Dynamical refinement spots a difference: For chiral molecules used in drugs, one isomer can have beneficial bioactivity, whereas the others are useless or even harmful. Determining the absolute configuration of molecules with chiral centers is often achieved through x-ray crystallography, but this requires relatively large crystals and high-quality data. Brázda et al. used electron diffraction to determine the absolute structure of an extremely radiation-sensitive crystal with micrometer dimensions (see the Perspective by Xu and Zou). In a strategy analogous to serial crystallography methods, many frames were combined to generate a complete dataset. Refinement incorporating dynamical effects differentiated the correct and incorrect molecular configuration. Science , this issue p. 667 ; see also p. 632

96 nano-crystallization trials can be done with just (sub)-milligram amounts of an organic salt to directly yield single crystal structures.

Multicomponent solid forms of active pharmaceutical ingredients represent a modern method of tuning their physicochemical properties. Typically, salts are the most commonly used multicomponent solid form in the pharmaceutical industry. More than 38% are formulated as organic cations. Salt screening is an essential but demanding step when identifying the most appropriate formulation. The microbatch under-oil crystallization technique of proteins has been combined with the previously developed high-throughput vapour-diffusion screening for use as a novel method of primary salt screening of organic cations. The procedure allows the set up of about 100 crystallization experiments per 30 min. This requires between 17 and 564 mg of screened cationic active pharmaceutical ingredients, which were of moderate to very high water solublity. Five distinct organic salts, three of them diverse active pharmaceutical compounds or the other enantiomer thereof, in the form of chloride salts were tested. The screening was extremely successful; at least two new single-crystal structures could be obtained for each particular compound and many more salts as single crystals were formed compared with our previous vapour-diffusion method.