BEST-CSP Benchmark Study of Polymorphs I and II of Sulfamerazine and the Perils of Polytype Polymorphs

Wood, William P.; Arhangelskis, Mihails; Bartůňková, Erika; Bernardes, Carlos E. S.; Boese, A. Daniel; Braun, Doris E.; Bučar, Dejan-Krešimir; Butkiewicz, Helena; Červinka, Ctirad; Civalleri, Bartolomeo; Couvrat, Nicolas; de Ronde, Erik; Donà, Lorenzo; Dračínský, Martin; Firaha, Dzmitry; Fulem, Michal; Geronia II, Reynaldo; Goncharova, Natalia; Gryl, Marlena; Hoja, Johannes; Hoser, Anna; Krzeszczakowska, Joanna; List, Alexander; Lončarić, Ivor; Mladineo, Bruno; Nyman, Jonas; Olehovics, Edgar; Raimondo, Mattia; Rietveld, Ivo B. (2026) BEST-CSP Benchmark Study of Polymorphs I and II of Sulfamerazine and the Perils of Polytype Polymorphs. Crystal Growth & Design, 26 (1). pp. 476-493. ISSN 1528-7483

PDF - Published Version - article Available under License Creative Commons Attribution. Download (12MB)

Abstract

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 13C 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 degrees C in various differential scanning calorimetry (DSC) experiments, depending on sample and heating rate. The enthalpy of transition at 150 degrees C is measured as Delta 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/H2O above 50 degrees 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.

Item Type:	Article
Uncontrolled Keywords:	Crystal structure; Lattices; Phase transitions; Thermodynamic properties
Subjects:	NATURAL SCIENCES > Chemistry
Divisions:	Theoretical Physics Division
Projects:	Project title Project leader Project code Project type Povećanje prostorne i vremenske skale modeliranja materijala iz prvih principa pomoću strojnog učenja-ExtMatModelML Ivor Lončarić UIP-2020-02-5675 HRZZ
Depositing User:	Ema Buhin Šaler
Date Deposited:	04 Mar 2026 08:27
URI:	http://fulir.irb.hr/id/eprint/11306
DOI:	10.1021/acs.cgd.5c01406

Actions (login required)

View Item