Exploration of the polymorphic solid-state landscape of an amide-linked organic cage using computation and automation

Organic cages can possess complex, functionalised cavities that make them promising candidates for synthetic enzyme mimics. Conformationally flexible, chemically robust structures are needed for adaptable guest binding and catalysis, but rapidly exchanging systems are difficult to resolve in solution. Here, we use low-cost calculations and high-throughput crystallisation to identify accessible conformers of a recently reported organic cage by 'locking' them in the solid state. The conformers exhibit varying distances between the internal carboxylic acid groups, suggesting adaptability for binding a wide array of target guest molecules. Inexpensive calculations and high-throughput crystallisations were used to identify accessible cage conformations by 'locking' them in the solid state. The conformers suggest adaptability towards binding a wide array of target guest molecules.