Synthetic receptors are modern tools for investigations into the forces involved in recognition. A widely exploited class of receptors are the resorcin[4]arene-based cavitands and capsules. This critical review (71 references) describes the evolution of water-soluble versions of these structures, along with insights the resulting host-ndash complexes have provided with regard to complexation driving forces in water. An emphasis has been placed on the influence of host structure on guest affinity and dynamics.

We describe here the synthesis and characterization of a molecular receptor that forms kinetically and thermodynamically stable host-guest complexes in water. This cavitand-based host is composed of a preorganized aromatic pocket whose rim is decorated with four negatively charged carboxylate groups. (1)H NMR and isothermal titration calorimetry have been used to characterize the behavior of the resulting complexes in response to changes in pH, buffer identity, and salt concentration and in the presence of sodium dodecyl sulfate micelles.

We have developed and studied water-soluble [M 4 L 6 ] 12metal ligand clusters such as 1 (Figure 1; M = Ga(III), L = 1,5biscatecholamide naphthalene). These clusters contain a hydrophobic cavity of approximately 300-500 Å 3. 2,3 Surveys of potential guests have led to the finding that the clusters are capable of encapsulating a variety of monocations including tetraalkylammonium salts, 4 reactive phosphonium species 5 and half-sandwich ruthenium complexes. 6,7 Early studies 8 with the Et 4 N[Ga 4 L 6 ] 11complex did not show neutral guest encapsulation; since then, it has been generally assumed that because of the highly anionic character of these clusters, encapsulation requires a positively charged guest. Recently, we found that the [Ga 4 L 6 ] 12host catalyzes the hydrolysis of orthoformates 9 and acetals 10 in an enzyme-like manner. In these studies, kinetic evidence suggested that the initial event in the catalytic cycle involved the binding of the neutral substrate to give a transient orthoformate-or acetal-cluster intermediate. 9,10 Intrigued by these results, we sought to determine whether we could directly observe the binding of neutral guest molecules by this highly charged, anionic host. We now report that this cluster binds neutral, hydrophobic guests, including saturated hydrocarbons, 11,12 in aqueous solution, with both size and shape selectivity. 13

A deep, water-soluble cavitand extracts n-alkanes and other water-insoluble species into its cavity via hydrophobic forces: alkanes bind in a helical manner, and tumble rapidly on the NMR timescale inside the binding pocket.

The design and synthesis of alpha-helix peptidomimetics using inverse electron demand Diels-Alder reactions is described. The potency of the resulting pyridazine-based library to disrupt the Bak/Bcl-X(L) interaction was tested using an in vitro fluorescence polarization assay.