Guests Within Large Synthetic Hydrophobic Pockets Synthesized via Self-Assembly


Bruce C. Gibb Department of Chemistry, University of New Orleans

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This review focuses on how self-assembly can form hosts capable of binding large guests. Its sister article, “Guests within Large Synthetic Hydrophobic Pockets Synthesized Using Polymer and Conventional Techniques,” reviews like-minded work using either polymers or hosts synthesized by traditional synthetic approaches. As described in more detail in that paper, the focus here is on hosts capable of binding organic molecules of more than seven nonhydrogen atoms. Likewise, a similar definition of a “pocket” is retained, with the focus on hosts possessing well-defined, highly concave or enclosed surfaces. An arbitrary value of greater than approximately 50% encapsulation has been set. “Comprehensive Supramolecular Chemistry” covers much of our discussion topic up to 1995. This review is therefore primarily interested with the literature since that time.

Motivators for supramolecular chemists include molecular storage/delivery, the detection of substances, and the conversion of one substance into another via catalytic processes. All these processes include at some point the binding of a guest to a host. The hard part in these endeavors is the synthesis of the host, with all the required functionality gathered in a converging array. One approach uses self-assembly, whereby molecular subunits are designed to merge in a specific pattern that possesses a hydrophobic pocket. In this regard, both self-assembly and self-assembly with covalent modification have been used. As with the polymer and traditional synthetic strategies, the self-assembly approach has pros and cons. Normally, relatively rigid subunits are used and so a common worry in cavity design—hydrophobic pocket collapse—is generally avoided. On the other hand, at our current level of understanding we are limited to relatively symmetrical subunits and assembled structures. Nevertheless, testimony to the power of this approach is found in the large cavities formed, some in the order of thousands of cubic Ångströms.

The bulk of recent self-assembly research has focused on understanding the rules that govern how one product can arise out of a reaction mixture that, if all things were equal, would lead to a highly complex mixture. Hence in a manner analogous to contemporary polymer research, the emphasis is on understanding how the structure of the product is reached, rather than on understanding the properties of any cavity in the product. As a result, many of the very large cavities created by self-assembly are “simply” filled with a large number of (small) solvent molecules. Such examples are not dealt with explicitly here but can be found in citations throughout the text.