Particle Shape Calculator for CCDC/Mercury

This tutorial will introduce you to the morphology calculation features included with Mercury under the CSD-Particle toolset, namely BFDH Morphology and VisualHabit. BFDH crystal morphology is an approximation based on crystallographic geometrical considerations. For a given structure, the BFDH algorithm will predict the habit or shape of a crystal using the corresponding unit cell and symmetry operator information. The VisualHabit tool calculates a morphology for your material based on its crystal structure. Using a range of forcefields, we can calculate the intermolecular interactions, or synthons, in a crystal structure; the sum of these gives the lattice energy for that system. From these lattice energies, we can calculate slice energies and, consequently, the attachment energy for each slice. Crystal growth rates assumed to be proportional to these attachment energies and can be used to predict crystal shapes. The VisualHabit tool is used to calculate and analyze these energies and to visualize the resulting morphologies, an instrumental step in enabling solid form and particle design for small molecule crystal structures

BFDH

1. Open Mercury by double-clicking the Mercury icon on the desktop.

2. In the Structure Navigator toolbar type the refcode KAXXAI10.

3. We want to identify facets of interest in this morphology. We will first create the morphology using the BFDH morphology feature.

4. From the top-level menu select CSD-Particle > Morphology > BFDH… to generate the morphology. BFDH morphology uses the unit cell to create the morphology you see, therefore it does not account for the chemistry of the structure.

5. Rotate the structure to view the various facets that have been generated. If you wish, explore options in the Morphology window.

6. The morphology can be modified, for example, if you want to represent a crystal observed from growth experiments. In the Morphology window, click Save… and place the .cif file in a folder where you have permission.

7. Using a text editor of your choice open the morphology .cif file. You will see the data that corresponds to the HKLs and perpendicular distances. You can modify these values to change the morphology. For the sake of example, we will simply switch the values of some of the perpendicular distances. Note that these changes are not based on experimental observation

8. Back in Mercury, In the Morphology window click Open… and select your modified .cif file to visualize your new morphology

VisualHabit

The shape of a crystal results from the relative growth rates in different directions. Strong intermolecular interactions, or synthons, in one direction, can result in elongated crystal shapes like needles forming. Needle-shaped crystals are common in pharmaceuticals and are undesirable due to their poor processing characteristics. Being able to predict needle formation from a crystal structure is helpful to understand potential manufacturing challenges.

1. Launch Mercury by clicking its icon. In the Structure Navigator toolbar, type UREAXX to bring up the structure for urea.

2. Click on the CSD-Particle menu, select Morphology, then select VisualHabit… 3. In the VisualHabit dialogue box, you will see several options. On the left, you will find options to change the calculation settings, such as which forcefield is used and the limiting radius for the calculation. You can also choose whether to add an electrostatic correction or not. On the right you will see where the lattice energy results will appear once the calculation is complete. For the purposes of this tutorial, we will keep the default options. These typically work well for most situations, but if you know you are looking at specific chemistry or a charged system, you may want to change these settings. 4. Click the Calculate button to start. 5. The dialogue box will now update to show the results of the VisualHabit calculation. The lattice energy results are shown in the section on the right in kJ mol-1 . From here, you can see the total lattice energy as well as the contributions from the electrostatic, van der Waals, and hydrogen bonding energy terms. It’s clear from these results that the lattice energy for urea is dominated by the hydrogen bonding energy in the crystal structure. 6. The convergence chart shows how the lattice energy changes over the course of the calculation out to the limiting radius and gives an indication of whether the calculation has converged successfully (indicated by the green tick at the bottom of the chart). This chart tells us that the lattice energy comes close to its final value in a small distance for this structure. Urea is a small molecule, so this is what we would expect to see. 7. If we look at the Mercury visualizer, we will see that the calculated morphology for urea is now shown. VisualHabit calculates an elongated morphology for urea where the long axis is aligned to the polar axis of the urea molecule. 8. We will now explore the reasons for this elongated shape by examining the nature of the intermolecular interactions, or synthons, in more detail. Click on the Synthons tab in the VisualHabit dialogue to change the information that is shown. 9. The synthons that contribute to the lattice energy, along with the centroid-centroid distance and component energy terms, are now shown. Click on the Interaction Energy header (you may need to scroll along to see it) to sort this column from the strongest interaction to the weakest. Once again, you will see that the lattice energy for urea is dominated by a small number of strong hydrogen bonding interactions. 10. Now let’s look at the two most important interactions. Click on one of the rows in the table to highlight that interaction and show the synthon in the Mercury visualizer. You can select multiple rows by holding down Ctrl and clicking on the rows of interest. Holding down Shift and clicking will let you select multiple rows at once. Select the top two interactions for UREAXX (synthons 8 and 9). 11. You will see in the Mercury visualizer that two other urea molecules have appeared above and below the central molecule. The red dashed lines between the molecules highlight the synthon, and the value beside the line shows the interaction energy. You can clearly see that the strongest interaction in urea aligns with the fastest growth direction. 12. Click the Visualiser tab in the VisualHabit dialogue. From this tab you can change the way that the morphology is displayed in Mercury, such as changing the colour of the faces and the edges. You can also change how synthons are displayed. 13. Click the radio dial in the Synthons section to display Distance rather than Energy. 14. The Mercury visualizer will update to show the centroid-centroid distance of the synthons in Å. These short, strong types of hydrogen bonds in the crystal structure of urea are key to understanding its growth and the shape of its crystals.

Conclusion

Crystal shape is governed by the relative growth rates in different directions. Strong intermolecular interactions, or synthons, in one direction can result in elongated morphologies. The crystal structure of urea is dominated by strong hydrogen bonding interactions that occur in tapes that propagate along the crystallographic c-axis. This results in an elongated morphology for urea.

You should now know how to calculate a morphology using VisualHabit for a CSD structure in Mercury and how to visualize and explore the key interactions in that structure relative to the calculated crystal shape.