Sterically and guest-controlled self-assembly of calix[4]arene derivatives

In solvents such as chloroform or benzene, tetraurea calix[4]-arenes I form dimeric capsules in which one solvent molecule is usually included as guest. To explore the structural requirements for the formation of such hydrogen-bonded dimers we replaced one p-tolylurea residue by a simple acetamide function. The resulting calix[4]arene 2a, substituted at its wide rim with one acetamide and three p-tolylurea functions, assumes a C-1-symmetrical conformation in apolar solvents as shown by H-1 NMR, which is not compatible with the usual capsule. In the crystalline state, four molecules of 2a, adopting a pinched cone conformation, assemble into a quasi S,symmetrical tetramer stabilized by a cyclic array of 24 (NHO)-O-...=C hydrogen bonds and four NH(...)pi interactions. Four acetamide groups are hydrogen-bonded to each other and pack tightly in the center of the assembly. All polar residues are buried inside the tetramer, the surface of which is lipophilic. Extensive NMR studies revealed similar structures in apolar solvents such as [D]chloroform or [D-6]benzene for calix-acetamides 2a-c. The formation of these tetramers in solution is critically dependent on the size of the amide fragment, so that propionamide 2d, butyramide 2 e, and p-tolylamide 2f form only ill-defined aggregates. This is caused by steric crowding inside the tetrameric assembly. The tetramers persist during molecular dynamics simulations, and the optimized average structure of the MD run is similar to that found in the crystalline state. Theoretical studies revealed that cooperation of hydrogen bonds with multiple NH(...)pi, C-H(...)pi, and pi(...)pi attractions make the tetramer more stable than the capsular dimer with the solvent as guest. In the presence of tetraethylammonium salts, however, compounds 2a-e form dimeric capsular assemblies, each incorporating a single ammonium cation. Only one of two possible regioisomeric dimers is formed, in which both acetamide groups are surrounded by two urea residues. These examples give striking evidence of how self-assembly in solution can be strongly dependent on subtle structural factors and of how the formation of dimeric capsules can be induced by the presence of an appropriate guest.