Molecular Recognition within the Cavity of a Foldamer Helix Bundle: Encapsulation of Primary Alcohols in Aqueous Conditions

Artificial
synthetic molecules able to adopt well-defined stable
secondary structures comparable to those found in nature (“foldamers”)
have considerable potential for use in a range of applications such
as biomaterials, biorecognition, nanomachines and as therapeutic agents.
The development of foldamers with the ability to bind and encapsulate
“guest” molecules is of particular interest; as such
an ability is a key step toward the development of artificial sensors,
receptors and drug-delivery vectors. Although significant progress
has been reported within this context, foldamer capsules reported
thus far are largely restricted to organic solvent systems, and it
is likely that the move to aqueous conditions will prove challenging.
Toward this end, we report here structural studies into the ability
of a recently reported water-soluble self-assembled foldamer helix
bundle to encapsulate simple guest molecules within an internal cavity.
Seven high-resolution aqueous crystal structures are reported, accompanied
by molecular dynamics and high-field NMR solution data, showing for
the first time that encapsulation of guests by a complex self-assembled
foldamer in aqueous conditions is possible. The findings also provide
ample insight for the future functional development of this system.