Proton-detected 3D 1 H anisotropic/ 14 N/ 1 H isotropic chemical shifts correlation NMR under fast magic angle spinning on solid samples without isotopic enrichment.

The chemical shift anisotropy (CSA) interaction of a nucleus is an important indicator of the local electronic environment particularly for the contributions arising from hydrogen (H)-bonding, electrostatic and π-π interactions. CSAs of protons bonded to nitrogen atoms are of significant interest due to their common role as H-bonding partners in many chemical, pharmaceutical and biological systems. Although very fast (∼100 kHz) magic angle sample spinning (MAS) experiments have enabled the measurement of proton CSAs directly from solids, due to a narrow chemical shift (CS) distribution, overlapping NH proton resonances are common and necessitate the introduction of an additional frequency dimension to the regular 2D 1 H CSA/1 H CS correlation method to achieve sufficient resolution. While this can be accomplished by using the isotropic shift frequency of 14 N or 15 N nuclei, the use of the naturally-abundant 14 N nucleus avoids 15 N isotopic labeling and therefore would be useful for a variety of solids. To this end, we propose a proton-detected 3D 1 H CSA/14 N/1 H CS correlation method under fast MAS (90 kHz) to determine the CSA tensors of NH protons in samples without isotopic enrichment. Our experimental results demonstrate that the proposed 3D NMR experiment is capable of resolving the overlapping 1 H resonances of amide (NH) groups through the 14 N isotropic shift frequency dimension and enables the accurate measurement of site-specific 1 H CSAs directly from powder samples under fast MAS conditions. In addition to the 3D 1 H CSA/14 N/1 H CS experiment, an approach employing 14 N-edited 2D 1 H CSA/1 H CS experiment is also demonstrated as an additional means to address spectral overlap of NH resonances with aliphatic and other proton resonances in solids.