TY - JOUR A1 - Zuffa, Caterina A1 - Cappuccino, Chiara A1 - Casali, Lucia A1 - Emmerling, Franziska A1 - Maini, Lucia T1 - Liquid reagents are not enough for liquid assisted grinding in the synthesis of [(AgBr)(n-pica)]n N2 - This study investigates the mechanochemical reactions between AgBr 3-picolylamine and 4-picolylamine. The use of different stoichiometry ratios of the reagents allows [(AgBr)(n-pica)]n and [(AgBr)2(n-pica)]n to be obtained, and we report the new structures of [(AgBr)2(3-pica)]n and [(AgBr)2(4-pica)]n which are characterized by the presence of the following: (a) infinite inorganic chains, (b) silver atom coordinated only by bromide atoms and (c) argentophilic interactions. Furthermore, we studied the interconversion of [(AgBr)(n-pica)]n/[(AgBr)2(n-pica)]n by mechanochemical and thermal properties. The in situ experiments suggest that [(AgBr)(3-pica)]n is kinetically favoured while [(AgBr)2(3-pica)]n is converted into [(AgBr)(3-pica)]n only with a high excess of the ligand. Finally, the liquid nature of the ligands is not sufficient to assist the grinding process, and the complete reaction is observed with the addition of a small quantity of acetonitrile. KW - Mechanochemistry KW - Complex PY - 2024 UR - https://nbn-resolving.org/urn:nbn:de:kobv:b43-594755 DO - https://doi.org/10.1039/d3cp04791a SN - 1463-9076 SP - 1 EP - 10 PB - Royal Society of Chemistry (RSC) AN - OPUS4-59475 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Stolar, Tomislav A1 - Alić, Jasna A1 - Casali, Lucia A1 - Gugin, Nikita A1 - Baláž, Matej A1 - Michalchuk, Adam A1 - Emmerling, Franziska ED - Stolar, Tomislav T1 - Mechanochemistry: Looking back and ahead N2 - Starting with the discovery of fire and the preparation of food in prehistoric times, mechanochemistry is the oldest form of chemistry that humans have controlled. Mechanochemical practices, such as grinding with a mortar and pestle, continued into the Middle Ages until dedicated scientific studies began in the 19th century. Since then,research in mechanochemistry has shown that many chemicalreactions can be performed via mechanical force without or with small amounts of solvent. Besides being time, material, and energy efficient, mechanochemical reactions often yield products that differ from those obtained in solution. Therefore, not only is mechanochemistry greener and more sustainable than conventional solution chemistry, but it also has the added value of providing new reactivity and selectivity. This is especially important today, when chemists need to invent high-performance materials, intermediates, and products with the use of sustainable feedstocks and develop environmental remediation pathways. At the same time, time-resolved in situ monitoring and computational modeling are necessary for addressing fundamental questions about the atomistic, molecular, and electronic nature of mechanochemical reactivity. Integrating digitalization, robotics, and artificial intelligence tools promises to increase the reproducibility and scalability of mechanochemical processes. Further evolution of mechanochemistry is expected to have a transformative effect on the chemical industry. KW - Mechanochemistry PY - 2026 UR - https://nbn-resolving.org/urn:nbn:de:kobv:b43-653962 DO - https://doi.org/10.1016/j.chempr.2025.102880 SN - 2451-9294 VL - 12 IS - 2 SP - 1 EP - 27 PB - Elsevier BV AN - OPUS4-65396 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Casali, Lucia A1 - Carta, Maria A1 - Michalchuk, Adam A1 - Delogu, Francesco A1 - Emmerling, Franziska T1 - Kinetics of the mechanically induced ibuprofen–nicotinamide co-crystal formation by in situ X-ray diffraction N2 - Mechanochemistry is drawing attention from the pharmaceutical industry given its potential for sustainable material synthesis and manufacture. Scaling mechanochemical processes to industrial level remains a challenge due to an incomplete understanding of their underlying mechanisms. We here show how time-resolved in situ powder X-ray diffraction data, coupled with analytical kinetic modelling, provides a powerful approach to gain mechanistic insight into mechanochemical reactions. By using the ibuprofen–nicotinamide co-crystal mechanosynthesis as a benchmark system, we investigate the behaviour of the solids involved and identify the factors that promote the reaction. As mechanochemical mechanisms become increasingly clear, it promises to become a breakthrough in the industrial preparation of advanced pharmaceuticals. KW - Mechanochemistry KW - Kinetics PY - 2024 UR - https://nbn-resolving.org/urn:nbn:de:kobv:b43-608820 DO - https://doi.org/10.1039/D4CP01457J SN - 1463-9084 VL - 26 SP - 22041 EP - 22048 PB - Royal Society of Chemistry (RSC) CY - Cambridge AN - OPUS4-60882 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Emmerling, Franziska A1 - Michalchuk, Adam A1 - Casali, Lucia A1 - May, Anastasia T1 - Real-Time Monitoring and Temperature Control for Optimized Polymorph Engineering N2 - Integrating real-time monitoring with precise temperature control and mechanochemical processing represents a transformative approach to the controlled engineering of polymorphic forms in molecu-lar solids. Combining these methodologies overcomes the limitations of traditional solution-based or purely thermal approaches, enabling access to metastable or otherwise elusive polymorphs under milder and more sustainable conditions. Recent studies have shown that mechanochemical trans-formations proceed through distinct kinetic stages, including prolonged induction periods that can be tuned by adjusting the mechanical energy input[1]. These induction periods are associated with pro-cesses of mechanical activation, such as the accumulation of defects and increased surface energy, which lower the effective energy barriers for polymorphic transitions. Crucially, it is the total accumu-lated mechanical energy, rather than the duration or intensity of milling alone, that dictates the onset of polymorphic conversion, offering a new dimension of kinetic control[2-5]. Variable temperature ball milling reveals that the temperature required to induce polymorphic trans-formations can be significantly lower than under conventional thermal methods. For instance, tran-sitions that typically require high temperatures under equilibrium conditions can be achieved at sub-stantially lower temperatures in the presence of mechanical activation. This has been demonstrated in cocrystal systems such as nicotinamide-pimelic acid and isonicotinamide-glutaric acid, where the transition temperature was lowered by up to 25°C[2,3]. Real-time, in situ powder X-ray diffraction and temperature monitoring are essential for capturing transient phases and elucidating the interplay between thermal and mechanical effects. This confirms that combining mechanical energy with con-trolled temperature not only accelerates transformation kinetics, but also expands the accessible polymorphic landscape [2,3]. Collectively, these advances underscore the potential of real-time monitored, temperature-controlled mechanochemistry as a robust platform for the selective design and manufacturing of polymorphs. This approach provides unprecedented control over solid-state reactivity and opens new avenues for the sustainable and targeted engineering of functional materials and pharmaceuticals. T2 - 13th Bologna´s convention on Crystal Forms - CF@Bo n.13 University of Bologna CY - Bologna, Italy DA - 07.09.2025 KW - Plymorhism KW - Pre-activation PY - 2025 AN - OPUS4-64839 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Lopes, Chrystal A1 - Casali, Lucia A1 - Emmerling, Franziska A1 - Leyssens, Tom A1 - Dupray, Valérie A1 - Brandel, Clement A1 - Cartigny, Yohann T1 - Efficient racemization of the pharmaceutical compound Levetiracetam using solvent-free mechanochemistry N2 - We present the racemization of an active pharmaceutical ingredient Levetiracetam using a novel approach. We demonstrate the design of a 100% solvent-free process that proceeds by high energy milling inside a regular mixer mill. The kinetics of the racemization process is drastically improved compared to the solution-based approach and illustrates the tremendous potential of mechanochemistry. In this study, we highlight the importance of mixing efficiency regarding data reproducibility, and we show, in particular, that water contamination has a negative impact on the reaction rate. Moreover, in situ X-ray diffraction gives us first insights into the mechanisms involved in the solid state during the mechanochemical racemization process. KW - Mechanochemistry PY - 2025 UR - https://nbn-resolving.org/urn:nbn:de:kobv:b43-646108 DO - https://doi.org/10.1039/d4mr00103f SN - 2976-8683 VL - 2 IS - 1 SP - 83 EP - 90 PB - Royal Society of Chemistry (RSC) AN - OPUS4-64610 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Macchietti, Laura A1 - Casali, Lucia A1 - Emmerling, Franziska A1 - Braga, Dario A1 - Grepioni, Fabrizia T1 - Deriving kinetic insights from mechanochemically synthesized compounds using multivariate analysis (MCR-ALS) of powder X-ray diffraction data N2 - Kinetics information on the progress of the mechanochemical reactions is key to their understanding and subsequent scale-up. For crystalline materials, the most robust and tested method for obtaining kinetic data is the Quantitative Phase Analysis (QPA) via Rietveld refinement. In this work, we tested the feasibility of the Multivariate Curve Resolution-Alternating Least Squares (MCR-ALS) method on powder X-ray diffraction (PXRD) data of mechanochemical processes by studying the system theophylline (TP) and malonic acid (MA) in a 1 : 1 stoichiometric ratio at different milling conditions. We have highlighted the strengths and weaknesses of the MCR-ALS method, and we demonstrated why it may be an alternative route to obtain quantitative information on mechanochemical kinetics. KW - Mechanochemistry PY - 2024 UR - https://nbn-resolving.org/urn:nbn:de:kobv:b43-646115 DO - https://doi.org/10.1039/d3mr00013c SN - 2976-8683 VL - 1 IS - 1 SP - 106 EP - 115 PB - Royal Society of Chemistry (RSC) AN - OPUS4-64611 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Kadri, Lena A1 - Casali, Lucia A1 - Emmerling, Franziska A1 - Tajber, Lidia T1 - Mechanochemical comparison of ball milling processes for levofloxacin amorphous polymeric systems N2 - This study aimed to investigate the amorphization capabilities of levofloxacin hemihydrate (LVXh), a fluoroquinolone drug, using a polymer excipient, Eudragit® L100 (EL100). Ball milling (BMing) was chosen as the manufacturing process and multiple mill types were utilized for comparison purposes. The product outcomes of each mill were analyzed in detail. The solid-state of the samples produced was comprehensively characterized by Powder X-ray Diffraction (PXRD), In-situ PXRD, Differential Scanning Calorimetry (DSC), Solid-State Fourier Transform Infrared Spectroscopy (FT-IR), and Dynamic Vapor Sorption (DVS). The crystallographic planes of LVXh were investigated by in-situ PXRD to disclose the presence or absence of weak crystallographic plane(s). The mechanism of LVXh:EL100 system formation was discovered as a two-step process, first involving amorphization of LVXh followed by an interaction with EL100, rather than as an instantaneous process. DVS studies of LVXh:EL100 samples showed different stability properties depending on the mill used and % LVXh present. Overall, a more sustainable approach for achieving full amorphization of the fluoroquinolone drug, LVXh, was accomplished, and advancements to the fast-growing world of pharmaceutical mechano- and tribo-chemistry were made. KW - Levofloxacin KW - Eudragit® L100 KW - Mechanochemistry KW - Phase transformation KW - In situ monitoring PY - 2024 UR - https://nbn-resolving.org/urn:nbn:de:kobv:b43-611129 DO - https://doi.org/10.1016/j.ijpharm.2024.124652 SN - 0378-5173 VL - 665 SP - 1 EP - 16 PB - Elsevier B.V. AN - OPUS4-61112 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Casali, Lucia T1 - Use of the solvent-free mechanochemical method for a sustainable preparation of pharmaceuticals N2 - With the growing interest in environmental issues on the part of governments and institutions, pharmaceutical industries are asked to reduce their environmental footprint. Given the major impact related to the use of solvents, the development of methodologies less solvent demanding is nowadays even more urgent. In light of that, mechanochemistry would be a suitable solvent-free technology since it promotes the activation of the chemical reactions between (generally) solid materials via inputs of mechanical energy. Since such reactions may occur outside the kinetic and thermodynamic rules of conventional solution chemistry, the main limit of mechanochemistry is the poor mechanistic understanding of the solid-state transformations involved, which is still hindering a widespread use of the method, as well a scale-up to the industrial level. However, the development of methods for real-time monitoring of the mechanochemical reactions enables obtaining (in)accessible information on reaction intermediates, new products, or reaction time, thus getting closer to a better understanding of the mechanistic behaviour. With the rules of this chemistry becoming increasingly clear, the new reaction pathways of mechanochemistry wouldn’t represent a limit anymore, but an asset, that may lead to lot of opportunities for the pharmaceutical industry. T2 - Post Doc Day Berlin CY - Berlin, Germany DA - 02.11.2023 KW - Mechanochemistry KW - Sustainability KW - Pharmaceuticals PY - 2023 AN - OPUS4-59010 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Casali, Lucia T1 - Kinetics of the mechanically induced ibuprofen-nicotinamide co-crystal formation by in-situ X-ray diffraction N2 - Mechanochemistry offers sustainable synthesis for pharmaceuticals, though scaling remains challenging. By combining time-resolved in situ X-ray diffraction with kinetic modeling on the mechanosynthesis of the co-crystal ibuprofen-nicotinamide, we identified the reaction-driving factors. This deeper insight opens the way for a scale-up of mechanochemistry in the pharmaceutical industry. T2 - CGOM15 (15th International Workshop on Crystal Growth of Organic Materials) CY - Phuket, Thailand DA - 23.07.2024 KW - Mechanochemistry KW - Kinetics KW - In-situ monitoring PY - 2024 AN - OPUS4-61756 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Casali, Lucia T1 - Kinetics of the mechanically induced ibuprofen-nicotinamide co-crystal formation by in-situ X-ray diffraction N2 - Mechanochemistry offers sustainable synthesis for pharmaceuticals, though scaling remains challenging. By combining time-resolved in situ X-ray diffraction with kinetic modeling on the mechanosynthesis of the co-crystal ibuprofen-nicotinamide, we identified the reaction-driving factors. This deeper insight opens the way for a scale-up of mechanochemistry in the pharmaceutical industry. T2 - BESSY User meeting CY - Berlin, Germany DA - 11.12.2024 KW - Mechanochemistry KW - Kinetics KW - In-situ monitoring PY - 2024 AN - OPUS4-62193 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - GEN A1 - Casali, Lucia A1 - Carta, Maria A1 - Michalchuk, Adam A1 - Delogu, Francesco A1 - Emmerling, Franziska T1 - Correction: Kinetics of the mechanically induced ibuprofen–nicotinamide co-crystal formation by in situ X-ray diffraction N2 - Correction for ‘Kinetics of the mechanically induced ibuprofen–nicotinamide co-crystal formation by in situ X-ray diffraction’ by Lucia Casali et al., Phys. Chem. Chem. Phys., 2024, 26, 22041–22048, https://doi.org/10.1039/D4CP01457J. PY - 2026 UR - https://nbn-resolving.org/urn:nbn:de:kobv:b43-656362 DO - https://doi.org/10.1039/d6cp90028c SN - 1463-9076 VL - 28 IS - 8 SP - 5587 PB - Royal Society of Chemistry (RSC) CY - Cambridge AN - OPUS4-65636 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER -