Revealing the Local Proton Network through Three-Dimensional 13 C/ 1 H Double-Quantum/ 1 H Single-Quantum and 1 H Double-Quantum/ 13 C/ 1 H Single-Quantum Correlation Fast Magic-Angle Spinning Solid-State NMR Spectroscopy at Natural Abundance.

1 H double quantum (DQ)/1 H single quantum (SQ) correlation solid-state NMR spectroscopy is widely used to obtain internuclear 1 H-1 H proximities, especially at fast magic-angle spinning (MAS) rate (>60 kHz). However, to date, 1 H signals are not well-resolved because of intense 1 H-1 H homonuclear dipolar interactions even at the attainable maximum MAS frequencies of ∼100 kHz and/or under 1 H-1 H homonuclear dipolar decoupling irradiations. Here we introduce novel three-dimensional (3D) experiments to resolve the 1 H DQ/1 H SQ correlation peaks using the additional 13 C dimension. Although the low natural abundance of 13 C (1.1%) significantly reduces the sensitivities, the 1 H indirect measurements alleviate this issue and make this experiment possible even in naturally abundant samples. The two different implementations of 13 C/1 H DQ/1 H SQ correlations and 1 H DQ/13 C/1 H SQ correlations are discussed and demonstrated using l-histidine·HCl·H2 O at natural abundance to reveal the local 1 H-1 H networks near each 13 C. In addition, the complete 1 H resonance assignments are achieved from a single 3D 13 C/1 H DQ/1 H SQ experiment. We have also demonstrated the applicability of our proposed method on a biologically relevant molecule, capsaicin.