Solid-State 15N NMR Chemical Shift Anisotropy of Histidines: Experimental and Theoretical Studies of Hydrogen Bonding

The principal values of the 15 N chemical shift tensors of crystalline histidine and histidine-containing peptides have been measured to document for the first time the systematic trends in values of imidazole CSA with changes in hydrogen bonds. NMR measurement of imidazole groups, both 15 N and 1 H, is a key method for studying strong and p K a -matched hydrogen bonds and their roles in enzymes, but appropriate model compound data and calculations are largely lacking in the literature. On the basis of this database of experimental values for imidazole groups interacting with carboxylate hydrogen-bonding partners, and of ab initio calculations for similar structures, a correlation was found between the 15 N δ 22 tensor value and the hydrogen bond length for cationic species. As the hydrogen bond distance decreases, the δ 22 tensor value shifts downfield. No correlation was found between the 15 N CSA tensor elements of neutral imidazole and the corresponding hydrogen bond distance, probably because the range of hydrogen-bonding distances in our compounds is limited (∼0.05 Å) and because this functionality is not involved in nearly p K a -matched hydrogen bonds. Ab initio 15 N shielding calculations for an imidazolium acetate (cationic) model showed general agreement with the trends in the experimental results, although the breadths of the calculated CSA tensors are systematically larger than those determined experimentally, and the variation in the calculated CSA tensor values is somewhat smaller than that obtained experimentally.