Crystal structure and Hirshfeld surface analysis of dimethyl 5-[2-(2,4,6-trioxo-1,3-diazinan-5-ylidene)hydrazin-1-yl]benzene-1,3-dicarboxylate 0.224-hydrate

In the crystal, the whole molecule of the title compound, C14H12N4O7·0.224H2O, is nearly planar with a maximum deviation from the least-squares plane of 0.352 (1) Å. The molecular conformation is stabilized by an intramolecular N—H...O hydrogen bond, generating an S(6) ring motif. In the crystal, molecules are linked by centrosymmetric pairs of N—H...O hydrogen bonds, forming ribbons along the c-axis direction. These ribbons connected by van der Waals contacts, forming sheets parallel to the ac plane. There are also intermolecular van der Waals contacts and and C—H...π interactions between the sheets. A Hirshfeld surface analysis indicates that the most prevalent interactions are O...H/H...O (41.2%), H...H (19.2%), C...H/H...C (12.2%) and C...O/ O...C (8.4%).

Clostridioides difficile specific DNA adenine methyltransferase CamA squeezes and flips adenine out of DNA helix

Clostridioides difficile infections are an urgent medical problem. The newly discovered C.difficileadenine methyltransferase A (CamA) is specified by all C. difficile genomes sequenced to date (>300), but is rare among other bacteria. CamA is an orphan methyltransferase, unassociated with a restriction endonuclease. CamA-mediated methylation at CAAAAA is required for normal sporulation, biofilm formation, and intestinal colonization by C. difficile. We characterized CamA kinetic parameters, and determined its structure bound to DNA containing the recognition sequence. CamA contains an N-terminal domain for catalyzing methyl transfer, and a C-terminal DNA recognition domain. Major and minor groove DNA contacts in the recognition site involve base-specific hydrogen bonds, van der Waals contacts and the Watson-Crick pairing of a rearranged A:T base pair. These provide sufficient sequence discrimination to ensure high specificity. Finally, the surprisingly weak binding of the methyl donor S-adenosyl-l-methionine (SAM) might provide avenues for inhibiting CamA activity using SAM analogs.

Crystal structure of tofacitinib dihydrogen citrate (Xeljanz®), (C16H21N6O)(H2C6H5O7)

The crystal structure of tofacitinib dihydrogen citrate (tofacitinib citrate) has been solved and refined using synchrotron X-ray powder diffraction data, and optimized using density functional techniques. Tofacitinib dihydrogen citrate crystallizes in space group P212121 (#19) with a = 5.91113(1), b = 12.93131(3), c = 30.43499(7) Å, V = 2326.411(6) Å3, and Z = 4. The crystal structure consists of corrugated layers perpendicular to the c-axis. Within the layers, cation⋯anion and anion⋯anion hydrogen bonds link the fragments into a two-dimensional network parallel to the ab-plane. Between the layers, there are only van der Waals contacts. A terminal carboxylic acid group in the citrate anion forms a strong charge-assisted hydrogen bond to the ionized central carboxylate group. The other carboxylic acid acts as a donor to the carbonyl group of the cation. The citrate hydroxy group forms an intramolecular charge-assisted hydrogen bond to the ionized central carboxylate. Two protonated nitrogen atoms in the cation act as donors to the ionized central carboxylate of the anion. These hydrogen bonds form a ring with the graph set symbol R2,2(8). The powder pattern has been submitted to ICDD® for inclusion in the Powder Diffraction File™ (PDF®).

Crystal structure of 2-hydroxy-2-phenylacetophenone oxime

The title compound [systematic name: 2-(N-hydroxyimino)-1,2-diphenylethanol], C14H13NO2, consists of hydroxy phenylacetophenone and oxime units, in which the phenyl rings are oriented at a dihedral angle of 80.54 (7)°. In the crystal, intermolecular O—HOxm...NOxm, O—HHydr...OHydr, O—H′Hydr...OHydr and O—HOxm...OHydr hydrogen bonds link the molecules into infinite chains along the c-axis direction. π–π contacts between inversion-related of the phenyl ring adjacent to the oxime group have a centroid–centroid separation of 3.904 (3) Å and a weak C—H...π(ring) interaction is also observed. A Hirshfeld surface analysis of the crystal structure indicates that the most important contributions for the crystal packing are from H...H (58.4%) and H...C/C...H (26.4%) contacts. Hydrogen bonding and van der Waals contacts are the dominant interactions in the crystal packing.