Hydrogen-bonding patterns in pyrimethaminium pyridine-3-sulfonate

In the asymmetric unit of the title salt [systematic name: 2,4-diamino-5-(4-chlorophenyl)-6-ethylpyrimidin-1-ium pyridine-3-sulfonate], C12H14N4Cl+·C5H4NSO3 −, there are two independent pyrimethaminium cations and two 3-pyridine sulfonate anions. Each sulfonate group interacts with the corresponding protonated pyrimidine ring through two N—H⋯O hydrogen bonds, forming a cyclic hydrogen-bonded bimolecular R 2 2(8) motif. Even though the primary mode of association is the same, the next higher level of supramolecular architectures are different due to different hydrogen-bonded networks. In one of the independent molecules in the asymmetric unit, the pyrimethamine cation is paired centrosymmetrically through N—H⋯N hydrogen bonds, generating an R 2 2(8) ring motif. In the other molecule, the pyrimethamine cation does not form any base pairs; instead it forms hydrogen bonds with the 3-pyridine sulfonate anion. The structure is further stabilized by C—H⋯O, C—H⋯N and π–π stacking [centroid–centroid distance = 3.9465 (13) Å] interactions.

In the asymmetric unit of the title salt [systematic name: 2,4diamino-5-(4-chlorophenyl)-6-ethylpyrimidin-1-ium pyridine-3-sulfonate], C 12 H 14 N 4 Cl + ÁC 5 H 4 NSO 3 À , there are two independent pyrimethaminium cations and two 3-pyridine sulfonate anions. Each sulfonate group interacts with the corresponding protonated pyrimidine ring through two N-HÁ Á ÁO hydrogen bonds, forming a cyclic hydrogen-bonded bimolecular R 2 2 (8) motif. Even though the primary mode of association is the same, the next higher level of supramolecular architectures are different due to different hydrogen-bonded networks. In one of the independent molecules in the asymmetric unit, the pyrimethamine cation is paired centrosymmetrically through N-HÁ Á ÁN hydrogen bonds, generating an R 2 2 (8) ring motif. In the other molecule, the pyrimethamine cation does not form any base pairs; instead it forms hydrogen bonds with the 3-pyridine sulfonate anion. The structure is further stabilized by C-HÁ Á ÁO, C-HÁ Á ÁN andstacking [centroid-centroid distance = 3.9465 (13) Å ] interactions.

Experimental
It is therefore of interest, to investigate the packing preferences and supramolecular architectures of the title compound (Scheme 1). The compound crystallizes in the triclinic space group P1, with two molecules in the asymmetric unit ( Figure   1). The crystallographically independent pyrimethamine molecules (A and B) are protonated at N1A and N1B positions as is evident from the increase in respective bond angle at C-N-C, when compared to its neutral form (Sethuraman & Thomas Muthiah, 2002). The bond lengths and angles between the two molecules are in good agreement, with those observed in computer modeling studies on dihydrofolate reductase DHFR-PMN complexes (Sansom et al., 1989) and the crystal structure of metoprine (De et al., 1989).
Despite this analogy, what makes things interesting is the higher level of supramolecular organization assumed by the two independent molecules. The pyrimethaminium cation A is centrosymmetrically paired through N4-H···N3 hydrogen bonds involving the 4-amino group and the N3 atom of the pyrimidine to form the ring motif  (Stanley et al., 2002).
The pyrimethaminium cation B does not form any base pairs across its inversion related molecule, instead it forms hydrogen bonds with the 3-pyridine sulfonate(A) through N2B-H···O3A, C16A-H···N3B, N4B-H···N17A interactions to form motifs with R 2 2 (9) and R 2 2 (7) graph set notations ( Figure 2). Combination of these motifs leads to the formation of a triplet hydrogen bond array. A previous report from our laboratory on a closely related system, pyrimethaminium benzene sulfonate salt did not yield such an array. This might be due to the absence of acceptor in the benzene ring (Balasubramani et al., 2007).
supplementary materials sup-2 Other than these strong interactions, the crystal structure is stabilized by C-H···O, C-H···N interactions and π-π stacking interactions between the PMN (B) molecules, with a centroid-to-centroid distance of 3.9465 (13) Å, an interplanar spacing of 3.4332 (8) Å and a centroid offset of 1.946 Å.
From this analysis, it is evident that sulfonates, as usual has a penchant for the formation of bidentate motif and the intermolecular interactions involved in this structure paves way to the formation of two different hydrogen bonded arrays.
Identification of such patterns will help in design and construction of preferred hydrogen bonding patterns on drug like molecules.

Experimental
To obtain crystals of compound (I) suitable for X-ray study, pyrimethamine (31 mg; Shah Pharma Chemicals, India) was dissolved in hot n-propanol (20 ml) and 3-pyridine sulf77onic acid (20 mg; Merck) was dissolved in hot n-propanol (20 ml). The two solutions were mixed and warmed for 20 minutes over a water bath. The solution was allowed to evaporate slowly. After a few days, colourless crystals were obtained.