The crystal structure of olanzapine form III

This paper reports the crystal structure determination of olanzapine form III by 3D electron diffraction, the last unknown anhydrous polymorph in the olanzapine complex polytypism scenario.

continuous rotation mode as reported in the paper by Gemmi & Lanza.(Gemmi & Lanza, 2019) During the data collection the crystal position was tracked in high magnification scanning transmission electron microscopy (STEM) imaging as proposed by Yang et al. (Yang et al., 2022).Diffraction patterns were collected in nanodiffraction mode with a parallel beam of 150 nm obtained using a 5 µm condenser aperture.3D ED diffraction data were recorded using an ASI Timepix detector.(Ballabriga et al., 2020) Peak indexing and intensity integration were performed using Pets2.(Palatinus et al., 2019) Space group determination and structure solution for phase III were obtained with Superflip (Palatinus & Chapuis, 2007) in Jana2020.(Petříček et al., 2023) Structure of form II was solved by directs methods in Sir2019.(Burla et al., 2015) Dynamical refinements for form III were performed against two data set of two different crystals at a resolution of 1 Å.The lattice parameters of crystal 2, therefore, were fixed to be the same as those of crystal 1.The data sets collected from crystals 1 and 2 were kept in two data blocks (Block 1 and Block 2 respectively) and a combined refinement against the two blocks was performed in Jana2020.(Petříček et al., 2023) The processed data set for continuous rotation was refined with the thick model wedge (Palatinus et al., 2015).The orientation of each pattern was optimized, and the ADPs were refined as anisotropic (ADPs of hydrogen were kept anisotropic with the riding model on).In the thick model wedge the crystal is assumed to be wedge shaped.Structure of form II was kinematically refined with SHELXL (Sheldrick, 2015) in Olex2 GUI.(Dolomanov et al., 2009) IUCrJ (2024).IUCrJ (2024).11, https://doi.org/10.1107/S2052252524007383Supporting information, sup-5 Crystallographic information of the kinematical refinements results performed on the structure of form III obtained from the data collected with 3D ED from crystal 1 (first column), crystal 2 (second column) and from the merged data of crystal 1 and crystal 2. Difference Fourier map of OLZP form III before adding hydrogen atoms calculated at a 3σ isosurface level.Just a few hydrogen atoms can be seen.Positive and negative isosurfaces are plotted in yellow and blue, respectively.

Figure S7
The two difference Fourier map of OLZP form III calculated at the same isosurface value of 0.27 eÅ -1 before (left) and after (right) adding the expected hydrogen atoms viewed along the caxis direction.Positive and negative isosurfaces are plotted in yellow and blue, respectively.

S5. Le Bail intensity extraction and Rietveld refinements results of the multiphase mixture
The unit cell parameters of forms I were not refined due to its little content.Table S4 Unit cell parameters of OLZP form III and the predicted structure UNOGIN_eq125.

Figure S5
Figure S5 Images of the reciprocal sections projections hk0, h0l and 0kl respectively of phase I (a), phase II (b) and III (c).

Figure S8
Figure S8 Le bail intensities extraction of the mixed forms I, II and III of OLZP obtained after recrystallisation.

Figure
Figure S10 (top) shows the packing of two layers (green and pink) of the structure A162 viewed along the relative b-axis direction.Hiding the pink layer and viewing the structure along [-1 2 0] direction what we see is the equivalent of the green layer encountered in forms II and III (fig.S10 bottom left).On the other hand, omitting the green layer and viewing the structure along the [1 2 0] direction (fig.S10 bottom right) the pink layer appears shifted of one half along the bc-plane, but the presence of the glide plane parallel to the (001) and normal to the (010) causes the exchange of the SC0 enantiomers every second layer.

Figure S10 (
Figure S10 (Top) Packing of two layers in structure A162 viewed along the b-axis; (bottom left) green equivalent layer viewed along the [-1 2 0] direction and (bottom right) the pink layer viewed along the [1 2 0] direction.The unit cell axis are coloured in red (a-axis), green (b-axis) and blue (caxis).

Figure S12
Figure S12 Comparison of the calculated PXRD patterns of phase III (black) with the predicted structure UNOGIN_eq125.The two graphs differ especially between the 2θ range of 15° and 25°.

Table S1
Crystallographic information and dynamical refinement results of structure form II.

Table S3
Percentage contributions to the Hirshfeld surface area of the different close intermolecular contacts of OLZP molecule in forms II and III.