Computational Investigation on Metoprolol Anisotropic Lattice Expansion

Different variation of one crystallographic axis respect the other ones leds to the so called anisotropic lattice expansion. It could be visualized as a significant shift of a family of peaks during a temperature dependent X-Ray Powder Diffraction experiment. Wrong conclusions on the purity and/or composition of a crystalline phase could be drawn looking to the diffractogram without considering the effect of anisotropic expansion. We first observed anisotropic lattice expansion in metoprolol succinate salt ( metoprolol = (±)-1-isopropylamino-3-[4-(2-methoxy-ethyl)-phenoxy]-propan-2-ol) salt. It is interesting to note that in the case of the related and structural close, metoprolol tartrate salt no such behavior was found. [1] Also the metoprolol free base is subject to anisotropic expansion while the betaxolol expands isotropically beside few structural differences and close solid state arrangement. [2] At the moment we have no easy rationalization for the phenomena. [1, 2] With the aim to shed some light on this phenomenon and to rationalize the factors responsible for it, we started an investigation using semiempirical HF-3c method. [3] We were able to reproduce the experimental observations at a reasonable computational cost within the standard error in reproducing crystal structures. [4] The method was tested against the DFT B3LYP with dispersion correction. [5] The anisotropic expansion was predicted to be active for the solid structure of other molecules with the metoprolol core.