2.1.3. 1D 15N-NMR
In comparison to the previous example, 15N has a lower shift dispersion (~100ppm) than 13C, but higher than that of 1H. Here, the situation is unfortunately severely limited due to an even lower natural abundance (0.37%) and a gyromagnetic ratio ~10 times smaller than 1H. This means that 15N’s combined sensitivity is around 260,000 times lower than 1H. As a result, isotopic enrichment of 15N combined with 1H-mediated enhancement via indirect detection is often needed in order to obtain a satisfactory 1D 15N spectra. Similar to 13C, a few methods are available to overcome such low sensitivity. One of them focuses on tagging molecules with carboxyl groups using 15N-ethanolamine and later detecting the signal using a 2D heteronuclear correlation NMR experiment [113]. Currently, novel approaches such as “smart isotope labeling” have been developed [114]. Also, the SOFAST (Band-Selective Optimized Flip Angle Short Transient) technique can help but results in substantial hardware considerations/drawbacks and often increased concentrations, and/or dramatically longer experiments are still required [115,116,117].
Promising methods are on the horizon. These methods include 15N heteronuclear signal enhancement via Signal Amplification by Reversible Exchange in SHield Enables Alignment Transfer to Heteronuclei (SABRE-SHEATH); however, more work and research are required before such methods can be applied for biomedical purposes [118].