COMPUTATIONAL PROTOCOL FOR SIMULATING THE ANISOTROPIC LATTICE EXPANSION IN ORGANIC CRYSTALS

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. [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.