Application of Fast 2D NMR Methods in the Pharmaceutical Industry

Abstract

NMR spectroscopy is considered a benchmark analytical technique in the pharmaceutical industry for the structural characterization of organic molecules and identification of target–ligand interactions. Two- and higher-dimensional NMR experiments provide especially rich data sets that demonstrate connectivity between a variety of atoms within a diversity of molecular chemotypes. However, multidimensional NMR experiments are often limited by long acquisition times and insufficient sensitivity and/or resolution. One strategy that can mitigate these limitations is non-uniform sampling (NUS). NUS acquisition achieves faster recording times through the reduction of the number of data points in the indirectly detected dimensions. The spectrum can then be mathematically reconstructed using a variety of different algorithms. This approach can reduce the acquisition time or increase the resolution to resolve overlapping resonances. A second developing approach for the reduction of acquisition times is that of supersequences or nested experiments, such as NMR by ordered acquisition using 1H-detection (NOAH) in which multiple experiments are performed either in sequence or concomitantly in a manner to maximize data acquisition per unit time. Using these pulse sequences, the saved acquisition time can be used to increase throughput, improve sensitivity, or enhance resolution. Application of NUS and NOAH in the pharmaceutical industry will be described.