Structure and electrostatic properties of the pyrimethamine-3,5-dihydroxybenzoic acid cocrystal in water solvent studied using transferred electron-density parameters.

Pyrimethamine is an antimalarial drug. The cocrystal salt form of pyrimethamine with 3,5-dihydroxybenzoic acid in water solvent has been synthesized, namely 2,4-diamino-5-(4-chlorophenyl)-6-ethylpyrimidin-1-ium 3,5-dihydroxybenzoate hemihydrate, C12H14ClN4+·C7H5O4-·0.5H2O. X-ray diffraction data were collected at room temperature. Refinement of the crystal structure was carried out using the classical Independent Atom Model (IAM), while the electrostatic properties were studied by transferring electron-density parameters from an electron-density database. The Cl atom was refined anharmonically. The results of both refinement methods were compared. Topological analyses were carried out using Bader's theory of Atoms in Molecules (AIM). The three-dimensional Hirshfeld surface analysis and the two-dimensional fingerprint maps of individual molecules revealed that the crystal structures are dominated by H...O/O...H and H...H contacts. Other close contacts are also present, including weak C...H/H...C contacts. Charge transfer between the pyrimethamine and 3,5-dihydroxybenzoic acid molecules results in a molecular assembly based on strong intermolecular hydrogen bonds. This is further validated by the calculation of the electrostatic potential based on transferred electron-density parameters. The current work proves the significance of the transferability principle in studying the electron-density-derived properties of molecules in cases where high-resolution diffraction data at low temperature are not available.

Electrostatic properties of the pyrimethamine-2,4-dihydroxybenzoic acid cocrystal in methanol studied using transferred electron-density parameters.

The crystal structure of the cocrystal salt form of the antimalarial drug pyrimethamine with 2,4-dihydroxybenzoic acid in methanol [systematic name: 2,4-diamino-5-(4-chlorophenyl)-6-ethylpyrimidin-1-ium 2,4-dihydroxybenzoate methanol monosolvate, C12H14ClN4+·C7H5O4-·CH3OH] has been studied using X-ray diffraction data collected at room temperature. The crystal structure was refined using the classical Independent Atom Model (IAM) and the Multipolar Atom Model by transferring electron-density parameters from the ELMAM2 database. The Cl atom was refined anharmonically. The results of both refinement methods have been compared. The intermolecular interactions have been characterized on the basis of Hirshfeld surface analysis and topological analysis using Bader's theory of Atoms in Molecules. The results show that the molecular assembly is built primarily on the basis of charge transfer between 2,4-dihydroxybenzoic acid and pyrimethamine, which results in strong intermolecular hydrogen bonds. This fact is further validated by the calculation of the electrostatic potential based on transferred electron-density parameters.

Transferred multipolar atom model for 10ß,17ß-dihydroxy-17α-methylestr-4-en-3-one dihydrate obtained from the biotransformation of methyloestrenolone.

Biotransformation is the structural modification of compounds using enzymes as the catalysts and it plays a key role in the synthesis of pharmaceutically important compounds. 10ß,17ß-Dihydroxy-17α-methylestr-4-en-3-one dihydrate, C19H28O3·2H2O, was obtained from the fungal biotransformation of methyloestrenolone. The structure was refined using the classical independent atom model (IAM) and a transferred multipolar atom model using the ELMAM2 database. The results from the two refinements have been compared. The ELMAM2 refinement has been found to be superior in terms of the refinement statistics. It has been shown that certain electron-density-derived properties can be calculated on the basis of the transferred parameters for crystals which diffract to ordinary resolution.