Hydrophobic Collapse of Foldamer Capsules Drives Picomolar-Level Chloride Binding in Aqueous Acetonitrile Solutions

Aqueous media are competitive environments
in which to perform
host–guest chemistry, particularly when the guest is highly
charged. While hydrophobic binding is a recognized approach to this
challenge in which apolar pockets can be designed to recognize apolar
guests in water, complementary strategies are required for hydrophilic
anions like chloride. Here, we present evidence of such an alternative
mechanism, used everyday by proteins yet rare for artificial receptors,
wherein hydrophobic interactions are shown to be responsible for organizing
and stabilizing an aryl-triazole foldamer to help extract hydrophilic
chloride ions from increasingly aqueous solutions. Therein, a double-helical
complex gains stability upon burial of ∼80% of the π
surfaces that simultaneously creates a potent, solvent-excluding microenvironment
for hydrogen bonding. The chloride’s overall affinity to the
duplex is substantial in 25% water v/v in acetonitrile (log β2 = 12.6), and it remains strong (log β2 = 13.0) as the water content is increased to 50%. With the rise
in predictable designs of abiological foldamers, this water-assisted
strategy can, in principle, be utilized for binding other hydrophilic
guests.