Fast Magic-Angle Spinning Three-Dimensional NMR Experiment for Simultaneously Probing H-H and N-H Proximities in...

A fast magic-angle spinning (MAS, 70 kHz) solid-state NMR experiment is presented that combines ¹H Double-Quantum (DQ) and ¹⁴N-¹H HMQC (Heteronuclear Multiple-Quantum Coherence) pulse-sequence elements, so as to simultaneously probe H-H and N-H proximities in molecular solids. The proposed experiment can be employed in both two-dimensional (2D) and three-dimensional (3D) versions: first, a 2D ¹⁴N HMQC-filtered ¹H-DQ experiment provides specific DQ-SQ correlation peaks for proton pairs that are in close proximities to the nitrogen sites, thereby achieving spectral filtration. Second, a proton-detected three-dimensional (3D) ¹H(DQ)-¹⁴N(SQ)-¹H(SQ) experiment correlates ¹H(DQ)-¹H(SQ) chemical shifts with ¹⁴N shifts such that longer range N···H-H correlations are observed between protons and nitrogen atoms with internuclear NH distances exceeding 3 Å. Both 2D and 3D versions of the proposed experiment are demonstrated for an amino acid hydrochloride salt, l-histidine·HCl·H₂O, and a DNA nucleoside, guanosine·2H₂O. In the latter case, the achieved spectral filtration ensures that DQ cross peaks are only observed for guanine NH and CH8 ¹H resonances and not ribose and water ¹H resonances, thus providing insight into the changes in the solid-state structure of this hydrate that occur over time; significant changes are observed in the NH and NH₂¹H chemical shifts as compared to the freshly recrystallized sample previously studied by Reddy et al., Cryst. Growth Des. 2015, 15, 5945.