Non-Uniform Sampling for All: More NMR Spectral Quality, Less Measurement Time

摘要

Introduction: Nuclear Magnetic Resonance (NMR) spectroscopy is an indispensable tool in the pharmaceutical industry, with uses in drug discovery, development, and manufacturing. The majority of NMR performed in drug discovery is one-dimensional (1D) ~1H, ~13С, and ~19F NMR, used by synthetic chemists to quickly confirm a structural modification to a familiar molecule, and an NMR instrument configured for "walk-up" service can measure hundreds of such spectra daily. In more challenging cases, for example when the structure of a molecule is unfamiliar or the structure of a familiar molecule must be elucidated more completely, two-dimensional (2D) NMR is used. There are a great variety of 2D experiments, which can correlate atoms in a molecule according to chemical bonds or according to the distance between them in space. One practical consequence is that the structure of most small molecules can be determined completely from a few 2D measurements. Another consequence is that from the variety of experiments available, there is generally some combination of 2D measurements that will allow elucidation of even the most complex molecules.