Molecular structure determination is very useful for the development of medicines, aroma chemicals and agrochemicals. Single crystal X-ray diffraction (SC-XRD) analysis is the most powerful technique for molecular structure determination. However, SC-XRD analysis requires good quality crystals. In fact, the biggest hurdle for SC-XRD analysis is crystallization. Crystallization trials require a large amount of high-purity target compounds. Moreover, despite performing tedious and time-consuming trials, sometimes good quality crystals for SC-XRD analysis may not be obtained. In this case, we have to give up on structure determination. As one way to address this situation, Fujita et al. have reported the crystalline sponge method (CS method) for the structure determination of small molecules .
With this method, crystallization of the target compound is not required. The CS method uses a metal-organic framework (MOF). The target compounds are incorporated into the CS crystal by soaking and are oriented in the porous coordination network of the MOF. Then, the structure can be determined by SC-XRD analysis. As a result, the CS method allows the SC-XRD analysis of many compounds that cannot be crystallized. However, as with other analysis techniques, the CS method has some limitations. The method is not applicable to all types of compounds.
The CS method uses the MOF as the “container” for the compounds. Looking at CS method figures, we came up with a new idea—the container does not have to be an MOF. We wanted to prepare a container with the ability to bind to a wide variety of compounds; therefore, we focused on proteins because they can bind to organic compounds. Some proteins can bind to a wide variety of compounds, such as anionic, cationic and neutral compounds. Therefore, we started to develop a new crystalline sponge method that is different from the existing method.