Knotting a tetrahedral cage mechanically locks guests inside

Interwoven molecular structures underpin the functions of many biomolecules,1–3 yet synthesizing artificial topologically-complex structures in high yield remains challenging.4,5 Here we describe a streamlined, high yield one-pot synthesis of knotted cage frameworks through the use of a subcomponent designed to bridge over the faces of a predesigned cage framework. A ZnII4L3 open-faced cage framework was employed as the basis for a topologically chiral ‘perplexane’,6 and a ZnII4L4 tetrahedron was built into a topologically chiral ‘trefoil tetrahedron’. Both interwoven architectures can be prepared through one-pot subcomponent self-assembly from a trialdehyde, the bridging triamine, and a zinc(II) salt. The ‘trefoil tetrahedron’ was observed to mechanically lock guests inside the cavity, resulting in a guest exchange half-life 17000 times longer than that of the original tetrahedral cage. Both cage frameworks were reduced and demetallated to yield metal-free interwoven structures, with the ‘perplexane’ producing an achiral product, and the ‘trefoil tetrahedron’ maintaining its topological chirality. Our strategy may enable the many existing cage frameworks produced using subcomponent self-assembly to be knotted, enhancing their robustness and locking guests inside.