Crystalline Forms of Trazodone Dihydrates

In this study, treatment of anhydrous trazodone powder with ammonium carbamate in warm water crystallised two new polymorphs or dihydrates of trazodone after 5 h, whose structures were determined by X-ray single crystal diffraction. Each dihydrate contains infinite zigzag hydrogen-bonded chains of water molecules, which are stabilised by the N4 acceptor atom of the piperazine ring and the pendant carbonyl O1 atom of the triazole ring, as well as other water molecules. The strong dipole moment expected for the O1 atom makes it a good hydrogen bond acceptor for stabilising the chains of water molecules. Each molecule of trazodone has a similar conformation in both hydrates, except for the propyl chains, which adopt different conformations: anti-gauche in the β hydrate (triazole N-C-C-C and C-C-C-piperazine N) and anti-anti in the γ hydrate. Both piperazine rings adopt chair conformations, and the exocyclic N-C bonds are in equatorial orientations. The Hirshfeld surfaces and two-dimensional fingerprint plots for the polymorphs were calculated using CrystalExplorer17, which indicated contacts significantly shorter than the sum of the van der Waals radii in the vicinity of the piperazine N4 and triazole O1 atoms corresponding to the strong hydrogen bonds accepted by these atoms.

A test of ab initio-generated, radial intermolecular potential energy functions for five axially-symmetric, hydrogen-bonded complexes B⋯HF, where B = N2, CO, PH3, HCN and NH3

Radial P.E. functions of hydrogen-bonded complexes B⋯HF (B = N2, CO, PH3, HCN and NH3) have been calculated ab initio at the CCSD(T)(F12C)/cc-pVTZ-F12 level as a function of the hydrogen-bond length r(Z⋯H), where Z is the H-bond acceptor atom of B.

Leloir glycosyltransferases of natural product C-glycosylation: structure, mechanism and specificity

A prominent attribute of chemical structure in microbial and plant natural products is aromatic C-glycosylation. In plants, various flavonoid natural products have a β-C-d-glucosyl moiety attached to their core structure. Natural product C-glycosides have attracted significant attention for their own unique bioactivity as well as for representing non-hydrolysable analogs of the canonical O-glycosides. The biosynthesis of natural product C-glycosides is accomplished by sugar nucleotide-dependent (Leloir) glycosyltransferases. Here, we provide an overview on the C-glycosyltransferases of microbial, plant and insect origin that have been biochemically characterized. Despite sharing basic evolutionary relationships, as evidenced by their common membership to glycosyltransferase family GT-1 and conserved GT-B structural fold, the known C-glycosyltransferases are diverse in the structural features that govern their reactivity, selectivity and specificity. Bifunctional glycosyltransferases can form C- and O-glycosides dependent on the structure of the aglycon acceptor. Recent crystal structures of plant C-glycosyltransferases and di-C-glycosyltransferases complement earlier structural studies of bacterial enzymes and provide important molecular insight into the enzymatic discrimination between C- and O-glycosylation. Studies of enzyme structure and mechanism converge on the view of a single displacement (SN2)-like mechanism of enzymatic C-glycosyl transfer, largely analogous to O-glycosyl transfer. The distinction between reactions at the O- or C-acceptor atom is achieved through the precise positioning of the acceptor relative to the donor substrate in the binding pocket. Nonetheless, C-glycosyltransferases may differ in the catalytic strategy applied to induce nucleophilic reactivity at the acceptor carbon. Evidence from the mutagenesis of C-glycosyltransferases may become useful in engineering these enzymes for tailored reactivity.

Existence of untypical halogen-involving interactions in crystal packings: a statistical and first-principles study

There is a common perception by the scientific community that a halogen-involving interaction forms when the distance between the donor atom and the acceptor atom is less than the sum of their van der Waals (vdW) radii.

Crystal structure of pirfenidone (5-methyl-1-phenyl-1H-pyridin-2-one): an active pharmaceutical ingredient (API)

The crystal structure of pirfenidone, C12H11NO [alternative name: 5-methyl-1-phenylpyridin-2(1H)-one], an active pharmaceutical ingredient (API) approved in Europe and Japan for the treatment of Idiopathic pulmonary fibrosis (IPF), is reported here for the first time. It was crystallized from toluene by the temperature gradient technique, and crystallizes in the chiral monoclinic space groupP21. The phenyl and pyridone rings are inclined to each other by 50.30 (11)°. In the crystal, molecules are linked by C–H...O hydrogen bonds involving the same acceptor atom, forming undulating layers lying parallel to theabplane.

Crystal structure of diethyl {2,2,2-trichloro-1-[2-(1,3-dioxo-2,3-dihydro-1H-isoindol-2-yl)-4-methylpentanamido]ethyl}phosphonate

In the title phosphorylated compound, C20H26Cl3N2O6P, the phthalimide unit is essentially planar (r.m.s. deviation = 0.0129 Å) and the O atoms of this unit deviate from the mean plane by 0.080 (3) and 0.041 (3) Å. In the crystal, pairs of molecules are linked by N—H...O and weak C—H...O hydrogen bonds involving the same acceptor atom, forming inversion dimers. In addition, π–π stacking interactions between the phthalimide groups, with a centroid–centroid distance of 3.7736 (13) Å, and further weak C—H...O hydrogen bonds connect the inversion dimers into columns along [0-11].

1-{[3-(Thiophen-2-yl)-4,5-dihydro-1,2-oxazol-5-yl]methyl}-2,3-dihydro-1H-indole-2,3-dione

In the title compound, C16H12N2O3S, the indoline and thiophene rings are inclined to one another by 2.01 (2)°. The isoxazole ring adopts an envelope conformation, with the methine C atom as the flap, and its mean plane is inclined to the thiophene and indoline ring mean planes by 19.78 (14) and 20.83 (12)°, respectively. In the crystal, molecules are linked by C—H...O hydrogen bonds involving the same acceptor atom, forming chains propagating along [010]. The chains are linked by further C—H...O hydrogen bonds, forming slabs parallel to the (-103) plane. The slabs are linked by offset π–π interactions [intercentroid distance = 3.792 (1) Å], forming a three-dimensional supramolecular structure.

Crystal structure and Hirshfeld surface analysis of ethyl 5-phenylisoxazole-3-carboxylate

The title compound, C12H11NO3, is an intermediate used in the synthesis of many drug-like molecules. The molecule is almost planar, with the phenyl ring inclined to the isoxazole ring by 0.5 (1)°. The ester moiety has an extended conformation and is almost in the same plane with respect to the isoxazole ring, as indicated by the O—C—C—N torsion angle of −172.86 (18)°. In the crystal, molecules are linkedviapairs of C—H...O hydrogen bonds with the same acceptor atom, forming inversion dimers with twoR21(7) ring motifs. The molecules stack in layers lying parallel to (10-3). Analysis using Hirshfeld surface generation and two-dimensional fingerprint plots explores the distribution of weak intermolecular interactions in the crystal structure.

Ethyl (E)-2-(2,7-dimethyl-5-oxo-4H,5H-pyrano[4,3-b]pyran-4-ylidene)acetate

In the title compound, C14H14O5, the two heterocyclic rings are coplanar (r.m.s. deviation = 0.008 Å), with the largest deviation from the mean plane being 0.012 (1) Å. The mean plane through the acetate group is inclined slightly with respect to the oxopyrano[4,3-b]pyran-4-yl system, as indicated by the dihedral angle of 1.70 (7)° between them. Two intramolecular hydrogen bonds, completingS(6) ring motifs, are observed in the molecule. In the crystal, molecules are linked by weak C—H...O hydrogen bonds involving the same acceptor atom, forming chains propagating along thec-axis direction and enclosingR21(6) ring motifs. The chains are linkedviaoffset π–π interactions [intercentroid distance = 3.622 (1) Å], involving inversion-related oxopyrano[4,3-b]pyran-4-yl ring systems, forming slabs parallel to thebcplane.

(Z)-3-Allyl-5-(4-fluorobenzylidene)-2-sulfanylidenethiazolidin-4-one

In the title compound, C13H10FNOS2, the sulfanylidenethiazolidine ring and the benzylidene ring are almost coplanar [dihedral angle between the two planes = 0.1 (2)°]. The mean plane through the allyl group is nearly perpendicular to the sulfanylidenethiazolidine ring, as indicated by the dihedral angle of 69.5 (5)° between them. In the crystal, molecules are linked together by weak C—H...O hydrogen bonds involving the same acceptor atom, forming dimers parallel to (1-22).