Packing similarity in polymorphs of sulfathiazole

Abstract

The packing of molecules in polymorphs I–V of sulfathiazole is compared using the XPac method (CrystEngComm, 2005, 7, 324). The forms denoted III, IV, V in the pharmaceutical literature, equivalent to forms III, II and IV of the CSD, exhibit 2D packing similarity. Linking this purely geometrical analysis with H-bonding information reveals that the common building unit of III–V is a 2D layer composed of rows of helical chains of doubly H-bonded sulfathiazole molecules. The H-bonded chains are further H-bonded in the third direction to chains of adjacent layers. However, these connections involve different combinations of H-bond donor and acceptor sites in each polymorph. One consequence of this relationship is the presence of sets of local (non-crystallographic) symmetry elements in polymorph III (Z′ = 2), while forms IV and V may be interpreted as its two Z′ = 1 parent phases. The connectivity of the doubly bonded chain of modifications III–V is also present in form II, which additionally contains 2D H-bonded sheets, but the conformation of the chain and its further connectivity is quite different to forms III–V. The molecular packing and hydrogen bonding of form I is unique among the investigated structures. This study shows that useful new information is obtained from a strictly geometric comparison of crystal structures. Forms III–V provide yet another example for the connection between polymorphism, packing similarity and the formation of a structure with Z′ > 1 exhibiting non-crystallographic symmetry.