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

Abstract

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 (AH-I–V), two monohydrate polymorphs (Hy1-I and Hy1-II), and nine solvates (with tetrahydrofuran, methanol, ethanol, t-butanol, acetone, cyclohexanone, dimethyl sulfoxide, dimethyl formamide, and dimethyl acetamide). Notably, nine novel structures–two anhydrates and seven solvates–are reported, solved from powder X-ray diffraction data. Calorimetric measurements have revealed that AH-II is the thermodynamically stable polymorph at room and low temperatures. In contrast, AH-I 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 AH-I, AH-II, and, notably, AH-V 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 AH-IV 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.

Flavone Cocrystals: A Comprehensive Approach Integrating Experimental and Virtual Methods

“…All other characterized polymorphs ( I DDS , II DDS , and IV DDS ), the isostructural H DDS dehydrate, as well as a theoretical isostructural DCM desolvate, were found within a range of 10 kJ mol –1 of the global minimum (Figure a). As recently reported by us, the three structurally characterized SG polymorphs ( I SG , III SG , and V SG ) correspond to the three lowest-energy structures in the crystal energy landscape (Figure b) …”

“…Single-component crystal energy landscapes were computed for SA and FL to complement the crystal energy landscapes previously generated for DDS and SG . It should be highlighted that the energy landscape for DDS was recalculated using the methodology outlined in Section .…”

“…This means that the aniline group remains conformationally identical when exceeding 180°, and the rotation of the guanidine group results in an inversion symmetry relation, creating regions A and B. In the cocrystal searches, two conformations were utilized: the global minimum and a higher-energy conformation, in alignment with our previous SG study …”

“…SG, also a sulfonamide, acts locally in the gastrointestinal tract against bacterial pathogens and is commonly employed in animal treatment . Five polymorphic forms (I, II, III, IV, and V , ), two monohydrate forms, , nine solvates, and cocrystals with antipyrine, 1,10-phenantholine, thiobarbituric acid, 1,2-di­(4-pyridyl)­ethylene, 4-nitrobenzoic acid, 3-nitrobenzoic acid, and phenazine are reported.…”