Introduction to NMR and Its Application in Metabolite Structure Determination

The broad utility of nuclear magnetic resonance (NMR) was first recognized in 1951 from a series of experiments that observed a relationship between chemical structure and corresponding shifts in the NMR resonances. Since that time, NMR has evolved from continuous wave (CW) spectroscopy to Fourier transform (FT) spectroscopy, from permanent magnets to super conducting magnets and from one dimensional to multidimensional NMR spectra. The range of NMR applications has also grown significantly and includes (i) chemical structure elucidation (Breitmaier, 2002; Martin and Zektzer, 1988) (ii) three-dimensional conformational studies of biomolecules (Betz, 2006; Pellecchia, 2005), (iii) analysis of enzyme kinetics (Schutz et al., 2005), (iv) determination of reaction mechanisms (Lycka et al., 2007; Moreno et al., 1996; Munro and Craik, 1994; Schaefer 1982), and (v) ligand binding screening for drug discovery (Hajduk, 2006; Lepre et al., 2004; Orry et al., 2006; Zartler et al. 2006). In the field of drug metabolism (Corcoran and Spraul, 2003), NMR is an extremely valuable tool in understanding biotransformation pathways and the potential involvement of metabolites in observed drug toxicities. Metabolite structure elucidation is particularly useful when the site of metabolism cannot be readily assigned by other techniques.