Mechanochemistry has shown impressive improvements in past decades for developing sophisticated materials such as pharmaceutical cocrystals, zeolite-based catalysts or metal-organic frameworks (MOFs). [1] The latter are elaborate porous materials exhibiting interesting applications in storage of fuels, capture of CO₂, catalysis... [2] Being able to control the nature of MOFs synthesized under mechanochemical conditions thus appears as an important goal. In this context, recently, in-situ methods for mechano-synthesis, such as X-Ray diffraction under synchrotron beam or Raman spectroscopy, have emerged so that information about reaction rates and presence of intermediates are now becoming accessible. [3]

In this contribution, we have studied the formation of zinc-based MOFs using terephthalic acid as organic ligand. The observation of several intermediate phases was made possible by in-situ Raman spectroscopy during ball-milling synthesis (see Fig. 1 a)). Solid-state NMR spectroscopy was then used, along with FTIR, to obtain information about unknown structures observed during the synthetic route. ¹³C chemical shifts were proven to be sensitive to the binding mode of the dicarboxylic acids on the zinc atoms, in line with previous studies. [4] Chemical shift differences up to 5 ppm (Fig. 1 b)) helped to distinguish between monodentate and bridging binding modes. Moreover, further structural information could be obtained through the use of ¹⁷O NMR studies of enriched compounds.

[1] Friščić, T., Mottillo, C. & Titi, H. M. (2020). Angew. Chem. Int. Ed. 59, 1018-1029. [2] Furukawa, H., Cordova, K. E., O’Keeffe, M. & Yaghi, O. M. (2013). Science. 341, 1230444.[3] Kulla, H., Haferkamp, S., Akhmetova, I., Röllig, M., Maierhofer, C., Rademann, K. & Emmerling, F. (2018). Angew. Chem. Int. Ed. 57, 5930-5933. [4] Habib, H. A., Hoffmann, A., Höppe, H. A. & Janiak, C. (2009). Dalton. Trans. 10, 1742-1751.

A NMR crystallography study is presented for Lorlatinib, an active pharmaceutical ingredient (API) used in the treatment of lung cancer. Various one-dimensional and two-dimensional solid-state magic-angle spinning (MAS) NMR experiments have been performed that provide the ¹H and ¹³C chemical shifts as well as the ¹⁴N shifts. A ¹H(DQ)-¹H(SQ) MAS NMR spectrum was obtained with BaBa recoupling that reveals proton-proton proximities interactions between the ¹H nuclei that are typically within 3.5 Å of each other. A ¹⁴N-¹H HMQC MAS NMR spectrum reveals that one of the NH₂¹H resonances has a significantly low ¹H chemical shift; this is interpreted in terms of differences in intermolecular hydrogen bonding. Enhanced resolution is observed in two-dimensional ¹H-¹³C heteronuclear MAS NMR experiments at 1 GHz.