Comprehensive Insights into Sulfaguanidine in the Solid State: An Experimental and Computational Study.

A thorough re-examination of sulfaguanidine's (SGD) solid-state behavior was conducted, 65 years after the initial report on SGD polymorphism. This investigation focuses on the polymorphic nature of the compound, the formation of hydrates and solvates, and the pivotal role of experimental and computational methods in screening, assessing stability, and understanding transformation processes. The findings confirm the presence of five anhydrates (-), two monohydrate polymorphs ( and ), and nine solvates (with , , , , , , , , and ). Notably, nine novel structures-two anhydrates and seven solvates-are reported, solved from powder X-ray diffraction data. Calorimetric measurements have revealed that is the thermodynamically stable polymorph at room and low temperatures. In contrast, emerges as the stable polymorph at higher temperatures, yet it exhibits remarkable kinetic stability at RT and demonstrates greater stability in terms of hydration. The anhydrate forms exhibit distinctive packing arrangements, while the two hydrates share a close structural resemblance. Among the seven structurally characterized solvates, only the tetrahydrofuran and dimethyl sulfoxide solvates are isostructural. Controlled desolvation experiments enabled the formation of , , and, notably, for the first time. The anhydrate and monohydrate crystal structure prediction studies reveal that the computed lowest-energy structures correspond to experimentally observed forms and propose models for the elusive structure. Overall, the exploration of SGD's solid-state landscape confirms a rich array of highly stable H-bonding motifs and packing arrangements, positioning this study as an ideal model for complex solid-state systems and shedding light on its intricate solid-state nature.