Selected Research Publications

This tutorial review summarizes the continuing exploration of three prominent water-soluble hosts: cucurbiturils, pillar[n]arenes and deep-cavity cavitands. As we describe, these hosts are revealing how orchestrating the hydrophobic effect can lead to a broad range of properties and applications, from: nano-reactors, supramolecular polymers, stimuli-responsive biointerfaces, switches, and novel purification devices. We also describe how their study is also revealing more details about the properties of water and aqueous solutions.

This review focuses on papers published since 2000 on the topic of the properties of solutes in water. More specifically, it evaluates the state of the art of our understanding of the complex relationship between the shape of a hydrophobe and the hydrophobic effect. To highlight this, we present a selection of references covering both empirical and molecular dynamics studies of small (molecular-scale) solutes. These include empirical studies of small molecules, synthetic hosts, crystalline monolayers, and proteins, as well as in silico investigations of entities such as idealized hard and soft spheres, small solutes, hydrophobic plates, artificial concavity, molecular hosts, carbon nanotubes and spheres, and proteins.

Previously we have demonstrated that host 1 is capable of hydrocarbon gas separation by selective sequestration of butane from a mixture with propane in the headspace above a solution of the host (C. L. D. Gibb, B. C. Gibb, J. Am. Chem. Soc., 2006, 128, 16498–16499). Expanding on the idea of using this host as a means to affect guest discrimination, we report here on NMR studies of the binding of constitutional isomers of two classes of small molecules: hexanes and chloropentanes. Our results indicate that even with these relatively straightforward classes of molecules, guest binding is complicated. Overall, host 1 displays a preference to bind guests with a X–C(R2)–C(R2)–Me (X = Cl or Me) structure, and more generally, a preference for branched guests rather than highly flexible, unbranched derivatives. The complexity of binding of these isomers is magnified when considering molecular differentiation between pairs of guests. In such cases, different guests demonstrated different propensities to self-sort; some self-sort exclusively, while others show very little propensity to do so. However, whereas the pool of guests reveals some general correlations between binding strength and structure, no obvious relationship between structure and degree of self-sorting was observed.

This review focuses on molecular containers formed by assembly processes driven by the hydrophobic effect, and summarizes the progress made in the field over the last ten years. This small but growing facet of supramolecular chemistry discusses three classes of molecules used by researchers to investigate how self-assembly can be applied to form discrete, mono-dispersed, and structurally well-defined supramolecular entities. The approaches demonstrate the importance of preorganization of arrays of rigid moieties to define a specific form predisposed to bind, fold, or assemble. As the examples demonstrate, studying these systems and their properties is teaching us how to control supramolecular chemistry in water, shedding light on aspects of aqueous solutions chemistry, and illustrating novel applications that harness the unique properties of the hydrophobic effect.

The extent of self-sorting in systems comprised of two different deep-cavity cavitands is investigated. The nature of the guest(s) encapsulated in the resulting assemblies is shown to profoundly influence the extent of self-sorting.

Abstract The self-assembly of structurally discrete entities, and supramolecular chemistry in general, continues to expand into the aqueous realm. To do so, however, requires a firm understanding of the properties of aqueous solution, and how these “change the rules” for binding and assembly relative to organic solvents. In this mini-review we highlight the state-of-the-art understanding of the supramolecular properties of water, and how these influence the design of hosts and self-assembling systems.

The surface modification of deep-cavity cavitands has been demonstrated by using the azide-alkyne “click” coupling to attach dendritic macromolecules or linear polymers onto their periphery. The resulting set of macromolecular cavitands exhibited tuneable solubility yet retained the ability to encapsulate guest molecules.

The organic co-solvent induced denaturation of a series of capsular complexes formed between trioxolane guests and a water-soluble deep-cavity cavitand was examined. The results obtained demonstrate a wide range of denaturation properties, and suggest the important factors governing capsule stability.

Over the past five years, an important development in the area of self-assembling containers has been the increase in interest in those containers that function in aqueous solution. This progress is a reflection of a similar trend within supramolecular chemistry in general, and is driven in part by the need to address issues and challenges within the biological sciences, as well as a desire to develop new strategies for greener chemistries carried out in water. It is also an opportunity to learn more about fundamental topics such as the hydrophobic effect. In this critical review we discuss progress in aqueous-based self-assembling container molecules since 2005 (177 references).