Distinguishing Hydrogen Bonding in Structurally Similar Pharmaceutical Compounds With ¹H-¹⁴N HMQC MAS NMR at 100 kHz

Solid-state NMR experiments provide valuable insights into the structure of pharmaceutical compounds, many of which contain nitrogen. Recent literature indicates that the indirect detection of ¹⁴N offers significant advantages for structural analysis, particularly when using two-dimensional ¹H-¹⁴N HMQC experiments. The advantage of these experiments is that they allow us to rapidly collect information about the hydrogen bonding interaction with a minimal amount of the compound. In our study, we have carried out ¹H-¹⁴N HMQC experiments on structurally similar pharmaceutical compounds sorafenib and regorafenib monohydrate to explore the hydrogen bonding interactions and differentiate different nitrogen signals which are difficult to obtain using ¹⁵N solid-state NMR experiments on unlabeled compounds. Our findings enable us to distinguish between intramolecular and intermolecular hydrogen bonding interactions and identify different nitrogen atoms in their structures. Thus, our results show that the ¹H-¹⁴N HQMC experiments provide a rapid and effective method for distinguishing different hydrogen bonding interactions.