SYNTHESES OF MACROCYCLIC ENZYME MODELS .7. OCTOPUS CYCLOPHANES HAVING L-ASPARTATE RESIDUES AS NOVEL WATER-SOLUBLE HOSTS - AGGREGATION BEHAVIOR AND INDUCED-FIT MOLECULAR RECOGNITION

Octopus cyclophanes (1 and 2), having chiral L-aspartate residues as connector units interposed between a rigid 2,11,20,29-tetraaza[3.3.3.3]paracyclophane skeleton and four double-chain hydrocarbon segments, were prepared. Aggregation behavior of the octopus cyclophanes in aqueous media was characterized by means of electron microscopy as well as by surface tension and dynamic light scattering measurements. Its consequence in guest recognition was clarified by employing 1H NMR, fluorescence, and circular dichroism (CD) spectroscopy. Multiwalled bilayer vesicles were observed in an aqueous dispersion of 1 by negative-staining electron microscopy. The present cationic hosts strongly bind anionic and nonionic hydrophobic guests, such as 8-anilinonaphthalene-1-sulfonate, 6-p-toluidinonaphthalene-2-sulfonate, N-phenyl-1-naphthylamine, and N-phenyl-2-naphthylamine, to form inclusion complexes in 1:1 stoichiometry, regardless of aggregation status of the hosts, monomeric or vesicular. Two types of guest-binding behavior were exercised by the octopus cyclophanes, depending on the nature of media used for preparation of their stock solutions. When an aqueous stock solution of the host was injected into an aqueous buffer containing a guest, the host-guest complexation immediately reached an equilibrium state, as monitored by fluorescence spectroscopy. Concurrently, the chiral L-aspartate residues of the host molecule underwent conformational changes so as to attain effective guest incorporation. 1H NMR spectroscopy applied to the host-guest complexation indicated that the guest molecule was undoubtedly incorporated into the three-dimensional cavity provided intramolecularly by the macrocyclic ring and the eight hydrocarbon chains. On the other hand, when an organic stock solution of 1 in methanol, ethanol, tetrahydrofuran, or dioxane was injected into an aqueous buffer containing a guest, time-dependent and biphasic complexation behavior was observed as reflected in various fluorescence parameters, such as fluorescence intensity, maximum, polarization, lifetime, and rotational correlation time, attributable to the incorporated guest molecule. This behavior is consistent with fast incorporation of a guest molecule into the hydrophobic host cavity followed by slow and long-range conformational changes of the host, as induced by the incorporated guest. Such biphasic complexation behavior was very sensitive to molecular architecture at the connector portions in the hosts. Dynamic aspects of the induced-fit molecular recognition by the present octopus cyclophanes arc discussed. © 1990, American Chemical Society. All rights reserved.