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

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