A new crystal form of the NSAID dexketoprofen

2019 ◽  
Vol 75 (6) ◽  
pp. 783-792 ◽  
Author(s):  
Patrizia Rossi ◽  
Paola Paoli ◽  
Andrea Ienco ◽  
Diletta Biagi ◽  
Maurizio Valleri ◽  
...  
Keyword(s):  
Single Crystal ◽  
Crystal Packing ◽  
Solid Phase ◽  
Crystal Form ◽  
Interaction Energies ◽  
Scanning Calorimetry ◽  
Short Term Treatment ◽  
Experimental Conditions ◽  
Crystal Forms ◽  
Anti Inflammatory

Dexketoprofen [(2S)-2-(3-benzoylphenyl)propanoic acid], C16H14O3, is the S-enantiomer of ketoprofen, a nonsteroidal anti-inflammatory drug (NSAID) that has analgesic, antipyretic and anti-inflammatory properties, and finds applications for the short-term treatment of mild to moderate pain. A new crystalline phase of dexketoprofen is reported. Its solid-state structure was determined by single-crystal X-ray diffraction (SCXRD). The molecular structure of the two independent molecules found in the asymmetric unit of this new phase (DXKP-β) were compared to those of the already known crystal form of dexketoprofen (DXKP-α) and with the S-enantiomer of the racemic compound. The three different conformers of dexketoprofen found in DXKP-α and DXKP-β were then investigated by computational methods. The optimized structures are very close to the corresponding starting geometries and do not differ significantly in energy. The crystal packing of DXKP-β was studied by means of Hirshfeld surface (HS) analysis; interaction energies were also calculated. A comparison with DXKP-α shows close similarities between the two crystal forms, i.e. in both cases, molecules assemble through the catemer O—H...O synthon of the carboxylic acid stabilized by additional C—H...O contacts and, accordingly, the interaction energies, as well as the contributions to the HS area, are very similar. Finally, the thermal behaviour of the two polymorphs of dexketoprofen was assessed by means of XRD (both from single crystal and microcrystalline powder) and differential scanning calorimetry (DSC); both crystal forms are stable under the experimental conditions adopted (air, 300–350 K for DXKP-α and 300–340 K DXKP-β) and no solid–solid phase transition occurs between the two crystal forms in the investigated temperature range (from 100 K up to ca 350 K).

scholarly journals Effect of pressure on the crystal structure of L-serine-I and the crystal structure of L-serine-II at 5.4 GPa

2005 ◽  
Vol 61 (1) ◽  
pp. 58-68 ◽  
Author(s):  
Stephen A. Moggach ◽  
David R. Allan ◽  
Carole A. Morrison ◽  
Simon Parsons ◽  
Lindsay Sawyer
Keyword(s):  
Crystal Structure ◽  
Phase Transition ◽  
Hydrogen Bonds ◽  
Single Crystal ◽  
Ambient Pressure ◽  
Crystal Form ◽  
Hydroxyl Groups ◽  
Orthorhombic Space Group ◽  
Crystal Forms ◽  
Hydrogen Bonded

The crystal structure of L-serine has been determined at room temperature at pressures between 0.3 and 4.8 GPa. The structure of this phase (hereafter termed L-serine-I), which consists of the molecules in their zwitterionic tautomer, is orthorhombic, space group P212121. The least compressible cell dimension (c), corresponds to chains of head-to-tail NH...carboxylate hydrogen bonds. The most compressible direction is along b, and the pressure-induced distortion in this direction takes the form of closing up voids in the middle of R-type hydrogen-bonded ring motifs. This occurs by a change in the geometry of hydrogen-bonded chains connecting the hydroxyl groups of the —CH2OH side chains. These hydrogen bonds are the longest conventional hydrogen bonds in the system at ambient pressure, having an O...O separation of 2.918 (4) Å and an O...O...O angle of 148.5 (2)°; at 4.8 GPa these parameters are 2.781 (11) and 158.5 (7)°. Elsewhere in the structure one NH...O interaction reaches an N...O separation of 2.691 (13) Å at 4.8 GPa. This is amongst the shortest of this type of interaction to have been observed in an amino acid crystal structure. Above 4.8 GPa the structure undergoes a single-crystal-to-single-crystal phase transition to a hitherto uncharacterized polymorph, which we designate L-serine-II. The OH...OH hydrogen-bonded chains of L-serine-I are replaced in L-serine-II by shorter OH...carboxyl interactions, which have an O...O separation of 2.62 (2) Å. This phase transition occurs via a change from a gauche to an anti conformation of the OH group, and a change in the NCαCO torsion angle from −178.1 (2)° at 4.8 GPa to −156.3 (10)° at 5.4 GPa. Thus, the same topology appears in both crystal forms, which explains why it occurs from one single-crystal form to another. The transition to L-serine-II is also characterized by the closing-up of voids which occur in the centres of other R-type motifs elsewhere in the structure. There is a marked increase in CH...O hydrogen bonding in both phases relative to L-serine-I at ambient pressure.

New polymorphs of an old drug: conformational and synthon polymorphism of 5-nitrofurazone

2016 ◽  
Vol 72 (2) ◽  
pp. 263-273 ◽  
Author(s):  
Dorota Pogoda ◽  
Jan Janczak ◽  
Veneta Videnova-Adrabinska
Keyword(s):  
Hydrogen Bond ◽  
Molecular Conformation ◽  
Crystal Packing ◽  
Molecular Organization ◽  
Hydrogen Bond Donor ◽  
Scanning Calorimetry ◽  
Geometrical Isomers ◽  
Crystal Forms ◽  
Donor And Acceptor ◽  
Polymorphic Forms

Two new polymorphic forms of 5-nitrofurazone (5-nitro-2-furaldehyde semicarbazone) have been synthesized and structurally characterized by single-crystal and powder X-ray diffraction methods, vibrational spectroscopy (FT–IR and temperature Raman), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA) and Hirshfeld surface analysis. The compound crystallizes in three different polymorphic formsP21/a(polymorph α),P21(polymorph β) andP21/c(polymorph γ), the crystal structures of two of which (polymorphs β and γ) represent new structure determinations. The solid-state molecular organization in the three crystal forms is analyzed and discussed in terms of molecular conformation, crystal packing and hydrogen-bonded networks. All three crystals are formed fromtransgeometrical isomers, but the molecular conformation of the α-polymorph issyn–anti–anti–anti, while that of β- and γ-polymorphs issyn–anti–syn–syn. As a consequence of this the hydrogen-bond donor and acceptor sites of the molecules are oriented differently, which in turn results in different hydrogen-bond connectivity and packing patterns.

scholarly journals Single-Crystal-to-Single-Crystal Transformation and Catalytic Properties of New Hybrid Perhalidometallates

Catalysts ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 758
Author(s):  
Ali Rayes ◽  
Stephany Zárate-Roldán ◽  
Irene Ara ◽  
Manel Moncer ◽  
Necmi Dege ◽  
...  
Keyword(s):  
Single Crystal ◽  
Catalytic Properties ◽  
Crystal Packing ◽  
Structural Rearrangement ◽  
Crystal Form ◽  
Intermolecular Forces ◽  
Water Molecules ◽  
X Ray Diffraction ◽  
First Time ◽  
Thermally Triggered

Two new organic–inorganic salts of perhalidometallates with protonated organic amine cations have been synthesized and characterized by X-ray diffraction and thermal analysis. (CHBMAH2)ZnBr4·3/2H2O 1 and (CHBMAH2)ZnCl4 4 [(CHBMAH2)2+: 1,3-cyclohexanebis(methylammonium)] were obtained in single-crystal form. The crystal packing in all of the obtained compounds is governed by the formation of various non-covalent intermolecular forces between tetrahalidometallate anions and organic cations, assisted by water molecules in the hydrates. Hirshfeld surface analysis denotes that the most important contributions to the crystal packing are X···H/H···X (X: Cl, Br, I) and H···H interactions. Interestingly, the compound 1,3-cyclohexanebis(methylammonium)tetrachloridozincate (II) dihydrate, (CHBMAH2)ZnCl4·2H2O 2, undergoes thermally-triggered single-crystal-to-single-crystal (SCSC) transformation upon dehydration to produce a supramolecular solid compound, 1,3-cyclohexanebis(methylammonium) tetrachloridozincate (II), (CHBMAH2)ZnCl4 4. The SCSC transformation causes changes in the lattice parameters and a structural rearrangement. Furthermore, the catalytic properties of (CHBMAH2)ZnCl4·2H2O 2 and (CHBMAH2)CdI4·2H2O 3 have been explored in the acetalization process using various uncommon alcohols, beyond methanol or ethanol, for the first time in the literature, with outstanding results, and opening the door to the formation of alternative acetals.

scholarly journals Conformational changes in Apolipoprotein N-acyltransferase (Lnt)

2018 ◽  
Author(s):  
Benjamin Wiseman ◽  
Martin Högbom
Keyword(s):  
Conformational Changes ◽  
Crystal Packing ◽  
Cell Envelope ◽  
Crystal Form ◽  
Covalent Attachment ◽  
Gram Negative Bacteria ◽  
Asymmetric Unit ◽  
Cellular Functions ◽  
Crystal Forms ◽  
Potential Mode

SUMMARYIn bacteria, lipoproteins are important components of the cell envelope and are responsible for many essential cellular functions. They are produced by the post-translational covalent attachment of lipids that occurs via a sequential 3-step process controlled by three essential integral membrane enzymes. The last step of this process, unique to Gram negative bacteria, is the N-acylation of the terminal cysteine by Apolipoprotein N-acyltransferase (Lnt) to form the final mature lipoprotein. Here we report 2 crystal forms of this enzyme. In one form the enzyme crystallized with two molecules in the asymmetric unit. In one of those molecules the thioester acyl-intermediate is observed. In the other molecule, the crystal packing suggests one potential mode of apolipoprotein docking to Lnt. In the second crystal form the enzyme crystallized with one molecule in the asymmetric unit in an apparent apo-state remarkably devoid of any bound molecules in the large open substrate entry portal. Taken together, these structures suggest that the movement of the essential W237 is triggered by substrate binding and could help direct and stabilize the interaction between Lnt and the incoming substrate apolipoprotein.Graphical Abstract

Effect of Heat Treatment on the Properties of PB-1/PP Blends

2013 ◽  
Vol 721 ◽  
pp. 125-129
Author(s):  
Wei Zeng ◽  
Han Lin Hu ◽  
Shu Cai Li
Keyword(s):  
Mechanical Properties ◽  
Heat Treatment ◽  
Crystal Form ◽  
Dynamic Mechanical Properties ◽  
Melting Enthalpy ◽  
Standard Samples ◽  
Scanning Calorimetry ◽  
Melt Temperature ◽  
Crystal Forms ◽  
Dynamic Mechanical

PB-1/PP blend was prepared by blending isotactic polybutene-1 and polypropylene with the ratio of 80/20 through Brabender extruder under melted condition, injected into the standard samples. After heat treatment at 75°C, the crystallization, crystal forms, dynamic mechanical properties, mechanical properties of the blends were studied via differential scanning calorimetry (DSC), X-ray Diffraction (XRD), dynamic mechanical analyzer (DMA) and mechanical testing machines, respectively. It was found that after heat treatment: both the melt temperature and the melting enthalpy of crystal form I in PB-1 component increased, the melt peak of crystal form II decreased gradually, while the melt temperature and melting enthalpy of PP as a disperse phase, maintained unchanged basically; the storage modulus of the blend increased and the tan δ decreased a bit; the mechanical properties of the blend were improved noticeable.

Unravelling the chemical basis of the bathochromic shift in the lobster carapace; new crystal structures of unbound astaxanthin, canthaxanthin and zeaxanthin

2007 ◽  
Vol 63 (2) ◽  
pp. 328-337 ◽  
Author(s):  
Giuditta Bartalucci ◽  
Jennifer Coppin ◽  
Stuart Fisher ◽  
Gillian Hall ◽  
John R. Helliwell ◽  
...  
Keyword(s):  
Hydrogen Bonding ◽  
Hydrogen Bonds ◽  
Crystal Structures ◽  
Crystal Packing ◽  
Bathochromic Shift ◽  
Crystal Form ◽  
Crystal Forms ◽  
Bonding Interaction ◽  
Crystallization Conditions ◽  
Intermolecular Distances

The crystal structures of the unbound carotenoids, synthetic astaxanthin (3S,3′S:3R,3′S:3R,3′R in a 1:2:1 ratio), canthaxanthin and (3R,3′S, meso)-zeaxanthin are compared with each other and the protein bound astaxanthin molecule in the carotenoprotein, β-crustacyanin. Three new crystal forms of astaxanthin have been obtained, using different crystallization conditions, comprising a chloroform solvate, a pyridine solvate and an unsolvated form. In each structure, the astaxanthin molecules, which are similar to one another, are centrosymmetric and adopt the 6-s-cis conformation; the end rings are bent out of the plane of the polyene chain by angles of −42.6 (5), −48.9 (5) and −50.4 (3)°, respectively, and are disordered, showing the presence of both R and S configurations (in a 1:1 ratio). In the crystal packing of the chloroform and pyridine solvates, the astaxanthin molecules show pair-wise end-to-end intermolecular hydrogen bonding of the adjacent 3-hydroxyl and 4-keto oxygens, whereas in the unsolvated crystal form, the hydrogen-bonding interaction is intermolecular. In addition, there are intermolecular C—H hydrogen bonds in all three structures. The canthaxanthin structure, measured at 100 and 293 K, also adopts the 6-s-cis conformation, but with disorder of one end ring only. The rotation of the end rings out of the plane of the polyene chains (ca −50 ° for each structure) is similar to that of astaxanthin. A number of possible C—H hydrogen bonds to the keto O atoms are also observed. (3R,3′S, meso)-zeaxanthin is centrosymmetric with a C5—C6—C7—C8 torsion angle of −74.9 (3)°; the molecules show pair-wise hydrogen bonding between the hydroxyl O atoms. In addition, for all the crystal structures the polyene chains were arranged one above the other, with intermolecular distances of 3.61–3.79 Å, indicating the presence of π-stacking interactions. Overall, these six crystal structures provide an ensemble of experimentally derived results that allow several key parameters, thought to influence colour tuning of the bathochromic shift of astaxanthin in crustacyanin, to be varied. The fact that the colour of each of the six crystals remains red, rather than turning blue, is therefore especially significant.

X-ray powder diffraction: A powerful tool for industrial protein production

2014 ◽  
Vol 70 (a1) ◽  
pp. C1559-C1559
Author(s):  
Christian Frankær ◽  
Majbritt Thymark ◽  
Kenny Ståhl ◽  
Olga Moroz ◽  
Keith Wilson ◽  
...  
Keyword(s):  
Single Crystal ◽  
Powder Diffraction ◽  
Large Scale ◽  
Crystal Form ◽  
Industrial Applications ◽  
Analysis Tool ◽  
Crystal Forms ◽  
X Ray ◽  
Bacillus Lentus ◽  
Crystal Density

X-ray powder diffraction (XRPD) offers a method of characterizing a crystalline protein suspension [1], and data can be collected within 30 minutes, which is appealing for industrial applications. In industry, enzymes are produced and handled in high concentrations, which can in turn cause problems for the processes due to protein precipitation in the production pipeline. XRPD is useful for identification of the crystal forms present, by fitting calculated patterns of known single crystal forms to the observed XRPD pattern. For this purpose we have developed a streamlined program for calculation of diffraction patterns from pdb-files taking into account bulk-solvent, peak asymmetry and background [2]. XRPD was applied to a suspension from a large-scale industrial production of the widely used Bacillus lentus subtilisin. A dominant crystal form was identified by XRPD, but two other different crystal forms were found by a complementary single crystal micro-diffraction analysis of the larger single crystals present in the sample [3]. The study serves as a reminder that when a crystal is picked out from a batch crystallization for single crystal analysis, it might not be representative of the bulk microcrystalline material in the sample. To estimate the fraction of the different crystal forms in production samples with significant polymorphism, a further XRPD study was performed on binary mixtures of different lysozyme and subtilisin crystal forms. Quantitative XRPD generally requires careful sample preparation, and working with protein slurries leads to further challenges in terms of varying crystal density. After careful optimisation of suspension medium, the relative composition of crystal forms can be determined within 10%. This work demonstrates the value of in-house XRPD as an analysis tool in industrial enzyme production, and its potential to help troubleshooting the production process and to provide information for further refining the manufacturing of enzymes.

A time-resolved SAXS study on the crystalline morphology of long-term stored isotactic polypropylene

2004 ◽  
Vol 37 (2) ◽  
pp. 295-299 ◽  
Author(s):  
Jun-Ting Xu ◽  
Yu-Jin Zhang ◽  
Zhi-Qiang Fan
Keyword(s):  
Isotactic Polypropylene ◽  
Crystal Form ◽  
Crystalline Morphology ◽  
X Ray Diffraction ◽  
Scanning Calorimetry ◽  
Time Resolved ◽  
Crystal Forms ◽  
X Ray ◽  
X Ray Scattering

The crystalline morphology of a long-term stored metallocene isotactic polypropylene (mPP) has been studied with time-resolved small-angle X-ray scattering (SAXS), differential scanning calorimetry (DSC) and wide-angle X-ray diffraction (WAXD), and compared with that of the freshly crystallized sample. It was found that both α and γ crystal forms occur in the long-term stored mPP, whereas freshly crystallized mPP contains only the α crystal form. Double SAXS peaks were observed for the long-term stored mPP, which can be assigned to the α and γ crystals. Based on the SAXS result, it is inferred that the crystal stacks of the α and γ forms in the long-term stored mPP are arranged according to the block mode.

scholarly journals Analysis of dihydroquercetin physical modification via in vitro and in silico methods

2019 ◽  
Vol 65 (2) ◽  
pp. 152-158 ◽  
Author(s):  
R.P. Terekhov ◽  
I.A. Selivanova ◽  
A.K. Zhevlakova ◽  
Yu.B. Porozov ◽  
A.V. Dzuban
Keyword(s):  
Crystal Engineering ◽  
In Silico ◽  
Materials Science ◽  
Solid Phase ◽  
Computational Simulation ◽  
In Silico Analysis ◽  
Functional Materials ◽  
Crystal Form ◽  
Scanning Calorimetry

Flavonoid-mediated materials are promising substances for the design of new functional materials because of their bioactivity, eco-friendliness, and cost-effectiveness. Dihydroquercetin (DHQ) is the major flavonoid in the wood of Larix dahurica Turcz. Previously some new modifications were created on the basis of DHQ, they were characterized by different morphological, physico-chemical and biopharmaceutical properties. This study was performed to research the influence of the solvent on the formation of the solid phase in DHQ microtubes and crystal form as commercially available active pharmaceutical ingredient (API). The choice of the models for the computational simulation was based on the data of differential scanning calorimetry. All calculations were performed using Materials Science Suite. In silico analysis demonstrated that the molecules of solvent are a key player in the formation of the solid phase of the flavonoid-mediated material. Also the comparative analysis of physical characteristics between DHQ microtubes and crystal form was performed. These data give an opportunity to suggest, that DHQ microtubes may have a grate application as the dressing material and in the drug delivering. The results of this study could be helpful for the design of the new flavonoid-mediated materials by crystal engineering.

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