Dataset for BEST-CSP benchmark study of polymorphs I and II of sulfamerazine and the perils of polytype polymorphs

We report the outcome of an interdisciplinary investigation by the BEST-CSP network of the kinetically favoured form I and the low temperature stable form II of the drug sulfamerazine (SMZ). A new structure determination of form II at 150 K is presented, allowing a better comparison with form I (SLFNMA04). Attempts to find the solvent-mediated transition temperature were complicated by observing that various slurrying experiments produce a new 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 distinguishable by high-quality X-ray diffraction. Form V appears to be marginally more stable than form I above 50 °C. The experimental data, including heat capacities and thermal expansion are used to test a wide range of assumptions and energy models for calculating free energy differences between these, polymorphs, in particular the composite quasi-harmonic approximation, relying on DFT and DFTB quantum-chemical theories. This work illustrates the challenges in computational the thermodynamic transition temperature between form I and II. The complications caused by the discovery of form V are discussed.