Acid-Base and Tautomeric Equilibria in the Solid State: 15N NMR Spectroscopy of Histidine and Imidazole

Abstract

Lyophilized powders of 15N-enriched histidine and imidazole, prepared from aqueous solutions with pH values ranging between 2 and 12.5, were examined using solid-state NMR techniques. Isotropic and anisotropic chemical shifts for the histidine ring nitrogens were determined for the various ionic forms. The 15N shift anisotropy is strongly influenced by the protonation state of the nitrogen and is found to double upon the deprotonation of the π nitrogen at neutral pH. The “pH” dependence of the isotropic shifts closely parallels that seen in solution except that only one tautomer, the Nτ-H, is observed for the neutral and anionic species; this form is the predominant one in solution. Although the isotropic shift values for the various species in the solid do not differ appreciably from those measured in solution, both acid-base and tautomeric exchange processes are slow and each form is separately identified. These solid-state results therefore permit a more precise description of tautomeric structure (and possibly of hydrogen-bond interactions) than can be obtained from solution 15N chemical shift data alone. © 1982, American Chemical Society. All rights reserved.