Template-Directed Synthesis of Bivalent, Broad-Spectrum Hosts for Neuromuscular Blocking Agents

We report on the synthesis of bivalent water-soluble calix[4]arene and calix[5]arene hosts, Super-sCx4 and Super-sCx5 as new broad-spectrum supramolecular binders of neuromuscular blocking agents (NMBAs). Synthesis was achieved using the target bisquaternary amine NMBAs as a template to link two highly anionic p-sulfonatocalixarene building blocks in aqueous solution. Bivalent anionic hosts Super-sCx4 and Super-sCx5 bind by engaging both quaternary amines present on a variety of NMBAs. We report low μM binding to structurally diverse alkyl, steroidal, curarine and benzylisoquinoline NMBAs with high selectivity over the neurotransmitter acetylcholine and a variety of other hydrophobic amines.