Thermodynamical and geometrical characterization of molecular recognition by cage-type and peptide azapara-cyclophanes in aqueous media

A cage-type cyclophane which is constructed with two rigid macrocyclic skeletons, tetraaza[6.1.6.1]paracyclophane and tetraaza[3.3.3.3]paracyclophane, and four chiral bridging components strongly binds anionic and hydrophobic guests, such as 8-anilinonaphthalene-1-sulfonate and 6-p-toluidinonaphthalene-2-sulfonate. Thermodynamic parameters were evaluated from temperature-dependent complexation constants for the cage-type host and a peptide cyclophane, which was prepared by introducing four valine residues into a tetraaza[6.1.6.1]-paracyclophane skeleton, with the hydrophobic guests as determined by fluorescence spectroscopy. The complexation of the former and latter hosts with the guests gave positive and negative AS values, respectively. The positive AS values come primarily from effective desolvation of the guest molecule incorporated into the hydrophobic host cavity and partly from conformational changes around the bridging moieties of the cage-type host upon complexation, as evidenced by fluorescence polarization and circular dichroism measurements. The geometrical arrangements of the guest molecules in the respective inclusion complexes were clarified by detailed ¹H NMR analysis.