjugates were transported across a three-phase liquid membrane system with significant enhancements in the presence of calixarenes 1 , 2 , and 4 . [1] The parent compounds carboxyfluorescein and NBD chloride, both lacking receptor complementary choline handles failed to undergo such transport. We now show that this strategy extends beyond fluorophores; an amino acid, acetaminophen, ibuprofen and bentiromide also are amenable to such transport processes.…”

“…[1] Our results indicated that the presence of ionizable, pre-organized functional groups such as those on a calixarene scaffold enable effective transport of choline-fluorophore conjugates. Moreover, the tetraphosphonic acid calix[4]arene 1 was capable of transporting choline conjugates without a complementary inverse pH gradient.…”