Acyclic Cucurbit[n]uril Type Receptors: Secondary Versus Tertiary Amide Arms.

Two acyclic CB[]-type hosts ( and ) which possess four 2° or 3° amide arms are reported; and are slightly soluble in water and do not self-associate. Host has four 3° amide arms that exist as a mixture of E- and Z-isomers. H NMR was used to qualitatively investigate the binding properties of and which indicates they retain the essential binding features of macrocyclic CB[] hosts (e.g. cavity binding of hydrophobic residues and portal binding of cationic groups). We measured the K values of and toward guests - , methamphetamine, and fentanyl by ITC to evaluate their potential as sequestration agents. Neutral hosts and bind less tightly than tetraanionic hosts , , and . We attribute the lower K values to the absence of secondary ion-ion (ammonium•••sulfonate or ammonium•••carboxylate) electrostatic interactions for host•guest complexes of and . The secondary amide functionality on decreases affinity by formation of intramolecular NH•••O=C H-bonds. Tertiary amide host binds even more weakly than due to backfolding of the amide N-CH-groups of into its own cavity. The x-ray crystal structure of supports this conclusion.