Hydrogen-bonding patterns in 5-fluorocytosine–melamine co-crystal (4/1)

The asymmetric unit of the title compound comprises two independent 5-fluorocytosine molecules and one half-molecule of melamine. The 5-fluorocytosine molecules are linked through two different homosynthons; one is formed via a pair of N—H⋯O hydrogen bonds and the second via a pair of N—H⋯N hydrogen bonds. The 5-fluorocytosine and melamine molecules interact via N—H⋯O, N—H⋯N and N—H⋯O, N—H⋯N, C—H⋯F hydrogen bonds.

The asymmetric unit of the title compound, 4C 4 H 4 FN 3 OÁC 3 H 6 N 6 , comprises of two independent 5-fluorocytosine (5FC) molecules (A and B) and one halfmolecule of melamine (M). The other half of the melamine molecule is generated by a twofold axis. 5FC molecules A and B are linked through two different homosynthons [R 2 2 (8) ring motif]; one is formed via a pair of N-HÁ Á ÁO hydrogen bonds and the second via a pair of N-HÁ Á ÁN hydrogen bonds. In addition to this pairing, the O atoms of 5FC molecules A and B interact with the N2 amino group on both sides of the melamine molecule, forming a DDAA array of quadruple hydrogen bonds and generating a supramolecular pattern. The 5FC (molecules A and B) and two melamine molecules interact via N-HÁ Á ÁO, N-HÁ Á ÁN and N-HÁ Á ÁO, N-HÁ Á ÁN, C-HÁ Á ÁF hydrogen bonds forming R 6 6 (24) and R 4 4 (15) ring motifs. The crystal structure is further strengthened by C-HÁ Á ÁF, C-FÁ Á Á andstacking interactions.

Chemical context
Pyrimidine derivatives are used in the treatment of antiviral, antifungal, antitumor and cardiovascular diseases. 5-Fluorocytosine (5FC), a synthetic antimycotic compound, first synthesized in 1957 and widely used as an antitumor agent as a cytosine derivative (Tassel & Madoff, 1968;Benson & Nahata, 1988;Bennet, 1977;Polak & Scholer, 1980). It is active against fungal infection and was released in the year 1968 (Vermes et al., 2000). It becomes active by deamination of 5FC into 5-fluorouracil by the enzyme cytosine deaminase (CD) and inhibits RNA and DNA synthesis (Larsen et al., 2003;Mullen et al., 1994;Morschhä user, 2003). Melamine is a triazine derivative. It shows antitumor activity as well as biological activities such as antiangiogenesis and antimicrobial effects. Triazine derivatives are useful synthons in supramolecular chemistry. In particular, aminotriazines have been used for the formation of supramolecular architectures using hydrogen bonds (Russell et al., 1998;MacDonald & Whitesides, 1994;Whitesides et al., 1991). The organic and inorganic salts develop well-defined non-covalent molecular recognition via multiple hydrogen bonds by self assembly of components which contain a complementary array of hydrogen-bonding sites (Desiraju, 1989). The present work is focused on the supramolecular hydrogen-bonding patterns exhibited by the co-crystal of 5-fluorocytosine with melamine.

Structural commentary
The asymmetric unit comprises two independent 5-fluorocytosine (5FC) molecules (A and B) and half a molecule of melamine (M). The twofold axis of melamine coincides with the crystallographic twofold axis. An ORTEP view of the crystal structure is shown in Fig. 1. The values for the C-F bond distance in the two molecules [1.3491 (18) in 5FC A and 1.3492 (18) Å in 5FC B and the corresponding internal angles at the carbon-carrying fluorine atom [C2A-N3A-C4A = 119.96 (13) in 5FC A and C2B-N3B-C4B = 119.92 (13) in 5FC B] agree with those reported in the literature (Louis et al., 1982).
In this co-crystal, 5FC molecules A and B form two types of homosynthons (two types of base pairing) while the melamine molecule interacts with them via N-HÁ Á ÁO and N-HÁ Á ÁN hydrogen bonds, generating the supramolecular architecture.

Synthesis and crystallization
Hot aqueous solutions of 5-fluorocytosine (32 mg) and melamine (31 mg) were mixed in a 1:1 molar ratio. The resulting solution was warmed to 353 K using a water bath for half an hour and kept at room temperature for crystallization. After one week, colourless crystals were obtained.