Polymorphs and solvates of Sulfathiazole: X-ray diffraction studies

Abstract

A detailed study has been made of the crystal structures of the polymorphs and some solvates of sulfathiazole, one of the well-known sulfadrugs. The objective of this work was to attempt to gain an insight into the mechanism of the assembly of molecules into crystal structure forms.

Sulfathiazole has a number of potential hydrogen bonding sites, and it was assumed that differences in hydrogen bonding patterns created the different assembly structures. Accordingly, considerable attention was paid to the connectivity and topology of the hydrogen bonding patterns found.

At the heart of the study is a new approach to describing H-bonding patterns, that improves on approaches previously adopted and described in the literature. The approach introduced here follows two schemes of description. The first considers the chemical connectivity of the H-bonds, which is represented by a connectivity matrix. The second scheme considers the topology of the H-bonding pattern. For this, each molecule is considered as a node, and the H-bonds are drawn as connecting vectors, to produce a topology diagram. This allows identification of OD (isolated single molecule or dimers) ID (chain), 2D (sheet) or 3D (framework) structures. The representation can highlight symmetry relationships between connected molecules, where present, but also recognises connections not involving symmetry relationships.

In this way, the four previously known polymorphs, plus one new structure, identified as part of this work, are found to comprise one 3D framework, with an interpenetrating 2D sheet structure (polymorph I) and four differently connected 2D sheet structures (polymorphs II, III, IV, V). Polymorph III was shown to be a hybrid of ID tapes present in the layers of the polymorph IV and V structures.

The same approach was used to describe the structures of 29 solvates of sulfathiazole, in which the additional solvate was an oxygen-containing molecule. These have been shown to comprise ID chain, 2D sheet and 3D framework assemblies of sulfathiazole molecules, with guest, solvent molecules in channel, layer or cavity regions of the sulfathiazole assemblies, or, in some cases, solid solution cocrystal assemblies, where solvate molecules isolate sulfathiazole molecules via heteromolecular hydrogen bonding. The binary structures show some relationships with the polymorph structures, but there are also many significant differences. These are discussed in detail.

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