Multisite Binding of Drugs and Natural Products in an Entropically Favorable, Heteroleptic Receptor

The cavities of artificial receptors
are defined by how their components
fit together. The encapsulation of specific molecules can thus be
engineered by considering geometric principles; however, intermolecular
interactions and steric fit scale with receptor size, such that the
ability to bind multiple guests from a specific class of compounds
remains a current challenge. By employing metal–organic self-assembly,
we have prepared a triangular prism from two different ligands that
is capable of binding more than 20 different natural products, drugs,
and steroid derivatives within its prolate cavity. Encapsulation inflates
the host, enhancing its ability to bind other guests in peripheral
pockets and thus enabling our system to bind combinations of different
drug and natural product cargoes in different locations simultaneously.
This new mode of entropically favorable self-assembly thus enables
central encapsulation to amplify guest-binding events around the periphery
of an artificial receptor.