R(2)(2)(8) motifs in Aminopyrimidine sulfonate/carboxylate interactions: Crystal structures of pyrimethaminium benzenesulfonate monohydrate (2:2:1) and 2-amino-4,6-dimethylpyrimidinium sulfosalicylate dihydrate (4:2:2)

BACKGROUND: Pyrimethamine [2,4-diamino-5-(p-chlorophenyl)-6-ethylpyrimidine] is an antifolate drug used in anti-malarial chemotherapy. Pyrimidine and aminopyrimidine derivatives are biologically important compounds owing to their natural occurrence as components of nucleic acids. RESULTS: In the crystal structures of two organic salts, namely pyrimethaminium benzenesulfonate monohydrate 1 and 2-amino-4, 6-dimethylpyrimidinium 3-carboxy-4-hydroxy benzenesulfonate dihydrate 2, pyrimethamine (PMN) and 2-amino-4,6-dimethylpyrimidine (AMPY) are protonated at one of the nitrogens in the pyrimidine rings. In both the PMN and AMPY sulfonate complexes, the protonated pyrimidine rings are hydrogen bonded to the sulfonate groups, forming a hydrogen-bonded bimolecular ring motif with graph-set notation R(2)(2)(8). The sulfonate group mimics the carboxylate anion's mode of association, which is more commonly seen when binding with 2-aminopyrimidines. In compound 1, the PMN moieties are centrosymmetrically paired through a complementary DADA array of hydrogen bonds. In compound 2, two types of bimolecular cyclic hydrogen bonded R(2)(2)(8) motifs (one involving the carboxylate group and the other involving sulfonate group) coexist. Furthermore, this compound is stabilized by intra and intermolecular O-H...O hydrogen bonds. CONCLUSION: The crystal structures of pyrimethaminium benzenesulfonate monohydrate and 2-amino-4,6-dimethylpyrimidinium sulfosalicylate dihydrate have been investigated in detail. In compound 1, the R(2)(2)(8) motif involving the sulfonate group is present. The role the sulfonic acid group plays in mimicking the carboxylate anions is thus evident. In compound 2, two types of bimolecular cyclic hydrogen bonded R(2)(2)(8) motifs (one involving the carboxylate group and the other involving sulfonate group) coexist. In both the compounds base pairing also occurs. Thus homo and hetero synthons are present.