Mechanochemistry is a widespread synthesis technique in all areas of chemistry. Various materials have been synthesized by this technique when the classical wet chemistry route is not satisfactory. Characterization of the reaction mixture is however much less accessible than in solutions.
Recently, in situ observations of mechanochemical reactions have been achieved by X-ray diffraction and Raman spectroscopy. Solid-state reactions can be directly tracked, revealing phase transitions and other material transformations during synthesis in a ball mill jar. This technique has become increasingly popular in different fields of mechanochemistry.
As the X-rays go through the entire jar, the diffraction patterns present a high background due to the scattering from the thick walls of the jar. Also, broad diffraction peaks are expected from the sample as a result of probing a large sample area covering the entire jar. An extra complexity arises from diffraction on the milling balls.
Tumanov et al. [(2017). J. Appl. Cryst. 50. doi:10.1107/S1600576717006744] reasoned that these issues can be resolved by modifying the geometry and material of the milling jar. But, making a jar with a complex geometry using traditional production techniques is complicated, especially at the stage of creating a prototype, when introducing changes into a design should be facile. For this reason they decided to use a 3D printer for the purpose. They show how this useful production tool can quickly make milling jars optimized for improved background, absorption and angular resolution in X-ray powder diffraction experiments; the jars are also more resistant to solvents compared with standard acrylic jars. 3D printing allows for low-cost fast production on demand.
Source files for printing the jars are available as supporting information for the paper.
Gorrec F, MRC Laboratory of Molecular Biology, Cambridge, UK
Technology developments, including innovative crystallization screens, are needed to obtain X-ray diffraction-quality crystals from increasingly challenging protein and other macromolecular samples. MORPHEUS crystallization screens are continuously developed to further enhance initial screening. MORPHEUS screens integrate small molecules frequently observed in the PDB to co-crystallize with proteins. These molecules are included to function as additives that act as protein stabilizers, crystal packing bridges, or any other role beneficial to protein crystallization.
Each MORPHEUS screen integrates 96 conditions, a minimal format for limiting amounts of sample. To limit the number of conditions employed, the potential ligands found in the PDB are combined into mixes. Other mixes of compounds are used, such as buffer systems and precipitant mixes that also act as convenient and effective cryoprotectants. The different types of compound mixes are combined using a fixed ratio to generate 3-D grid screens. The preparation of a screen and the optimization of conditions are amenable to automation.
A multitude of test crystallization screens are used against novel and challenging samples produced at the LMB before making choices about the formulation. The main goal is to produce exclusive crystallization hits that were not observed in other screens. MORPHEUS screens, I and II, are now used routinely in many laboratories, while MORPHEUS III is being developed. Before describing the developments related to the MORPHEUS screens, I will briefly present theoretical and pragmatic aspects of macromolecular crystallography that were taken into consideration during the early stages of MORPHEUS development. In the last section I will show how to optimize conditions following the 4-corner method.
A recording of this webinar is now available to view: https://www.youtube.com/watch?v=Gpb4SypWnQY
A complementary event is also available: https://www.youtube.com/watch?v=8cH0YNmDshY