Water is the dominant
liquid on Earth. Despite this, the main focus
of supramolecular chemistry research has been on binding and assembly
events in organic solvents. This arose because it is more straightforward
to synthesize organic-media-soluble hosts and because of the relative
simplicity of organic solvents compared to water. Nature, however,
relies on water as a solvent, and spurred by this fact, supramolecular
chemists have recently been making forays into the aqueous domain
to understand water-mediated non-covalent interactions. These studies
can benefit from the substantial understanding of the hydrophobic
effect and electrostatic interactions developed by physical chemists.
Nearly 20 years ago, the Gibb group first synthesized a class of water-soluble
host molecules, the deep-cavity cavitands, that possess non-polar
pockets that readily bind non-polar moieties in aqueous solution and
are capable of assembling into a wide range of complexes with distinct
stoichiometries. As such, these amphipathic host species are ideal
platforms for studying the role of negatively curved features on guest
complexation and the structural requirements for guided assembly processes
driven by the hydrophobic effect. Here we review the collaborative
experimental and computational investigations between Gibb and Ashbaugh
over the past 10 years exploring questions including the following:
How does water wet/solvate the non-polar surfaces of non-polar pockets?
How does this wetting control the binding of non-polar guests? How
does wetting affect the binding of anionic species? How does the nature
and size of a guest size impact the assembly of cavitand hosts into
multimeric capsular complexes? What are the conformational motifs
of guests packed within the confines of capsular complexes? How might
the electrostatic environment engendered by hosts impact the properties
and reactivity of internalized guests?