Hydrogen bonded oligohydrazide foldamers and their recognition for saccharides

This paper describes the synthesis and characterization of the first series of hydrogen bonding-driven hydrazide foldamers and their recognition for alkyl saccharides in chloroform. Oligomers 1, 2-4, 5, 6, and 7, which contain one, two, four, six, or twelve repeated dibenzoyl hydrazide residues, respectively, have been prepared. The rigid and planar conformations of 1 and 2 or 4 have been established with X-ray analysis and H-1 NMR spectroscopy, whereas the folding and helical conformations of 5-7 have been evidenced by the 1D and 2D H-1 NMR and IR spectroscopy and molecular mechanics calculations. Molecular mechanics calculations also revealed that 5, 6, and 7 possess a rigid cavity with size of ca. 10.6 to 11.1 Angstrom, and half of the carbonyl groups in the folding conformations are orientated inwardly inside the cavity. H-1 NMR and CD experiments revealed that 5-7 efficiently complex alkylated mono- and disaccharides 32-35 in chloroform. The association constants (K-assoc) of the complexes have been determined with the H-1 NMR and fluorescent titration methods. The energy-minimized conformation of 6(.)34 has been obtained with molecular mechanics calculation. The hydrazide-based folding structures described here represent novel examples of hydrogen bonding-driven foldamers that act as artificial receptors for selective molecular recognition.