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- Mechanochemistry (10)
- In situ (4)
- XRD (4)
- Metal phosphonate (3)
- Single-shot XAFS (3)
- Time resolution (3)
- cocrystal (3)
- Cocrystal (2)
- ELISA (2)
- LC-MS/MS (2)
Eingeladener Vortrag
- nein (1)
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.
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.
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.
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.
Synthesen in der Kugelmühle
(2016)
A new cocrystal of pyrazinamide with oxalic acid was prepared mechanochemically and characterized by PXRD, Raman spectroscopy, solid-state NMR spectroscopy, DTA-TG, and SEM. Based on powder X-ray diffraction data the structure was solved. The formation pathway of the reaction was studied in situ using combined synchrotron PXRD and Raman spectroscopy. Using oxalic acid dihydrate the initially neat grinding turned into a rapid self-accelerated liquid-assisted grinding process by the release of crystallization water. Under these conditions, the cocrystal was formed directly within two minutes.
A new concept that comprises both time- and lateral-resolved X-ray absorption fine-structure information simultaneously in a single shot is presented. This uncomplicated set-up was tested at the BAMline at BESSY-II (Berlin, Germany). The primary broadband beam was generated by a double multilayer monochromator. The transmitted beam through the sample is diffracted by a convexly bent Si (111) crystal, producing a divergent beam. This, in turn, is collected by either an energy-sensitive area detector, the so-called color X-ray camera, or by an area-sensitive detector based on a CCD camera, in θ-2θ geometry. The first tests were performed with thin metal foils and some iron oxide mixtures. A time resolution of lower than 1 s together with a spatial resolution in one dimension of at least 50 µm is achieved.
Sulfamethoxazol (SMX),a sulfonamide, is a widely used bacteriostatic antibiotic and therefore a promising marker for the entry of anthropogenic Pollution in the environment. SMX is frequently found in wastewater and surface water. This study presents the production of high affinity and selective polyclonal antibodies for SMX and the development and Evaluation of a direct competitive enzyme-linked immunosorbent assay(ELISA)for the quantification of SMX in environmental watersamples. The crystal structures of the cross-reacting compounds sulfamethizole, N4-acetyl-SMX andsuccinimidyl-SMX were determined by x-ray diffraction aiming to explain their high cross-reactivity. These crystal structures are described for the first time. The quantification range of the ELISA is 0.82–63 µg/L. To verify our results, the SMX concentration in 20 environmental samples,including wastewater and surfacewater,was determined by ELISA and tandem mass spectrometry(MS/MS).A good Agreement of the measured SMX concentrations was found with average recoveries of 97–113%for the results of ELISA compared to LC-MS/MS.