scholarly journals Crystal structure, interaction energies and experimental electron density of the popular drug ketoprophen

IUCrJ ◽  
2018 ◽  
Vol 5 (6) ◽  
pp. 841-853 ◽  
Author(s):  
Sylwia Pawlędzio ◽  
Anna Makal ◽  
Damian Trzybiński ◽  
Krzysztof Woźniak
Keyword(s):  
Crystal Structure ◽  
Hydrogen Bonds ◽  
Crystal Packing ◽  
X Ray Diffraction ◽  
Scanning Calorimetry ◽  
Crystal Forms ◽  
Racemic Form ◽  
Closed Ring ◽  
Experimental Electron Density

The crystal and molecular structure of the pure (S)-enantiomer of the popular analgesic and anti-inflammatory drug ketoprophen (α-ket) is reported. A detailed aspherical charge-density model based on high-resolution X-ray diffraction data has been refined, yielding a high-precision geometric description and classification of the O—H...O interactions as medium strength hydrogen bonds. The crystal structure of the racemic form of ketoprophen (β-ket) was also redetermined at 100 K, at 0.5 Å resolution. A previously unreported disorder (10% occupancy) was discovered. In contrast to the racemic β-ket case, the (S)-enantiomer crystallizes with two independent molecules in the asymmetric unit with two distinct conformations. The major difference between the β-ket and α-ket crystal forms lies in the formation of distinct hydrogen-bonded motifs: a closed ring motif in β-ket versus infinite chains of hydrogen bonds in the chiral α-ket structure. However, the overall crystal packing of both forms is surprisingly similar, with close-packed layers of antiparallel-oriented benzophenone moieties bound by C—H...π interactions. Notably, the most important stabilizing term in the total lattice energies in both instances proved to be the dispersion related to these interactions. Both forms of the title compound (α- and β-ket) were additionally characterized by differential scanning calorimetry and thermogravimetric analysis.

Comparison of the crystal structures and thermochemistry of a novel soluble guanylate cyclase stimulator riociguat and its solvates

2017 ◽  
Vol 73 (5) ◽  
pp. 891-898 ◽  
Author(s):  
Xinbo Zhou ◽  
Xiurong Hu ◽  
Jianming Gu ◽  
Jianrong Zhu
Keyword(s):  
Crystal Structure ◽  
Thermogravimetric Analysis ◽  
Crystal Structures ◽  
Guanylate Cyclase ◽  
Soluble Guanylate Cyclase ◽  
Crystal Packing ◽  
X Ray Diffraction ◽  
Scanning Calorimetry ◽  
X Ray ◽  
Soluble Guanylate Cyclase Stimulator

Riociguat (Rio) is the first oral soluble guanylate cyclase stimulator to be approved for pulmonary arterial hypertension. In this study, form (II) of riociguat and three solvates with acetonitrile [form (III)],N,N-dimethylformamide [form (IV)] and ethyl acetate [form (V)] were crystallized. They were identified and characterized by differential scanning calorimetry, thermogravimetric analysis, X-ray powder diffraction, and their crystal structures were determined by single-crystal X-ray diffraction. No crystal structure has previously been reported for the known form (II) of riociguat. Crystal structure determination of Rio and its new solvates revealed that the dimericR22(14) motif is common in both structures. The crystal packing of solvates adopts channel-like patterns, whereas form (II) of riociguat adopts sheet-like patterns. Strong π–π interactions exist in the above four forms. The conformation of the riociguat in one molecule of 0.5-DMF solvate was found to be significantly different from the conformations found in the other solvates. Desolvation of the three solvates was studied by thermogravimetric analysis and X-ray diffraction, and was shown to transform them into form (I) of riociguat.

Supramolecular synthesis based on piperidone derivatives and pharmaceutically acceptable co-formers

2013 ◽  
Vol 69 (4) ◽  
pp. 421-427 ◽  
Author(s):  
Bhupinder Sandhu ◽  
Sergiu Draguta ◽  
Tiffany L. Kinnibrugh ◽  
Victor N. Khrustalev ◽  
Tatiana V. Timofeeva
Keyword(s):  
Crystal Structure ◽  
Melting Point ◽  
Ir Spectroscopy ◽  
Hydrogen Bonds ◽  
Crystal Packing ◽  
Aqueous Solubility ◽  
Active Pharmaceutical Ingredient ◽  
Ethanol Solution ◽  
X Ray Diffraction ◽  
X Ray

The target complexes, bis{(E,E)-3,5-bis[4-(diethylamino)benzylidene]-4-oxopiperidinium} butanedioate, 2C27H36N3O+·C4H4O42−, (II), and bis{(E,E)-3,5-bis[4-(diethylamino)benzylidene]-4-oxopiperidinium} decanedioate, 2C27H36N3O+·C10H16O42−, (III), were obtained by solvent-mediated crystallization of the active pharmaceutical ingredient (API) (E,E)-3,5-bis[4-(diethylamino)benzylidene]-4-piperidone and pharmaceutically acceptable dicarboxylic (succinic and sebacic) acids from ethanol solution. They have been characterized by melting point, IR spectroscopy and single-crystal X-ray diffraction. For the sake of comparison, the structure of the starting API, (E,E)-3,5-bis[4-(diethylamino)benzylidene]-4-piperidone methanol monosolvate, C27H35N3O·CH4O, (I), has also been studied. Compounds (II) and (III) represent salts containing H-shaped centrosymmetric hydrogen-bonded synthons, which are built from two parallel piperidinium cations and a bridging dicarboxylate dianion. In both (II) and (III), the dicarboxylate dianion resides on an inversion centre. The two cations and dianion within the H-shaped synthon are linked by two strong intermolecular N+—H...−OOC hydrogen bonds. The crystal structure of (II) includes two crystallographically independent formula units,AandB. The cation geometries of unitsAandBare different. The main N—C6H4—C=C—C(=O)—C=C—C6H4—N backbone of cationAhas a C-shaped conformation, while that of cationBadopts an S-shaped conformation. The same main backbone of the cation in (III) is practically planar. In the crystal structures of both (II) and (III), intermolecular N+—H...O=C hydrogen bonds between different H-shaped synthons further consolidate the crystal packing, forming columns in the [100] and [10\overline 1] directions, respectively. Salts (II) and (III) possess increased aqueous solubility compared with the original API and thus enhance the bioavailability of the API.

scholarly journals Reversible De-/Rehydration Process in Paroxetine Hydrobromide

2014 ◽  
Vol 70 (a1) ◽  
pp. C999-C999
Author(s):  
Paulo Carvalho-Jr ◽  
Javier Ellena ◽  
Alejandro Ayala
Keyword(s):  
Crystal Structure ◽  
Crystal Packing ◽  
Pharmaceutical Formulations ◽  
Ambient Atmosphere ◽  
X Ray Diffraction ◽  
Scanning Calorimetry ◽  
X Ray ◽  
The Stability ◽  
Dehydration Behavior ◽  
Rehydration Process

Paroxetine (PRX) is an antidepressant widely used in depression treatment for decades. The anhydrous and hemidrate chloride forms have been used in pharmaceutical formulations. During their developing a discussion associated with its physical forms and the complex hydration/dehydration behavior involving these phases were established. To improve our understanding of this issue we investigate the crystal structure of paroxetine bromide hemidrate, (PRX+.Br-).H2O, as a model for understanding the stability anhydrous/hemihydrate paroxetine arrangements and the nature of the intermolecular interaction of water within the crystal lattice by single crystal X-ray diffraction experiments. A combination of complementary characterization techniques were also used including Differential Scanning Calorimetry (DSC), thermogravimetric analysis (TGA), Hot Stage microscopy and solubility measurements. As expected the paroxetine bromide hemidrate, (PRX+.Br-).H2O, is isostructural with the paroxetine chloride hemidrate, (PRX+.Cl-).H2O. As in that case, the crystal packing of (PRX+.Br-).H2O is stabilized by strong NH2+...O and NH2+...Br hydrogen bonds which forms infinite channels along the b axis. The water and bromide anions are located along these channels. The DSC/TGA analysis for (PRX+.Br-).H2O show an endothermic desolvation process with an onset temperature of 77.09 °C, that is not present in the paroxetine chloride hemidrate DSC curve. This process leaves to a paroxetine anhydrous bromide crystal structure that is isomorphic to the anhydrous chloride one. However, this structure is spontaneously rehydrated at ambient atmosphere. This rehydration phenomenon probe the stability of paroxetine hemihydrate arrangement, since (PRX+.Br-) is slightly more soluble that its hydrate form. As opposed to chloride hemidrate, the rehydration of paroxetine bromide only involves a rearrangement of the water molecule within the cavities.

Exploring a solvated dimer of Gefitinib: a quantitative analysis

2018 ◽  
Vol 74 (8) ◽  
pp. 944-950 ◽  
Author(s):  
Deekshi Angira ◽  
Althaf Shaik ◽  
Sivapriya Kirubakaran ◽  
Vijay Thiruvenkatam
Keyword(s):  
Crystal Structure ◽  
Crystal Lattice ◽  
Crystal Packing ◽  
Theoretical Calculations ◽  
Three Dimensional ◽  
Hirshfeld Surface ◽  
Stable Form ◽  
X Ray Diffraction ◽  
Scanning Calorimetry ◽  
Plot Analysis

Gefitinib or Iressa is an orally administered anilinoquinazoline used in cancer chemotherapy for the treatment of lung and breast cancer. It is reported to exist in two polymorphic forms, a stable form I and a metastable form II. Both of the forms belong to the triclinic P\overline{1} space group. In this work, we report the crystallization of Gefitinib to form a methanol solvate [systematic name: N-(3-chloro-4-fluorophenyl)-7-methoxy-6-[3-(morpholin-4-yl)propoxy]quinazolin-4-amine methanol hemisolvate, C22H24ClFN4O3·0.5CH3OH] that was theoretically and experimentally investigated. The unit cell is composed of two independent Gefitinib molecules (A and B) that form a stable molecular complex with methanol in the crystal lattice. To understand the crystal lattice stabilization, a combination of techniques, namely X-ray diffraction, IR spectroscopy, thermogravimetric/differential scanning calorimetry (TG-DSC), Hirshfeld surface analysis and CLP-PIXEL methods were used. The analysis of the crystal structure of this dimer revealed a three-dimensional isostructurality with the already reported form II. The A and B molecules are connected via trifurcated C—H...O and N—H...O hydrogen bonding. In addition, the presence of the methanol molecule stabilizes the crystal structure via C—H...O, N—H...O and C—H...Cl interactions between the two monomers. The IR analysis of the dimer has shown characteristic fingerprint values when compared to the commercial form. The TG-DSC analysis of the solvated dimer is in good agreement with the patent reporting cocrystals of Gefitinib. Finally, theoretical calculations by the CLP-PIXEL method and Hirshfeld surface and two-dimensional (2D) fingerprint plot analysis were carried out in order to quantify the different intermolecular interactions and their energies in the crystal packing.

Crystal Forms of Semisynthetic Ergot Alkaloid Terguride

2002 ◽  
Vol 67 (4) ◽  
pp. 479-489 ◽  
Author(s):  
Michal Hušák ◽  
Bohumil Kratochvíl ◽  
Ivana Císařová ◽  
Ladislav Cvak ◽  
Alexandr Jegorov ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Ergot Alkaloid ◽  
Simplified Model ◽  
Quantum Mechanical ◽  
Quantum Mechanical Calculations ◽  
X Ray Diffraction ◽  
Torsion Angles ◽  
Crystal Forms ◽  
X Ray ◽  
Independent Molecules

Two new structures of semisynthetic ergot alkaloid terguride created by unusual number of symmetry-independent molecules were determined by X-ray diffraction methods at 150 K. Form A (monoclinic, P212121, Z = 12) contains three symmetry-independent terguride molecules and two molecules of water in the asymmetric part of the unit cell. The form CA (monoclinic, P21, Z = 8) is an anhydrate remarkable by the presence of four symmetry-independent molecules in the crystal structure. Conformations of twelve symmetry-independent molecules that were found in four already described terguride structures are compared with torsion angles obtained by ab initio quantum-mechanical calculations for the simplified model of N-cyclohexyl-N'-diethylurea.

scholarly journals Crystal structure of 3-benzyl-2-[(E)-2-(furan-2-yl)ethenyl]-2,3-dihydroquinazolin-4(1H)-one and 3-benzyl-2-[(E)-2-(thiophen-2-yl)ethenyl]-2,3-dihydroquinazolin-4(1H)-one from synchrotron X-ray diffraction

2018 ◽  
Vol 74 (1) ◽  
pp. 10-14
Author(s):  
Flavien A. A. Toze ◽  
Vladimir P. Zaytsev ◽  
Lala V. Chervyakova ◽  
Elisaveta A. Kvyatkovskaya ◽  
Pavel V. Dorovatovskii ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Hydrogen Bonds ◽  
Axial Position ◽  
Isatoic Anhydride ◽  
X Ray Diffraction ◽  
X Ray ◽  
Bond Angles ◽  
Pyramidal Geometry ◽  
Three Component Reaction ◽  
Racemic Crystals

The chiral title compounds, C21H18N2O2, (I), and C21H18N2OS, (II) – products of the three-component reaction between benzylamine, isatoic anhydride and furyl- or thienyl-acrolein – are isostructural and form isomorphous racemic crystals. The tetrahydropyrimidine ring in (I) and (II) adopts a sofa conformation. The amino N atom has a trigonal–pyramidal geometry [sum of the bond angles is 347.0° for both (I) and (II)], whereas the amido N atom is flat [sum of the bond angles is 359.3° for both (I) and (II)]. The furyl- and thienylethenyl substituents in (I) and (II) are planar and the conformation about the bridging C=C bond isE. These bulky fragments occupy the axial position at the quaternary C atom of the tetrahydropyrimidine ring, apparently, due to steric reasons. In the crystals, molecules of (I) and (II) form hydrogen-bonded helicoidal chains propagating along [010] by strong intermolecular N—H...O hydrogen bonds.

Study on a Novel Structure of Zn Phenanthroline Malic Acid Hydrate, [Zn (C12H8N2)(C4H4O5)(H2O)](H2O)

2013 ◽  
Vol 739 ◽  
pp. 26-29
Author(s):  
Hai Xing Liu ◽  
Jing Zhong Xiao ◽  
Huan Mei Guo ◽  
Qing Hua Zhang ◽  
Zhang Xue Yu ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Malic Acid ◽  
Hydrothermal Reaction ◽  
Crystal Packing ◽  
X Ray Diffraction ◽  
Acid Anion ◽  
X Ray ◽  
Hydrogen Bonding Interactions ◽  
Novel Structure ◽  
Acid Hydrate

A novel Zn complex [Zn (C12H8N2)(C4H4O5)(H2O)](H2O) has been synthesized from a hydrothermal reaction and the crystal structure has been determined by means of single-crystal X-ray diffraction. The Zn atom is six-coordinated by two phenanthroline N atoms, three O atoms from malic acid anion and one O atom from water. The crystal packing is stabilized by O-H...O hydrogen bonding interactions.

Salts of purine alkaloids caffeine and theobromine with 2,6-dihydroxybenzoic acid as coformer: structural, theoretical, thermal and spectroscopic studies

2021 ◽  
Vol 77 (11) ◽  
Author(s):  
Mateusz Gołdyn ◽  
Anna Komasa ◽  
Mateusz Pawlaczyk ◽  
Aneta Lewandowska ◽  
Elżbieta Bartoszak-Adamska
Keyword(s):  
Hydrogen Bonds ◽  
Water Solubility ◽  
Theoretical Calculations ◽  
Spectroscopic Studies ◽  
X Ray Diffraction ◽  
Dihydroxybenzoic Acid ◽  
Scanning Calorimetry ◽  
X Ray ◽  
Purine Alkaloids ◽  
Vis Spectroscopy

The study of various forms of pharmaceutical substances with specific physicochemical properties suitable for putting them on the market is one of the elements of research in the pharmaceutical industry. A large proportion of active pharmaceutical ingredients (APIs) occur in the salt form. The use of an acidic coformer with a given structure and a suitable pK a value towards purine alkaloids containing a basic imidazole N atom can lead to salt formation. In this work, 2,6-dihydroxybenzoic acid (26DHBA) was used for cocrystallization of theobromine (TBR) and caffeine (CAF). Two novel salts, namely, theobrominium 2,6-dihydroxybenzoate, C7H9N4O2 +·C7H5O4 − (I), and caffeinium 2,6-dihydroxybenzoate, C8H11N4O2 +·C7H5O4 − (II), were synthesized. Both salts were obtained independently by slow evaporation from solution, by neat grinding and also by microwave-assisted slurry cocrystallization. Powder X-ray diffraction measurements proved the formation of the new substances. Single-crystal X-ray diffraction studies confirmed proton transfer between the given alkaloid and 26DHBA, and the formation of N—H...O hydrogen bonds in both I and II. Unlike the caffeine cations in II, the theobromine cations in I are paired by noncovalent N—H...O=C interactions and a cyclic array is observed. As expected, the two hydroxy groups in the 26DHBA anion in both salts are involved in two intramolecular O—H...O hydrogen bonds. C—H...O and π–π interactions further stabilize the crystal structures of both compounds. Steady-state UV–Vis spectroscopy showed changes in the water solubility of xanthines after ionizable complex formation. The obtained salts I and II were also characterized by theoretical calculations, Fourier-transform IR spectroscopy (FT–IR), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC) and elemental analysis.

1-Benzoyl-3-(4-chlorophenyl)thiourea

2006 ◽  
Vol 62 (4) ◽  
pp. o1419-o1420 ◽  
Author(s):  
M. Khawar Rauf ◽  
Amin Badshah ◽  
Ulrich Flörke ◽  
Aamer Saeed
Keyword(s):  
Crystal Structure ◽  
Hydrogen Bonds ◽  
Aromatic Ring ◽  
Dihedral Angle ◽  
Title Compound ◽  
Crystal Packing ◽  
Compound C

In the crystal structure of the title compound, C14H11ClN2OS, the dihedral angle between the two aromatic ring planes is 43.93 (6)°. The crystal packing shows dimers formed by intermolecular N—H...S hydrogen bonds which are stacked along [100].

scholarly journals Preparation and Characterization of Spherical Submicron CL-20 by Siphon Spray Refinement

2020 ◽  
Vol 2020 ◽  
pp. 1-9 ◽  
Author(s):  
Jiangtao Xing ◽  
Weili Wang ◽  
Wenzheng Xu ◽  
Tianle Yao ◽  
Jun Dong ◽  
...  
Keyword(s):  
Impact Sensitivity ◽  
X Ray Diffraction ◽  
Scanning Calorimetry ◽  
Crystal Forms ◽  
Refined Method ◽  
Diffraction Angle ◽  
Ultrasonic Assisted ◽  
The Impact ◽  
Thermal Stability Of

In order to improve the safety of hexanitrohexaazaisowurtzitane (CL-20), submicron CL-20 particles were prepared by a siphon ultrasonic-assisted spray refining experimental device. The samples were characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD), and differential scanning calorimetry (DSC), and the impact sensitivity of the samples was tested. The results show that the particle size of siphon-refined CL-20 is about 800 nm~1 μm, which is more smooth, mellow, and dense than that of CL-20 prepared by a traditional pressure-refined method. The peak diffraction angle of pressure- and siphon-refined CL-20 is basically the same as that of raw CL-20, and their crystal forms are ε type. The peak strength of pressure- and siphon-refined CL-20 decreased obviously. The apparent activation energy of pressure-refined CL-20 and siphon-refined CL-20 is 13.3 kJ/mol and 11.95 kJ/mol higher than that of raw CL-20, respectively. The thermal stability of CL-20 is improved. The activation enthalpy (ΔH#) is significantly higher than that of raw CL-20, and the characteristic drop is 70.4% and 82.7% higher than that of raw CL-20. The impact sensitivity of siphon-refined CL-20 is lower than that of pressure-refined CL-20, so the safety performance of an explosive is improved obviously.

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