MS29-03 - Structure Specific Restraints for Least-Squares Refinement from Tight Binding Quantum Chemistry

Birger Dittrich (Novartis Pharma)

Disordered crystal structures [1] can cause problems in a statistical post analysis as performed as part of solid-form selection in the pharmaceutical industry [2]. Underlying challenges posed by disorder are inaccurate atomic positions in a crystal structure. Their determination is especially difficult when atoms with disordered split sites are closer to each other than the resolution of a single-crystal diffraction experiment. While non-hydrogen atom positions can usually be resolved, the situation is even more difficult for hydrogen-atom positions due to their scattering power [3], especially when these are rotationally disordered. This asks for a “quantum-chemical aide” [4]. We have therefore extended the functionality of the program Baerlauch [5] to read/write input/output files of the dispersion-corrected tight-binding program XTB [6]. The output of Baerlauch cluster computations then (among other results) provides bond distance and bond angle restraints for use in classical independent-atom model refinements e.g. with SHELXL. Results of this generally applicable workflow to optimize crystal structures (or only their hydrogen atoms) are presented.

[1] Müller, P., et al. (2006). Crystal Structure Refinement: A Crystallographer’s Guide to SHELXL. New York, Oxford University Press.

[2] Galek, P. T. A., et al. (2009). CrystEngComm 11(12): 2634.

[3] Dittrich, B., et al. (2017). Chem. Eur. J. 23, 4605-4614.

[4] Deringer, V. L., et al. (2012). Cryst. Growth Des. 12: 1014-1021.

[5] Dittrich, B., et al. (2012). Acta Cryst. A 68: 110-116.

[6] Grimme, S., et al. (2017). J Chem Theory Comput 13(5): 1989-2009.

We acknowledge helpful discussions with A. Udvarhelyi and T. Wager