Structural characterization of three norfloxacin salts with N-heterocyclic mono- and di-carb-oxy-lic acids

Cocrystallization of norfloxacin (NFX) with three heterocyclic coformers, namely, pyridine-3,5-di-carb-oxy-lic acid, pyridazine-3-carb-oxy-lic acid and pyrimidine-5-carb-oxy-lic acid, yielded three mol-ecular salts: norfloxacinium [4-(3-carb-oxy-1-ethyl-6-fluoro-4-oxo-1,4-di-hydro-quinolin-7-yl)piperazin-1-ium] 5-carb-oxy-pyridine-3-carboxyl-ate trihydrate, 2C₁₆H₁₉FN₃O₃ ⁺·2C₇H₄NO₄ ^-·3H₂O, (1), norfloxacinium pyridazine-3-carboxyl-ate, C₁₆H₁₉FN₃O₃ ⁺·C₅H₃N₂O₂ ^-, (2), and norfloxacinium pyrimidine-5-carboxyl-ate monohydrate, C₁₆H₁₉FN₃O₃ ⁺·C₅H₃N₂O₂ ^-·H₂O, (3). In all structures, the quinolone skeleton of the norfloxacin cation is essentially planar, while the piperazine ring adopts a chair conformation. The crystal packing is governed primarily by N-H⋯O and N-H⋯N hydrogen bonds, which generate distinct mono-periodic and di-periodic motifs depending on the coformer. These assemblies are further linked by weak C-H⋯O and C-H⋯N inter-actions into tri-periodic supra-molecular networks. The crystal structures are additionally stabilized by aromatic π-π inter-actions, which differ in their stacking arrangements among the three salts. Hirshfeld surface analysis of the norfloxacin cations shows that H⋯H and O⋯H/H⋯O contacts dominate, whereas variations in the contributions from C⋯C, C⋯H/H⋯C and N⋯H/H⋯N contacts reflect differences in the supra-molecular packing.