Hydrogen-bonding patterns in trimethoprim picolinate and 2-amino-4,6-dimethylpyrimidinium picolinate hemihydrate

Abstract

In the title compounds, namely 2,4-diamino-5-[(3,4,5-trimethoxyphenyl)methyl]pyrimidin-1-ium pyridine-2-carboxylate, C14H19N4O3+.C6H4NO2-, (I), and 2-amino-4,6-dimethylpyrimidin-1-ium pyridine-2-carboxylate hemihydrate, C6H10N3+.C6H4NO2-.0.5H2O, (II), the trimethoprim and 2-amino-4,6-dimethylpyrimidin-1-ium cations are protonated at one of the pyrimidine N atoms. In (I), bifurcated hydrogen bonds are observed between a picolinate O atom, the protonated N atom and the 2-amino group; the graph-set designator is R2(1)(6). The pyrimidine moieties of the trimethoprim cations are centrosymmetrically paired through a pair of N-H...N hydrogen bonds. In addition to the base pairing, one of the picolinate O atoms bridges the 2- and 4-amino groups on either side of the paired bases, resulting in a complementary DADA array. In (II), the carboxylate group of the picolinate anion binds with the protonated pyrimidine N atom and the 2-amino group of the pyrimidine moiety through a pair of N-H...O hydrogen bonds, leading to the common ring motif R2(2)(8). The water molecule, which resides on a twofold rotation axis, bridges the carboxylate group of the picolinate anion via O-H...O hydrogen bonds.

Supramolecular hydrogen-bonding patterns in salts of the antifolate drugs trimethoprim and pyrimethamine

“…5a). Similar DADA arrays have been reported in TMP salts (Subashini et al, 2011;Hemamalini et al, 2006). One of the 2-amino H atoms acts as a bifurcated donor with atoms O1W i and O2 (of TPA), leading to an R 2 2 (4) ring motif.…”

“…R 1 2 (6) ring involving one of the O atoms of the anion has also been observed in the crystal structures of trimethoprim benzenesulfonate monohydrate, trimethoprim sulfanilate monohydrate and trimethoprim 3-carboxy-4-hydroxybenzoate (Baskar Raj et al, 2003), pyrimethaminium dinitrate (Balasubramani et al, 2005) and trimethoprim picolinate (Hemamalini et al, 2006). A self-complementary base pairing via a pair of N2A-H2AÁ Á ÁN3A i hydrogen bonds (Table 9) is observed [supramolecular homosynthon, R 2 2 (8) ring motif] (see Scheme 3).…”

“…Selfcomplementary base pairing via a pair of N2-HÁ Á ÁN3 hydrogen bonds, forming an R 2 2 (8) ring motif (supramolecular homosynthon), is also present (see Scheme 3). The quadruple DADA array is formed via N-HÁ Á ÁO1W and N-HÁ Á ÁN hydrogen bonds with fused R 2 3 (8), R 2 2 (8) and R 2 3 (8) ring motifs (Subashini et al, 2011;Hemamalini et al, 2006). The water molecule connects the two layers of MTPC and TMP ions, generating a three-dimensional supramolecular sheet structure ( Fig.…”