The conformational flexibility of a receptor is usually considered unfavorable to binding, due to the entropy loss upon binding. Inspired by the biological receptor with intra-receptor secondary binding sites which can strengthen guest binding, two series of artificial receptors with similar structures were constructed: pseudo crown ethers with aromatic donor/acceptor groups and aromatic tweezer molecules with carboxylic acids. When the guest binding was weakened by the solvents, i.e., pseudo crown ethers bound with cations in polar solvents and aromatic tweezers bound with counterparts in non-polar solvents, intra-receptor interactions became stronger and contributed to the guest binding. The overall binding showed a reversed solvent effect and unusually strong affinity.

Molecular imprinting with cross-linked micelles and functional templates created binding sites after removal of templates. The binding site complementary to the template can be used to study the chemical reactions in the confined nanospace, which can be different from those in homogeneous solution. Imine formation between amines and the aldehyde inside the binding site was studied. It was found the binding influenced reaction reactivity more than the electronic property of the amine. Besides the study of reaction reactivity, the binding site can be further functionalized with a fluorescent group to achieve sensitive and selective sensing.