The power of single crystal X-ray analysis
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Probably the most powerful structure determination technique a crystallographer has at his/her disposal is single crystal X-ray diffraction.  This non-destructive technique provides data suitable to determine the crystal structure within a few hours.  Information obtained from this technique includes unit cell dimensions, molecular conformation, packing and intermolecular interactions, such as hydrogen bonds and π-π interactions. 

In a typical situation where an Active Pharmaceutical Ingredient (API) crystallizes in multiple crystal forms, understanding the crystal structure provides important insights on the molecular interactions responsible for a specific molecular conformation and crystal packing.

For solubility and acceptability reasons, hydrate and solvate formations of APIs are to be avoided.  However, the nature of pharmaceutical compounds with their multitude of functional moieties often leads to the formation of solvates and hydrates.  For these solid forms of an API, the driving forces for a specific solvate/hydrate formation can be inferred from X-ray single crystal diffraction through the observed molecular conformation and interactions with the solvent molecule in the structure.

With that knowledge, it is possible to design the crystallization process such that solvate formation is avoided. Thus, selecting solvents which do not favor solvate formation and resulting in the desired polymorphic form will not be a matter of trial and error, but rather of intelligent design.  

Where structural data assists in the selection of solvents to avoid solvate formation, single crystal X-ray diffraction is also used in the selection of co-crystal formers.  The interactions between the API and the co-former are similar to those observed in solvates.  Single crystal X-ray diffraction is, next to solid state NMR, an easily accessible technique that can ultimately distinguish between salts and co-crystals or identify mixed salt/co-crystal. 

In addition, single crystal X-ray diffraction has proved its use in the determination of the absolute configuration of chiral compounds.