Crystal structures of resorcin[4]arene and pyrogallol[4]arene complexes with proline: A model for proline recognition through C H···π interaction

Abstract Resorcin[ 4 ]arene (resorcinol cyclic tetramer, abbreviated as RCT) or pyrogallol[ 4 ]arene (pyrogallol cyclic tetramer, PCT) form host–guest 1:1 complexes with DL-proline (DL-Pro) or l -proline (L-Pro), [RCT·DL-Pro]·2MeOH·3.5H2O (1) and 2[PCT·L-Pro]·2EtOH·10H2O (2), whose crystal structures have been determined. In each complex, the proline ligand is incorporated into the bowl-shaped cavity of RCT or PCT host molecules through C H … π interactions between alkyl protons of the pyrrolidine ring of proline and π-rings of RCT or PCT, forming an [RCT/PCT·Pro] structural fragment. In the crystal lattice, two [RCT/PCT·Pro] fragments self-associate to form a ligand-mediated dimeric structure, [RCT·D-Pro·L-Pro·RCT] in 1 or [PCT·L-Pro·L-Pro·PCT] in 2. A 1H NMR solution study gave the host‒ligand binding constants of 10.0 ± 1.1 M–1 for the RCT–DL-Pro system and 17.3 ± 1.3 M–1 for the PCT–L-Pro system. These complexes provide a synthetic model for the recognition of the proline residue in proline-containing substrates or inhibitors by enzymes through C H … π interaction. The CSD survey revealed that the absolute value of the torsion angle N–Cα–C O1 (O1 is cis to N) about the carboxyl Cα–C bond of proline is significantly smaller than that of the Cβ–Cα–C O2 (O2 is cis to Cβ) torsion angle.