For natural biological molecules to interact effectively they need to identify that they are at the correct location, and the most effective means for achieving this lies in recognising their partner’s shape and the chemistry of their interaction. The best-known instance of this molecular recognition is the way in which enzymes are shaped exactly to suit their own substrates, so that they can act like flexible locks that will only accept and embrace the appropriate shaped key. The 1987 Nobel Prize in Chemistry rewarded three chemists who constructed the first artificial chemicals whose in-built shape began to mimic the selective behaviour of biological molecules.
Charles Pedersen provided the initial breakthrough by synthesizing a group of chemicals that he called crown ethers on account of their structure – two-dimensional and flexible rings shaped like a royal crown that consist of chains of carbon atoms with oxygen atoms appearing at regular intervals. Pedersen discovered that introducing more or less atoms into a ring to vary its size affected which metal element the ring could house within its centre. The molecular accommodation process was exquisitely sensitive; smaller rings were able to distinguish between even closely related elements like potassium and sodium.
Pedersen’s flat crown ethers provided the platform for Jean-Marie Lehn and Donald Cram to develop increasingly sophisticated compounds that selectively recognised the type of chemicals found in a living cell. Lehn succeeded in creating three-dimensional crown ethers from multiple layers of atoms with interconnected chains, which contained an internal cavity that could completely encapsulate a molecule. He also constructed a compound that interacts in a specific manner with acetylcholine, one of the major chemicals transmitted along nerves. Cram designed a series of progressively complex prototype molecules and then successfully synthesized them in the laboratory. Among the hundreds of chemicals he created, Cram successfully built a set of crown ethers that attach to specific amino acids, the building blocks of proteins. Lehn and Cram defined their research using different names – Lehn called it supramolecular chemistry, while Cram termed the field guest-host chemistry – but what both have in common is that they helped shape the ways in which chemists could reproduce life’s selection processes.