Filtern
Erscheinungsjahr
Dokumenttyp
- Zeitschriftenartikel (319)
- Vortrag (50)
- Posterpräsentation (20)
- Beitrag zu einem Tagungsband (5)
- Forschungsdatensatz (3)
- Buchkapitel (1)
- Forschungsbericht (1)
Sprache
- Englisch (365)
- Deutsch (32)
- Mehrsprachig (2)
Schlagworte
- Mechanochemistry (105)
- In situ (44)
- XRD (34)
- Polymorphism (18)
- Crystallization (17)
- Crystal structure (14)
- SAXS (12)
- Cocrystal (11)
- X-ray diffraction (11)
- Raman spectroscopy (10)
Organisationseinheit der BAM
- 6 Materialchemie (181)
- 6.3 Strukturanalytik (175)
- 6.0 Abteilungsleitung und andere (73)
- 1 Analytische Chemie; Referenzmaterialien (16)
- 1.4 Prozessanalytik (9)
- 6.5 Synthese und Streuverfahren nanostrukturierter Materialien (7)
- 4 Material und Umwelt (6)
- 6.1 Oberflächen- und Dünnschichtanalyse (6)
- 4.2 Material-Mikrobiom Wechselwirkungen (4)
- 1.2 Biophotonik (3)
Paper des Monats
- ja (3)
Eingeladener Vortrag
- nein (50)
The successful mechanochemical syntheses of three cadmium phenylphosphonates indicates that mechanochemistry is ideally suited for synthesizing metal phosphonates. With this powerful synthesis tool it is possible to synthesize rapidly and efficiently both known and novel phosphonates. The Crystal structures of the two new compounds, and, were solved from PXRD data. They contain monodeprotonated phenylphosphonate and neutral phenylphosphonic acid ligands. The synthesis pathways of all three compounds were investigated in situ. A diffusion mechanism is corroborated by our findings.
Intermediates could be detected and identified. The kinetically favored product (3) could always be detected during the syntheses. The thermodynamic stability of the compounds and the stoichiometric ratio of the starting materials are the two directing factors for the synthesis of the final products.
The synthesis of the polymorphic cocrystal caffeine:anthranilic acid was investigated to obtain a better understanding of the processes leading to the formation of different polymorphic forms. In the case of these cocrystal polymorphs synthesized by liquid-assisted grinding a distinct influence of the dipole moment of the solvent was found. A pre-coordination between the solvent molecules and the caffeine:anthranilic acid cocrystal could be identified in the formation of form II. In the case of form II the solvent can be regarded as a catalyst. The formation pathway of each polymorph was evaluated using synchrotron X-ray diffraction.
Mechanochemical reactions often result in 100% yields of single products, making purifying procedures obsolete. Mechanochemistry is also a sustainable and eco-friendly method. The ever increasing interest in this method is contrasted by a lack in mechanistic understanding of the mechanochemical reactivity and selectivity. Recent in situ investigations provided direct insight into formation pathways. However, the currently available theories do not predict temperature T as an influential factor. Here, we report the first determination of an apparent activation energy for a mechanochemical reaction. In a temperaturedependent in situ study the cocrystallisation of ibuprofen and nicotinamide was investigated as a model system. These experiments provide a pivotal step towards a comprehensive understanding of milling reaction mechanisms.
The stability of different theophylline cocrystals under milling conditions was investigated by competitive cocrystal reactions. To determine the most stable cocrystal form under milling conditions, the active pharmaceutical ingredient theophylline was either ground with two similar coformers (benzoic acid, benzamide, or isonicotinamide), or the existing theophylline cocrystals were ground together with a competitive coformer. All competitive reactions were investigated by in situ powder X-ray diffraction disclosing the formation pathway of the milling processes. On the basis of these milling reactions, a stability order (least to most stable) was derived: tp/bs < tp/ba < tp/ina < bs/ina.
The driving forces triggering the formation of co-crystals under milling conditions were investigated by using a set of multicomponent competitive milling reactions. In these reactions, different active pharmaceutical ingredients were ground together with a further compound acting as coformer. The study was based on new co-crystals including the coformer anthranilic acid. The results of the competitive milling reactions indicate that the formation of co-crystals driven by intermolecular recognition are influenced and inhibited by kinetic aspects including the formation of intermediates and the stability of the reactants.
The combination of two analytical methods including time-resolved in situ X-ray diffraction (XRD) and Raman spectroscopy provides a new opportunity for a detailed analysis of the key mechanisms of milling reactions. To prove the general applicability of our setup, we investigated the mechanochemical synthesis of four archetypical model compounds, ranging from 3D frameworks through layered structures to organic molecular compounds. The reaction mechanism for each model compound could be elucidated. The results clearly show the unique advantage of the combination of XRD and Raman spectroscopy because of the different information content and dynamic range of both individual methods. The specific combination allows to study milling processes comprehensively on the level of the molecular and crystalline structures and thus obtaining reliable data for mechanistic studies.
Synthesis, structure determination, and formation of a theobromine: oxalic acid 2:1 cocrystal
(2015)
The structure and the formation pathway of a new theobromine : oxalic acid (2 : 1) cocrystal are presented. The cocrystal was synthesised mechanochemically and its structure was solved based on the powder X-ray data. The mechanochemical synthesis of this model compound was studied in situ using synchrotron XRD. Based on the XRD data details of the formation mechanism were obtained. The formation can be described as a self-accelerated ('liquid like') process from a highly activated species.
Benzamide has been known for its polymorphism for almost 200 years.Three polymorphic forms are described. To date,itwas only possible to crystallizeametastable form in amixture together with the thermodynamically most stable form I. Acomplete transformation of form Iinto the metastable form III by mechanochemical treatment has been achieved. Catalytic amounts of nicotinamide seeds were used to activate the conversion by mechanochemical seeding. NMR experiments indicated that the nicotinamide molecules were incorporated statistically in the crystal lattice of benzamide form III during the conversion. The transformation pathway was evaluated using in situ powder X-ray diffraction.
Proline has been widely used for various cocrystallization applications, including pharmaceutical cocrystals. Combining enantiopure and racemic flurbiprofen and proline, we discovered 18 new crystal structures. Liquid-assisted grinding proved highly efficient to explore all the variety of crystal forms. A unique combination of stateof-the-art characterization techniques, comprising variable temperature in situ X-ray diffraction and in situ ball-milling, along with other physicochemical methods and density functional theory calculations, was indispensable for identifying all the phases. Analyzing the results of in situ ball-milling, we established a stepwise mechanism for the formation of several 1:1 cocrystals via an intermediate 2:1 phase. The nature of the solvent in liquidassisted grinding was found to significantly affect the reaction rate and, in some cases, the reaction pathway.
The liquid-assisted grinding cocrystallisation of theophylline with benzamide leading to polymorphic compounds was investigated. A solvent screening with seventeen different solvents was performed. The dipole moment of the solvent used in the synthesis determines the structure of the polymorphic product. A detailed investigation leads to the determination of the kinetically and thermodynamically favored product. In situ observations of the formation pathway during the grinding process of both polymorphs show that the thermodynamically favored cocrystal is formed in a two-step mechanism with the kinetic cocrystal as intermediate.
Theophylline has been used as an active pharmaceutical ingredient (API) in the treatment of pulmonary diseases, but due to its low water solubility reveals very poor bioavailability. Based on its different hydrogen-bond donor and acceptor groups, theophylline is an ideal candidate for the formation of cocrystals. The crystal structure of the 1:1 benzamide cocrystal of theophylline, C7H8N4O2·-C7H7NO, was determined from synchrotron X-ray powder diffraction data. The compound crystallizes in the tetragonal space group P41 with four Independent molecules in the asymmetric unit. The molecules form a hunter’s fence packing.
The crystal structure was confirmed by dispersion-corrected DFT calculations.
The possibility of salt formation was excluded by the results of Raman and 1H solid-state NMR spectroscopic analyses.
A newly established in situ technique using Raman spectroscopy was employed for the detailed kinetic investigation of mechanochemical reaction pathways. This approach was applied for the systematic investigation of the direct influence of colliding balls on the reaction rate constants of a mechanochemical cocrystallization reaction. As a model reaction, the mechanochemical cocrystallization of felodipine and the coformer imidazole was investigated. Keeping the total ball mass constant by varying the number of milling balls, our study reveals that the impact of each single collision has a more significant influence on the reaction kinetics than expected.
We present a first direct measurement of the temperature during milling combined with in situ Raman spectroscopy monitoring. The data reveal a low temperature increase due to the mechanical impact and clear temperature increases as a consequence of the reaction heat. Based on the data, temperature rises as postulated in the magma plasma and hot spot theory can be excluded for soft matter milling syntheses.
Synthesen in der Kugelmühle
(2016)
The mechanochemical Knoevenagel condensation of malononitrile with p-nitrobenzaldehyde was studied in situ using a tandem approach. X-ray diffraction and Raman spectroscopy were combined to yield time-resolved information on the milling process. Under solvent-free conditions, the reaction leads to a quantitative conversion to p-nitrobenzylidenemalononitrile within 50 minutes. The in situ data indicate that the process is fast and proceeds under a direct conversion. After stopping the milling process, the reaction continues until complete conversion. The continuous and the stopped milling process both result in crystalline products suitable for single crystal X-ray diffraction.
We present naproxen/proline cocrystals discovered when combining enantiopure and racemic naproxen and proline. Using liquid-assisted grinding as the main method to explore the variety of crystal forms in this system, we found 17 cocrystals, of which the structures of only four of them were previously known. The naproxen/proline system exhibited multiple polymorphs of 1 : 1 stoichiometry as well as more rare cocrystals with 1 : 2 and 2 : 3 stoichiometries, two cocrystal hydrates and one cocrystal solvate. In situ ballmilling, used to monitor liquid-assisted grinding reactions, revealed that the solvent dictates the reaction intermediates even if the final reaction product stays the same. Synchrotron X-ray diffraction data collected in situ upon heating allowed us to monitor directly the phase changes upon heating and gave access to pure diffraction patterns of several cocrystals, thus enabling their structure determination from powder X-ray diffraction data; this method also confirmed the formation of a conglomerate in the RS-naproxen/DL-proline system. Proline in cocrystals kept its ability to form charge-assisted head-to-tail
N-H⋯O hydrogen bonds, typical of pure crystalline amino acids, thus increasing the percentage of strong chargeassisted interactions in the structure and consequently providing some of the cocrystals with higher melting points as compared to pure naproxen. The majority of drugs are chiral, and hence, these data are of importance to the pharmaceutical industry as they provide insight into the challenges of chiral cocrystallization.
The effect of the ball to reactant ratio on mechanochemical reaction times studied by in situ PXRD
(2017)
The effect of the reactant powder mass on reaction times for the mechanochemical formation of a soft matter model system was studied by in situ PXRD. The syntheses were performed at a constant ball mass in a shaker mill with and without glassy SiO2 as an inert additive. Reaction times decreased with the increase of the ball to reactant ratio (BRR). The kinetic influence of the SiO2 powder was excluded. The decrease in the reaction time with decreasing mass of reactants was related to the rise in the stress energy transferred to the powder by a higher ball impact. The BRR had no effect on the induction time. But the product conversion was accelerated by raising the BRR. While a certain temperature is needed for the activation of reactants in the induction phase, the conversion of soft matter reactants is rather controlled by impact than temperature.
Mechanochemistry is increasingly used as a ‘green alternative’ for synthesizing various materials including pharmaceutical cocrystals. Herein, we present the mechanochemical synthesis of three new cocrystals containing the API carbamazepine (cocrystals CBZ:Indometacin 1:1, CBZ:Benzamide 1:1, and CBZ:Nifedipine 1:1). The mechanochemical reaction was investigated in situ documenting a fast and complete reaction within one minute. Online NMR spectroscopy proved the direct influence of the dissolution behaviour of the coformers to the dissolution behaviour of the API carbamazepine. The dissolution behaviour of the organic cocrystals is compared to the behaviour of the pure drug indicating a general applicability of this approach for detailed cocrystal dissolution studies.
For the investigation of small sample volumes, the use of an acoustic levitator was tested as a `sample holder' for hovering droplets in a synchrotron beam. It might be advantageous to use levitated droplets instead of samples confined in solid holders, especially for the study of crystallization processes where the influence of containing walls has to be minimized. In a first experiment, the crystallization of sodium chloride in a small droplet of aqueous solution has been followed with a time resolution of 30 s. The collected diffraction peaks are compared with data in the ICSD database.
Crystal structures of four different di-aryl-1,3,4-oxadiazole compounds (aryl = 2-pyridyl-, 3-pyridyl-, 2-aminophenyl-, 3-aminophenyl-) are determined. Crystallization of di(2-pyridyl)-1,3,4-oxadiazole yielded monoclinic and triclinic polymorphs. The structures are characterized by the occurrence of ππ interactions. Additionally, in case of the aminophenyl compounds intra- as well as intermolecular hydrogen bonds are found that influence the packing motif as well. Since these molecules are often used as ligands in metalorganic complexes similarities and differences of the molecular conformation between the molecules in the pure crystals and that of the ligands in the complexes are discussed.
The molecular and crystal structures of the hydrochlorides of d-nebivolol, dl-nebivolol, and seven nebivolol isomers have been determined by X-ray structure analysis. The absolute configuration of all the compounds could be determined unambiguously using anomal dispersion effects. Two compounds, dl-nebivolol (NEB-1d,l) and the (S,R,S,R) nebivolol isomer (NEB-6), crystallize as racemic mixtures in the centrosymmetric space group P-1. d-Nebivolol and six nebivolol isomers crystallize in space group P212121. The d- and l-nebivolol molecules in NEB-1d and NEB-1d,l adopt a conformation which is significantly different compared with that of all nebivolol isomers. With the exception of dl-nebivolol (NEB-1d,l) numerous intermolecular hydrogen bonds connect the molecules forming molecular layers.
Bromotricarbonyl{15-[2-(methylsulfanyl)ethylsulfanyl]pentadecanoic acid-kappa2S,S'}rhenium(I)
(2006)
The title compound, [ReBr(C18H36O2S2)(CO)3], was synthesized and characterized as a non-radioactive surrogate of a novel Tc-containing fatty acid derivative prepared according to the tricarbonyl/dithioether design with the objective of developing new Tc-based radiopharmaceuticals for the non-invasive diagnosis of myocardial metabolism. The Re chelate contains the metal in the oxidation state +1 and is attached to the terminal position of a fatty acid. The complex formation was accomplished by a ligand exchange reaction using [NBu4]2[Re(CO)3Br3] as starting material.
The Keggin type polyoxotungstate [Ti2W10PO40]7- forms stable associates with the biopolymer chitosan in the nanometer size range. The cluster compound crystallizes from aqueous solution as K4H3[Ti2W10PO40] · 15H2O having a tetragonal structure. Both, the cluster compound and the chitosan/[Ti2W10PO40] associates show a high hydrolytic stability at pH 7.4. The associates formed between the cluster anion [Ti2W10PO40]7- with the polyaminosaccharide chitosan have been characterized by photon correlation spectroscopy, scanning electron microscopy, filtration, centrifugation and zeta potential measurements. The size of the associates formed is in the range of ca. 5×101 to 5×102 nm. These particles have a defined stoichiometry with 56 cluster anions bound per molecule chitosan. The isoelectric point determined by zeta potential measurements was found for a cluster anion to chitosan molar ratio of 5.5, indicating the charge neutralization between protonated chitosan and [Ti2W10PO40]7- anions. Cellular uptake studies with [Ti2W10PO40]7- using tumor cell lines FaDu (human squamous carcinoma) and HT-29 (human adenocarcinoma) showed that the tungsten amount inside the cells is remarkably enhanced in the presence of chitosan.
The CuII complex of H4TETP (H4TETP = 1,4,8,11-tetraazatetradecane-1,4,8,11-tetrapropionic acid) is five-coordinate with a distorted square-pyramidal structure (τ = 0.45; i.e. the geometry is nearly half-way between square-pyramidal and trigonal-bipyramidal) and a relatively long Cu–N and a short Cu–O bond; the comparison between powder and solution electronic spectroscopy, the frozen solution EPR spectrum and ligand-field-based calculations (angular overlap model, AOM) indicate that the solution and solid state structures are very similar, i.e. the complex has a relatively low 'in-plane' and a significant axial ligand field with a dx²-y² ground state. The ligand-enforced structure is therefore shown to lead to a partially quenched Jahn–Teller distortion and to a relatively low complex stability, lower than with the corresponding acetate-derived ligand H4TETA. This is confirmed by potentiometric titration and by the biodistribution with 64Cu-labeled ligands which show that the uptake in the liver is significantly increased with the H4TETP-based system.
Polyoxometalates (POMs) are inorganic cluster compounds that have been shown to possess a number of pharmacological properties, including antidiabetic, antibacterial, antiprotozoal, antiviral and anticancer activities. Their molecular mechanism of action is largely unknown. However, several studies indicate that many of their activities may be due to the inhibition of enzymes, in particular, of those enzymes that are accessible from the extracellular space and do not require the penetration of cell membranes. In this review, we describe the recent progress in the preparation and optimization of POMs, and an evaluation of their use as inhibitors of different families of enzymes. The next important steps in this area of research will be to gain a better understanding of the interactions of POMs with enzymes on a structural level through an X-ray crystallographic study of enzyme–POM complexes and the analysis of structure–activity relationships. Furthermore, POMs with increased stability and in vivo half-lives have to be prepared. Surface modification may allow the targeting of POM drugs at their sites of action.
The unusually fast crystallization of the organic compound nifedipine has been investigated in detail using different solutions as precursors for the formation of the initial glassy nifedipine films. Starting from these amorphous films the crystallization process was investigated by time-resolved light microscopy at different temperatures around Tg of nifedipine. In all studied cases (acetone, acetonitrile, ethyl acetate, dichloromethane, tetrahydrofuran) the measured mean crystallization rates are, on average, 10000 times higher than rates reported in previous studies. Such high rates cannot be explained by a classical diffusional crystal growth mechanism of nifedipine. Instead, nifedipine shows a strong propensity for diffusionless growth. Solvent assisted or solvent induced preordering of the glassy modification is suggested to be the most probable driving force behind these fast crystallization processes. The nifedipine crystallization rates can be controlled not only by specific solvent–molecule interactions but also by temperature. Below 40 °C, the temperature dependence of the rates is generally small. Above 40 °C, a slowing down of the crystallization rates with increasing temperatures indicates a kinetic competition between different polymorphs. The molecular dynamics of nifedipine molecules in the amorphous phase as well as the relaxation times are studied by dielectric measurements. The dielectric data corroborate the inherently strong propensity of nifedipine to crystallize diffusionlessly under all conditions.
Hydrated actinide(IV) ions undergo hydrolysis and further polymerization and precipitation with increasing pH. The resulting amorphous and partly crystalline oxydydroxides AnOn(OH)4-2n·xH2O can usually be observed as colloids above the An(IV) solubility limit. The aging process of such colloids results in crystalline AnO2. The presence of carboxylates in the solution prevents the occurrence of such colloids by formation of polynuclear complexes through a competing reaction between hydrolysis and ligation. The majority of recently described carboxylates reveals a hexanuclear core of [An6(µ3-O)4(µ3-OH)4]12+ terminated by 12 carboxylate ligands. We found that the An(IV) carboxylate solution species remain often preserved in crystalline state. The An(IV) carboxylates show An–An distances which are ~ 0.03 Å shorter than the An–An distances in AnO2 like colloids. The difference in the distances could be used to identify such species in solution.
The compound MOF-14 (Cu3(BTB)2, BTB = 4,4',4''-benzenetribenzoate) was synthesized by ball milling and characterized by powder X-ray diffraction (XRD). The raw material was activated using an efficient single washing step to ensure a free pore access. Nitrogen adsorption measurements were carried out to determine the specific areas of the samples before and after activation. To interpret the activation process in terms of blocking effects in the micropore channels, NLDFT evaluations (Nonlocal Density Functional Theory) of the MOF-14 nitrogen isotherms were carried out. In connection with the appearance of additional hysteresis loops in the nitrogen isotherms, calculations of the mesopore size distribution were performed using the method of Barret, Joyner, and Halenda (BJH). The results are compared to those of a structurally analogue MOF, namely HKUST-1 (Cu3(BTC)2, BTC = 1,3,5-benzenetricarboxylate). This comparison showed notable differences regarding the impact of the activation step on the formation of mesopores and their size distribution.
The formation and growth of hydroxylamine reduced silver nanoparticles were investigated by simultaneous Raman and UV/Vis spectroscopy coupled to an acoustic levitator as a sample holder. Based on the UV/Vis spectra, a two step particle formation mechanism with fast initial formation and adjacent coalescence can be proposed for the reduction of silver nitrate with hydroxylamine. The presence of the analyte adenine during particle formation resulted in differences in the adenine SERS signature compared to experiments, where adenine was added after particle synthesis. It was possible to monitor the adenine and sodium chloride induced aggregation of the nanoparticles and its dynamics based on both the extinction spectra and the SERS data. Correlating the information from the extinction spectra with the SERS intensity, the maximum SERS signals were observed at maximum extinction of the aggregated nanoparticle solution at the Raman excitation wavelength.
The formation of magnesium fluoride sols and xerogels according to the fluorolytic sol–gel synthesis based on the reaction of Mg(OMe)2 with non-aqueous HF has been thoroughly investigated by X-ray scattering (WAXS/XRD), TEM, SAXS, DLS and 19F MAS NMR spectroscopy. Mechanistic insights were gained by following the reaction progress and formation of intermediate phases of the fluorination of magnesium alkoxides. For F:Mg ratios of 0.3 and 0.4 the formation of two crystalline phases was observed containing the recently obtained compound [Mg6F2(OCH3)10(CH3OH)14] hexanuclear dicubane units. The stoichiometric reaction yields magnesium fluoride nanoparticles with crystallite sizes below 5 nm, which show broad reflections in the X-ray diffraction pattern. Metal fluoride sols prepared by this way undergo tremendous changes over the first several weeks after synthesis. Immediately after the fluorination, particles of about 120 nm—probably agglomerates—are formed, which break apart in the course of about one month of ageing and low-viscous, transparent sols with particles of about 12 nm are obtained. At the same time structural re-organisation processes within the magnesium fluoride particles are observed by an increase of the (110) reflection in WAXS.
Quinaldine (2-methyl quinoline) is a liquid at room temperature, which can be supercooled to reach finally the glassy state. By heating the glass above the glass transition temperature Tg = 180 K the sample performs two subsequent transitions into, likewise, dielectrically active phases. Thus, the reorientational relaxations of these phases as well as the kinetics of the phase transitions can be tracked in a highly resolved way by dielectric spectroscopy. X-ray diffraction analysis clearly shows two structurally different crystalline phases in addition to the supercooled liquid. Calorimetric measurements support the notion of first order phase transitions, occurring irreversibly in the supercooled regime, and suggest that the intermediate crystalline phase is metastable, too. Analyzing the quite distinct dielectric relaxation strengths, we discuss the possible nature of the two crystalline phases. Additionally, a very similar behavior to quinaldine is observed for 3-methyl quinoline, indicating a broad field of polymorphism among the quinoline derivatives.
Monodisperse, citrate-stabilized gold nanoparticles of sizes ranging from 15 to 40 nm were synthesized and characterized by small angle X-ray scattering and UV-vis experiments. Identical surface properties of nanoparticles of different sizes to avoid variation in the chemical surface-enhanced Raman scattering (SERS) enhancement, as well as selection of experimental conditions so that no aggregation took place, enabled the investigation of enhancement of individual nanospheres. Enhancement factors (EFs) for SERS were determined using the dye crystal violet (CV). EFs for individual gold nanospheres ranged from 102 to 103, in agreement with theoretical predictions. An increase of the EFs of individual spheres with size can be correlated to changes in the extinction spectra of nanoparticle solutions. This confirms that the increase in enhancement with increasing size results from an increase in electromagnetic enhancement. Beyond this dependence of EFs of isolated gold spheres on their size, EFs were shown to vary with analyte concentration as a result of analyte-induced aggregation. This has implications for the application of nanoparticle solutions as SERS substrates in quantitative analytical tasks.
Fractionation of a 70% ethanolic extract from twigs of Lindera obtusiloba BLUME (Japanese spicebush, Tohaku) yielded fi ve fractions of different polarity. The antifi brotic activity within the chloroform phase was best assessed by an in vitro bioassay using rat hepatic stellate cell (HSC) proliferation and their autocrine transforming growth factor beta (TGF-β) expression as sensitive fibrosis-associated read out. Chromatography of the chloroform extract on Sephadex LH-20 or liquid-liquid extractions yielded a crystalline compound as an active principle, which was identifi ed from NMR and ESI-MS analyses, its melting point, and its optical rotation as (7S,7'S,8S,8'S)-3,4:3',4'-bis(methylenedioxy) -7,9':7',9-diepoxy-lignane [(+)-episesamin]. X-Ray diffraction confirmed the structure and provided, for the fi rst time, directly its absolute confi guration. (+)-Episesamin blocked proliferation and the profi brotic autocrine TGF-β expression HSC without signifi cant cytotoxicity.
The impact of the ovo proteins ovalbumin and lysozyme—present in the first stage of egg shell formation—on the homogeneous formation of the liquid amorphous calcium carbonate (LACC) precursor, was studied by a combination of complementing methods: in situ WAXS, SANS, XANES, TEM, and immunogold labeling. Lysozyme (pI = 9.3) destabilizes the LACC emulsion whereas the glycoprotein ovalbumin (pI = 4.7) extends the lifespan of the emulsified state remarkably. In the light of the presented data: (a) Ovalbumin is shown to behave commensurable to the 'polymer-induced liquid precursor' (PILP) process proposed by Gower et al. Ovalbumin can be assumed to take a key role during eggshell formation where it serves as an effective stabilization agent for transient precursors and prevents undirected mineralization of the eggshell. (b) It is further shown that the emulsified LACC carries a negative surface charge and is electrostatically stabilized. (c) We propose that the liquid amorphous calcium carbonate is affected by polymers by depletion stabilization and de-emulsification rather than 'induced' by acidic proteins and polymers during a so-called polymer-induced liquid-precursor process. The original PILP coating effect, first reported by Gower et al., appears to be a result of a de-emulsification process of a stabilized LACC phase. The behavior of the liquid amorphous carbonate phase and the polymer-induced liquid-precursor phase itself can be well described by colloid chemical terms: electrostatic and depletion stabilization and de-emulsification by depletion destabilization.
Allergen-specific immunotherapy is an important treatment procedure in IgE-mediated allergic diseases such as allergic rhinitis or insect toxin allergies. A reduction in the clinical reaction to the allergens to which the patient is known to be sensitized is intended by means of antigen-specific influence on the immune system. The allergenspecific immunotherapy can be applied by subcutaneous injections, and for selected allergens by means of sublingual application of the appropriate allergen. Occasionally, the injection of aluminium hydroxide-adsorbed sera induces a usually transient formation of granulomas. We are reporting on a rare case of cutaneous-subcutaneous pseudolymphoma in the injection area of both upper arms, probably induced by subcutaneous allergen-specific immunotherapy.
A new proton-transfer organic salt, quinolinium hydrogensquarate (C13H9NO4), has been synthesized and fully characterized by single crystal x-ray diffraction. The salt crystallizes in the monoclinic space group P21/n with the parameters:
a = 3.8290(12) Å, b = 20.960(6) Å, c = 13.802(4) Å, β = 95.452(5)°, V = 1102.7(6) Å3, Z = 4 formula units. The structure consists of uncommon supramolecular neutral dimers which pile up parallel to [100] forming infinite sheets. These centrosymmetric dimers are held together by lateral hydrogen-bonds whereby two neighboring coplanar hydrogensquarate anions act as a bridge between two terminal quinolinium cations and C-H...O bridgings interlink next neighboring sheets. The bulk structure of this salt is consolidated by weak ππ interactions within the sheets which are neatly ordered side-by-side relative to one another.
Cementitious materials, in particular concrete, are durable materials if prepared appropriately and the Service life of concrete structures is now often required to last 120 years or more. Concrete durability depends strongly on intrinsic (e.g. composition, porosity) and exterior factors (e.g. moisture condition and composition, frost cycles, load pattem). Deleterious actions leading to concrete degradation are often created by the environment. Extemal sulfate attack is one of the more spectacular damage scenarios for concrete structures caused by the ingress of sulfate ions into the pore System of the material and successive formation of expanding phases. Though in recent years well studied there are still many questions remaining conceming the mechanisms of sulfate attack. In particular over the last ten years, with the increased utilization of blended cements, new questions arose concerning the sulfate resistance of those binder Systems. In the presented study therefore a method was developed to analyze the changes of the phase composition within the micro structure due to sulfate attack. The analytical method was based on pX-Ray diffraction (pXRD) using Synchrotron radiation in Debye-Scherrer (transmission) geometry. The spatial resolution of the method is ca. 10 pm and allows the characterization of phase transformations in the wake of damaging processes in more detail compared to other techniques. Furthermore, the experimental setup provides the possibility for analyzing the phase assemblage of a given sample without destroying the micro structure. This is possible because the specimens for phase analysis consists of thick sections, which can be used for further microscopic analysis of the micro structure and micro chemistry (e.g. by SEM-EDX). Samples containing supplementary cementitious materials were measured in comparison and to reconstruct the influence of the degradation process in detail. Additionally, reaction ffonts within the samples were localized by micro x-ray fluorescence analysis (MXRF).
The title compound, {2-[(2-carbamoylethyl)amino]-3-methylpentanoic acid}, C9H18N2O3, is of interest with respect to its biological activity. It was formed during an addition reaction between acrylamide and the amino acid isoleucine. The crystal structure is a three-dimensional network built up by intermolecular N–H···O and O–H···N hydrogen bonds.
rac-2,3-Dibromopropionamide
(2013)
The racemic title compound, C3H5Br2NO, was crystallized from methanol. In the crystal, adjacent molecules are linked through N–H···O hydrogen bonds, forming chains along the c-axis direction. These chains are linked through N–H···O hydrogen bonds, forming an undulating two-dimensional network lying parallel to the bc plane. There are also short Br···Br contacts present [3.514 (3) Å].
The title compound [systematic name: (2R,3R,4S,5R,6R) 2-(acetoxymethyl)-6-propoxytetrahydro-2H-pyran-3,4,5-triyl triacetate], C17H26O10, was formed by a Koenigs-Knorr reaction of 2,3,4,6-tetra-O-acetyl-α-D-glucopyranosyl bromide and n-propanol. The central ring adopts a chair conformation. The crystal does not contain any significant interactions such as hydrogen bonds.
In any given matrix control over the final particle size distribution requires a constitutive understanding of the mechanisms and kinetics of the particle evolution. In this contribution we report on the formation mechanism of silver nanoparticles embedded in a soda-lime silicate glass matrix. For the silver ion-exchanged glass it is shown that at temperatures below 410 °C only molecular clusters (diameter <1 nm) are forming which are most likely silver dimers. These clusters grow to nanoparticles (diameter >1 nm) by annealing above this threshold temperature of 410 °C. It is evidenced that the growth and thus the final silver nanoparticle size are determined by matrix-assisted reduction mechanisms. As a consequence, particle growth proceeds after the initial formation of stable clusters by addition of silver monomers which diffuse from the glass matrix. This is in contrast to the widely accepted concept of particle growth in metal–glass systems, in which it is assumed that the nanoparticle formation is predominantly governed by Ostwald ripening processes.
Thermal decomposition of Zr(C2O4)2·4H2O within an autoclave or in a conventional tube furnace at temperatures below 380 °C resulted in nano- and micron-sized ZrO2, respectively. Reactions under autogenic pressure yielded monodisperse monoclinic (m) and tetragonal (t) ZrO2 nanoparticles with an average diameter of ~8 nm and interconnected t-ZrO2 nanoparticles with diameters of ~4 nm, depending on the synthesis temperature. Samples were characterised by X-ray diffraction (XRD), small angle X-ray scattering (SAXS), scanning electron microscopy (SEM), transmission electron microscopy (TEM) associated with energy dispersive X-ray spectroscopy (EDS), Raman microspectroscopy and photoluminescence spectroscopy (PL). Nanostructured zirconia materials exhibited high specific areas of 276–385 m2 g-1 which make them promising candidates as catalysts and catalyst supports. Co-existence of m- and t-ZrO2 nanoparticles with diameters of 6–9 nm, i.e. above the critical particle size of 6 nm for the formation of t-ZrO2, demonstrated that the particle size is not the only factor for stabilisation of the t-ZrO2 modification at room temperature.
An unusually fast crystallization of the organic glass former nifedipine has been observed. The crystallization process, starting from an amorphous film to crystalline material, was investigated by time resolved Raman microspectroscopy. The crystallization rates of the initially crystallizing metastable β-form are four orders of magnitude higher than those of previous studies.