Resolution enhancement and proton proximity probed by 3D TQ/DQ/SQ proton NMR spectroscopy under ultrafast magic-angle-spinning beyond 70 kHz.

Proton nuclear magnetic resonance (NMR) in solid state has gained significant attention in recent years due to the remarkable resolution and sensitivity enhancement afforded by ultrafast magic-angle-spinning (MAS). In spite of the substantial suppression of H-H dipolar couplings, the proton spectral resolution is still poor compared to that of C or N NMR, rendering it challenging for the structural and conformational analysis of complex chemicals or biological solids. Herein, by utilizing the benefits of double-quantum (DQ) and triple-quantum (TQ) coherences, we propose a 3D single-channel pulse sequence that correlates proton triple-quantum/double-quantum/single-quantum (TQ/DQ/SQ) chemical shifts. In addition to the two-spin proximity information, this 3D TQ/DQ/SQ pulse sequence enables more reliable extraction of three-spin proximity information compared to the regular 2D TQ/SQ correlation experiment, which could aid in revealing the proton network in solids. Furthermore, the TQ/DQ slice taken at a specific SQ chemical shift only reveals the local correlations to the corresponding SQ chemical shift, and thus it enables accurate assignments of the proton peaks along the TQ and DQ dimensions and simplifies the interpretation of proton spectra especially for dense proton networks. The high performance of this 3D pulse sequence is well demonstrated on small compounds, L-alanine and a tripeptide, N-formyl-L-methionyl-L-leucyl-L-phenylalanine (MLF). We expect that this new methodology can inspire the development of multidimensional solid-state NMR pulse sequences using the merits of TQ and DQ coherences and enable high-throughput investigations of complex solids using abundant protons.