Crystallographic Study of Solvates and Solvate Hydrates of an Antibacterial Furazidin

Abstract

In this study we present a detailed crystallographic analysis of multiple solvates of an antibacterial furazidin. Solvate formation of furazidin was investigated by crystallizing it from pure solvents and solvent-water mixtures. Crystal structure analysis of the obtained solvates and computational calculations were used to rationalize the main factors leading to the intermolecular interactions present in the solvate crystal structures as well as resulting in formation of the observed solvates and solvate hydrates. Furazidin forms pure solvates and solvate hydrates with solvents having large hydrogen bond acceptor propensity as well as with a hydrogen bond donor and acceptor formic acid. In solvate hydrates the incorporation of water allows formation of additional hydrogen bonds and results in more efficient hydrogen bond network in which water is “hooking” the organic solvent molecule, and this slightly reduces the cut-off of solvent hydrogen bond acceptor propensity required for obtaining a solvate. The crystal structures of all pure solvates are formed from molecule layers and in almost all structures solvent is hydrogen bonded to the furazidin, but the packing in each solvate is unique. In contrast, the hydrogen bonding and packing in most solvate hydrates are nearly identical.

Crystallographic and Computational Analysis of Solid Form Landscape of Three Structurally Related Imidazolidine-2,4-dione Active Pharmaceutical Ingredients: Nitrofurantoin, Furazidin and Dantrolene

“…In NF solvates with alcohols (IPA, MeOH and BnOH) solvent molecules act as a linkers and NF molecules and solvent molecules form hydrogen bond chains C 2 2 (6) via two strong hydrogen bonds N1-H1 … O solv and O solv -H solv … O2 (see Figure 7 b). This is true also for three of four FUR solvate-hydrates (FUR S DMF MH, FUR S DXN MH and FUR S THF MH), which are structurally highly similar 59 and water molecule links FUR molecules forming N1-H1 … O w -H w … O2 chains C 2 2 (6) (see Figure 7 f). In these solvate-hydrates FUR molecule is not directly bonded to the organic solvent molecule but acts as a linker providing additional Ow-Hw … Osolv bond.…”

“…However, no hydrate for FUR was obtained, meaning there is no stable hydrate for this compound. Nevertheless, FUR showed higher propensity to form solvates, as, if compared to NF, FUR also forms solvates with weaker hydrogen bond acceptor 1,4-dioxane, formic acid as well as several solvate-hydrates 59 . Conversely, DAN had the highest propensity to form different solid forms, as six polymorphs, four hydrates, ten solvates formed by solvents with notably different properties as well as a solvate-hydrate was characterized structurally, and formation of several other solvates, solvate-hydrates and hydrates was observed, with these phases not fully or just structurally characterized 53 .…”

“…) and 4 solvate-hydrates (FUR S DMF MH 60 , FUR S THF MH 60 , FUR S DXN MH 59 and FUR S HCOOH MH 59 ) were previously reported. Here we report and use crystal structures of FUR polymorphs I and II as well as a new polymorph III determined from SCXRD experiments.…”

“…NF forms two hydrates and DAN forms four hydrates. In contrast, there is no information that FUR would form any simple hydrate, although based on the rather complex solid form landscape of FUR 59 formation of its hydrate under some specific condition cannot be excluded. The pairwise interaction energies between molecules linked by hydrogen bonds in NF and DAN hydrates are collected in Table 5, while a graphic representation of the hydrogen bonds present in the hydrates is given in Figure 6.…”