Assembling the Puzzle of Taxifolin Polymorphism Terekhov, Roman P; Selivanova, Irina A; Tyukavkina, Nonna A ...
Molecules (Basel, Switzerland),
11/2020, Letnik:
25, Številka:
22
Journal Article
Recenzirano
Odprti dostop
A large amount of the current literature dedicated to solid states of active pharmaceutical ingredients (APIs) pays special attention to polymorphism of flavonoids. Taxifolin (also known as ...dihydroquercetin) is an example of a typical flavonoid. Some new forms of taxifolin have been reported previously, however it is still unclear whether they represent polymorphic modifications. In this paper, we tried to answer the question about the taxifolin polymorphism. Taxifolin microtubes and taxifolin microspheres were synthesized from raw taxifolin API using several methods of crystal engineering. All forms were described with the help of spectral methods, scanning electron microscopy (SEM), X-ray powder diffraction (XRPD), and thermal analysis (TA). SEM reveals that the morphology of the solid phase is very specific for each sample. Although XRPD patterns of raw taxifolin and microtubes look similar, their TA profiles differ significantly. At the same time, raw taxifolin and microspheres have nearly identical thermograms, while XRPD shows that the former is a crystalline and the latter is an amorphous substance. Only the use of complex analyses allowed us to put the puzzle together and to confirm the polymorphism of taxifolin. This article demonstrates that taxifolin microtubes are a pseudopolymorphic modification of raw taxifolin.
Dihydroquercetin (DHQ) is a promising antioxidant for medical applications. The poor water solubility of this flavanonol at ambient conditions inhibits its implementation in clinical practice as an ...injectable dosage form. Thus, increasing water solubility is a critical step toward solving this problem. Herein we attempted to deal with this problem via DHQ phase modification while at the same time adhering to the principles of green chemistry as much as possible. Lyophilization is an appropriate method to achieve phase modification in an environment-friendly way. This method was employed to generate new phase modifications of DHQ that were then characterized. Mixtures of water with ethanol or acetonitrile were used as solvents for the preparation of the lyophilizates, DHQ
, and DHQ
, respectively. The results of dissolution testing of the obtained DHQ
and DHQ
demonstrated that the lyophilization increased water solubility at least 30-fold times. These new DHQ modifications were studied by scanning electron microscopy, mass-spectrometry, nuclear magnetic resonance spectroscopy, infrared spectroscopy, X-ray powder diffraction, and thermal analysis. Their solid-state phases were confirmed to differ from the initial DHQ substance without any changes in the molecular structure. Both DHQ
and DHQ
showed as high antioxidant activity as the initial DHQ. These data demonstrate the potential of DHQ
and DHQ
as active pharmaceutical ingredients for injectable dosage forms.
Solubility constants of rare earth (RE) nitrates crystalline hydrates are determined in a wide temperature range (−30 to 120°C), salts solubilities and phase diagrams of water–RE nitrate systems are ...calculated. For multicomponent (
n
> 5) solutions of RE nitrates the assessment of solution properties as well as phase diagrams are shown to be feasible within experimental uncertainty. In case of mixtures of RE nitrates with similar hydrodynamic radii of ions, the parameters of RE1–RE2 interparticle interaction can be ignored without losing accuracy of thermodynamic modeling.
A direct synthetic approach to four single-decker and one double-decker novel Pr(III) and Nd(III) complexes with 2,3,9,10,16,17,23,24-octachlorophthalocyaninate and ...1,2,3,4,8,9,10,11,15,16,17,18,22,23,24,25-hexadecachlorophthalocyaninate has been developed. Synthesis of hexadeca-Cl-substituted Nd(III) bisphthalocyaninate has been carried out utilizing two preformed synthetic blocks: Nd(III) octachlorophthalocyaninate acetate and octachlorophthalocyanine ligand. Due to the electron withdrawing effect of 16 chlorine groups, this Nd(III) bisphthalocyaninate was obtained as a redox stable anionic form. Upfield lanthanide-induced shifts of the aromatic proton signals (up to 2.04 ppm for Pr(III) octachlorophthalocyaninate acetate) were observed in the 1H NMR spectra of the obtained phthalocyaninates. Thermal stability of the lanthanide (III) complexes was examined using thermogravimetric analysis combined with mass-spectrometry. The double-decker compound was shown to possess an increased thermal stability in comparison with the single-deckers up to ~400 °C. Linear and nonlinear optical properties of the Cl-substituted Nd(III) and Pr(III) phthalocyaninates have been investigated using z-scan technique. The best nonlinear optical response with the highest excited state absorption cross-section (σ1 = 1.1 × 10−15 cm−2) was found for the hexadeca-Cl-substituted Nd(III) monophthalocyaninate.
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-Synthesys of new chloro-substituted Nd and Pr phthalocyaninates was carried out.-Neodymium bisphthalocyaninate was obtained in redox stable anionic form.-Double-decker structure possesses high thermal stability up to 400°C.-The best nonlinear optical response was found for chloro-substituted Nd complex.-Upfield lanthanide-induced shifts of aromatic proton signals were observed.
A novel chloro-substituted terbium(III)phthalocyaninate was synthesised. A comparison of the linear and nonlinear optical properties was carried out for perchlorinated phthalocyaninates of europium, ...terbium and lutetium.
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A novel hexadecachloro-substituted terbium(III)phthalocyaninate was synthesised and identified by mass-spectrometry, infrared and UV–Vis spectroscopies. Its elemental composition was proved using high resolution mass spectrometry, while thermal analysis revealed sufficiently high thermal stability up to 220 °C. For the first time for lanthanide(III)mono(phthalocyaninates), the influence of the lanthanide ion nature on the nonlinear optical properties was investigated. The values of the absorption cross-sections of the first excited state were determined using the z-scan technique. The highest value (σ1 = 1.96 × 10−16 cm2) was observed for the terbium complex.
A series of heteroleptic quadruple-decker bislanthanide(III) complexes based on a flexible spacer-linked phthalocyanine ligand of clamshell-type, denoted sandwich-clamshell complexes, have been ...prepared. Complexation of 1,1’-benzene-1,2-diylbis(methanediyloxy)-bis9(10),16(17),23(24)-tri-tert-butylphthalocyanine (clam,tBuPc2H4, 1) with 2(3),9(10),16(17),23(24)-tetra-tert-butylphthalocyaninato lanthanide(III) acetates tBuPcLnOAc, 2a–d; Ln = Eu (a), Gd (b), Tb (c), Lu(d) afforded quadruple-deckers clam, tBuPc4Ln2 (3a–d) with good to excellent yields. The complexes reveal intrinsic UV–Vis–NIR absorption by analogy to classical double-decker phthalocyaninates, while demonstrating high thermal stability up to 350 °C. At the same time, a combination of 1H NMR, electrochemistry and SQUID magnetometry supported by DFT theoretical calculations indicates that bis(phthalocyanine) subunits in 3 are in close contact mainly governed by the spacer group and, in some extent, by the presence of bulky tert-butyl peripheral substituents in the four phthalocyanine decks.
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•The family of sandwich-clamshell phthalocyaninato quadruple-deckers was extended by Eu, Gd and Tb compounds.•Conditions for the rational synthesis were found with a multiple increase in the yield compared to literature.•A complex physicochemical and theoretical study of sandwich-clamshell quadruple-deckers was first conducted.•Electrochemistry reveals specific intramolecular π-system interactions•NMR and SQUID data show the existence of intramolecular magnetic interactions.
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•A new method of phase diagram assessment based on the convex hull method is proposed.•Iso- and polythermal sections of ternary phase diagrams can be built by the method.•The method ...is robust in the case of isolated miscibility gaps (“islands”).•TernAPI program that implements the method is created.•NRTL parameters of CH3COOH-HCON(CH3)2-cyclohexene “island” system were optimized.
The first public version of TernAPI (ternary diagrams assessment programming interface) software package for ternary phase diagrams calculation by the convex hull method has been developed. Its reliability and efficiency have been proved on a large set of systems of different kind: organic liquids and fluids mixtures, water solutions, salts, oxides, metallic alloys. A remarkable advantage of TernAPI is a stable work in the case of isolated miscibility gaps (“islands”) described by a uniform Gibbs energy surface equation. It also contains several improvements of phase diagram calculation algorithm, a new module for x–T diagrams polythermal sections calculation and possibility of optimization of thermodynamic models parameters. NRTL model parameters for the acetic acid–N,N-dimethylformamide–cyclohexene ternary system have been optimized in this work. The specialized language based on Ruby and YAML is used for the description of thermodynamic models of phases.
► Heat capacities of Eu2Zr2O7 and Y2O3 are measured by DSC. ► Phase transformations are investigated by DTA and phase equilibration. ► Phases are identified using XRD and SEM/EDX. ► Thermodynamic ...parameters of the ZrO2–Eu2O3 system are assessed and phase diagram is calculated.
Temperature dependence of heat capacity of the Eu2Zr2O7 and Y2O3 is measured in the temperature range of 298.15–1373K by differential scanning calorimetry (DSC). Phase transformation in the Eu2Zr2O7 was experimentally studied using differential thermal analysis (DTA) up to 2173K and temperature of pyrochlore to fluorite transition was established to be 2128K. Eutectic reaction was determined by DTA to be 2326K. Peritectoid reaction F+B=C was established to occur at ∼1823K based phase equilibrium studies. Phase compositions were determined by SEM/EDX. The obtained results for heat capacity of the Eu2Zr2O7, temperatures of transformations and phase compositions were used to optimise thermodynamic parameters of the Eu2O3–ZrO2 system.
Solid–liquid equilibria in the system H
2
O–Gd(NO
3
)
3
were measured from –20 to 70°C using the isothermal saturation method. The Pitzer–Simonson–Clegg thermodynamic model was implemented to obtain ...the temperature dependence of Gd(NO
3
)
3
⋅6H
2
O solubility constant, to calculate salt solubility and to construct a phase diagram of the system from eutectic point to hydrate melting. Thermochemical properties of gadolinium nitrate aqueous solutions, such as dilution enthalpies and heat capacities, were assessed also. The model has shown to be reliable for phase equilibria calculation from –35 to 90°C and from 0 up to ~15 mol % of salt as well as the thermodynamic properties of Gd(NO
3
)
3
aqueous solutions at room temperature and around it.
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