Compartmentalization is an essential facet of living organisms and an intriguing method of introducing complexity into chemical systems. We are interested in the formation of extremely well defined supramolecular assemblies that display novel and or complex behavior via encapsulation. Beyond the search for new phenomena and the notion of complexity, we are interested in how the hydrophobic effect can drive self-assembly and encapsulation processes. To date, research into non-natural self-assemblies has primarily focused on those driven by enthalpy. In contrast, entropy is more often than not the principle contributor to both intra- and inter-molecular associations of organic systems in water. That said, although the hydrophobic effect has been recognized for some seventy years, there are still many contradictions in the empirical data gathered and much still to learn. Thus, in addition to engendering complexity and revealing new phenomena, the self-assembling systems we are studying offer a unique view on the hydrophobic effect.
Water-soluble cavitands such as that shown below (Figure 1) are central to our studies. They form 1:1 host-guest complexes with amphiphilic guest molecules, and 2:1 and 2:2 capsular complexes with more hydrophobic guests. Figure 1b shows the encapsulation of two different guest molecules. Many unusual phenomena are engendered by these assemblies, some of which are highlighted below.
Figure 1: a) A water-soluble deep-cavity cavitand. b) Cartoon of its assembly in the presence of a suitable guest.
Drug Delivery with Supramolecular capsules
Aqueous-based supramolecular assemblies that assemble via the hydrophobic effect are ideal candidates for drug delivery systems. With this long-term goal in mind, we are examining how supramolecular capsules can bestow thermodynamic and kinetic stability to drug candidates that proved unsuccessful because their essential pharmacophore is insufficiently stable in aqueous solution. Stabilization relies on a complex relationship between the structures of the host and guest, and the nature of the attacking species in free solution (Figure 2). In a similar vein, we are also looking at how encapsulation can solubilize drug candidates whose activity is inhibited by limited solubility in water.
Figure 2: Schematic representation of stabilization of drug candidates via encapsulation.
We are also interested in how supramolecular assemblies can be used as external (concave) templates to control reactions carried out within their interiors. Synthetically, the easiest way to do this is to study the photochemistry of encapsulated guests. This work is therefore carried out in collaboration with the Ramamurthy Group at the University of Miami, and the Turro Group at Columbia University. One recent example is an analysis of how the packing motif of the guest influences the photochemistry of the encapsulated guest (Figure 3). For the range of dibenzyl ketone guest from R = Me to R = n-octyl, three distinct packing motifs are observed depending on the length of the alkyl chain. Each motif results in a distinct product or set of products, many of which are not observed when the reaction is carried out in free solution.
Figure 3: Different guest packing motifs within supramolecular capsules lead to very different reaction outcomes.
With two thirds of the world’s hydrocarbon energy reserves in the form of methane – the majority of which exists as currently inaccessible clathrate – and the increasing prominence of biofuels such as low molecular weight alcohols, there is considerable interest in identifying new ways to isolate and/or separate these substances. We are interested in developing aqueous solution-based technologies for these goals. By way of example (Figure 4), we have reported on how aqueous solutions of cavitands can be used to selectively sequester hydrocarbon gases from the gas-phase and hence bring about their separation. Thus, only butane is extracted from a gas-phase containing both butane and propane; something that cannot yet be accomplished with membrane technologies.
Figure 4: The separation of propane and butane by selective encapsulation.