A Solid-State ¹⁷O NMR Study of l-Tyrosine in Different Ionization States: Implications for Probing Tyrosine Side Chains in Proteins

We report experimental characterization of ¹⁷O quadrupole coupling (QC) and chemical shift (CS) tensors for the phenolic oxygen in three l-tyrosine (l-Tyr) compounds: l-Tyr, l-Tyr·HCl, and Na₂(l-Tyr). This is the first time that these fundamental ¹⁷O NMR tensors are completely determined for phenolic oxygens in different ionization states. We find that, while the ¹⁷O QC tensor changes very little upon phenol ionization, the ¹⁷O CS tensor displays a remarkable sensitivity. In particular, the isotropic ¹⁷O chemical shift increases by approximately 60 ppm upon phenol ionization, which is 6 times larger than the corresponding change in the isotropic ¹³C chemical shift for the C^ζ nucleus of the same phenol group. By examining the CS tensor orientation in the molecular frame of reference, we discover a “cross-over” effect between δ₁₁ and δ₂₂ components for both ¹⁷O and ¹³C CS tensors. We demonstrate that the knowledge of such “cross-over” effects is crucial for understanding the relationship between the observed CS tensor components and chemical bonding. Our results suggest that solid-state ¹⁷O NMR can potentially be used to probe the ionization state of tyrosine side chains in proteins.