Experimental and Theoretical Investigation of Hydrogen-Bonding Interactions in Cocrystals of Sulfaguanidine

[Image: see text] Pharmaceutical cocrystals, a type of multicomponent crystalline material incorporating two or more molecular and/or ionic compounds connected by noncovalent interactions (such as hydrogen bonds, π–π interactions, and halogen bonds), are attracting increasing attention in crystal engineering. Sulfaguanidine (SGD), one of the most frequently used sulfonamide compounds, was chosen as a model compound in this work to further investigate the hydrogen bond interactions in cocrystals, since it possesses various hydrogen bond donor and acceptor sites. Five cocrystals of SGD, synthesized successfully by slurry and slow evaporation methods, were fully characterized by thermal analysis, X-ray techniques, and Fourier transform infrared spectroscopy. To gain insight into the nature of hydrogen-bonding interactions, theoretical calculations including the analysis of Hirshfeld surface, MEPS (molecular electrostatic potential surface), and QTAIM (quantum theory of atoms in molecules) were conducted. The results are a part of a systematic study of cocrystals of sulfonamides that aims to establish synthon hierarchies in cocrystals containing molecules with multiple hydrogen-bonding functional groups.