Artificial receptors for molecular recognition of amino acids, peptides and carbohydrates

A convenient method for creating neutrally charged, water soluble calix[4]arenes that contain hydroxyamides attached to their lower rims has been developed; selective amidation reactions of a diacid calix[4]arene with several unprotected hydroxyamides was achieved using EEDQ as the coupling agent. The solubilities of the derivatized calix[4]arenes depended on the structure of the hydroxyamide, as well as, the number of hydroxyl groups. Molecular simulations of the derivatized compounds in water revealed that intramolecular H-bond formation is an important component of solubility. Calix[4]arenes containing ten hydroxyl groups were as soluble in water as a calix[4]arene that contained two carboxylates.; Dialkylammonium templated self-assembled association has been used to synthesize DCC-rotaxanes; N-Boc protected diaminobenzo[24]crown-8 and 5-(3,5-di-tert-butyl-benzylamino)-pentanoic acid hexafluorophosphate salt form a self-assembled complex in chloroform, which is mechanically locked by reacting with DCC. N-Boc protected DCC-rotaxane was used to synthesize phenylalanine and di-p-phenylcalix[4]arene host-[2]rotaxanes. Upon deprotection, corresponding amino host-[2]rotaxanes were obtained in high yields and used for synthesis of artificial receptors. N-acetyl-arginine derivatized di-p-phenylcalix[4]arenes and N-acetyl-arginine derivatized host-[2]rotaxanes were prepared and their ability to perform as artificial receptors was studied. Rotaxane receptors bound N-acetyl protected amino acid carboxylates much stronger than calix[4]arene receptors containing same functional groups. N-acetyl-arginine and glutaric acid derivatized phenylalanine host-[2]rotaxanes were prepared and their structure-function relationship was studied in detail. A relative measure of the intramolecular interaction energies between the functional groups in DMSO-water mixtures was obtained by comparing their p K_a's. Rotaxane structures were investigated through 2D-NMR analysis and molecular dynamics simulations. Association constants for complexes of these rotaxanes and amino acids were determined in a variety of solvent systems by 1H NMR analysis.