The extensive solid-form landscape of sulfathiazole: hydrogen-bond topology and node shape

• Published in: CrystEngComm Vol. 24; no. 37; pp. 6587 - 6599
• Main Authors: Hughes, David S, Bingham, Ann L, Hursthouse, Michael B, Threlfall, Terry L, Bond, Andrew D
• Format: Journal Article
• Language: English
• Published: Cambridge Royal Society of Chemistry 26.09.2022
• Subjects: Centroids; Chemical bonds; Crystal structure; Crystals; Density functional theory; Hydrogen bonds; Query languages; Similarity; Topology
• ISSN: 1466-8033; 1466-8033
• DOI: 10.1039/d2ce00964a

Patterns of N-H O and N-H N hydrogen bonds are described in a set of 101 crystal structures containing sulfathiazole (SLFZ). The structure set comprises five SLFZ polymorphs, 63 co-crystals, 30 salts and three other structures, standardised by application of dispersion-corrected density functional theory (DFT-D) calculations. The hydrogen bonds between SLFZ molecules define a broad range of motifs, from 3-D to 0-D. The topologies of the higher-dimensional motifs are dominated by the 3-D bnn and 2-D sql nets, each of which account for roughly one quarter of the structure set. The bnn net is principally seen in co-crystals where SLFZ generally does not form any hydrogen bond to the partner molecules. The sql net is seen in both co-crystals and salts where hydrogen bonds are formed between SLFZ and the partner molecules. Both the bnn and sql nets occur with a variety of specific donor/acceptor connectivity patterns, so the defined topological similarity does not immediately indicate structural similarity. Some isolated examples are identified of topological similarity between multi-component structures and the SLFZ polymorphs, but in general similarity between the polymorphs and multi-component structures is limited. The topological analysis is augmented by comparison of the shapes of the nodes extracted from each net, which represent the local geometry of each SLFZ molecule using only the centroids of connected SLFZ molecules. This reductive method is found to be effective to highlight fully isostructural groups and also to indicate sub-structure similarity and relationships between structures that may not emerge from a full geometrical comparison. This method may be a useful filter when seeking similarity within a large structure set. One new instance of 3-D isostructurality is identified, which was not evident from a previous geometrical analysis. Cases are also described where structures show close geometrical similarity but it is reasonable to assign different hydrogen-bond schemes. These examples illustrate the uncertainties and ambiguities inherent in tolerance-based methods to compare molecular crystal structures. Patterns of hydrogen bonds are described in a set of 101 crystal structures containing sulfathiazole. Topological analysis of the hydrogen-bond nets is augmented by comparison of the shapes of the nodes extracted from each net.