Lyle Isaacs and his research team from the University of Maryland have further advanced the structure of the pillararenes to make the host–guest interactions stronger and more specific. “We envisioned to create a higher negative charge density around the mouth of the cavity by introducing acidic sulfate functional groups,” the authors wrote. The negatively charged sulfate groups attract and bind quaternary ammonium ions, which are a hallmark of several clinically important neuromuscular blocking agents. The sulfate groups also stiffened the molecular structure of the barrels, the researchers found, so that the drug guest was smoothly pulled into the cavity by hydrophobic forces.
The researchers dubbed the molecular containers Pillar[n]MaxQ, where n indicates a target-size-dependent diameter that is variable. They observed that this class of sequestering agents binds the neuromuscular blockers up to 100,000-fold more tightly than the cyclodextrin container Sugammadex, which is in clinical use. Moreover, the sequestering agent discriminated against acetyl choline, a natural transmitter substance of nerve impulses within the central and peripheral nervous systems, which should not be sequestered.
Weijian Xue, Peter Y. Zavalij, Lyle Isaacs (2020) Pillar[n]MaxQ: A New High Affinity Host Family for Sequestration in Water. Angew. Chem. 59, 13313-13319. https://doi.org/10.1002/anie.202005902