Crystal structure of 4-amino-5-fluoro-2-oxo-2,3-dihydropyrimidin-1-ium 3-hydroxypyridine-2-carboxylate

The protonated N atom and 2-amine group of the 5-fluorocytosinium (5FC) cation interact with the 3-hydroxypicolinate (3HAP) anion through a pair of nearly-parallel N—H⋯O hydrogen bonds, forming a robust (8) ring motif. The ions are further linked by N—H⋯N, O—H⋯O, N—H⋯O and C—H⋯O hydrogen bonds, leading to supramolecular wave-like sheets and the crystal structure is further stabilized by C—H⋯π interactions, generating a three-dimensional architecture.


Chemical context
Fluorinated pyrimidine and purine derivatives have received much interest because of their wide range of biological applications (Giner-Sorolla & Bendich, 1958). 5-Fuorocytosine is a fluorinated pyrimidine derivative anti-metabolite drug and is also extensively used as an anti-fungal agent for the treatment of Candida and Cryptococcus (Vermes et al., 2000). 5-Fluorocytosine is a versatile molecule that plays essential roles in many biological applications, such as antitumour, potential gene therapy and gene-directed prodrug therapy (GDEPT) in the treatment of cancer (Kohila et al., 2012). The crystal structures of 5-fluorocytosine monohydrate, 5-fluorocytosine co-crystals and salts have also been reported (Louis et al., 1982;Tutughamiarso et al., 2012;Perumalla & Sun, 2014;Prabakaran et al., 2001). The crystal structures of various salts and complexes of 3-hydroxypicolinic acid have also been reported (Quintal et al., 2000;Soares-Santos et al., 2003;Betz and Gerber, 2011;Nirmalram et al., 2011).

Structural commentary
The asymmetric unit contains a 5-fluorocytosinium cation and a 3-hydroxypicolinate anion (Fig. 1). The 5-fluorocytosine molecule is protonated at N3, as is evident from the increase in the internal angle at N3 from 120.8 (5) in neutral 5-fluorocytosine (Louis et al., 1982) to 124.85 (15) . There is an intramolecular N-HÁ Á ÁF hydrogen bond with an S(5) ring motif between the N4 amino group and the F atom of the 5fluorocytosinum cation. These hydrogen-bonding parameters are similar to those observed in 5-fluorocytosinium salicylate (Prabakaran et al., 2001). An intramolecular O-HÁ Á ÁO interaction forms an S(6) motif between the phenolic OH and carboxylate group, which is also observed in 3-hydroxypyridinium-2-carboxylate (Betz & Gerber, 2011).

Supramolecular features
In the crystal structure, the carboxylate group of the 3-hydroxypicolinate anion (O3 and O4) interacts with the protonated N3 atom and the 4-amino group of the 5-fluorocytosinium moiety through a pair of N-HÁ Á ÁO hydrogen bonds, forming a robust R 2 2 (8) motif (Etter, 1990;Bernstein et al., 1995). The 3-hydroxypicolinate (N2 and C12) atoms interact with the N1 atom and the exocyclic oxygen O2 atom of the 5-fluorocytosinium moiety through a pair of N-HÁ Á ÁN and C-HÁ Á ÁO hydrogen bonds, forming an R 2 2 (7) motif. This type of motif rarely occurs in cytosinium carboxylate interactions (Benali-Cherif et al., 2009). The motif is further research communications Figure 1 The asymmetric unit of the title compound, showing 30% probability displacement ellipsoids. Dashed lines represent hydrogen bonds.
Cg is the centroid of the N2/C8-C12 ring.

Figure 3
The wavy sheets interlinked by C-HÁ Á ÁO hydrogen bonds. Dashed lines represent hydrogen bonds (see Table 1 for details).

Synthesis and crystallization
Hot aqueous solutions of 5-fluorocytosine (32 mg, Alfa Aesar) and 3-hydroxypicolinic acid (37 mg, Alfa Aesar) were mixed in a 1:1 molar ratio. The resulting solution was warmed over a water bath for half an hour and then kept at room temperature for crystallization. After a week, colourless prismatic crystals were obtained.

Refinement
Crystal data, data collection and structure refinement details are summarized in Table 2. All H atoms were initially located in difference Fourier maps and were subsequently treated as A view of the C-HÁ Á Á interactions shown as dashed lines. Symmetry codes are given in Table 1.

Special details
Experimental. 185 frames in 5 runs of ω scans. Crystal-detector distance = 55.0 mm. Geometry. All s.u.'s (except the s.u. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell s.u.'s are taken into account individually in the estimation of s.u.'s in distances, angles and torsion angles; correlations between s.u.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell s.u.'s is used for estimating s.u.'s involving l.s. planes. Refinement. Refinement of F 2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F 2 , conventional R-factors R are based on F, with F set to zero for negative F 2 . The threshold expression of F 2 > 2σ(F 2 ) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F 2 are statistically about twice as large as those based on F, and R-factors based on ALL data will be even larger.