Long-Range ¹H−¹⁵N Heteronuclear Shift Correlation at Natural Abundance

Despite the inherently low sensitivity of ¹⁵N NMR because of its low gyromagnetic ratio (γ_N) and its relatively low natural abundance (0.37%), this important nuclide still has useful potential as a structural probe even at natural abundance. Inverse-detected NMR methods coupled with major advances in NMR probe designs have made it possible to acquire long-range ¹H−¹⁵N heteronuclear shift correlation data on samples as small as a micromole overnight. Chemical shift referencing schemes for ¹⁵N and the range of ¹⁵N shifts are discussed, followed by a discussion of the currently available pulse sequences, pulse calibration, parametrization and processing of long-range ¹H−¹⁵N data, and the implications of probe selection. These topics are followed by a review of the applications contained in the literature that have utilized ¹H−¹⁵N heteronuclear shift correlation experiments at natural abundance, with emphasis placed on the observed long-range coupling pathways.