Direct Detection of Natural-Abundance Low-γ Nuclei NMR Signals of Minute Quantities of Organic Solids

Low-γ nuclei signal enhancement in solid-state NMR spectroscopy is typically achieved via cross-polarization (CP) using abundant ¹H polarization in organic solids. Nevertheless, direct low-γ nuclei signal detection via a single CP process is quite challenging with minute quantities of samples due to the extremely limited signal-to-noise ratio (SNR) of the acquired spectra. Herein, we demonstrated the robust performance of a multiple-contact CP experiment with multiple acquisition periods (MCP) in each transient scan, leading to several-fold SNR enhancement over a conventional single-CP experiment at fast MAS conditions with slightly increased experimental time. Spin thermodynamic analysis was further performed to achieve maximum SNR by adding the obtained <i>N</i>_max CP spectra from each transient, where <i>N</i>_max ∼ <i>T</i>_1ρ/<i>τ</i>_cw. Here, <i>T</i>_1ρ is the proton spin-lattice relaxation time in the rotating frame, and <i>τ</i>_cw is the total time of CP and a heteronuclear decoupling period. The theoretical analysis is in good agreement with experimental results, and more than 4.5-fold SNR enhancement can be achieved for the pharmaceutical danazol/vanillin cocrystals. Besides, MCP was also used for proton <i>T</i>₁ and <i>T</i>_1ρ measurement with high-resolution ¹³C detection, where both proton <i>T</i>₁ and <i>T</i>_1ρ can serve as the spectral-editing basis to identify different immiscible components in complex molecular systems.