Dokument-ID Dokumenttyp Autoren/innen Persönliche Herausgeber/innen Haupttitel Abstract Auflage Verlagsort Verlag Herausgeber (Institution) Erscheinungsjahr Titel des übergeordneten Werkes Jahrgang/Band ISBN Veranstaltung Veranstaltungsort Beginndatum der Veranstaltung Enddatum der Veranstaltung Ausgabe/Heft Erste Seite Letzte Seite URN DOI Lizenz Datum der Freischaltung OPUS4-59563 Zeitschriftenartikel Thiele, Isabel; Santolin, Lara; Meyer, Klas; Machatschek, Rainhard; Bölz, Uwe; Tarazona, Natalia A.; Riedel, Sebastian L. Microbially synthesized poly(hydroxybutyrate-co-hydroxyhexanoate) with low to moderate hydroxyhexanoate content: Properties and applications Plastic pollution is the biggest environmental concern of our time. Breakdown products like micro- and nanoplastics inevitably enter the food chain and pose unprecedented health risks. In this scenario, bio-based and biodegradable plastic alternatives have been given a momentum aiming to bridge a transition towards a more sustainable future. Polyhydroxyalkanoates (PHAs) are one of the few thermoplastic polymers synthesized 100 % via biotechnological routes which fully biodegrade in common natural environments. Poly(hydroxybutyrate-cohydroxyhexanoate) [P(HB-co-HHx)] is a PHA copolymer with great potential for the commodity polymers industry, as its mechanical properties can be tailored through fine-tuning of its molar HHx content. We have recently developed a strategy that enables for reliable tailoring of the monomer content of P(HB-co-HHx). Nevertheless, there is often a lack of comprehensive investigation of the material properties of PHAs to evaluate whether they actually mimic the functionalities of conventional plastics. We present a detailed study of P(HB-co-HHx) copolymers with low to moderate hydroxyhexanoate content to understand how the HHx monomer content influences the thermal and mechanical properties and to link those to their abiotic degradation. By increasing the HHx fractions in the range of 2 - 14 mol%, we impart an extension of the processing window and application range as the melting temperature (Tm) and glass temperature (Tg) of the copolymers decrease from Tm 165 ◦C to 126 ◦C, Tg 4 ◦C to − 5.9 ◦C, accompanied by reduced crystallinity from 54 % to 20 %. Elongation at break was increased from 5.7 % up to 703 % at 14 mol% HHx content, confirming that the range examined was sufficiently large to obtain ductile and brittle copolymers, while tensile strength was maintained throughout the studied range. Finally, accelerated abiotic degradation was shown to be slowed down with an increasing HHx fraction decreasing from 70 % to 55 % in 12 h. Elsevier B.V. 2024 International Journal of Biological Macromolecules 263 1 9 urn:nbn:de:kobv:b43-595636 10.1016/j.ijbiomac.2024.130188 https://creativecommons.org/licenses/by-nc-nd/4.0/deed.de 2024-02-26 OPUS4-57094 Zeitschriftenartikel Tchipilov, Teodor; Meyer, Klas; Weller, Michael G. Quantitative 1H Nuclear Magnetic Resonance (qNMR) of Aromatic Amino Acids for Protein Quantification Hydrolysis of protein samples into amino acids facilitates the use of NMR spectroscopy for protein and peptide quantification. Different conditions have been tested for quantifying aromatic amino acids and proteins. The pH-dependent signal shifts in the aromatic region of amino acid samples were examined. A pH of 12 was found to minimize signal overlap of the four aromatic amino acids. Several aromatic compounds, such as terephthalic acid, sulfoisophthalic acid, and benzene tricarboxylic acid, were applied as internal standards. The quantification of amino acids from an amino acid standard was performed. Using the first two suggested internal standards, recovery was ~97% for histidine, phenylalanine, and tyrosine at a concentration of approximately 1 mM in solution. Acidic hydrolysis of a certified reference material (CRM) of bovine serum albumin (BSA) and subsequent quantification of Phe and Tyr yielded recoveries of 98% ± 2% and 88% ± 4%, respectively, at a protein concentration of 16 g/L or 250 µM. Basel, Schweiz MDPI 2023 Methods and Protocols 6 1 1 13 urn:nbn:de:kobv:b43-570943 10.3390/mps6010011 https://creativecommons.org/licenses/by/4.0/deed.de 2023-03-09 OPUS4-56919 Zeitschriftenartikel Srivastava, Priyanka; Tavernaro, Isabella; Scholtz, Lena; Genger, C.; Welker, P.; Schreiber, Frank; Meyer, Klas; Resch-Genger, Ute Dual color pH probes made from silica and polystyrene nanoparticles and their performance in cell studies Ratiometric green-red fluorescent nanosensors for fluorometrically monitoring pH in the acidic range were designed from 80 nm-sized polystyrene (PS) and silica (SiO2) nanoparticles (NPs), red emissive reference dyes, and a green emissive naphthalimide pH probe, analytically and spectroscopically characterized, and compared regarding their sensing performance in aqueous dispersion and in cellular uptake studies. Preparation of these optical probes, which are excitable by 405 nm laser or LED light sources, involved the encapsulation of the pH-inert red-fuorescent dye Nile Red (NR) in the core of self-made carboxylated PSNPs by a simple swelling procedure and the fabrication of rhodamine B (RhB)-stained SiO2-NPs from a silane derivative of pH-insensitive RhB. Subsequently, the custom-made naphthalimide pH probe, that utilizes a protonation-controlled photoinduced electron transfer process, was covalently attached to the carboxylic acid groups at the surface of both types of NPs. Fluorescence microscopy studies with the molecular and nanoscale optical probes and A549 lung cancer cells confirmed the cellular uptake of all probes and their penetration into acidic cell compartments, i.e., the lysosomes, indicated by the switching ON of the green naphthalimide fluorescence. This underlines their suitability for intracellular pH sensing, with the SiO2-based nanosensor revealing the best performance regarding uptake speed and stability. London Nature 2023 Scientific Reports 13 1 1321 1336 urn:nbn:de:kobv:b43-569198 10.1038/s41598-023-28203-0 https://creativecommons.org/licenses/by/4.0/deed.de 2023-01-30 OPUS4-57921 Zeitschriftenartikel Bornemann-Pfeiffer, Martin; Meyer, Klas; Lademann, J.; Kraume, M.; Maiwald, Michael Contributions towards variable temperature shielding for compact NMR instruments The application of compact NMR instruments to hot flowing samples or exothermically reacting mixtures is limited by the temperature sensitivity of permanent magnets. Typically, such temperature effects directly influence the achievable magnetic field homogeneity and hence measurement quality. The internal-temperature control loop of the magnet and instruments is not designed for such temperature compensation. Passive insulation is restricted by the small dimensions within the magnet borehole. Here, we present a design approach for active heat shielding with the aim of variable temperature control of NMR samples for benchtop NMR instruments using a compressed airstream which is variable in flow and temperature. Based on the system identification and surface temperature measurements through thermography, a model predictive control was set up to minimise any disturbance effect on the permanent magnet from the probe or sample temperature. This methodology will facilitate the application of variable-temperature shielding and, therefore, extend the application of compact NMR instruments to flowing sample temperatures that differ from the magnet temperature. John Wiley & Sons Ltd. 2023 Magnetic Resonance in Chemistry 1 10 urn:nbn:de:kobv:b43-579219 10.1002/mrc.5379 https://creativecommons.org/licenses/by-nc-nd/4.0/deed.de 2023-07-17 OPUS4-54640 Zeitschriftenartikel Wander, Lukas; Lommel, Lukas; Meyer, Klas; Braun, Ulrike; Paul, Andrea Development of a low-cost method for quantifying microplastics in soils and compost using near-infrared spectroscopy Near-infrared (NIR) spectroscopy is a promising candidate for low-cost, nondestructive, and high-throughput mass quantification of micro¬plastics in environmental samples. Widespread application of the technique is currently hampered mainly by the low sensitivity of NIR spectroscopy compared to thermo-analytical approaches commonly used for this type of analysis. This study shows how the application of NIR spectroscopy for mass quantification of microplastics can be extended to smaller analyte levels by combining it with a simple and rapid microplastic enrichment protocol. For this purpose, the widely used flotation of microplastics in a NaCl solution, accelerated by centrifugation, was chosen which allowed to remove up to 99 % of the matrix at recovery rates of 83-104 %. The spectroscopic measurements took place directly on the stainless-steel filters used to collect the extracted particles to reduce sample handling to a minimum. Partial least squares regression (PLSR) models were used to identify and quantify the extracted microplastics in the mass range of 1-10 mg. The simple and fast extraction procedure was systematically optimized to meet the requirements for the quantification of microplastics from common PE-, PP-, and PS-based packaging materials with a particle size < 1 mm found in compost or soils with high natural organic matter content (> 10 % determined by loss on ignition). Microplastics could be detected in model samples at a mass fraction of 1 mg g-1. The detectable microplastic mass fraction is about an order of magnitude lower compared to previous studies using NIR spectroscopy without additional enrichment. To emphasize the cost-effectiveness of the method, it was implemented using some of the cheapest and most compact NIR spectrometers available. UK IOP Publishing Ltd. 2022 Measurement Science and Technology 33 7 075801 075814 urn:nbn:de:kobv:b43-546405 10.1088/1361-6501/ac5e5f https://creativecommons.org/licenses/by/4.0/deed.de 2022-04-13 OPUS4-55934 Zeitschriftenartikel Völzke, Jule L.; Hodjat Shamami, Parya; Gawlitza, Kornelia; Feldmann, Ines; Zimathies, Annett; Meyer, Klas; Weller, Michael G. High-Purity Corundum as Support for Affinity Extractions from Complex Samples Nonporous corundum powder, known as an abrasive material in the industry, was functionalized covalently with protein binders to isolate and enrich specific proteins from complex matrices. The materials based on corundum were characterized by TEM, ESEM, BET, DLS, EDS, and zeta potential measurements. The strong Al-O-P bonds between the corundum surface and amino phosphonic acids were used to introduce functional groups for further conjugations. The common crosslinker glutaraldehyde was compared with a hyperbranched polyglycerol (PG) of around 10 kDa. The latter was oxidized with periodate to generate aldehyde groups that can covalently react with the amines of the surface and the amino groups from the protein via a reductive amination process. The amount of bound protein was quantified via aromatic amino acid analysis (AAAA). This work shows that oxidized polyglycerol can be used as an alternative to glutaraldehyde. With polyglycerol, more of the model protein bovine serum albumin (BSA) could be attached to the surface under the same conditions, and lower non-specific binding (NSB) was observed. As a proof of concept, IgG was extracted with protein A from crude human plasma. The purity of the product was examined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). A binding capacity of 1.8 mg IgG per gram of corundum powder was achieved. The advantages of corundum include the very low price, extremely high physical and chemical stability, pressure resistance, favorable binding kinetics, convenient handling, and flexible application. Basel MDPI 2022 Separations 9 9 1 13 urn:nbn:de:kobv:b43-559342 10.3390/separations9090252 https://creativecommons.org/licenses/by/4.0/deed.de 2022-10-10 OPUS4-54188 Zeitschriftenartikel Westwood, S.; Martos, G.; Josephs, R.; Choteau, T.; Wielgosz, R.; Davies, S.; Moawad, M.; Tarrant, G.; Chan, B.; Alamgir, M.; de Rego, E.; Wollinger, W.; Garrido, B.; Fernandes, J.; de Sena, R.; Oliveira, R.; Melanson, J.; Bates, J.; Mai Le, P.; Meija, J.; Quan, C.; Huang, T.; Zhang, W.; Ma, R.; Zhang, S.; Hao, Y.; He, Y.; Song, S.; Wang, H.; Su, F.; Zhang, T.; Li, H.; Lam, W.; Wong, W.; Fung, W.; Philipp, Rosemarie; Dorgerloh, Ute; Meyer, Klas; Piechotta, Christian; Riedel, Juliane; Westphalen, Tanja; Giannikopoulou, P.; Alexopoulos, Ch.; Kakoulides, E.; Kitamaki, Y.; Yamazaki, T.; Shimizu, Y.; Kuroe, M.; Numata, M.; Pérez-Castorena, A.; Balderas-Escamilla, M.; Garcia-Escalante, J.; Krylov, A.; Mikheeva, A.; Beliakov, M.; Palagina, M.; Tkachenko, I.; Spirin, S.; Smirnov, V.; Tang Lin, T.; Pui Sze, C.; Juan, W.; Lingkai, W.; Ting, L.; Quinde, L.; Yizhao, C.; Lay Peng, S.; Fernandes-Whaley, M.; Prevoo-Franzsen, D.; Quinn, L.; Nhlapo, N.; Mkhize, D.; Marajh, D.; Chamane, S.; Ahn, S.; Choi, K.; Lee, S.; Han, J.; Baek, S.; Kim, B.; Marbumrung, S.; Jongmesuk, P.; Shearman, K.; Boonyakong, C.; Bilsel, M.; Gündüz, S.; Ün, I.; Yilmaz, H.; Bilsel, G.; Gökçen, T.; Clarkson, C.; Warren, J.; Achtar, E. Mass fraction assignment of Bisphenol-A high purity material The CCQM-K148.a comparison was coordinated by the BIPM on behalf of the CCQM Organic Analysis Working Group for NMIs and DIs which provide measurement services in organic analysis under the CIPM MRA. It was undertaken as a "Track A" comparison within the OAWG strategic plan. CCQM-K148.a demonstrates capabilities for assigning the mass fraction content of a solid organic compound having moderate molecular complexity, where the compound has a molar mass in the range (75 - 500) g/mol and is non-polar (pKow < −2), when present as the primary organic component in a neat organic solid and where the mass fraction content of the primary component in the material is in excess of 950 mg/g. Participants were required to report the mass fraction of Bisphenol A present in one supplied unit of the comparison material. Participants using a mass balance method for the assignment were also required to report their assignments of the impurity components present in the material. Methods used by the seventeen participating NMIs or DIs were predominantly based on either stand-alone mass balance (summation of impurities) or qNMR approaches, or the combination of data obtained using both methods. The results obtained using thermal methods based on freezing-point depression methods were also reported by a limited number of participants. There was excellent agreement between assignments obtained using all three approaches to assign the BPA content. The assignment of the values for the mass fraction content of BPA consistent with the KCRV was achieved by most of the comparison participants with an associated relative standard uncertainty in the assigned value in the range (0.1 - 0.5)%. IOP Publishing Bureau International des Poids et Mesures (BIPM) 2021 Metrologia 58 1A 08015 10.1088/0026-1394/58/1A/08015 2022-01-05 OPUS4-53941 Zeitschriftenartikel Fricke, F.; Brandalero, M.; Liehr, Sascha; Kern, Simon; Meyer, Klas; Kowarik, Stefan; Hierzegger, R.; Westerdick, S.; Maiwald, Michael; Hübner, M. Artificial Intelligence for Mass Spectrometry and Nuclear Magnetic Resonance Spectroscopy Using a Novel Data Augmentation Method Mass Spectrometry (MS) and Nuclear Magnetic Resonance Spectroscopy (NMR) are valuable analytical and quality control methods for most industrial chemical processes as they provide information on the concentrations of individual compounds and by-products. These processes are traditionally carried out manually and by a specialist, which takes a substantial amount of time and prevents their utilization for real-time closed-loop process control. This paper presents recent advances from two projects that use Artificial Neural Networks (ANNs) to address the challenges of automation and performance-efficient realizations of MS and NMR. In the first part, a complete toolchain has been realized to develop simulated spectra and train ANNs to identify compounds in MS. In the second part, a limited number of experimental NMR spectra have been augmented by simulated spectra, to train an ANN with better prediction performance and speed than state-of-the-art analysis. These results suggest that, in the context of the digital transformation of the process industry, we are now on the threshold of a strongly simplified use of MS and MRS and the accompanying data evaluation by machine-supported procedures, and can utilize both methods much wider for reaction and process monitoring or quality control. IEEE 2021 Transactions on Emerging Topics in Computing 10 1 87 98 urn:nbn:de:kobv:b43-539412 10.1109/TETC.2021.3131371 https://creativecommons.org/licenses/by/4.0/deed.de 2021-12-08 OPUS4-53126 Zeitschriftenartikel Bornemann-Pfeiffer, Martin; Wolf, Jakob; Meyer, Klas; Kern, S.; Angelone, D.; Leonov, A.; Cronin, L.; Emmerling, Franziska Standardization and control of Grignard reactions in a universal chemical synthesis machine using online NMR A big problem with the chemistry literature is that it is not standardized with respect to precise operational parameters, and real time corrections are hard to make without expert knowledge. This lack of context means difficult reproducibility because many steps are ambiguous, and hence depend on tacit knowledge. Here we present the integration of online NMR into an automated chemical synthesis machine (CSM aka. "Chemputer" which is capable of small-molecule synthesis using a universal programming language) to allow automated analysis and adjustment of reactions on the fly. The system was validated and benchmarked by using Grignard reactions which were chosen due to their importance in synthesis. The system was monitored in real time using online-NMR, and spectra were measured continuously during the reactions. This shows that the synthesis being done in the Chemputer can be dynamically controlled in response to feedback optimizing the reaction conditions according to the user requirements. Weinheim Wiley-VCH 2021 Angewandte Chemie - International Edition 60 43 1 6 urn:nbn:de:kobv:b43-531260 10.1002/anie.202106323 https://creativecommons.org/licenses/by/4.0/deed.de 2021-08-23 OPUS4-52750 Zeitschriftenartikel Kuner, Maximilian; Kühn, S.; Haase, H.; Meyer, Klas; Koch, Matthias Cleaving Ergot Alkaloids by Hydrazinolysis - A Promising Approach for a Sum Parameter Screening Method Ergot alkaloids are mycotoxins formed by fungi of the Claviceps genus, which are some of the most common contaminants of food and feed worldwide. These toxins are a structurally heterogeneous group of compounds, sharing an ergoline backbone. Six structures and their corresponding stereoisomers are typically quantified by either HPLC-FLD or HPLC-MS/MS and the values subsequently summed up to determine the total ergot alkaloid content. For the development of a screening method targeting all ergot alkaloids simultaneously, the alkaloids need to be transferred to one homogeneous structure: a lysergic acid derivative. In this study, two promising cleaving methods—acidic esterification and hydrazinolysis—are compared, using dihydroergocristine as a model compound. While the acidic esterification proved to be unsuitable, due to long reaction times and oxidation sensitivity, hydrazinolysis reached a quantitative yield in 40-60 min. Parallel workup of several samples is possible. An increasing effect on the reaction rate by the addition of ammonium iodide was demonstrated. Application of hydrazinolysis to a major ergot alkaloid mix solution showed that all ergopeptines were cleaved, but ergometrine/-inine was barely affected. Still, hydrazinolysis is a suitable tool for the development of a sum parameter screening method for ergot alkaloids in food and feed. Basel, Switzerland MDPI 2021 Toxins 13 5 342 urn:nbn:de:kobv:b43-527508 10.3390/toxins13050342 https://creativecommons.org/licenses/by/4.0/deed.de 2021-06-03 OPUS4-55360 Zeitschriftenartikel Fricke, F.; Mahmood, S.; Hoffmann, J.; Brandalero, M.; Liehr, Sascha; Kern, Simon; Meyer, Klas; Kowarik, S.; Westerdick, S.; Maiwald, Michael; Hübner, M. Artificial Intelligence for Mass Spectrometry and Nuclear Magnetic Resonance Spectroscopy Mass Spectrometry (MS) and Nuclear Magnetic Resonance Spectroscopy (NMR) are critical components of every industrial chemical process as they provide information on the concentrations of individual compounds and by-products. These processes are carried out manually and by a specialist, which takes a substantial amount of time and prevents their utilization for real-time closed-loop process control. This paper presents recent advances from two projects that use Artificial Neural Networks (ANNs) to address the challenges of automation and performance-efficient realizations of MS and NMR. In the first part, a complete toolchain has been developed to develop simulated spectra and train ANNs to identify compounds in MS. In the second part, a limited number of experimental NMR spectra have been augmented by simulated spectra to train an ANN with better prediction performance and speed than state-of-theart analysis. These results suggest that, in the context of the digital transformation of the process industry, we are now on the threshold of a possible strongly simplified use of MS and MRS and the accompanying data evaluation by machine-supported procedures, and can utilize both methods much wider for reaction and process monitoring or quality control. IEEE 2021 2021 Design, Automation & Test in Europe Conference & Exhibition (DATE) 2021 Design, Automation & Test in Europe Conference & Exhibition (DATE) Grenoble, France 01.02.2021 05.02.2021 615 620 10.23919/DATE51398.2021.9473958 2022-07-25 OPUS4-51726 Zeitschriftenartikel Bornemann-Pfeiffer, Martin; Kern, Simon; Maiwald, Michael; Meyer, Klas Calibration-Free Chemical Process and Quality Control Units as Enablers for Modular Production Modular chemical production is a tangible translation of the digital transformation of the process industry for specialty chemicals. In particular, it enables the speeding-up of process development and thus a quicker time to market by flexibly connecting and orchestrating standardised physical modules and bringing them to life (i.e., parameterising them) with digitally accumulated process knowledge. We focus on the specific challenges of chemical process and quality control, which in its current form is not well suited for modular production and provide possible approaches and examples of the change towards direct analytical methods, analytical model transfer or machine-supported processes. Weinheim Wiley-VCH 2021 Chemie Ingenieur Technik 93 1-2 62 70 urn:nbn:de:kobv:b43-517264 10.1002/cite.202000150 https://creativecommons.org/licenses/by/4.0/deed.de 2020-12-03 OPUS4-52453 Zeitschriftenartikel Gottu Mukkula, A. R.; Kern, Simon; Salge, M.; Holtkamp, M.; Guhl, Svetlana; Fleischer, C.; Meyer, Klas; Remelhe, M.; Maiwald, Michael; Engell, S. An Application of Modifier Adaptation with Quadratic Approximation on a Pilot Scale Plant in Industrial Environment The goal of this work is to identify the optimal operating input for a lithiation reaction that is performed in a highly innovative pilot scale continuous flow chemical plant in an industrial environment, taking into account the process and safety constraints. The main challenge is to identify the optimum operation in the absence of information about the reaction mechanism and the reaction kinetics. We employ an iterative real-time optimization scheme called modifier adaptation with quadratic approximation (MAWQA) to identify the plant optimum in the presence of plant-model mismatch and measurement noise. A novel NMR PAT-sensor is used to measure the concentration of the reactants and of the product at the reactor outlet. The experiment results demonstrate the capabilities of the iterative optimization using the MAWQA algorithm in driving a complex real plant to an economically optimal operating point in the presence of plant-model mismatch and of process and measurement uncertainties. Amsterdam Elsevier 2020 IFAC-PapersOnLine 53 2 11773 11779 urn:nbn:de:kobv:b43-524531 10.1016/j.ifacol.2020.12.685 https://creativecommons.org/licenses/by-nc-nd/4.0/deed.de 2021-04-19 OPUS4-48062 Zeitschriftenartikel Kern, Simon; Wander, Lukas; Meyer, Klas; Guhl, Svetlana; Gottu Mukkula, A. R.; Holtkamp, M.; Salge, M.; Fleischer, C.; Weber, N.; Engell, S.; Paul, Andrea; Pereira Remelhe, M.; Maiwald, Michael Flexible automation with compact NMR spectroscopy for continuous production of pharmaceuticals Modular plants using intensified continuous processes represent an appealing concept for the production of pharmaceuticals. It can improve quality, safety, sustainability, and profitability compared to batch processes; besides, it enables plug-and-produce reconfiguration for fast product changes. To facilitate this flexibility by real-time quality control, we developed a solution that can be adapted quickly to new processes and is based on a compact nuclear magnetic resonance (NMR) spectrometer. The NMR sensor is a benchtop device enhanced to the requirements of automated chemical production including robust evaluation of sensor data. Beyond monitoring the product quality, online NMR data was used in a new iterative optimization approach to maximize the plant profit and served as a reliable reference for the calibration of a near-infrared (NIR) spectrometer. The overall approach was demonstrated on a commercial-scale pilot plant using a metal-organic reaction with pharmaceutical relevance. Heidelberg Springer Nature 2019 Analytical and Bioanalytical Chemistry 411 14 3037 3046 urn:nbn:de:kobv:b43-480623 10.1007/s00216-019-01752-y https://creativecommons.org/licenses/by/4.0/deed.de 2019-05-27 OPUS4-50282 Zeitschriftenartikel Martins, Inês C.B.; Al-Sabbagh, Dominik; Meyer, Klas; Maiwald, Michael; Scholz, G.; Emmerling, Franziska Insight into the Structure and Properties of Novel Imidazole-Based Salts of Salicylic Acid The preparation of new active pharmaceutical ingredient (API) multicomponent Crystal forms, especially co-crystals and salts, is being considered as a reliable strategy to improve API solubility and bioavailability. In this study, three novel imidazole-based salts of the poorly water-soluble salicylic acid (SA) are reported exhibiting a remarkable improvement in solubility and dissolution rate properties. All structures were solved by powder X-ray diffraction. Multiple complementary techniques were used to solve co-crystal/salt ambiguities: density functional Theory calculations, Raman and 1H/13C solid-state NMR spectroscopies. In all molecular salts, the Crystal packing interactions are based on a common charged assisted +N-H SA)...O-(co-former) hydrogen bond interaction. The presence of an extra methyl group in different positions of the co-former, induced different supramolecular arrangements, yielding salts with different physicochemical properties. All salts present much higher solubility and dissolution rate than pure SA. The most promising results were obtained for the salts with imidazole and 1-methylimidazole co-formers. MDPI 2019 Molecules 24 22 4144 urn:nbn:de:kobv:b43-502825 10.3390/molecules24224144 https://creativecommons.org/licenses/by/4.0/deed.de 2020-01-27 OPUS4-44847 Zeitschriftenartikel Kern, Simon; Meyer, Klas; Guhl, Svetlana; Gräßer, Patrick; Paul, Andrea; King, R.; Maiwald, Michael Online low-field NMR spectroscopy for process control of an industrial lithiation reaction—automated data analysis Monitoring specific chemical properties is the key to chemical process control. Today, mainly optical online methods are applied, which require time- and cost-intensive calibration effort. NMR spectroscopy, with its advantage being a direct comparison method without need for calibration, has a high potential for closed-loop process control while exhibiting short set-up times. Compact NMR instruments make NMR spectroscopy accessible in industrial and rough environments for process monitoring and advanced process control strategies. We present a fully automated data analysis approach which is completely based on physically motivated spectral models as first principles information (Indirect Hard Modelling - IHM) and applied it to a given pharmaceutical lithiation reaction in the framework of the European Union's Horizon 2020 project CONSENS. Online low-field NMR (LF NMR) data was analysed by IHM with low calibration effort, compared to a multivariate PLS-R (Partial Least Squares Regression) approach, and both validated using online high-field NMR (HF NMR) spectroscopy. Berlin, Heidelberg Springer 2018 Analytical and Bioanalytical Chemistry 410 14 3349 3360 10.1007/s00216-018-1020-z 2018-05-07 OPUS4-51391 Beitrag zu einem Tagungsband Kern, Simon; Guhl, Svetlana; Meyer, Klas; Wander, Lukas; Paul, Andrea; Bremser, Wolfram; Maiwald, Michael Mathematical and statistical tools for online NMR spectroscopy in chemical processes Monitoring chemical reactions is the key to chemical process control. Today, mainly optical online methods are applied, which require excessive calibration effort. NMR spectroscopy has a high potential for direct loop process control while exhibiting short set-up times. Compact NMR instruments make NMR spectroscopy accessible in industrial and harsh environ¬ments for advanced process monitoring and control, as demonstrated within the European Union's Horizon 2020 project CONSENS. We present a range of approaches for the automated spectra analysis moving from conventional multivariate statistical approach, (i.e., Partial Least Squares Regression) to physically motivated spectral models (i.e., Indirect Hard Modelling and Quantum Mechanical calculations). By using the benefits of traditional qNMR experiments data analysis models can meet the demands of the PAT community (Process Analytical Technology) regarding low calibration effort/calibration free methods, fast adaptions for new reactants or derivatives and robust automation schemes. New Jersey World Scientific 2018 Advanced Mathematical and Computational Tools in Metrology and Testing XI 89 978-9-813-27429-7 Advanced Mathematical and Computational Tools in Metrology and Testing conference Glasgow, United Kingdom 29.08.2017 31.08.2017 229 234 2020-10-06 OPUS4-38803 Zeitschriftenartikel Meyer, Klas; Rademann, K.; Panne, Ulrich; Maiwald, Michael Quantitative NMR spectroscopy for gas analysis for production of primary reference gas mixtures Due to its direct correlation to the number of spins within a sample quantitative NMR spectroscopy (qNMR) is a promising method with absolute comparison abilities in complex systems in technical, as well as metrological applications. Most of the samples studied with qNMR are in liquid state in diluted solutions, while gas-phase applications represent a rarely applied case. Commercially available NMR equipment was used for purity assessment of liquid and liquefied hydrocarbons serving as raw materials for production of primary reference gas standards. Additionally, gas-phase studies were performed within an online NMR flow probe, as well as in a high-pressure NMR setup to check feasibility as verification method for the composition of gas mixtures. 2017 Journal of Magnetic Resonance 275 1 10 10.1016/j.jmr.2016.11.016 2016-12-22 OPUS4-39032 Zeitschriftenartikel Paul, Andrea; Meyer, Klas; Ruiken, Jan-Paul; Illner, M.; Müller, D.-N.; Esche, E.; Wozny, G.; Westad, Frank; Maiwald, Michael Process spectroscopy in microemulsions — Raman spectroscopy for online monitoring of a homogeneous hydroformylation process A major industrial reaction based on homogeneous catalysis is hydroformylation for the production of aldehydes from alkenes and syngas. Hydroformylation in microemulsions, which is currently under investigation at Technische Universität Berlin on a mini-plant scale, was identified as a cost efficient approach which also enhances product selectivity. Herein, we present the application of online Raman spectroscopy on the reaction of 1-dodecene to 1-tridecanal within a microemulsion. To achieve a good representation of the operation range in the mini-plant with regard to concentrations of the reactants a design of experiments was used. Based on initial Raman spectra partial least squares regression (PLSR) models were calibrated for the prediction of 1-dodecene and 1-tridecanal. Limits of predictions arise from nonlinear correlations between Raman intensity and mass fractions of compounds in the microemulsion system. Furthermore, the prediction power of PLSR models becomes limited due to unexpected by-product formation. Application of the lab-scale derived calibration spectra and PLSR models on online spectra from a mini-plant operation yielded promising estimations of 1-tridecanal and acceptable predictions of 1-dodecene mass fractions suggesting Raman spectroscopy as a suitable technique for process analytics in microemulsions. UK IOP Publishing Ltd 2017 Measurement Science and Technology 28 3 035502-1 035502-11 10.1088/1361-6501/aa54f0 2017-01-26 OPUS4-39091 Zeitschriftenartikel Meyer, Klas; Ruiken, J.-P.; Illner, M.; Paul, Andrea; Müller, D.; Esche, E.; Wozny, G.; Maiwald, Michael Process spectroscopy in microemulsions - setup and multi-spectral approach for reaction monitoring of a homogeneous hydroformylation process Reaction monitoring in disperse systems, such as emulsions, is of significant technical importance in various disciplines like biotechnological engineering, chemical industry, food science, and a growing number other technical fields. These systems pose several challenges when it comes to process analytics, such as heterogeneity of mixtures, changes in optical behavior, and low optical activity. Concerning this, online nuclear magnetic resonance (NMR) spectroscopy is a powerful technique for process monitoring in complex reaction mixtures due to its unique direct comparison abilities, while at the same time being non-invasive and independent of optical properties of the sample. In this study the applicability of online-spectroscopic methods on the homogeneously catalyzed hydroformylation system of 1-dodecene to tridecanal is investigated, which is operated in a mini-plant scale at Technische Universität Berlin. The design of a laboratory setup for process-like calibration experiments is presented, including a 500 MHz online NMR spectrometer, a benchtop NMR device with 43 MHz proton frequency as well as two Raman probes and a flow cell assembly for an ultraviolet and visible light (UV/VIS) spectrometer. Results of high-resolution online NMR spectroscopy are shown and technical as well as process-specific problems observed during the measurements are discussed. IOP Publishing Ltd. 2017 Measurement Science and Technology 28 3 035501-1 035501-11 10.1088/1361-6501/aa54f3 2017-02-07