Calix[4]arenes and Resorcinarenes Bridged at the Wider Rim

The calixarenic receptors exhibit remarkable host-guest properties towards biologically relevant guests. Aspects of complex formation reactions between both native and derivatized amino acids, di-and tripeptides with calixarenic (chiral or not) receptors are summarized in this critical review. Thus, the discussions emphasize the parameters that affect the molecular binding selectivity and efficiency of functionalized calix[n]arenes towards these substrates. A brief survey on their application in separation of amino acids is also considered (123 references).

This Account reviews the synthesis, conformations, and supramolecular properties of calixarenes endowed with alpha-amino acids or peptides (Peptidocalixarenes) and carbohydrate units (Glycocalixarenes), with a major emphasis on calix[4]arenes functionalized on the aromatic nuclei (upper or wide rim). Most properties of N-linked peptidocalix[4]arenes are found to be quite different from those of the corresponding C-linked derivatives. An interesting example is the tendency of C-linked peptidocalix[4]arenes to form self-assembled nanotubes in the solid state. In several cases the hydrogen bonding donor and acceptor groups of the amino acid residues and the cavity of cone calix[4]arenes act cooperatively in guest binding in nonpolar solvents but not in water, where hydrophobic interactions dominate. Upper-rim bridged peptidocalix[4]arenes act as vancomycin mimics being able to bind d-alanyl-d-alanine (d-Ala-d-Ala) residues. Glycocalix[4]arenes show the phenomenon of multivalency in their binding to specific lectins, and those bearing thiourea spacers between the calix[4]arene scaffold and the sugar units are able to bind aromatic carboxylates and phosphates, making them attractive as novel site specific drug delivery systems.