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Supramolecular chemistry

Molecular crystal balls

Sorcerers have long gazed into crystal balls to conjure up information. Chemists are also getting in on the act, using porous crystals to trap unstable reaction intermediates and to reveal their structures.

The reactions of molecules with one another often proceed through intermediates before the final products are formed. Such intermediates are frequently short-lived and unstable, which restricts our ability to characterize them. Typically, the identification of such fleeting species is limited to fast, time-resolved spectroscopic measurements. But in this issue (page 633), Kawamichi et al.1 report that they have trapped an unstable chemical intermediate in a porous crystalline material, and were thereby able to characterize the structure of the intermediate unambiguously by X-ray crystallography. The authors suggest that such porous crystals can act as protective matrices within which chemical reactions can be performed, allowing us to peer into the details of reaction mechanisms in an unprecedented way.

Kawamichi et al. examined a reaction familiar to every student of organic chemistry: the combination of an amine and an aldehyde to form a Schiff base (Fig. 1a). Although the mechanism of this fundamental reaction has been extensively studied, direct observations of the ephemeral intermediate — a hemiaminal — are rare. The crystal structure of a hemiaminal trapped in the active site of an enzyme has been reported2, but structure determination in protein crystals is not a general approach for characterizing reaction intermediates.

Figure 1: Caught in a trap.

a, Kawamichi et al.1 have stabilized and observed the crystal structure of an elusive hemiaminal intermediate that is transiently formed during the reaction of an amine and an aldehyde to form a Schiff base. b, They did this by performing the reaction within the restrictive and orderly confines of a crystalline coordination network (a cage-like molecular structure) at low temperatures. The authors trapped amine reactants as guest molecules in the network as it self-assembled from its constituent parts — organic 'linker' molecules and zinc ions that act as nodes between the linkers. In the network structure, the amines are shown in green, and one is highlighted in the red box.

The authors1 use a 'coordination network' of organic ligand molecules and metal ions to trap the elusive hemiaminal. Coordination networks — also known as porous coordination polymers or metal–organic frameworks — are solid, crystalline materials that generally self-assemble from their molecular components (Fig. 1b). They have lattice structures that resemble climbing frames, in which the organic ligands (known as linkers) are the bars of the climbing frame, and the metal ions (nodes) are the rivets that connect the bars together. The result is a grand structure that consists largely of empty space. Just as children play within the lattice of a climbing frame, so molecules can diffuse and interact within the lattice of a coordination network.

Successful observation1 of the hemiaminal relied on two key features of the network. First, it could trap the intermediate as part of a 'guest' molecule in its pores at low temperatures, stabilizing the species within a shielded, confined space. And second, the highly crystalline structure of the network restricts the trapped molecules to a specific periodic arrangement that allowed them to be characterized by X-ray crystallography. To generate the hemiaminal, Kawamichi et al. gently passed a solution of an aldehyde over an intact crystal of their coordination network in which an amine was tightly bound as a guest molecule. This was done with the crystal already mounted on a diffractometer at low temperature, allowing the hemiaminal to be trapped and its structure determined directly. Confined within the network, identification of the elusive species by X-ray crystallography was as easy as determining the structure of the network itself. The authors then raised the temperature of the crystal and re-determined its structure, whereupon they observed that the reaction had proceeded within the crystal, yielding the expected Schiff base product.

The process used by Kawamichi and co-workers — modifying pristine crystals of a coordination network with soluble chemical reagents — is an example of postsynthetic modification, a strategy that has garnered increased attention from chemists in recent years3,4. A growing number of research groups have been investigating the types of network and scope of chemical reactions that such networks can undergo without losing their highly ordered structure. But unlike most reports, which have used postsynthetic modification to generate networks possessing new features or functions, Kawamichi et al. have cleverly focused on the ability of coordination networks to provide a well-defined, ordered and confined space within which to perform chemical reactions. In previous studies5, the same group highlighted this property of the networks by referring to them as “single-crystalline molecular flasks”. The current use1 of coordination networks logically and creatively extends their earlier work6 on discrete molecular capsules, also comprised of organic ligands and metal ions, within which the authors exerted unusual control over chemical reactivity.

Kawamichi and colleagues' strategy will not be a panacea for characterizing all reaction intermediates. For example, only reactions that do not degrade the somewhat fragile coordination network (or those that occur in conditions that do not degrade the network) can be studied by this approach. Nevertheless, Kawamichi et al.1 show that postsynthetic modification of coordination networks is a broadly applicable tool for isolating and characterizing transient intermediates that form during chemical reactions. It is likely that further studies will reveal the structure of other transient intermediates — organic and perhaps organometallic — that have been immobilized within porous networks. Performing chemical reactions within these crystals may also reveal new patterns of chemical reactivity, distinct from that observed in solution7. Furthermore, postsynthetic modification of coordination networks will probably have an increasing role in enhancing the stability, functionality and uses of these materials in real-world applications — for example, in the storage tanks of vehicles that use alternative transportation fuels such as hydrogen.


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Cohen, S. Molecular crystal balls. Nature 461, 602–603 (2009).

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