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 H-1 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 H-1 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 H-1 chemical-shift tensors and relating these to the electronic structures. We then present our experimental results on U-C-13,N-15-labeled histidine and demonstrate that H-1 chemical-shift tensors can be reliably determined for the (HN)-H-1-N-15 and (HC)-H-1-C-13 spin pairs in cationic and neutral forms of histidine. Finally, we demonstrate that the experimental H-1(C) and H-1(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.