Molecular structure determination is beneficial 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 highly purified target compounds. Moreover, good quality crystals for SC-XRD analysis might not be obtained despite performing tedious and time-consuming trials. In this case, we have to abandon the direct structure determination by SC-XRD. 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. However, as with other analysis techniques, the CS method has some limitations.
The CS method utilizes metal-organic frameworks (MOFs) as the pre-crystallized ‘‘container” for the analytes. The “container” is equipped with flexible features to fit various analytes and must have enough space to accommodate a wide variety of molecules. An MOF is a large structural object with three-dimensional networks; thus, the spaces to accommodate molecules have limitations in principle.
To overcome the above difficulty, we came up with the idea of a “molecular grabber,” utilizing an easy-to-crystallize protein that has a multi-site binding pocket to bind a variety of types of molecules and gives high-resolution spots.