A Magic‐Angle‐Spinning NMR Spectroscopy Method for the Site‐Specific Measurement of Proton Chemical‐Shift Anisotropy in Biological and Organic Solids

Proton chemical shifts are a rich probe of structure and hydrogen‐bonding environments in organic and biological molecules. Until recently, measurements of 1 H chemical‐shift tensors have been restricted to either solid systems with sparse proton sites or were based on the indirect determination of anisotropic tensor components from cross‐relaxation and liquid‐crystal experiments. We have introduced a magic‐angle‐spinning approach that permits site‐resolved determination of chemical‐shift‐anisotropy tensors of protons forming chemical bonds with labeled spin 1/2 nuclei in fully protonated solids with multiple sites, including organic molecules and proteins. This approach, originally introduced for the measurements of chemical‐shift tensors of amide protons, is based on three RN ‐symmetry‐based experiments, from which the principal components of the 1 H chemical‐shift tensor can be reliably extracted by simultaneous triple fit of the data. Herein, we expand our approach to a much more challenging system involving aliphatic and aromatic protons. We start with a review of prior work on experimental NMR spectroscopy and computational quantum chemical approaches for measurements of 1 H chemical‐shift tensors and relating these to the electronic structures. We then present our experimental results on U‐ 13 C, 15 N‐labeled histidine and demonstrate that 1 H chemical‐shift tensors can be reliably determined for the 1 H 15 N and 1 H 13 C spin pairs in cationic and neutral forms of histidine. Finally, we demonstrate that the experimental 1 H(C) and 1 H(N) chemical‐shift tensors are in agreement with DFT calculations; therefore, establishing the usefulness of our method for the characterization of structures and hydrogen‐bonding environments in organic and biological solids.