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Applications to Pharamaceuticals and Supramolecular Chemistry

2D MAS NMR experiments reveal details of how organic molecules pack in the solid-state. High-resolution 1H experiments (Brown 2012) are particularly powerful given the importance of intermolecular hydrogen bonding and CH-π interactions in determining the adopted self assembly.

Fig1



In collaboration with Astra Zeneca, we have shown how 1H-1H DQ (double-quantum) CRAMPS 2D spectra represent fingerprints of the anhydrous and hydrous form of an active pharmaceutical ingredient (API), enabling the identification of the anhydrous form in a tablet formulation containing the API and excipients (Griffin 2007).



fig2


We have further shown how 1H DQ build-up curves that plot the change in intensity of specific DQ peaks as a function of the DQ recoupling time reveal subtle differences for two polymorphs of the API viozan that is related to differences in inter-planar packing arrangements. (Bradley 2012)


Fig3


In collaboration with GlaxoSmithKline, we have demonstrated the applicability of 2D 14N-1H experiments for probing intermolecular hydrogen bonding in the API cimetidine (Tatton 2012). This work has further been extended to co crystals and amorphous dispersions. (Maruyoshi 2012, Tatton 2013)

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In collaboration with Professor Kenneth Harris, Cardiff University we have shown how NMR crystallography (CCPNC) can be used in synergy with structure solution by powder X-ray diffraction diffraction for an indomethacin-nicotinamide co-crystal – note the excellent 2D agreement with calculated (GIPAW, blue crosses) 13C and 1H chemical shifts for directly bonded CHs. (Dudenko 2013).



Fig 4



We have shown how different intermolecular hydrogen-bonding arrangements associated with distinct modes of self-assembly exhibited by guanosine derivatives synthesized in the group of Prof. Spada (Bologna, Italy) can be distinguished using 15N-15N refocused INADEQUATE experiments (for 15N-labelled derivatives (Pham 2005)) or 1H-1H DQ CRAMPS experiments (for derivatives at natural isotopic abundance (Webber 2011)).