Variable Temperature Powder X-ray Diffraction Research Articles

Polymorphism of Triamcinolone Acetonide Acetate and Its Implication for the Morphology Stability of the Finished Drug Product

Triamcinolone acetonide acetate (TAA) is a widely applied drug for rheumatoid arthritis and for the treatment of chronic inflammatory diseases. The drug was marketed as an injectable suspension with very low aqueous solubility. It was found that significant changes in crystal form, particle size, and morphology were observed during the shelf life period, which resulted in product lot failure and recall. TAA was thus an interesting subject for polymorphism screening and led to the discovery of multiple solid modifications, including three polymorphs (A, B, and C) and a monohydrate. These forms were fully characterized by powder X-ray diffraction, Fourier transform infrared spectroscopy, thermogravimetric analysis, differential scanning calorimetry, scanning electron microscopy, dynamic vapor sorption, and zeta potential. Single-crystal structures of four different forms and the transformation pathways among different modifications were discussed in detail. Single-crystal-to-single-crystal transformation behaviors were also analyzed and monitored by variable temperature-powder X-ray diffraction and hot stage microscopy. Morphological stability, form change, and particle size in suspension were also closely monitored, and the data were compared with the marketed product. It was found that crystal form selection plays a critical role in the stability of the injectable suspension products. The results indicate that form B has better physical stability in 0.5% NaCMC aqueous suspension compared to that of the currently marketed form.

Molecular reorientation in a dehydration process of an organic polar salt of 2,4-diaminotoluene/L(+)-tartaric acid

An organic polar hydrate was obtained through cocrystallization of 2,4-diaminotoluene (2,4-DAT) and L(+)-tartaric acid (TA) from ethanol. Dehydration behavior of the obtained hydrate was investigated using variable temperature powder X-ray diffraction (PXRD) and thermal analysis. Proton transfer from L(+)-TA to 2,4-DAT in both hydrate and dehydrated form was revealed via Fourier transform infrared spectroscopy. The crystal structures of both forms were determined using PXRD techniques. The similarities and differences between two crystal structures were analyzed and the role of water in the hydrate crystal structure was demonstrated.

Chiral Crystals of an Achiral Molecule Exhibit Plastic Bending and a Crystal-to-Crystal Phase Transition

The achiral molecule 2-cyano-4,6-dimethylpyrimidine (Me2pmCN) meets simple criteria that predict a supramolecular arrangement capable of exhibiting plastic bending. Indeed, crystals grown by sublimation bend readily without breaking under manual manipulation at room temperature. Compression of a crystal perpendicular to the bending direction easily “squashes” the crystal, a mechanical response akin to metal-like malleability. Single crystal X-ray diffraction (XRD) study reveals net alignment of the molecular dipoles propagating along the 21 screw axis in the monoclinic space group P21. Columnar π-stacked arrays of the planar molecules extend in [100], the long axis of the crystals. Weak interactions between the columnar structures account for the observed mechanical behavior. Variable temperature powder XRD and differential scanning calorimetry measurements of the plastic crystals indicate a solid-to-solid phase transition from one crystalline phase to another at 80.7 °C prior to melting at 83.3 °C.

The Room-Temperature Superionic Conductivity of Silver Iodide Nanoparticles under Pressure.

We performed variable-temperature synchrotron powder X-ray diffraction measurements and impedance spectroscopy under pressure for silver iodide (AgI) nanoparticles with a diameter of 11 nm. The superionic conducting α-phase of AgI nanoparticles was successfully stabilized down to at least 20 °C by applying a pressure of 0.18 GPa, whereas the transition temperature was 147 °C in bulk AgI at ambient pressure. To our knowledge, this is the first example of the α-phase of AgI existing stably at room temperature.

Solvent modified spin crossover in an iron(iii) complex: phase changes and an exceptionally wide hysteresis.

Solvent effects in a series of Fe(iii) spin crossover (SCO) complexes [Fe(qsal-I)2]OTf·sol (sol = MeOH 1, EtOH 2, n-PrOH 3, i-PrOH 4, acetone 5 and MeCN 6) are explored. SCO is abrupt in 1 (following MeOH loss) and 2, gradual for 3 (T1/2 = 199 K) and 4 (T1/2 = 251 K) and incomplete, even up to 350 K, for 5 and 6. In [Fe(qsal-I)2]OTf SCO occurs at T1/2↓ = 225 K and T1/2↑ = 234 K (ΔT = 9 K), while aged samples of 2 exhibit an exceptionally wide hysteresis of 80 K (T1/2↓ = 139 K and T1/2↑ = 219 K). In contrast, fresh samples of 2 exhibit stepped SCO with hysteresis varying from 2 to 42 K. VT-PXRD (variable temperature powder X-ray diffraction) studies indicate a new phase, 2b, is formed upon cooling below 180 K along with a minor LS phase 2c. Phase 2c and the HS phase 2a undergo a spin transition at T1/2↓ = 180 K and T1/2↑ = 215 K with phase 2b exhibiting two-step SCO. Structural studies in both spin states, except 6, show the cations are linked through extensive π-π interactions to form 1D chains. A combination of P4AE (parallel fourfold aryl embrace) and I···X (X = I, O, π) interactions create tightly packed 3D supramolecular networks. This study emphasizes that while solvent may result in only small structural changes SCO characteristics can be impacted dramatically.

CFA-4 - a fluorinated metal-organic framework with exchangeable interchannel cations.

The syntheses and crystal structures of the fluorinated linker 1,4-bis(3,5-bis(trifluoromethyl)-1H-pyrazole-4-yl)benzene (H2-tfpb; 1) and the novel metal-organic framework family M[CFA-4] (Coordination Framework Augsburg University-4), M[Cu5(tfpb)3] (M = Cu(i), K, Cs, Ca(0.5)), are described. The ligand 1 is fully characterized by single crystal X-ray diffraction, photoluminescence-, NMR-, IR spectroscopy, and mass spectrometry. The copper(i)-containing MOF crystallizes in the hexagonal crystal system within the chiral space group P6322 (no. 182) and the unit cell parameters are as follows: a = 23.630(5) Å, c = 41.390(5) Å, V = 20 015(6) Å3. M[CFA-4] features a porous 3-D structure constructed from pentanuclear copper(i) secondary building units {Cu(pz)6}- (pz = pyrazolate). Cu(I)[CFA-4] is fully characterized by synchrotron single crystal X-ray diffraction, thermogravimetric analysis, variable temperature powder X-ray diffraction, IR spectroscopy, photoluminescence and gas sorption measurements. Moreover, thermal stability and gas sorption properties of K[CFA-4] and Cu(I)[CFA-4] are compared.

Solvatomorphism and structural-spin crossover property relationship in bis[hydrotris(1,2,4-triazol-1-yl)borate]iron(ii)

Two solvatomorphs of the mononuclear bis[hydrotris(1,2,4-triazol-1-yl)borate]iron(II) complex, [Fe(HB(tz)3)2] (1) and [Fe(HB(tz)3)2]·6H2O (1·6H2O), were obtained by modifying the nature of the crystallization solvent. The crystal structure, thermal stability and spin crossover properties of the crystals and associated bulk powder samples were analysed using variable-temperature single-crystal and powder X-ray diffraction, thermogravimetry, calorimetry, and Raman and 57Fe Mossbauer spectroscopy as well as by means of magnetic susceptibility and optical microscopy measurements. The orthorhombic (Cmca) solvatomorph 1·6H2O loses water between ca. 323–353 K, leading to the disintegration of the crystals into the polycrystalline sample 1. The solvent-free crystals of 1 crystallize in the orthorhombic space group Pbca with half a complex molecule in the asymmetric unit. They exhibit a remarkably abrupt phase transition around 334 K between the high spin and low spin states. This (isostructural) spin transition is accompanied by a nearly isotropic change of the FeII–N bond lengths (8.3 ± 0.5%) and a highly anisotropic unit cell volume change (4.6 ± 0.1%). The very high cooperativity of the spin transition in 1 (Γ = 5700 ± 50 J mol−1) is rather unusual in mononuclear SCO compounds. This property can be related to the relatively high stiffness of the lattice (Debye temperature θD = 198 ± 2 K), which involves numerous C–H⋯N hydrogen contacts between each molecule with fourteen neighboring molecules.

Hydrogen Uptake by an Inclined Polycatenated Dynamic Metal-Organic Framework Based Material.

A 2D + 2D → 3D inclined polycatenated dynamic metal-organic framework of {[Cu(4-bpe)(2-ntp)(H2O)2]·2H2O}n [1, where 2-ntp2- = 2-nitroterephthalate and 4-bpe = 1,2-bis-(4-pyridyl)ethane] has been synthesized and characterized. The variable-temperature powder X-ray diffraction study indicates the dynamic nature of the inclined polycatenated framework, and the dehydrated framework with exposed metal centers exhibits excellent type I H2 adsorption of 1.94 wt % at 77 K and 1 bar of pressure.

High Proton Conduction in Two CoII and MnII Anionic Metal–Organic Frameworks Derived from 1,3,5-Benzenetricarboxylic Acid

Isostructural CoII and MnII organic frameworks with anionic frameworks and counterions (Me2NH2)+, namely {[M2Cl2(BTC)4/3]·(Me2NH2)+2·4/3H2O}n (M = Co (1) and Mn (2)), have been constructed by one-pot synthesis. Complexes 1 and 2 take paddle-wheel-like dinuclear metal cluster-based three-dimensional structures. Thermogravimetric analysis and variable-temperature powder X-ray diffraction spectra suggested that 1 displays better thermal stability than 2. Both exhibit relatively high proton conductivities at 65% relative humidity (RH) and room temperature (σ > 2.5 × 10–4 S cm–1); however, complex 1 possesses the better cycling capability and stability with Ea = 0.21 eV under 65% RH.

Investigating the Structural Features and Spectroscopic Properties of Bis(tetrazolato)-Based Coordination Polymers

The luminescent compound xylene-bis(2H-tetrazol-5-yl) (H2BTZPX) was prepared and employed in the construction of the novel coordination polymers (CPs) Zn(BTZPX), Ag2(BTZPX), and Hg(BTZPX), containing d10 transition metal ions. Powder X-ray diffraction (PXRD) structure determination enabled us to disclose the crystal and molecular structure of the three CPs: while Zn(BTZPX) features a 3-D polymeric network, Ag2(BTZPX) and Hg(BTZPX) show 2-D corrugated layers. Thermogravimetric analysis and variable-temperature PXRD revealed the appreciable thermal robustness of the three CPs, peaking up to 370 °C, in air, in the case of Ag2(BTZPX). Given the sizable fluorescence emission of the ligand in the solid state, both H2BTZPX and the three CPs were characterized as to their electronic-state transition spectroscopic properties. UV–visible absorption unveiled a bathochromic shift for both the ligand and the CPs with respect to the absorption maximum of the main chromophore of the spacer, i.e., the benzene ring. In or...

A High-Temperature Order-Disorder Phase Transition Coupled With Conformational Change in the Hybrid Material [C6 H13 NH]2 ⋅ZnBr4.

A new high-temperature, hybrid, phase-transition material, 1-methylpiperidinium tetrabromozincate (1), that shows a reversible transition at 345 K was synthesized. Differential scanning calorimetry and specific heat capacity measurements confirmed this reversible transformation with a large heat hysteresis of 25 K, which describes a typical first-order phase transition in 1. The dielectric constant exhibited a steplike anomaly and showed high and low dielectric states in the high- and room-temperature phases, respectively, and therefore, this hybrid might be considered as a potential switchable dielectric material. The variable-temperature powder X-ray diffraction patterns displayed remarkable shifts between the experimental patterns at the two different phases. Single-crystal X-ray diffraction analyses at various temperatures revealed that the origin of this transformation could be attributed to disordering of the bromine atoms in the anion and the nitrogen atom of the cation. The cation also assumed a conformational change, which was likely induced by the disordered nitrogen atom. The conformational onset of the transformation of the cation from a planar conformer into a relaxed chair also occurred upon decreasing the temperature below transition point; thus, the combined order-disorder and conformational change induced the structural transformation and the change in symmetry.

Solid State Investigation and Characterization of a Nepadutant Precursor: Polymorphic and Pseudopolymorphic Forms of MEN11282

MEN11282 (1) is a precursor of nepadutant (MEN11420), a potent and selective antagonist at the human tachykinin NK-2 receptor (hNK-2), that has been evaluated in clinical trials for different therapeutic indications. Three crystalline forms of 1 were identified and characterized by both single crystal and powder X-ray diffraction (SCXRD and XRPD): a monohydrate (1·H2O, SCXRD) and two different anhydrous forms, namely, 1_α and 1_β (XRPD). Because of the relevance that the solid form of a substance of pharmaceutical interest plays during the manufacturing process, variable temperature powder X-ray diffraction (VT-XRPD) in conjunction with differential scanning calorimetry were used to investigate the behavior of the different solid forms of 1. The rationale for the dehydration and hydration process involving 1·H2O and 1_α and the stability of 1_β toward water uptake is provided based on their crystal packings.

A Two-Dimensional Inorganic-Organic Hybrid Solid of Manganese(II) Hydrogenophosphate Showing High Proton Conductivity at Room Temperature.

The inorganic-organic hybrid metal hydrogenophosphate with a formula of (C2H10N2)[Mn2(HPO4)3](H2O) (1) shows layered crystal structure. The inorganic anion layer is built from Mn3O13 cluster units, and the interlayer spaces are filled by the charge-compensated ethylenediammonium dications together with the lattice water molecules. The thermogravimetry, variable-temperature powder X-ray diffraction, and the proton conductance under anhydrous and moisture environments were investigated for 1, disclosing that 1 shows high thermal stability and high proton transport nature, and the proton conductivity reaches to 1.64 × 10(-3) S·cm(-1) under 99%RH even at 293 K. The high proton conductivity is related to the formation of denser H-bond networks in the lattice.

Molecular Order and Mesophase Investigation of Thiophene-Based Forked Mesogens.

Thiophene-based rodlike molecules constructed from a three phenyl ring core and terminal dialkoxy chains recognized as forked mesogens are synthesized, and their mesophase properties as well as the molecular order are investigated. The synthesized forked mesogens would serve as model compounds for tetracatenar or biforked mesogens. On the basis of the position of the thiophene link with the rest of the core, 2-substituted and 3-substituted mesogens are realized in which the length of the terminal alkoxy chains is varied. The mesophase properties are evaluated using a hot-stage polarizing microscope and differential scanning calorimetry. For both homologues, the appearance of either nematic phase alone or in conjunction with smectic C phase is noticed depending on the length of the terminal alkoxy chains. The existence of layer ordering characteristic of the smectic C phase is confirmed for a representative mesogen using variable-temperature powder X-ray diffraction. High-resolution solid-state (13)C NMR measurements of C12 homologues of the two series reveal orientational order parameters of all rings of the core as well as terminal chains in the liquid crystalline phase. For both homologues, because of the asymmetry of ring I, the order parameter value is higher in contrast to ring II, ring III, and the thiophene ring. The chemical shifts and (13)C-(1)H dipolar couplings of OCH2 carbons of the terminal dodecyloxy chains provide contrasting conformations, reflecting the orientational constraints. Furthermore, the investigations also reveal that the mesophase range and the tendency for layer ordering are higher for 3-substituted mesogens compared to 2-substituted homologues.

Gd12Co5.3Bi and Gd12Co5Bi, Crystalline Doppelgänger with Low Thermal Conductivities

Attempts to prepare Gd12Co5Bi, a member of the rare-earth (RE) intermetallics RE12Co5Bi, which were identified by a machine-learning recommendation engine as potential candidates for thermoelectric materials, led instead to formation of the new compound Gd12Co5.3Bi with a very similar composition. Phase equilibria near the Gd-rich corner of the Gd-Co-Bi phase diagram were elucidated by both lab-based and variable-temperature synchrotron powder X-ray diffraction, suggesting that Gd12Co5.3Bi and Gd12Co5Bi are distinct phases. The higher symmetry structure of Gd12Co5.3Bi (cubic, space group Im3̅, Z = 2, a = 9.713(6) Å), as determined from single-crystal X-ray diffraction, is closely related to that of Gd12Co5Bi (tetragonal, space group Immm). Single Co atoms and Co-Co dumbbells are disordered with occupancies of 0.78(2) and 0.22(2), respectively, in Gd12Co5.3Bi, but they are ordered in Gd12Co5Bi. Consistent with this disorder, the electrical resistivity shows less dependence on temperature for Gd12Co5.3Bi than for Gd12Co5Bi. The thermal conductivity is low and reaches 2.8 W m(-1) K(-1) at 600 °C for both compounds; however, the temperature dependence of the thermal conductivity differs, decreasing for Gd12Co5.3Bi and increasing for Gd12Co5Bi as the temperature increases. The unusual trends in thermal properties persist in the heat capacity, which decreases below 2R, and in the thermal diffusivity, which increases at higher temperatures.

Metal Azolate/Carboxylate Frameworks as Catalysts in Oxidative and C-C Coupling Reactions.

The five metal azolate/carboxylate (MAC) compounds [Cd(dmpzc)(DMF)(H2O)] (Cd-dmpzc), [Pd(H2dmpzc)2Cl2] (Pd-dmpzc), [Cu(Hdmpzc)2] (Cu-dmpzc), [Zn4O(dmpzc)3]·Solv (Zn-dmpzc·S), and [Co4O(dmpzc)3]·Solv (Co-dmpzc·S) were isolated by coupling 3,5-dimethyl-1H-pyrazol-4-carboxylic acid (H2dmpzc) to cadmium(II), palladium(II), copper(II), zinc(II), and cobalt(II) salts. While Cd-dmpzc and Pd-dmpzc had never been prepared in the past, for Cu-dmpzc, Zn-dmpzc·S, and Co-dmpzc·S we optimized alternative synthetic paths that, in the case of the copper(II) and cobalt(II) derivatives, are faster and grant higher yields than the previously reported ones. The crystal structure details were determined ab initio (Cd-dmpzc and Pd-dmpzc) or refined (Cu-dmpzc, Zn-dmpzc·S, and Co-dmpzc·S) by means of powder X-ray diffraction (PXRD). While Cd-dmpzc is a nonporous 3D MAC framework, Pd-dmpzc shows a 3D hybrid coordination/hydrogen-bonded network, in which Pd(H2dmpzc)2Cl2 monomers are present. The thermal behavior of the five MAC compounds was investigated by coupling thermal analysis to variable-temperature PXRD. Their catalytic activity was assessed in oxidative and C-C coupling reactions, with the copper(II) and cadmium(II) derivatives being the first nonporous MAC frameworks to be tested as catalysts. Cu-dmpzc is the most active catalyst in the partial oxidation of cyclohexane by tert-butyl hydroperoxide in acetonitrile (yields up to 12% after 9 h) and is remarkably active in the solvent-free microwave-assisted oxidation of 1-phenylethanol to acetophenone (yields up to 99% at 120 °C in only 0.5 h). On the other hand, activated Zn-dmpzc·S (Zn-dmpzc) is the most active catalyst in the Henry C-C coupling reaction of aromatic aldehydes with nitroethane, showing appreciable diastereoselectivity toward the syn-nitroalkanol isomer (syn:anti selectivity up to 79:21).

Iron(III) metallomesogen of [N2O2] donor Schiff base ligand containing 4-substituted alkoxy chains

ABSTRACTTwo new square pyramidal iron(III)-complexes of ‘salen’-type Schiff base ligands containing 4-substituted long alkoxy arms on the aromatic rings, [Fe(4-C16H33O)2salcn)]Cl and [Fe(4-C16H33O)2salophen)]Cl {salcn = N,Nʹ-cyclohexanebis(salicylideneiminato) and salophen = N,Nʹ-phenylenebis(salicylideneiminato)}, have been successfully synthesised, and their mesomorphic property investigated. The ligands and complexes were characterised by elemental analyses, UV–Vis, FT-IR, ESI–MS, 1H and 13C NMR (for ligands only). The phase behaviour of the iron(III) complexes were ascertained by differential scanning calorimetry, polarising optical microscopy and variable temperature PXRD study. Ligands are non-mesomorphic, however, mesomorphism got induced upon complexation with the iron(III) centre. X-ray diffraction study revealed a layer-like arrangement of the five coordinated mesomorphic iron(III) complexes. The mesophase is stable over a wide range of temperature. The density functional theory calculations were carried out using Gaussian 09 program at B3LYP level using unrestricted 6–31G (d, p) basis set to obtain the optimised geometry of the iron(III) complexes.

Reviewing the Manifold Aspects of Ganciclovir Crystal Forms

Ganciclovir, an active pharmaceutical ingredient against cytomegalovirus, is known to crystallize in the form of anhydrous or hydrated phases. The crystal and molecular structures of two hydrated forms, the hydrochloride salt, and two pro-drug derivatives (i.e., the tri-N2,O,O-acetyl and di-O-acetyl) have been successfully unveiled from powder X-ray diffraction (PXRD) or single-crystal X-ray diffraction studies. The thermal behavior of the hydrates has been unraveled by juxtaposing the results of our thermal analysis and variable-temperature PXRD experiments to those previously reported on the topic. On the whole, this investigation revisits and complements the somehow incomplete and scattered information present in the literature. It is envisaged that this study can open the way to systematic PXRD qualitative and quantitative analysis of ganciclovir mixtures formed during synthesis, isolation, or processing.

Magnetocaloric Effect of Two Isostructural Heterometallic Organic Frameworks Based on {MII GdIII 2 } Clusters (MII =Mn, Ni).

Two isostructural heterometallic coordination polymers (HCPs) based on {MII GdIII 2 } clusters (MII =Mn and Ni) have been obtained from the conventional one-pot self-assembly of GdIII ions and H4 abtc ligands (H4 abtc=3,3',5,5'-azobenzenetetracarboxylic acid) with corresponding transition-metal ions in mixed N,N-dimethylformamide (DMF)/H2 O solvents. The formulas are expressed as {[NH2 (CH3 )2 ]2 [MII GdIII 2 (HCOO)2 (abtc)2 ]}n (MII =Mn for 1 and Ni for 2). The common features of both HCPs are that two GdIII ions and one MII ion interconnected through abtc4- ligands present "hourglass"-type {MII GdIII 2 } clusters, which are further linked by HCOO- and abtc4- ligands to produce 3D (4,4,10)-connected topological frameworks. Magnetic results reveal that both 1 and 2 possess remarkable magnetocaloric effects (MCE) with maximum -ΔSm values of 31.9 and 29.5 J kg-1 K-1 at 3.0 K for an applied field of 70 kOe, respectively. Furthermore, the skeletons of two HCPs were stable up to at least 310 °C as supported by thermogravimetric (TG) analyses and in situ variable-temperature powder X-ray diffraction (PXRD) patterns.

Diketonylpyridinium Cations as a Support of New Ionic Liquid Crystals and Ion-Conductive Materials: Analysis of Counter-Ion Effects.

Ionic liquid crystals (ILCs) allow the combination of the high ionic conductivity of ionic liquids (ILs) with the supramolecular organization of liquid crystals (LCs). ILCs salts were obtained by the assembly of long-chained diketonylpyridinium cations of the type [HOOR(n)pyH]+ and BF4−, ReO4−, NO3−, CF3SO3−, CuCl42− counter-ions. We have studied the thermal behavior of five series of compounds by differential scanning calorimetry (DSC) and hot stage polarized light optical microscopy (POM). All materials show thermotropic mesomorphism as well as crystalline polymorphism. X-ray diffraction of the [HOOR(12)pyH][ReO4] crystal reveals a layered structure with alternating polar and apolar sublayers. The mesophases also exhibit a lamellar arrangement detected by variable temperature powder X-ray diffraction. The CuCl42− salts exhibit the best LC properties followed by the ReO4− ones due to low melting temperature and wide range of existence. The conductivity was probed for the mesophases in one species each from the ReO4−, and CuCl42− families, and for the solid phase in one of the non-mesomorphic Cl− salts. The highest ionic conductivity was found for the smectic mesophase of the ReO4− containing salt, whereas the solid phases of all salts were dominated by electronic contributions. The ionic conductivity may be favored by the mesophase lamellar structure.