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It is these extreme confinement effects that ‘enables us to do chemistry that we can’t do in traditional ways’, says Angela Grommet from the Weizmann Institute of Science in Israel who recently wrote a review 2 on the topic. After 35 years of research, chemists are now starting to unlock the potential of confinement by designing molecular cages that fold up long molecules into huge macrocycles, or creating cavities that can separate deuterium from hydrogen. In the future, confined spaces could rival enzymes in their ability to catalyse reactions or protect unstable species, turning them into useful reagents. It all started with the discovery of carcerands more than three decades ago. Donald Cram wanted to take the chemistry of crown ethers – flat, circular molecules that can capture individual metal atoms on their inside – into the third dimension. In 1985, he functionalised big cyclic molecules so pairs of them could be brought together to form a capsule. Cram c ....