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

H-1 double quantum (DQ)/H-1 single quantum (SQ) correlation solid-state NMR spectroscopy is widely used to obtain internuclear H-1-H-1 proximities, especially at fast magic-angle, spinning (MAS) rate (>60 kHz). However, to,date, H-1 signals are not well-resolved because of intense H-1-H-1 homonuclear dipolar interactions even at the attainable maximum MAS frequencies of similar to 100 kHz and/or under H-1-H-1 homonuclear dipolar decoupling irradiations. Here we introduce novel three-dimensional (3D) experiments to resolve the H-1 DQ/H-1 SQ correlation peaks using the additional C-13 dimension. Although the low natural abundance of C-13 (1.1%) significantly reduces the sensitivities, the H-1 indirect measurements alleviate this issue and: make this experiment possible even in naturally abundant samples. The two different implementations of C-13/H-1 DQ/H-1 SQ correlations and H-1 DQ/C-13/H-1 SQ correlations are discussed and demonstrated using L-histidine center dot HCl center dot H2O at natural abundance to reveal the local H-1-H-1 networks near each C-13. In addition, the complete H-1 resonance assignments are achieved from a single 3D C-13/H-1 DQ/H-1 SQ experiment. We have also demonstrated the applicability of our proposed method on a biologically relevant molecule, capsaicin.