Molecular recognition properties of acyclic cucurbiturils toward amino acids,peptides, and a protein

The binding of 1 and 2 toward 19 amino acid amides by ¹H NMR and ITC is reported. Hosts 1 and 2 bind to aromatic or hydrophobic residues by cavity inclusion leaving the cationic residues at the C=O portals. K_a values range from 10² to >10⁶ M^?1 with H-Phe-NH₂, H-Trp-NH₂, and H-Tyr-NH₂ displaying sub-micromolar K_d values. Hosts 1 and 2 bind tightly to dicationic H-Lys-NH₂ and H-Arg-NH₂ which are poor guests for CB[7]. Comparison of the affinity of 1 and 2 toward the amino acid amide, N-acetyl-amino-acid amide, and amino acid forms of Phe revealed that the removal of the NH₃⁺ to O=C and SO₃^? electrostatic interactions costs 3.8 kcal/mol whereas the introduction of an unfavourable CO₂^? to O=C and SO₃^? electrostatic interactions costs 2.1 kcal/mol. Hosts 1 and 2 bind to insulin with low micromolar affinity. Acyclic CB[n] display high affinity toward a wider range of N-terminal amino acids residues than CB[n] which suggests a broad range of applications.