SPECIFIC MOLECULAR RECOGNITION BY CHIRAL CAGE-TYPE CYCLOPHANES HAVINGLEUCINE, VALINE, AND ALANINE RESIDUES

Chiral cage-type cyclophanes were constructed with two rigid macrocycl ic skeletons and four bridging components bearing chiral leucine, vali ne, and alanine residues, individually. These host molecules strongly bind anionic and hydrophobic guests, such as 8-anilinonaphthalene-1-su lfonate and 6-p-toluidinonaphthalene-2-sulfonate. Thermodynamic parame ters were evaluated from temperature-dependent complexation constants determined by fluorescence spectroscopy, and gave negative Delta H and positive Delta S values; especially large values for the cage-type cy clophanes having leucine residues. The positive Delta S values come pr imarily from effective desolvation of the guest molecules when incorpo rated into the hydrophobic: host cavities, as evidenced by fluorescenc e parameters. The four bridging segments of the cage-type hosts having chiral amino acid residues seem to undergo chiral twist in the same d irections in the light of circular dichroism (CD) spectroscopy. Such h elical conformations of the cyclophanes must be caused by chiral natur e of the amino acid residues, and the extent of twist in helical confo rmations is as follows; leucine > valine > alanine. In addition, the t wisted direction of bridging segments in the cage-type hosts having L- amino acid residues is opposite to that evaluated for those having D-a mino acid residues, so that the former and latter cyclophanes furnish M- and P-helical cavities, respectively. The chirality-based molecular recognition of the cage-type hosts toward an enantiomeric guest bilir ubin-IX alpha, was investigated by CD spectroscopy in aqueous media.