Internal Secondary Relaxation as a Dielectric Probe of Molecular Surroundings.

We investigated the secondary relaxation behavior in rotor molecules in a glassy and crystalline state by using the dielectric method. Without changing the molecular source of secondary relaxation, only by modifying the environment around the rotating unit we observed notable variations in spectral parameters. Our results show that internal rotation, like a probe, can sample the immediate surroundings with high sensitivity to molecular-level changes that impact the rotation parameters. Our research offers a new perspective on the dielectric behavior of internal secondary relaxations and challenges the paradigm of their irrelevant nature.

The influence of molecular shape on reorientation dynamics of sizable glass-forming isomers at ambient and elevated pressure.

We used dielectric spectroscopy to access the molecular dynamics of three isomers with a structure based on a sizable, partially rigid, and non-polar core connected to a polar phenylene unit differing in the position of the polar group, and, consequently, the direction and magnitude of the dipole moment to address the question how unique molecular properties, in particular large size and elongated shape, affect the dynamics. The position of the polar group differentiates the molecular shape and isomer's anisotropy and leads to different thermal and dynamic properties of the isomers. The shape of permittivity loss spectra was governed by magnitudes of the longitudinal and transverse components of dipole moment to a large extent. For para isomer with negligible traverse component of dipole moment, the narrowest loss peak was found while for meta isomer, the bimodal loss peak was observed at high temperatures. Its shape evolved on cooling limiting the possibility of individual mode separation near glass transition where the dynamics were more cooperative. High-pressure dielectric studies showed that sizable isomers were characterized by the pronounced sensitivity of glass transition temperature, Tg, to compression. Observed high activation volumes, such as 735 cm3/mol at Tg for para isomer, were found to correlate with the length scale of dynamic cooperativity. The number of dynamically correlated molecules depended on molecular shape and varied among isomers while the determined values were much smaller than that reported for other glass-forming liquids. We discussed here the obtained results in the context of the specific properties of the systems studied showing the overriding role of anisotropy.

Revealing the Elusive Structure and Reactivity of Iron Boride α-FeB.

Crystal structures can strongly deviate from bulk states when confined into nanodomains. These deviations may deeply affect properties and reactivity and then call for a close examination. In this work, we address the case where extended crystal defects spread through a whole solid and then yield an aperiodic structure and specific reactivity. We focus on iron boride, α-FeB, whose structure has not been elucidated yet, thus hindering the understanding of its properties. We synthesize the two known phases, α-FeB and ß-FeB, in molten salts at 600 and 1100 °C, respectively. The experimental X-ray diffraction (XRD) data cannot be satisfactorily accounted for by a periodic crystal structure. We then model the compound as a stochastic assembly of layers of two structure types. Refinement of the powder XRD pattern by considering the explicit scattering interference of the different layers allows quantitative evaluation of the size of these domains and of the stacking faults between them. We, therefore, demonstrate that α-FeB is an intergrowth of nanometer-thick slabs of two structure types, ß-FeB and CrB-type structures, in similar proportions. We finally discuss the implications of this novel structure on the reactivity of the material and its ability to perform insertion reactions by comparing the reactivities of α-FeB and ß-FeB as reagents in the synthesis of a model layered material: Fe2AlB2. Using synchrotron-based in situ X-ray diffraction, we elucidate the mechanisms of the formation of Fe2AlB2. We highlight the higher reactivity of the intergrowth α-FeB in agreement with structural relationships.

Study of Thermal Properties, Molecular Dynamics, and Physical Stability of Etoricoxib Mixtures with Octaacetylmaltose near the Glass Transition.

In this paper, we thoroughly investigated the physical stability of the anti-inflammatory drug etoricoxib, which has been reported earlier to be resistant to recrystallization in its glassy and supercooled states at ambient pressure. Our unique application of the standard refractometry technique showed that the supercooled liquid of the drug was able to recrystallize during isothermal experiments in atmospheric conditions. This enabled us to determine the crystallization onset timescale and nucleation energy barrier of etoricoxib for the first time. As the physical instability of etoricoxib requires working out an efficient method for improving the drug's resistance to recrystallization to maintain its amorphous form utility in potential pharmaceutical applications, we focused on finding a solution to this problem, and successfully achieved this purpose by preparing binary mixtures of etoricoxib with octaacetylmaltose. Our detailed thermal, refractometry, and molecular dynamics studies of the binary compositions near the glass transition revealed a peculiar behavior of the glass transition temperatures when changing the acetylated disaccharide concentration in the mixtures. Consequently, the anti-plasticization effect on the enhancement of physical stability could be excluded, and a key role for specific interactions in the improved resistance to recrystallization was expected. Invoking our previous results obtained for etoricoxib, the chemically similar drug celecoxib, and octaacetylmaltose, we formulated a hypothesis about the molecular mechanisms that may cause an impediment to crystal nuclei formation in the amorphous mixtures of etoricoxib with octaacetylmaltose. The most plausible scenario may rely on the formation of hydrogen-bonded heterodimers of the drug and excipient molecules, and the related drop in the population of the etoricoxib homodimers, which disables the nucleation. Nevertheless, this hypothesis requires further investigation. Additionally, we tested some widely discussed correlations between molecular mobility and crystallization properties, which turned out to be only partially satisfied for the examined mixtures. Our findings constitute not only a warning against manufacturing the amorphous form of pure etoricoxib, but also evidence for a promising outcome for the pharmaceutical application of the amorphous compositions with octaacetylmaltose.

Geoinspired syntheses of materials and nanomaterials.

The search for new materials is intimately linked to the development of synthesis methods. In the current urge for the sustainable synthesis of materials, taking inspiration from Nature's ways to process matter appears as a virtuous approach. In this review, we address the concept of geoinspiration for the design of new materials and the exploration of new synthesis pathways. In geoinspiration, materials scientists take inspiration from the key features of various geological systems and processes occurring in nature, to trigger the formation of artificial materials and nanomaterials. We discuss several case studies of materials and nanomaterials to highlight the basic geoinspiration concepts underlying some synthesis methods: syntheses in water and supercritical water, thermal shock syntheses, molten salt synthesis and high pressure synthesis. We show that the materials emerging from geoinspiration exhibit properties differing from materials obtained by other pathways, thus demonstrating that the field opens up avenues to new families of materials and nanomaterials. This review focuses on synthesis methodologies, by drawing connections between geosciences and materials chemistry, nanosciences, green chemistry, and environmental sciences.

Insight from high-pressure dielectric studies into molecular dynamics of the itraconazole-glycerol mixture in smectic and isotropic phases.

We present here the results of high-pressure broadband dielectric spectroscopy (BDS) measurements for a mixture of liquid-crystalline drug itraconazole (ITZ) and glycerol (GLY) at a critical concentration of 5% w/w in which the nematic order is eliminated. In the investigated system, smectic-A to isotropic phase transition leaves a clear fingerprint on the dielectric response, allowing for a phase diagram creation using BDS data. By following the α-relaxation dynamics under different thermodynamic conditions, we provide insights into the effect of pressure on temperature and the phenomenology of smectic-A to the isotropic phase transition. Additional measurements of specific volume as a function of pressure and temperature provide us with a deeper insight into material properties that could be analyzed comprehensively via the equation of state. We proved the validity of the density scaling concept, showing that the mixture's complexity does not exclude thermodynamic scaling of dynamic properties related to the α-process in the smectic-A phase. The low value of scaling exponent γ = 2.00 ± 0.02 and a high ratio of the activation energy at constant volume, EV, to the activation enthalpy at constant pressure, HP, indicate that temperature is a dominant variable controlling α-relaxation dynamics in the ordered smectic-A phase of the ITZ-GLY mixture.

Complex Reorientation Dynamics of Sizable Glass-Formers with Polar Rotors Revealed by Dielectric Spectroscopy.

We present the results of dielectric measurements for three sizable glass-formers with identical nonpolar cores linked to various dipole-labeled rotors that shed new light on the picture of reorientation of anisotropic systems with significant moment of inertia revealed by broadband dielectric spectroscopy. The dynamics of sizable glass-formers formed by partially rigid molecular cores linked to small polar rotors in many respects differs from that of typical glass-formers. For instance, the extraordinarily large prefactors (τ0 > 10-12 s) in the Vogel-Fulcher-Tammann equation were found. The rich and highly diverse relaxation pattern was governed by the location of a dipole, its ability to rotate freely, and the degree of coupling to the motion of the entire sizable system.

X-ray Free Electron Laser-Induced Synthesis of ε-Iron Nitride at High Pressures.

The ultrafast synthesis of ε-Fe3N1+x in a diamond-anvil cell (DAC) from Fe and N2 under pressure was observed using serial exposures of an X-ray free electron laser (XFEL). When the sample at 5 GPa was irradiated by a pulse train separated by 443 ns, the estimated sample temperature at the delay time was above 1400 K, confirmed by in situ transformation of α- to γ-iron. Ultimately, the Fe and N2 reacted uniformly throughout the beam path to form Fe3N1.33, as deduced from its established equation of state (EOS). We thus demonstrate that the activation energy provided by intense X-ray exposures in an XFEL can be coupled with the source time structure to enable exploration of the time-dependence of reactions under high-pressure conditions.

How can we improve the physical stability of co-amorphous system containing flutamide and bicalutamide? The case of ternary amorphous solid dispersions.

The article describes the preparation and characterization of binary mixtures of two antiandrogens used in prostate cancer treatment, i.e. flutamide (FL) and bicalutamide (BIC), as well as their ternary mixtures with either poly(methyl methacrylate-co-ethyl acrylate) (MMA/EA) or polyvinylpyrrolidone (PVP). The samples were converted into amorphous form to improve their water solubility and dissolution rate. Broadband dielectric spectroscopy and differential scanning calorimetry revealed that FL-BIC (65%) (w/w) does not tend to crystallize from the supercooled liquid state. We made the assumption that the drug-to-drug weight ratio should be maintained as in the case of monotherapy so we decided to investigate the system containing FL and BIC in 15:1 (w/w) ratio with 30% additive of polymers as stabilizers. Our research has shown that only in the case of the FL-BIC-PVP mixture the crystallization has been completely inhibited, both in glassy and supercooled liquid state, which was confirmed by X-ray diffraction studies. In addition, we performed solubility and dissolution rate tests, which showed a significant improvement in solubility of ternary system as compared to its crystalline counterpart. Enhanced physical stability and water solubility of the amorphous ternary system makes it promising for further studies.

In situ X-ray diffraction of silicate liquids and glasses under dynamic and static compression to megabar pressures.

Properties of liquid silicates under high-pressure and high-temperature conditions are critical for modeling the dynamics and solidification mechanisms of the magma ocean in the early Earth, as well as for constraining entrainment of melts in the mantle and in the present-day core-mantle boundary. Here we present in situ structural measurements by X-ray diffraction of selected amorphous silicates compressed statically in diamond anvil cells (up to 157 GPa at room temperature) or dynamically by laser-generated shock compression (up to 130 GPa and 6,000 K along the MgSiO3 glass Hugoniot). The X-ray diffraction patterns of silicate glasses and liquids reveal similar characteristics over a wide pressure and temperature range. Beyond the increase in Si coordination observed at 20 GPa, we find no evidence for major structural changes occurring in the silicate melts studied up to pressures and temperatures exceeding Earth's core mantle boundary conditions. This result is supported by molecular dynamics calculations. Our findings reinforce the widely used assumption that the silicate glasses studies are appropriate structural analogs for understanding the atomic arrangement of silicate liquids at these high pressures.

Photodynamic performance of amphiphilic chlorin e6 derivatives with appropriate properties: A comparison between different-type liposomes as delivery systems.

BACKGROUND: Many aspects are currently being investigated, with the aim of improving the application of PDT in the clinic by rendering it more effective. One of the current trends focuses on the use of nanocarriers. The aim of this study is to describe novel photosensitizers among polyol amide chlorin e6 derivatives for photodynamic therapy (PDT) using liposomes. METHODS: In addition to their intracellular localization and antiproliferative activity against HCT116 cells, appropriate photophysical features have been determined (especially high 1O2 quantum yield production). RESULTS AND CONCLUSIONS: Fluorescent microscopy demonstrated that the compounds entered the endoplasmic reticulum (ER), lysosomes, mitochondria and partially the cytoplasm. All of the chlorins showed no dark cytotoxicity; however, high phototoxicity was observed. Using optical and electron microscopy, we investigated the impact of chlorin-based PDT upon cell damage leading to cell death. Chl ara 3 was identified as the most promising compound among polyol amide chlorin e6 derivatives and improved phototoxicity was observed as compared with a clinically approved temoporfin. Our results indicate that newly-synthesized chlorins seem to be promising candidates for PDT application, and two of them (chl ara 3 and chl mme 2) may create promising new drugs, both in the form of a free compound and as a liposomal formulation.

Electrophoretic deposition of chitosan coatings on the Ti15Mo biomedical alloy from a citric acid solution.

Chitosan biocoatings were successfully deposited on the Ti15Mo alloy surface via cataphoretic deposition from a solution of 1 g dm-3 of chitosan in 4% (aq) citric acid. The influence of the cataphoretic deposition parameters on quality and morphology of the obtained coatings were investigated using fluorescence and scanning electron microscopy. The functional groups' presence in chitosan chine were confirmed by ATR-FTIR methods. X-ray analysis revealed the amorphous structure of the chitosan coatings on the Ti15Mo alloy surface. The conducted studies also include assessing the abrasion resistance and adhesion to the substrate of the obtained chitosan coatings. The results show that utilizing the citric acid as a solvent results in the formation of pore free coatings. The yield of the electrophoretic deposition process was in the range of 2-10 mg of deposited chitosan per 1 cm2. The obtained coatings through the unique properties of chitosan are a promising biomaterial for application in medicine.

Cobalt protoporphyrin IX increases endogenous G-CSF and mobilizes HSC and granulocytes to the blood.

Granulocyte colony-stimulating factor (G-CSF) is used in clinical practice to mobilize cells from the bone marrow to the blood; however, it is not always effective. We show that cobalt protoporphyrin IX (CoPP) increases plasma concentrations of G-CSF, IL-6, and MCP-1 in mice, triggering the mobilization of granulocytes and hematopoietic stem and progenitor cells (HSPC). Compared with recombinant G-CSF, CoPP mobilizes higher number of HSPC and mature granulocytes. In contrast to G-CSF, CoPP does not increase the number of circulating T cells. Transplantation of CoPP-mobilized peripheral blood mononuclear cells (PBMC) results in higher chimerism and faster hematopoietic reconstitution than transplantation of PBMC mobilized by G-CSF. Although CoPP is used to activate Nrf2/HO-1 axis, the observed effects are Nrf2/HO-1 independent. Concluding, CoPP increases expression of mobilization-related cytokines and has superior mobilizing efficiency compared with recombinant G-CSF. This observation could lead to the development of new strategies for the treatment of neutropenia and HSPC transplantation.

How can we improve the physical stability of co-amorphous system containing flutamide and bicalutamide? The case of ternary amorphous solid dispersions.

The article describes the preparation and characterization of binary mixtures of two antiandrogens used in prostate cancer treatment, i.e. flutamide (FL) and bicalutamide (BIC), as well as their ternary mixtures with either poly(methyl methacrylate-co-ethyl acrylate) (MMA/EA) or polyvinylpyrrolidone (PVP). The samples were converted into amorphous form to improve their water solubility and dissolution rate. Broadband dielectric spectroscopy and differential scanning calorimetry revealed that FL-BIC (65%) (w/w) does not tend to crystallize from the supercooled liquid state. We made the assumption that the drug-to-drug weight ratio should be maintained as in the case of monotherapy so we decided to investigate the system containing FL and BIC in 15:1 (w/w) ratio with 30% additive of polymers as stabilizers. Our research has shown that only in the case of the FL-BIC-PVP mixture the crystallization has been completely inhibited, both in glassy and supercooled liquid state, which was confirmed by X-ray diffraction studies. In addition, we performed solubility and dissolution rate tests, which showed a significant improvement in solubility of ternary system as compared to its crystalline counterpart. Enhanced physical stability and water solubility of the amorphous ternary system makes it promising for further studies.

Laser-heating system for high-pressure X-ray diffraction at the Extreme Conditions beamline I15 at Diamond Light Source.

In this article, the specification and application of the new double-sided YAG laser-heating system built on beamline I15 at Diamond Light Source are presented. This system, combined with diamond anvil cell and X-ray diffraction techniques, allows in situ and ex situ characterization of material properties at extremes of pressure and temperature. In order to demonstrate the reliability and stability of this experimental setup over a wide range of pressure and temperature, a case study was performed and the phase diagram of lead was investigated up to 80 GPa and 3300 K. The obtained results agree with previously published experimental and theoretical data, underlining the quality and reliability of the installed setup.

Unusual dielectric response of 4-methyl-1,3-dioxolane derivatives.

In this paper, we applied broadband dielectric spectroscopy (BDS) to investigate the molecular dynamics of three 4-methyl-1,3-dioxolane derivatives (MD) whose chemical structures differ in the length of non-polar alkyl side chains. We notice that small changes within their chemical structures have a pronounced impact on parameters characterizing the supercooled dynamics of the compounds selected for this study. Our detailed analysis of the dielectric response reveals that in the supercooled-liquid state besides the structural α-relaxation a sub-α Debye-like relaxation can be clearly distinguished. The observed two relaxation regimes mirror the structural complexity of the investigated MD derivatives. The amphiphilic nature of the investigated compounds and possible interactions between non-polar side chains can rationalize the observed behavior. To follow the molecular arrangement of MD derivatives at low temperatures, we also carried out Raman measurements. Additionally, we performed BDS measurements at elevated pressures which revealed that, as a result of compression, the sub-α contribution to the dielectric response disappeared. The paper concludes with a discussion of open questions about the possible molecular origin of the observed sub-α Debye-like process. These results provide fresh insight into the puzzling nature of the slow supramolecular relaxation modes in low-molecular glass forming liquids.

Changes in Physical Stability of Supercooled Etoricoxib after Compression.

In the case of formulations with amorphous active pharmaceutical ingredients the risk of pressure-induced recrystallization should be carefully considered. We reported here that supercooled etoricoxib (ETB), which was found as a relatively stable system with low crystallization tendency at atmospheric pressure, crystallized quickly after compression. The observed strong pressure-dependence of the induction period suggests that during compression the first step of crystallization that is nucleation may be accelerated. To overcome the experimental challenge associated with studies at elevated temperatures and high pressures we applied broadband dielectric spectroscopy. Dielectric measurements gave us detailed insight into crystallization kinetics of ETB at varying ( T, p) conditions corresponding to the supercooled liquid state of a drug. We found that pressure-induced recrystallization of supercooled ETB, constituting a serious impediment from a technological point of view, can be efficiently inhibited when amorphous solid dispersion containing ETB and polymer polyvinylpyrrolidone PVP (10% w/w) was prepared. Besides, we performed the comprehensive analysis of molecular dynamics of both systems at elevated pressure to address some fundamental issues related to the pressure sensitivity of their supercooled dynamics.

Distinguishing different classes of secondary relaxations from vapour deposited ultrastable glasses.

Secondary relaxations persistent in the glassy state after structural arrest are especially relevant for the properties of the glass. A major thrust in research in dynamics of glass-forming liquids is to identify what secondary relaxations exhibit a connection to the structural relaxation and are hence more relevant. Via the Coupling Model, secondary relaxations having such connection have been identified by properties similar to the primitive relaxation of the Coupling Model and are called the Johari-Goldstein (JG) ß-relaxations. They involve the motion of the entire molecule and act as the precursor of the structural α-relaxation. The change in dynamics of the secondary relaxation by aging an ordinary glass is one way to understand the connection between the two relaxations, but the results are often equivocal. Ultrastable glasses, formed by physical vapour deposition, exhibit density and enthalpy levels comparable to ordinary glasses aged for thousands of years, as well as some particular molecular arrangement. Thus, ultrastable glasses enable the monitoring of the evolution of secondary processes in case aging does not provide any definitive information. Here, we study the secondary relaxation of several ultrastable glasses to identify different types of secondary relaxations from their different relationship with the structural relaxation. We show the existence of two clearly differentiated groups of relaxations: those becoming slower in the ultrastable state and those becoming faster, with respect to the ordinary unaged glass. We propose ultrastability as a way to distinguish between secondary processes arising from the particular microstructure of the system and those connected in properties to and acting as the precursor of the structural relaxation in the sense of the Coupling Model.

Co-Stabilization of Amorphous Pharmaceuticals-The Case of Nifedipine and Nimodipine.

Currently, a research hotspot in amorphous active pharmaceutical ingredients (APIs) is to understand the key factors that dominate recrystallization and to develop effective methods for stabilizing amorphous forms. Consequently, we investigated the influence of the global molecular mobility and structural properties on the crystallization tendency of three 1,4-dihydropyridine derivatives (nifedipine, nisoldipine, and nimodipine) in their supercooled states using differential scanning calorimetry (DSC) and broadband dielectric spectroscopy (BDS) techniques. The BDS is also employed to monitor the isothermal crystallization kinetics of supercooled nifedipine and nimodipine at T = 333 K under ambient pressure. As a result, we found that nimodipine exhibits much slower crystallization in comparison to nifedipine. However, nimodipine crystallizes much faster when as little as 10 MPa of pressure is exerted on sample. Such compression-induced crystallization of nimodipine as well as the inherent instability of nifedipine can be solved effectively by preparing coamorphous nifedipine/nimodipine combinations. Interestingly, the high physical stability of nifedipine/nimodipine mixtures is achieved despite the fact that the nimodipine acts as a plasticizer.

Effect of Polymer Chain Length on the Physical Stability of Amorphous Drug-Polymer Blends at Ambient Pressure.

Rational selection of polymers for amorphous drug stabilization is necessary for further successful development of solid dispersion technology. In this paper, we investigate the effect of polymer chain length on the inhibition of amorphous drug recrystallization. To consider this problem, we prepared a drug-polymer blend (in 10:1 drug to polymer ratio) containing bicalutamide (BIC) and polyvinylpyrrolidone (PVP) with different chain lengths K10, K30, and K90. We applied broadband dielectric spectroscopy to compare the molecular dynamics of investigated samples and thoroughly recognize their crystallization tendencies from supercooled liquid state. Despite the lack of differences in molecular dynamics, we noticed significant changes in their crystallization rates. To rationalize such behavior, we performed positron annihilation lifetime spectroscopy measurements. The results showed that the value of free volume was the highest for blend with PVP K90, which at the same time was characterized by the greatest tendency to crystallize. We postulate that the polymer chain, depending on its length, can have different configurations in the space, leading to better or worse sample stabilization. Our results highlight how important is detailed understanding of physical properties of polymers for judicious selection of the best stabilization approach.