Polymorphism and Hydrated States in 5-Nitrouracil Crystallized from Aqueous Solution

Abstract

The crystallization of 5-nitrouracil (5NU) from pure aqueous solution yields two anhydrous polymorphs and a monohydrate depending on the temperature at which the process is carried out. 5NU mimics true polymorphism in that, when retained in aqueous solution, both metastable (anhydrous) forms undergo solvent mediated phase transformations (SMPTs) into the more thermodynamically stable hydrated form as would be predicted by Ostwald's rule of stages. The phase transformations can occur either in the classical manner of dissolution and recrystallization or, in one case, may in some circumstances be nucleated and morphologically templated by the original crystalline form. There is no appearance from aqueous solution of a known third acentric anhydrous form, previously prepared from acetonitrile solutions. Preliminary experiments suggest this nonappearance may result from the relatively high solubility of this form in aqueous solution.

Dehydration mechanism of a small molecular solid: 5-nitrouracil hydrate

“…A detailed description of the crystal growth of 5NU from aqueous solutions, the effects of polymorphism and the role of twinning has been given by Okoth et al 7 In the present studies; crystals of 5NU-h were thin, rhombohedral tablets (Fig. 2), with a main face of (010).…”

“…The earlier work of Okoth et al 7 has shown that there exists a limited structural relationship between 5NU-h and 5NU-o, which simply consists of a localized molecule-molecule motif; a loose dimer, with no extended supramolecular structure or long-range ordering. This local interaction is shown in Fig.…”

“…It has already been shown that even in aqueous solutions, it can take up to 8 days for a solvent mediated phase transformation to occur, turning the anhydrous forms into the hydrated form. 7 …”

“…Twinned crystals of this type are the most commonly seen, however as previously reported, a number of other twins also exist for 5NU-h. The indexing of the faces used in this study is derived from the recent crystallographic determination by Okoth et al 7…”

“…In crystallisation from aqueous solution, 5NU shows an Ostwald like staged behavior, in that the anhydrous forms crystallise first (which form crystallises depends upon temperature), followed by the final nucleation and growth of 5-nitrouracil monohydrate from the suspended anhydrates by a solvent mediated transformation. 7 In the only previous work on the dehydration of 5NU, Perrier and Byrn 5 noted that 5NU dehydrates by a randomly dispersed nucleation process. Inspection of the crystal structure led them to note the existence of molecular channels by way of which the product water molecules could leave the crystal and proposed that this was a key factor in the dehydration mechanism.…”