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

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 center dot DL-Pro]center dot 2MeOH center dot 3.5H(2)O (1) and 2[PCf center dot L-Pro]center dot 2EtOH center dot 10H(2)O (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 center dot center dot center dot pi interactions between alkyl protons of the pyrrolidine ring of proline and 7-rings of RCT or PCT, forming an [RCT/PCT center dot Pro] structural fragment. In the crystal lattice, two [RCT/PCT center dot Pro] fragments self-associate to form a ligand-mediated dimeric structure, [RCT center dot D-Pro center dot L-Pro center dot RCT] in I or [PCT center dot L-Pro center dot L-Pro center dot PCT] in 2. A H-1 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 center dot center dot center dot pi interaction. The CSD survey revealed that the absolute value of the torsion angle N-C-alpha-C-O1 (O1 is cis to N) about the carboxyl C-alpha-C bond of proline is significantly smaller than that of the C-beta-C-alpha-C-O2 (O2 is cis to C-beta) torsion angle. (C) 2018 Published by Elsevier B.V.