Evidence for inclusion complexation in solution between cucurbituril (C36H36N24012) and various alkyl-and aryl-substituted ammonium ions is elaborated. Induced NMR chemical shifts and UV spectral perturbations of guests complexed within cucurbituril are noted and may be used to quantitate binding. Dissociation constants (K¿) for over 50 guests are recorded, and the kinetics of complexation have also been investigated. On the basis of selectivity among bound species, a detailed model for the structure of the host-guest complexes is deduced. The cavity within cucurbituril has dimensions equivalent to the size of a para-disubstituted benzene ring. Successful inclusion is attributable to hydrophobic interactions (freeing of solvent molecules upon complexation) and to a charge-dipole attraction between ammonium cations and the electronegative oxygens of the urea moieties in cucurbituril.
For the synthetic receptor cucurbituril, the rate of inclusion complex formation correlates with the molecular diameter of alkylammonium ion ligands but not with the thermodynamic stability of the complexes formed. Measurements of 13C NMR spin-lattice relaxation allow comparison of molecular tumbling motions of the receptor with those of bound ligands, by determination at their respective correlation times. Guest ions appear to rotate relatively freely within cucurbituril, irrespective of the stability of the complexes. Results are interpreted in terms of shape complementarity between receptor and ligand.
Experimental binding energies for 24 substituted ammonium ion ligands for the synthetic receptor cucurbituril are adjusted for ligand solvation and then are factored by regression analysis into contributions from various fragments of the ligands in their inclusion complexes. This allows quantitative estimation of noncovalent forces occurring in the interaction of ligand with receptor. It is concluded that the center of cucurbituril constitutes a lipophilic region but that the entrances to the interior (ammonium ion binding site) are countervailingly lipophobic. Enhanced dispersion forces involving the thioether functional group may exist in the receptor complexes of such ligands, but they make no extra contribution to the hydrophobic effect generally. The specificity of cucurbituril as a molecular receptor is explained in terms of ion-dipole attractions and shape complementarity with ligands.The phenomenon of noncovalent bonding is a topic of major significance to investigators of interactions between biological molecules. The weak intrinsic affinities between nonpolar moieties in aqueous solution are thought to be responsible for the aggregation of lipids, and in many instances for the binding of enzyme substrates, inhibitors, hormones, antigens, etc. to their receptor sites. These noncovalent forces involving small molecules are sufficiently weak that as a practical matter they can only be studied when their effects are cumulative. In this regard the recent availability of synthetic molecular ligand-receptor systems introduces major opportunities for systematic chemical investigation of this important, but ill-understood topic.Cucurbituril (Figure 1) is a novel nonadecacyclic cage compound of hexagonal symmetry, which is readily assembled by
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