Challenges to large molecular encapsulation

One-to-one capture and confinement of a molecule within a finely designed synthetic scaffold is a highly topical field of research that aims to control the functions, properties, and stabilities of trapped molecules. In this account, a brief history of molecular encapsulation, for the design and synthesis of suitable molecular cages for large molecules, summarizes the daunting synthetic challenge associated with increasing molecular weight, and the attendant challenge to encapsulate macromolecules like proteins by synthetic hosts. Recent approaches toward the overall objective of large molecular encapsulation are discussed, and a personal account is given of the design and assembly of an advanced scaffolding system, which offers the promise of unprecedented progress toward this goal.