MS34-04 - Computational Protocol for Simulating the Anisotropic Lattice Expansion in Organic Crystals

    

Andrea Ienco (CNR-ICCOM)

New technologies are made possible by new materials, and until recently new materials could only be discovered experimentally. However, quantum mechanical approaches are now integrated to many design initiatives in academia and industry, underpinning efforts such as the computational crystal structure prediction (CSP[1]). The latest CSP blind test revealed two major remaining challenges:[2]
(i) Dealing with a vast search space, in particular for molecules with increased flexibility.The anisotropic lattice expansion is a different variation of one crystallographic axis respect the other ones. In a temperature dependent X-Ray Powder Diffraction experiment, the anisotropic lattice expansion can be visualized as a significant shift of a set of peaks while others practically did not move. As a consequence, the anisotropic expansion could lead wrong conclusions on the purity and/or composition of a crystalline phase.

We observed anisotropic lattice expansion for metoprolol succinate salt ( metoprolol = (±)-1-isopropylamino-3-[4-(2-methoxy-ethyl)-phenoxy]-propan-2-ol) salt. For the related and structural close, metoprolol tartrate salt no such behavior was found. [1] Moreover also the metoprolol free base is subject to anisotropic expansion while the related betaxolol, with similar solid state arrangement and very small structural difference, expands isotropically. [2]

In this work, we show that semiempirical HF-3c method [3] is able to reproduce the experimental observations at a reasonable computational cost within the standard error in reproducing crystal structures. [4]  Our protocol could help to shed some light on the anisotropic lattice expansion in organic crystals and to rationalize the factor responsible for the phenomenon.

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[1] P. Paoli, P. Rossi, E. Macedi, A. Ienco, L. Chelazzi, G. L. Bartolucci, B. Bruni Cryst. Growth Des. 2016, 16, 789.
[2] P. Rossi, P. Paoli, L. Chelazzi, L. Conti, A. Bencini Acta Cryst. 2019, C75, 87.
[3] R. Sure, S. Grimme J. Comput. Chem. 2013, 34, 1672.
[4] M. Cutini, B. Civalleri, M. Corno, R. Orlando, J. G. Brandenburg, L. Maschio, P. Ugliengo J. Chem. Theory Comput. 2016, 12, 3340.