BEST-CSP Benchmark Study of Polymorphs I and II of Sulfamerazine and the Perils of Polytype Polymorphs
Year: 2025
Type: article
Abstract: High Resolution Image Download MS PowerPoint Slide We report the outcome of an interdisciplinary investigation, by the BEST-CSP network, of the kinetically favored form I and the low-temperature stable form II polymorphs of the drug sulfamerazine (SMZ). Form II can be reproducibly obtained by slurrying in acetonitrile(MeCN)/water at room temperature, though seeding with form II significantly speeds up the conversion. New structure determinations have been obtained for both forms over a wide temperature range, with both single crystal and powder X-ray diffraction methods. Room temperature FT-IR and solid-state 13 C NMR spectra are provided. The enantiotropic but practically irreversible crystal-to-crystal transition from form II to form I is observed at temperatures ranging from 150 to 170 °C in various differential scanning calorimetry (DSC) experiments, depending on sample and heating rate. The enthalpy of transition at 150 °C is measured as Δ trs H m (II → I) = 3.15 ± 0.12 kJ mol –1 . The differences in the heat capacities mean that the DSC measured enthalpies vary with the onset temperature by about 0.55 kJ mol –1 over the range of heating rates commonly used in DSC experiments. Attempts to find the solvent-mediated transition temperature were complicated by observing that slurrying experiments in both methanol and MeCN/H 2 O above 50 °C produce a new, late-identified polymorph, sulfamerazine form V, which is closely related to form I but with an alternative packing of the double layers, i.e., is a polytype polymorph. Forms I and V are only easily distinguishable by high-quality powder X-ray diffraction. Form V appears to be marginally more stable than form I across the temperature range studied. The experimental data, including heat capacities and thermal expansion rates, are used to test a wide range of assumptions and energy models for calculating free energy differences between these polymorphs, illustrating the challenges in computationally modeling the thermodynamic transition temperature between form I and II. The implications of the discovery of form V on establishing the phase diagram of sulfamerazine are discussed.
Source: Crystal Growth & Design
Authors: William P. Wood, Mihails Arhangelskis, Erika Bartůňková, Carlos E. S. Bernardes, A. Daniel Boese, Doris E. Braun, Dejan-Krešimir Bučar, Helena Butkiewicz, Ctirad Červinka, Bartolomeo Civalleri, Nicolas Couvrat, Erik de Ronde, Lorenzo Donà, Martin Dračínský, Dzmitry Firaha, Michal Fulem, Reynaldo Geronia II, Natalia Goncharova, Marlena Gryl, Johannes Hoja, Anna Hoser, Joanna Krzeszczakowska, Alexander List, Ivor Lončarić, Bruno Mladineo, Jonas Nyman, Edgar Olehovics, Mattia Raimondo, Ivo B. Rietveld, Rute I. S. Rodrigues, Luca Russo, Matteo Salvalaglio, Mafalda Sarraguça, Jiří Šnajdr, Vojtěch Štejfa, Guangxu Sun, Paul Tinnemans, Pamela S. Whitfield, Zhuocen Yang, Yizu Zhang, Sarah L. Price
Institutions: University College London, University of Warsaw, Czech Academy of Sciences, Czech Academy of Sciences, Institute of Organic Chemistry and Biochemistry, University of Lisbon, Institut des Sciences Moléculaires, Centro de Química Estrutural, University of Graz, Universität Innsbruck, University of Chemistry and Technology, Prague, University of Turin, Laboratoire Sciences et Méthodes Séparatives, Université de Rouen Normandie, Radboud University Nijmegen, Jagiellonian University, Ruđer Bošković Institute, Cambridge Crystallographic Data Centre, Universidade do Porto, Rede de Química e Tecnologia, XtalPi (China)
Language: English
Subfield: Materials Chemistry
Field: Materials Science
Domain: Physical Sciences
Open Access status: hybrid
Estimated APC paid: $4,500
Funders: Dipartimenti di Eccellenza, European Cooperation in Science and Technology, Ministerstvo Školství, Mládeže a Tělovýchovy, Narodowe Centrum Nauki, Hrvatska Zaklada za Znanost, Christian Doppler Forschungsgesellschaft, Gauss Centre for Supercomputing, Engineering and Physical Sciences Research Council, Fundação para a Ciência e a Tecnologia, Academic Computer Centre Cyfronet, AGH University of Science and Technology
Awards: G1761812275, High Throughput Modelling of Molecular Crystals Out of Equilibrium (ht-MATTER), Centro de Química Estrutural, Instituto de Ciências Moleculares, G3388085869, INSTITUTO DE CIÊNCIAS DA TERRA, Desenvolvimento de Campos de Força Baseados em Algoritmos de Inteligência Artificial Evolucionários para Simulações de Dinâmica Molecular, Extending length and time scales of first principles material modelling via machine learning, G5386476940, G6622348432, G8228288059, G98318328
OpenAlex ID: W4417287035