The Discovery of New Crystal Forms of 5-Fluorocytosine Consistent with the Results of Computational Crystal Structure Prediction

A computational search for low-energy crystal structures of 5-fluorocytosine was performed in conjunction with a
manual crystallization screen to determine whether solid forms other than the known monohydrate structure could be discovered.
The predicted low-energy structures were based on a hydrogen-bonded ribbon, which was observed in two newly determined anhydrous
polymorphic crystal structures, a hemipentahydrate, and two solvates, as well as the known monohydrate. An alternative ribbon
structure present in some less-stable predicted structures was found in a disordered monohydrate structure. The anhydrous crystal
structure prediction was a success, by the criteria of the international crystal structure prediction blind tests. Thus we can rationalize
the crystal structure behavior of 5-fluorocytosine as having a strongly preferred two-dimensional ribbon structure, which exhibits
versatile methods of packing, leading to polymorphism and a number of closely related solvate structures.