Construction of receptors with binding sites of specific size, shape, and functional groups is important to both chemistry and biology. Covalent imprinting of a photocleavable template within surface–core doubly cross-linked micelles yielded carboxylic acid-containing hydrophobic pockets within the water-soluble molecularly imprinted nanoparticles. The functionalized binding pockets were characterized by their binding of amine- and acid-functionalized guests under different pH values. The nanoparticles, on average, contained one binding site per particle and displayed highly selective binding among structural analogues. The binding sites could be modified further by covalent chemistry to modulate their binding properties.

The concept of preorganization suggests that organizing a receptor around its guest during binding is detrimental, because the cost of conformational change is assumed to be paid out of the binding energy. Although this concept has historically guided the synthesis of a great many synthetic hosts, in recent years, chemists have begun to synthesize receptors that resemble proteins in their cooperative conformational changes. Such changes could enhance the host–guest interactions, in particular if the binding of the guest triggers previously unengaged noncovalent interactions within the host. These hosts, referred to as cooperatively enhanced receptors, corroborate with their biological counterparts to support the approach of creating high-affinity receptors through the combined strategies of cooperativity and preorganization. Solvents, often the invisible participants of any solution-based supramolecular process, should be properly considered in the design of synthetic receptors, whether preorganized or cooperatively enhanced.

Reverse micelles (RM) were formed in heptane/CHCl₃ with a surfactant carrying the triallylammonium (=triprop-2-en-1-ylammonium) head group (Scheme). Photo-cross-linking with dithiothreitol (=rel-(2R,3R)-1,4-dimercaptobutane-2,3-diol; DTT) captured the RMs and afforded organic, soluble nanoparticles in a one-step reaction. Similar to dendrimers, the cross-linked reverse micelles could encapsulate palladium nanoparticles within their hydrophilic cores and protect them in catalytic reactions. Good to excellent yields were obtained in the Heck coupling of a range of alkyl acrylates (=alkyl prop-2-enoates) and iodobenzenes (Tables 1 and 2). The catalytic activity of the palladium nanoparticles was maintained in several repeated runs.

Three cholate foldamers were synthesized by the click reaction between an azide-functionalized cholate trimer and different dialkynyl linkers. The foldamers were labeled with pyrene groups at the ends for their conformational study. The linkers between the two tricholate fragments were found to strongly influence the conformation of the foldamers in solution, as well as their ability to transport hydrophilic molecules across lipid bilayers. The folding of the oligocholates in mixed organic solvents was studied by fluorescence and UV/Vis spectroscopy. Although these molecules could not fold permanently in lipid bilayers, they were found to translocate carboxyfluorescein readily across by a carrier-based mechanism. The transport is proposed to happen when the oligocholates adopt transiently folded structures with a hydrophobic exterior and a hydrophilic internal cavity. The transport rate strongly depended on the structure of the oligocholates and was sensitive even to the change of a single bond in a foldamer 3000 Da in MW. Better folded oligocholates in solution gave slower transport in the membranes.