Crystal structures and properties of two hydrated conglomerate forms of the heart-rate-lowering agent ivabradine hydrochloride

2019 ◽  
Vol 75 (5) ◽  
pp. 545-553
Author(s):  
Xin-Bo Zhou ◽  
Jian-Rong Zhu ◽  
Ji-Yong Liu ◽  
Zhi-Ping Jin ◽  
Fei-Yu Tang ◽  
...  
Keyword(s):  
Crystal Form ◽  
Structural Features ◽  
Monoclinic Space Group ◽  
Orthorhombic Space Group ◽  
Scanning Calorimetry ◽  
Space Group ◽  
Symptomatic Management ◽  
Structures And Properties ◽  
The Stability ◽  
First Time

Ivabradine hydrochloride (IVA-HCl) (systematic name: {[3,4-dimethoxybicyclo[4.2.0]octa-1(6),2,4-trien-7-yl]methyl}[3-(7,8-dimethoxy-2-oxo-2,3,4,5-tetrahydro-1H-3-benzazepin-3-yl)propyl]methylazanium), is a novel medication used for the symptomatic management of stable angina pectoris. In many recent patents, it has been claimed to exist in a very large number of polymorphic, hydrated and solvated phases, although no detailed analysis of the structural features of these forms has been published to date. Here, we have successfully crystallized the tetrahydrate form of IVA-HCl (form β), C27H37N2O5 +·Cl−·4H2O, and elucidated its structure for the first time. Simultaneously, a new crystal form of IVA-HCl, i.e. the hemihydrate (form II), C27H37N2O5 +·Cl−·0.5H2O, was discovered. Its crystal structure was also accurately determined and compared to that of the tetrahydrate form. While the tetrahydrate form of IVA-HCl crystallized in the orthorhombic space group P212121, the new form (hemihydrate) was solved in the monoclinic space group P21. Detailed conformational and packing comparisons between the two forms have allowed us to understand the role of water in the crystal assembly of this hydrochloride salt. The stabilities of the two forms were compared theoretically by calculating the binding energy of the water in the crystal lattice using differential scanning calorimetry (DSC). The stability experiments show that the tetrahydrate is stable under high-humidity conditions, while the hemihydrate is stable under high-temperature conditions.

Experimental and theoretical studies of the products of addition–elimination reactions between benzil dihydrazone and three isomeric chlorobenzaldehydes

2015 ◽  
Vol 71 (7) ◽  
pp. 554-563 ◽  
Author(s):  
Yun-Na Liu ◽  
Shuang-Shuang Cheng ◽  
Chao Wang ◽  
Dian-Xiang Xing ◽  
Yun Liu ◽  
...  
Keyword(s):  
Schiff Bases ◽  
Density Functional ◽  
Double Helix ◽  
Structural Features ◽  
Supramolecular Interactions ◽  
Monoclinic Space Group ◽  
Orthorhombic Space Group ◽  
Space Group ◽  
Double Helix Structure ◽  
Homo Lumo

A series of mono- and di-Schiff bases formed between benzil dihydrazone {BDH; systematic name: (1Z)-[(2E)-2-hydrazinylidene-1,2-diphenylethylidene]hydrazine} and three isomeric chlorobenzaldehydes were designed and synthesized to be used as model compounds to help to explain the reaction mechanisms for the formation of Schiff bases. These compounds are 1-(2-chlorobenzylidene)-2-{2-[2-(2-chlorobenzylidene)hydrazin-1-ylidene]-1,2-diphenylethylidene}hydrazine (BDHOCB), and the 3-chloro (BDHMCB) and 4-chloro (BDHPCB) analogues, all having the formula C28H20Cl2N4. Surprisingly, only di-Schiff bases were obtained; our attempts to push the reaction in favour of the mono-Schiff bases all failed. Density functional theory (DFT) calculations were performed to explain the trend in the experimental results. In the case of the systems studied, the type of Schiff base produced exhibits a clear dependence on the HOMO–LUMO energy gaps (ΔEHOMO–LUMO),i.e.the product is mainly governed by its stability. The compounds were characterized by single-crystal X-ray diffractometry, elemental analysis, melting point,1H NMR and13C NMR spectroscopy. The structural features of the three new Schiff bases are similar. For instance, they have the same chemical formula, all the molecules have a symmetrical double helix structure, with each Ph—C=N—N=C—Ph arm exhibiting ananticonformation, and their supramolecular interactions include intermolecular π–π and weak C—H...π stacking interactions. The crystal systems are different, however,viz.triclinic (space groupP\overline{1}) for BDHPCB, monoclinic (space groupP21/n) for BDHOCB and orthorhombic (space groupPnna) for BDHMCB.

Diastereomeric salts of lactic acid and 1-phenylethylamine, their structures and relative stabilities

2002 ◽  
Vol 58 (6) ◽  
pp. 1044-1050 ◽  
Author(s):  
Annette Langkilde ◽  
Jette Oddershede ◽  
Sine Larsen
Keyword(s):  
Lactic Acid ◽  
Soluble Salt ◽  
Monoclinic Space Group ◽  
Orthorhombic Space Group ◽  
Scanning Calorimetry ◽  
Relative Stabilities ◽  
Space Group ◽  
Diastereomeric Salts ◽  
Entropy Effects ◽  
The Difference

Crystal structures have been determined for the two diastereomeric salts formed between S-lactic acid (S-LA) and 1-phenylethylamine (PEA). The relative stabilities of the salts have been investigated by differential scanning calorimetry and solubility measurements in acetonitrile. The less soluble salt obtained from water, (R-PEA)(S-LA), is the less dense. It belongs to the orthorhombic space group P2_12_12_1, Z = 4. The more soluble salt, (S-PEA)(S-LA)·H_2O, crystallized from ethanol is monoclinic, space group P2_1, Z = 2. The crystal structure showed that the water molecule is well integrated into the hydrogen-bond network in the more soluble salt, which explains the fruitless attempts made to obtain the corresponding unhydrated salt. The lactate ion adopts different conformations in the two salts. The relative energies were investigated by Hartree–Fock calculations, showing that the lactate ion is in a conformation with higher energy in the more soluble salt. The difference in solubility between the two salts can be attributed to an interplay of enthalpy and entropy effects.

Two novel polymorphic forms of iron-chelating agent deferiprone

2020 ◽  
Vol 76 (2) ◽  
pp. 193-200
Author(s):  
Satyasree Rajendrakumar ◽  
Anuja Surampudi Venkata Sai Durga ◽  
Jagadeesh Babu Nanubolu ◽  
Sridhar Balasubramanian
Keyword(s):  
Hydrogen Bonds ◽  
Crystal Packing ◽  
Bulk Material ◽  
Chelating Agent ◽  
Structural Features ◽  
Monoclinic Space Group ◽  
Orthorhombic Space Group ◽  
Space Group ◽  
Blood Disorder ◽  
Polymorphic Forms

Thalassemia is a genetic blood disorder requiring life-long blood transfusions. This process often results in iron overload and can be treated by an iron-chelating agent, like deferiprone (3-hydroxy-1,2-dimethylpyridin-4-one), C7H9NO2, in an oral formulation. The first crystal structure of deferiprone, (Ia), was reported in 1988 [Nelson et al. (1988). Can. J. Chem. 66, 123–131]. In the present study, two novel polymorphic forms, (Ib) and (Ic), of deferiprone were identified concomitantly with polymorph (Ia) during the crystallization experiments. Polymorph (Ia) was redetermined at low temperature for comparison of the structural features and lattice energy values with polymorphs (Ib) and (Ic). Polymorph (Ia) crystallized in the orthorhombic space group Pbca, whereas both polymorphs (Ib) and (Ic) crystallized in the monoclinic space group P21/c. The asymmetric units of (Ia) and (Ib) contain one deferiprone molecule, while polymorph (Ic) has three crystallographically independent molecules (A, B and C). All three polymorphs have similar hydrogen-bonding features, such as an R 2 2(10) dimer formed by O—H...O hydrogen bonds, an R 4 3(20) tetramer formed by C—H...O hydrogen bonds and π–π interactions, but the polymorphs differ in their molecular arrangements in the solid state and are classified as packing polymorphs. O—H...O and C—H...O hydrogen bonds lead to the formation of two-dimensional hydrogen-bonded parallel sheets which are interlinked by π–π stacking interactions. In the three-dimensional crystal packing, the deferiprone molecules were aggregated as corrugated sheets in polymorphs (Ia) and (Ic), whereas in polymorph (Ib), they were aggregated as a square-grid network. The characteristic crystalline peaks of polymorphs (Ia), (Ib) and (Ic) were established through powder X-ray diffraction analysis. The Rietveld analysis was also performed to estimate the contribution of the polymorphs to the bulk material.

Neue gemischte Zinn-reiche Erdalkalimetall-Stannide – Synthese, Strukturchemie und chemische Bindung / New Mixed Tin-rich Alkaline Earth Stannides – Synthesis, Structural Chemistry and Chemical Bonding

2011 ◽  
Vol 66 (3) ◽  
pp. 245-261
Author(s):  
Marco Wendorff ◽  
Caroline Röhr
Keyword(s):  
Structural Features ◽  
Monoclinic Space Group ◽  
Total Density ◽  
Orthorhombic Space Group ◽  
Space Group ◽  
Counting Rules ◽  
New Compounds ◽  
Tin Content ◽  
Type Orthorhombic ◽  
Total Density Of States

Ternary mixed Ca/Ba-Sr pentastannides AIISn5 (AII = Ca, Sr, Ba) have been synthesized from stoichiometric mixtures of the elements or from tin-rich melts. The crystal structures of two new compounds of overall composition ASn5 (A = Sr, Ba) were determined by means of single-crystal X-ray data. The structures of both Sr0.94Ba0.06Sn5 (monoclinic, space group C2/m, a = 1762.8(11), b = 704.1(3), c = 1986(2) pm, β = 100.31(6)º, Z = 14, R1 = 0.0996) and Sr0.89Ba0.11Sn5 (orthorhombic, space group Cmcm, a = 708.1(2), b = 1770.4(8), c = 2781.6(11) pm, Z = 20 , R1 = 0.0821) are closely related and can be described by different stacking sequences of comparable nets. They both resemble the structural features of the tristannides AIISn3 in forming dimers and trimers of facesharing Sn6-octahedra, which are further connected via common corners. According to the higher tin content, the rods formed of the octahedra are interspersed by additional Sn atoms, which themselves show a bonding situation resembling the structure of elementary tin. The complex tin network formed by the strong Sn-Sn bonds alone can be regarded as a cutout of the hexagonal diamond structure. In this view, the similarities of the title compounds to the known binary stannides BaSn5 and SrSn4 become apparent. The phase widths of the latter have been investigated and shown to reach up to Sr0.37Ba0.63Sn5 (BaSn5 type, hexagonal, space group P6/mmm, a = 536.8(2), c = 695.2(3) pm, R1 = 0.0312) and Sr0.79Ca0.21Sn4 (SrSn4 type, orthorhombic, space group Cmcm, a = 461.7(3), b = 1714.1(14), c = 706.7(4) pm, Z = 4, R1 = 0.0861), respectively. The total density of states calculated for the orthorhombic pentastannide within the FP-LAPW DFT band structure approach shows a broad minimum at the Fermi level, which can be explained using the Zintl and the Wade/Jemmis electron counting rules.

Strukturuntersuchungen an Diaryldichalkogeniden: Die Molekülstrukturen von [2,4,6-(CF3)3C6H2S]2,[2,4,6-Me3C6H2Te]2 und [2-Me2N-4,6-(CF3)2C6H2Te]2 / Structural Investigations of Diaryl Dichalcogenides: The Molecular Structures of [2,4,6-(CF3)3C6H2S]2, [2,4,6-Me3C6H2Te]2 and [2-Me2N-4,6-(CF3)2C6H2Te]2

1992 ◽  
Vol 47 (3) ◽  
pp. 305-309 ◽  
Author(s):  
Anja Edelmann ◽  
Sally Brooker ◽  
Norbert Bertel ◽  
Mathias Noltemeyer ◽  
Herbert W. Roesky ◽  
...  
Keyword(s):  
Molecular Structures ◽  
Monoclinic Space Group ◽  
Crystal Data ◽  
X Ray Diffraction ◽  
Orthorhombic Space Group ◽  
Structural Investigations ◽  
Space Group ◽  
X Ray

Abstract The Molecular Structures of [2,4,6-(CF3)3C6H2S]2 (1) [2,4,6-Me3C6H2Te]2 and [2-Me2N-4,6-(CF3)2C6H2Te]2 (3) have been determined by X-ray diffraction. Crystal data: 1: orthorhombic, space group P212121, Z = 4, a = 822.3(2), b = 1029.2(2), c = 2526.6(5) pm (2343 observed independent reflexions, R = 0.042); 2: orthorhombic, space group Iba 2, Z = 8, a = 1546.5(2), b = 1578.4(2), c = 1483.9(1) pm (2051 observed independent reflexions, R = 0.030); 3: monoclinic, space group P 21/c, Z = 4, a = 1118.7(1), b = 1536.5(2), c = 1492.6(2) pm, β = 98.97(1)° (3033 observed independent reflexions, R = 0.025).

Two lithium tricyanomethanide compounds: syntheses and single-crystal structure determination of LiK[C(CN)3]2 and Li[C(CN)3]·½ (H3C)2CO

2015 ◽  
Vol 70 (3) ◽  
pp. 191-196 ◽  
Author(s):  
Olaf Reckeweg ◽  
Francis J. DiSalvo
Keyword(s):  
Crystal Structure ◽  
Single Crystal ◽  
Single Crystals ◽  
Structure Determination ◽  
Monoclinic Space Group ◽  
Orthorhombic Space Group ◽  
Space Group ◽  
Cell Parameters ◽  
New Compounds

AbstractThe new compounds LiK[C(CN)3]2 and Li[C(CN)3]·½ (H3C)2CO were synthesized and their crystal structures were determined. Li[C(CN)3]·½ (H3C)2CO crystallizes in the orthorhombic space group Ima2 (no. 46) with the cell parameters a=794.97(14), b=1165.1(2) and c=1485.4(3) pm, while LiK[C(CN)3]2 adopts the monoclinic space group P21/c (no. 14) with the cell parameters a=1265.7(2), b=1068.0(2) and c=778.36(12) pm and the angle β=95.775(7)°. Single crystals of K[C(CN)3] were also acquired, and the crystal structure was refined more precisely than before corroborating earlier results.

Gemischte Alkalimetall-Oxidosulfidomolybdate A2[MoOxS4– x] (x = 1, 2, 3; A = K, Rb, Cs, NH4). Synthesen, Kristallstrukturen und Eigenschaften / Mixed Alkali Oxidosulfidomolybdates A2[MoOxS4−x] (x = 1, 2, 3; A = K, Rb, Cs, NH4).Synthesis, Crystal Structure and Properties

2012 ◽  
Vol 67 (2) ◽  
pp. 127-22
Author(s):  
Anna J. Lehner ◽  
Korina Kraut ◽  
Caroline Röhr
Keyword(s):  
Bathochromic Shift ◽  
Structure Type ◽  
Structure Theory ◽  
Monoclinic Space Group ◽  
Orthorhombic Space Group ◽  
Space Group ◽  
Coordination Numbers ◽  
Preparation Conditions ◽  
Vis Spectroscopy ◽  
Type Orthorhombic

Mixed sulfido/oxidomolybdate anions [MoOxS4−x]2− (x = 1, 2, 3) have been prepared by passing H2S gas through a solution of oxidomolybdates. The alkali salts of K+, Rb+, Cs+, and NH+4 precipitate as crystalline salts from these solutions depending on the pH, the polarity of the solvent, the educt concentrations and the temperature. Their structures have been determined by means of X-ray single-crystal diffraction data. All trisulfidomolybdates A2[MoOS3] (A = NH4/K/Rb/Cs) are isotypic with the tetrasulfido salts, exhibiting the β -K2[SO4] type (orthorhombic, space group Pnma, Z = 4; for A = Rb: a = 940.62(4), b = 713.32(4), c = 1164.56(5) pm, R1 = 0.0281). In contrast, the disulfidomolybdates exhibit a rich crystal chemistry, forming three different structure types depending on the preparation conditions and the size of the A cation: All four cations form salts crystallizing with the (NH4)2[WO2S2] structure type (monoclinic, space group C2/c, Z = 4, for A = Rb: a = 1144.32(11), b = 732.60(4), c = 978.99(10) pm, β = 120.324(7)°, R1 = 0.0274). For the three alkali metal cations a second polymorph with a new structure type (monoclinic, space group P21/c, Z = 4) is observed in addition (for A = Rb: a = 674.83(2), b = 852.98(3), c = 1383.10(9) pm, β = 115.19(1)°, R1 = 0.0216). The cesium salt also crystallizes with a third modification of another new structure type (orthorhombic, space group Pbcn, Z = 4, a = 915.30(6), b = 777.27(7), c = 1120.02(7) pm, R1 = 0.0350). Only for K, an anhydrous monosulfidomolybdate could be obtained (K2[MoO4] structure type, monoclinic, space group C2/m, Z = 4, a = 1288.7(3), b = 615.7(2), c = 762.2(1) pm, β = 109.59(1)°, R1 = 0.0736). The intramolecular chemical bonding in the molybdate anions is discussed and compared with the respective vanadates. Hereby aspects like bond lengths, bond strengths and force constants derived from Raman spectroscopy, are taken into account. Especially for the polymorphic disulfido salts, in-depth analyses of the local coordination numbers and the packing of the ions are presented. The gradual bathochromic shift of the crystal color with increasing S content and increasing size of the counter cations A and molar volumes (for the polymorphic forms), respectively, is in accordance with the increase of the experimental (UV/Vis spectroscopy) and calculated (FP-LAPW band structure theory) band gaps.

The Crystal and Molecular Structures of Two Modifications of cis-Dichloro-mer-tris-(dimethylphenylphosphine)hydridoiridium(III)

1988 ◽  
Vol 41 (3) ◽  
pp. 283 ◽  
Author(s):  
GB Robertson ◽  
PA Tucker
Keyword(s):  
Heavy Atom ◽  
Molecular Structures ◽  
Monoclinic Space Group ◽  
X Ray Diffraction ◽  
Orthorhombic Space Group ◽  
Space Group ◽  
X Ray ◽  
Bond Lengths ◽  
Metal Ligand ◽  
Ligand Bond

The structures of two crystalline modifications of mer -(Pme2Ph)3H-cis-Cl2IrIII, (1), have been determined from single-crystal X-ray diffraction data. Modification (A) is monoclinic, space group P21/c with a 12.635(1), b 30.605(3), c 14.992(2)Ǻ, β 110.01(2)° and Z = 8. Modification (B) is orthorhombic, space group Pbca with a 27.646(3), b 11.366(1), c 17.252(2)Ǻ and Z = 8. The structures were solved by conventional heavy atom techniques and refined by full-matrix least- squares analyses to conventional R values of 0.037 [(A), 8845 independent reflections] and 0.028 [(B), 5291 independent reflections]. Important bond lengths [Ǻ] are Ir -P(trans to Cl ) 2.249(1) av. (A) and 2.234(1) (B), Ir -P(trans to PMe2Ph) 2.339(2) av. (A) and 2.344(1), 2.352(1) (B), Ir-Cl (trans to H) 2.492(2), 2.518(2) (A) and 2.503(1) (B) and Ir-Cl (trans to PMe2Ph)2.452(2) av. (A) and 2.449(1)(B). Differences in chemically equivalent metal- ligand bond lengths emphasize the importance of non-bonded contacts in determining those lengths.

Cation ordering in the double tungstate LiFe(WO4)2

2012 ◽  
Vol 68 (2) ◽  
pp. i7-i8 ◽  
Author(s):  
Marjorie Albino ◽  
Stanislav Pechev ◽  
Philippe Veber ◽  
Matias Velazquez ◽  
Michael Josse
Keyword(s):  
High Temperature ◽  
Cation Ordering ◽  
Monoclinic Space Group ◽  
High Temperature Solution ◽  
Orthorhombic Space Group ◽  
Space Group ◽  
Double Tungstate ◽  
Growth Method ◽  
Temperature Solution ◽  
Expected Values

Single crystals of lithium iron tungstate, LiFe(WO4)2, were obtained using a high-temperature solution growth method. The analysis was conducted using the monoclinic space groupC2/c, with β = 90.597 (2)°, givingR1 = 0.0177. The Li and Fe atoms lie on twofold axes. The structure can also be refined using the orthorhombic space groupCmcm, giving slightly higher residuals. The experimental value of β and the residuals mitigate in favour of the monoclinic description of the structure. Calculated bond-valence sums for the present results are closer to expected values than those obtained using the results of a previously reported analysis of this structure.

The Dichloroplatinum(II) and Dichloropalladium(II) Complexes of 1,4-Diazacycloheptane: Preparative, Structural and Conformational Studies

1996 ◽  
Vol 49 (12) ◽  
pp. 1301 ◽  
Author(s):  
GW Allen ◽  
ECH Ling ◽  
LV Krippner ◽  
TW Hambley
Keyword(s):  
Crystal Structures ◽  
Chelate Ring ◽  
Chair Conformation ◽  
Monoclinic Space Group ◽  
Boat Conformation ◽  
X Ray Diffraction ◽  
Orthorhombic Space Group ◽  
Space Group ◽  
Membered Chelate Ring ◽  
Alternative Conformation

The preparation and purification of [Pt( hpip )Cl2] and [Pd( hpip )Cl2] ( hpip = homopiperazine = 1,4-diazacycloheptane) are described. Crystal structures of [Pt( hpip )Cl2] and [Pd( hpip )Cl2] have been determined by X-ray diffraction methods and refined to R values of 0.023 (932 F) and 0.023 (948 F). The crystals of [Pt( hpip )Cl2] are orthorhombic, space group Pbcm , a 7.7019(8), b 9.8080(12), c 12.1944(14) Ǻ, and those of [Pd( hpip )Cl2] are monoclinic, space group P21/m, a 6.1001(9), b 11.527(2), c 6.458(I) Ǻ, β 106.30(2)°. The seven- membered rings of the ligands in both complexes adopt boat-like conformations in which the five- membered chelate ring has an eclipsed N-C-C-N group and the six- membered chelate ring adopts a chair conformation. Molecular mechanics methods were used to investigate whether this conformation was a crystallographic artefact but it was found to be real. An alternative conformation in which the six-membered chelate ring adopts a skew-boat conformation was also investigated. It was found to be less stable than the conformation observed in the crystal structures, but to a degree that depends on whether non-bonded interactions involving the metal atom were included or not.

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