Determining the structures of intermediates in chemical reactions, and hence understanding reaction pathways, is a long-standing problem for chemists. Whilst various spectroscopic methods can be used to speculate about the nature of unstable and transient intermediates in many common reactions, ways to more precisely observe and analyze their structures remain scarce.

Fig. 1: A crystallographic depiction of a porous coordination network with guest molecules shown in green.

Now, Makoto Fujita and colleagues at the University of Tokyo1 have shown how X-ray crystallography can be used to observe the progress of a chemical reaction occurring within a porous coordination network. In their proof-of-concept reaction, an intermediate that is usually unstable is kinetically stabilized within the cavities of the material (Fig. 1) and X-ray ‘snapshots’ are taken to determine the structures present at different stages of the chemical transformation.

The well-studied reaction chosen by Fujita to demonstrate this new methodology was the formation of a Schiff-base product from an amine and aldehyde. The unstable intermediate — a hemiaminal — has been observed in the past using other methods. The team embedded an aromatic amine in a zinc iodide coordination network and then exposed the crystalline material to an aldehyde solution at low temperature. This resulted in the kinetic trapping of the hemiaminal intermediate in the pores. As a consequence of the crystalline order in the supporting network, X-ray analysis successfully revealed the hemiaminal structure. When the temperature was increased, the Schiff-base product was formed.

“X-ray crystallography has been difficult to apply to the structural analysis of reaction intermediates because the first and highest hurdle that must be overcome is the making of a single crystal,” says Fujita. “Our method does not require any effort to isolate and crystallize hard-to-handle intermediates, and moreover we can easily determine the structure of such intermediates.”

Whilst Fujita and colleagues recognize that not all coordination networks are suitable for this application, they believe the methodology could be more widely applied to other porous crystals and chemical reactions as a general technique.

Future studies by the Japanese team include the use of this method to investigate chemical transformations for which the reaction mechanisms remain unclear and to observe reactions that yield explosive or toxic molecules.