Revealing the Local Proton Network through Three-Dimensional ¹³C/¹H Double-Quantum/¹H Single-Quantum and ¹H...

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