Polyiodide salts of sulfanilamide and dapsone

Sulfanilamide and dapsone are broad-spectrum antibiotics classified as Biopharmaceutical Classification System (BCS) classes II and IV drugs, respectively, which often require high doses in oral formulations. One strategy to overcome this limitation is salt formation, aimed at increasing solubility. Here, two new sulfanilamide triiodide solvatomorphic salts, SFM[I₃]·0.5H₂O (hemihydrate) and SFM[I₃]·H₂O (monohydrate), and one dapsone triiodide/pentaiodide salt, DDS[I₃][I₅]·4H₂O, were prepared and structurally characterized by single-crystal X-ray diffraction. The three salts feature hydrogen- and halogen-bonding interactions, in which water molecules play an important role in assembling the crystal architecture. The packing of the two sulfanilamide salts involves π-aryl···π-aryl interactions, whereas the dapsone salt also exhibits π•••halogen interactions and side-by-side alignment of V-shaped cation molecules with I 5 − . Notably, DDS[I₃][I₅]·4H₂O lacks N–H•••O=S hydrogen bonding between DDS molecules, an interaction associated with unfavorable solvation and low solubility in related crystal forms. Hirshfeld surface analysis allowed us to quantify the contribution and strength of each interaction type.