Nature Commun. 6, 7129 (2015)

In the early days of host–guest chemistry, researchers would make molecular 'hosts' — typically in the form of rings or cages — and show how they could bind 'guest' species such as metal ions or other small molecules. These iconic molecules, with evocative names such as crown ethers and cryptands, launched a new subfield within chemistry and the award of the 1987 Nobel Prize in Chemistry can be traced back to them. A huge number of host compounds with an incredibly diverse range of structures have been made and studied over the years, some of which require significant synthetic effort to produce.

Credit: © 2015 NPG

Now, a team of researchers at Friedrich-Alexander-University Erlangen-Nürnberg in Germany led by Max von Delius has shown how dynamic covalent chemistry can be used to self-assemble cage-like molecules in one step from simple, commercially available compounds. When trimethyl orthoacetate reacts with diethylene glycol in the presence of an acid catalyst and a source of sodium ions, a monometallic complex (known as a cryptate) is formed. This complex features a sodium ion nestled inside an organic cage built from two orthoacetate caps linked together with three bridging diethylene glycol chains. Molecular sieves are crucial in the reaction to mop up the methanol produced by the orthoester exchange and thus drive the dynamic system to form the cryptate as the major product.

In the absence of a sodium template, the main product of the reaction is the simple eight-membered cyclic orthoester resulting from the 1:1 reaction between trimethyl orthoacetate and diethylene glycol. In the presence of other templates such as lithium or potassium ions, complexes reminiscent of crown ethers are observed, but no cryptates are formed. All of these systems are dynamic in acidic conditions, however, and the addition of an appropriate sodium salt leads to the formation of the sodium cryptate. Although the sodium ion is bound strongly inside the cryptate, it is not trapped there; NMR experiments show that it can move in and out of the cage, albeit relatively slowly.