A robust protein-mimicking metallo-amine cage showing proton-driven allostery with water as the effector

The allosteric effect is omnipresent in proteins with two distinct binding sites communicating over a distance to control biological functions and complex processes, which drives an everlasting innovation of molecular-scale devices and machines with allosteric functions. Herein, we report a protein-mimicking metallo-amine cage (MOC-68) with excellent tolerance for harsh acid-base conditions, presenting a proof-of-concept example of proton-driven allosteric regulation of multi-state transitions and molecular motions controlled by a water effector as in the natural system. Owing to its multiple N groups for proton transfer, 8 water-binding allosteric sites for remote control, and one endo-cavity and six exo-cavities for guest exchange, the acid-base or solvent switching protocols of cage conformation, charge-state, amphoteric property, phase transfer, guest dynamics, and, unprecedentedly, ring-on-cage sliding and capping/uncapping motions have been demonstrated; this not only provides a unique allosteric cage model for molecular machines and smart biomaterials but also promises potential in drug delivery and release.