Unlocking the computational design of metal–organic cages

Metal-organic cages are macrocyclic structures that can possess an intrinsic void that can hold molecules for encapsulation, adsorption, sensing, and catalysis applications. As metal-organic cages may be comprised from nearly any combination of organic and metal-containing components, cages can form with diverse shapes and sizes, allowing for tuning toward targeted properties. Therefore, their near-infinite design space is almost impossible to explore through experimentation alone and computational design can play a crucial role in exploring new systems. Although high-throughput computational design and screening workflows have long been known as powerful tools in drug and materials discovery, their application in exploring metal-organic cages is more recent. We show examples of structure prediction and host-guest/catalytic property evaluation of metal-organic cages. These examples are facilitated by advances in methods that handle metal-containing systems with improved accuracy and are the beginning of the development of automated cage design workflows. We finally outline a scope for how high-throughput computational methods can assist and drive experimental decisions as the field pushes toward functional and complex metal-organic cages. In particular, we highlight the importance of considering realistic, flexible systems.