Rapid Structural Analysis of Minute Quantities of Organic Solids by Exhausting ¹H Polarization in Solid-State NMR Spectroscopy Under Fast Magic Angle Spinning

Abstract

Solid-state nuclear magnetic resonance (NMR) often suffers from significant limitations due to the inherent low signal sensitivity when low-γ nuclei are involved. Herein, we report an elegant solid-state NMR approach for rapid structural analysis of minute amounts of organic solids. By encoding staggered chemical shift evolution in the indirect dimension and staggered acquisition in the 1H dimension, a proton-detected homonuclear 1H/1H and heteronuclear 13C/1H chemical shift correlation (HETCOR) spectrum can be obtained simultaneously in a single experiment at a fast magic-angle-spinning (MAS) condition with barely increasing the experimental time. We further show that during the conventional 1H-detected HETCOR experimental time, multiple homonuclear 1H/1H correlation spectra can be recorded in addition to the HETCOR spectrum, enabling the determination of 1H–1H distances. We establish that abundant 1H polarization can be efficiently manipulated and fully utilized in proton-detected solid-state NMR spectroscopy for extraction of more critical structural information and thus reduction of the total experimental time.

2D HETCOR Solid-State NMR Spectroscopy for Multiphase Materials with Mobility Contrast

“…Note that we cannot incorporate polarization inversion during the CP process in the HETCOR experiment because the initial 13 C signals of mobile components recovered during the recycle delay should be removed to avoid interference with 13 C signals obtained from the NOE-based polarization transfer. This is very similar to the 2D double-CP-based experiment under fast MAS for recording 1 H– 13 C HETCOR spectra, where the residual proton magnetizations are completely removed by the HORROR (homonuclear rotary resonance) sequences before proton detection. , For the benefits of discussions given below, the 13 C spectra obtained in the first and second signal acquisition periods in the CPPI- f -NOE experiment are denoted as S1 and S2 spectra, respectively. For the HETCOR experiments, the HETCOR spectrum based on S1 and S2 spectra is denoted as rigid-HETCOR and mobile-HETCOR, respectively.…”

Using Abundant 1H Polarization to Enhance the Sensitivity of Solid-State NMR Spectroscopy

“…In fact, any 2D 1 H/ 1 H homonuclear correlation experiment, including 2D DQ/SQ, 2D TQ/SQ, anti-z-cosy and its variants, etc . can be incorporated into the HETCOR sequence . Notably, a 2D 1 H SQ/SQ experiment usually takes 1–2 h, while a HETCOR experiment may take half a day or even more.…”

“…130,131 The core idea lies in encoding staggered chemical shift evolution in the indirect 13 C dimension and staggered acquisition in the direct 1 H dimension, as shown in Figure 5a. 130,131 After the CP period, the 13 C magnetization is flipped to the +z direction for storage, while the NOESY-type pulse sequence is implemented on the 1 H channel for achieving homonuclear 1 H/ 1 H SQ/SQ chemical shift correlations. After the first period of 1 H signal acquisition, the 13 C magnetization is flipped to the xy plane for t 1 evolution and then later transferred back to 1 H for signal detection to achieve heteronuclear 13 C/ 1 H chemical shift correlations.…”

“…Because 13 C or 15 N typically has a much longer spin–lattice relaxation time, making it easier for polarization storage, there are considerable efforts in exhausting 13 C or 15 N polarization in each transient scan to obtain multiple multidimensional solid-state NMR spectra in a single experiment in a combination of coevolution, multi-acquisition, multi-receiver, or multiplex phase cycling strategies. − However, harnessing the unused 1 H polarization in each transient scan is still challenging due to its typically short T 1 and T 1ρ relaxation times in rigid organic solids. Recently, we proposed an elegant solid-state NMR approach to exhaust the unused 1 H polarization in each transient scan, enabling simultaneous acquisition of 2D/3D homo/hetero-nuclear correlation spectra from a single experiment without any hardware modification. , The core idea lies in encoding staggered chemical shift evolution in the indirect 13 C dimension and staggered acquisition in the direct 1 H dimension, as shown in Figure a. , After the CP period, the 13 C magnetization is flipped to the + z direction for storage, while the NOESY-type pulse sequence is implemented on the 1 H channel for achieving homonuclear 1 H/ 1 H SQ/SQ chemical shift correlations. After the first period of 1 H signal acquisition, the 13 C magnetization is flipped to the xy plane for t 1 evolution and then later transferred back to 1 H for signal detection to achieve heteronuclear 13 C/ 1 H chemical shift correlations.…”

Selective Nuclear Magnetic Resonance Method for Enhancing Long-Range Heteronuclear Correlations in Solids

“…Heteronuclear correlation (HETCOR) plays a critical role in structural elucidation by nuclear magnetic resonance (NMR). − Typical HETCOR experiments, such as heteronuclear single-quantum coherence (HSQC) and heteronuclear multiple-quantum correlation (HMQC), utilize J-couplings to establish heteronuclear correlations. − In solid-state NMR (ssNMR), HETCOR is often implemented by utilizing dipolar couplings, which are 1–2 orders of magnitude larger than J-couplings. − While magic-angle spinning (MAS) for line narrowing attenuates heteronuclear dipolar couplings, many recoupling techniques are introduced to recover them to establish correlations. − Cross-polarization (CP) − is a routine technique for HETCOR experiments among 1 H, 13 C, 15 N, 19 F, and 31 P in studies of solid materials. − However, most existing techniques preferentially establish correlations of strongly coupled atoms due to dipolar truncation. , Therefore, correlations from short-range atoms are dominant in spectra, and those long-range correlations, which are more critical intermolecular structural restraints, are usually weak or even undetectable.…”