Department of Chemical and Biological Physics, Weizmann Institute of Science, Rehovot 7610001, Israel.
Department of Chemistry and Biochemistry, Florida State University, Tallahassee, Florida 32306, United States.
J Am Chem Soc. 2021 Dec 1;143(47):19778-19784. doi: 10.1021/jacs.1c08277. Epub 2021 Nov 18.
Chemical exchange saturation transfer (CEST) enhances solution-state NMR signals of labile and otherwise invisible chemical sites, by indirectly detecting their signatures as a highly magnified saturation of an abundant resonance─for instance, the H resonance of water. Stimulated by this sensitivity magnification, this study presents PROgressive Saturation of the Proton Reservoir (PROSPR), a method for enhancing the NMR sensitivity of dilute heteronuclei in static solids. PROSPR aims at using these heteronuclei to progressively deplete the abundant H polarization found in most organic and several inorganic solids, and implements this H signal depletion in a manner that reflects the spectral intensities of the heteronuclei as a function of their chemical shifts or quadrupolar offsets. To achieve this, PROSPR uses a looped cross-polarization scheme that repeatedly depletes H-H local dipolar order and then relays this saturation throughout the full H reservoir via spin-diffusion processes that act as analogues of chemical exchanges in the CEST experiment. Repeating this cross-polarization/spin-diffusion procedure multiple times results in an effective magnification of each heteronucleus's response that, when repeated in a frequency-stepped fashion, indirectly maps their NMR spectrum as sizable attenuations of the abundant H NMR signal. Experimental PROSPR examples demonstrate that, in this fashion, faithful wideline NMR spectra can be obtained. These H-detected heteronuclear NMR spectra can have their sensitivity enhanced by orders of magnitude in comparison to optimized direct-detect experiments targeting unreceptive nuclei at low natural abundance, using modest hardware requirements and conventional NMR equipment at room temperature.
化学交换饱和传递（CEST）通过间接检测其特征，增强了易变的和其他不可见的化学部位在溶液状态下的 NMR 信号，这些特征表现为对丰富共振（例如，水的 H 共振）的高度放大饱和。受这种灵敏度放大的启发，本研究提出了 PROgressive Saturation of the Proton Reservoir（PROSPR），这是一种在静态固体中增强稀核 NMR 灵敏度的方法。PROSPR 旨在利用这些异核来逐渐耗尽大多数有机和几种无机固体中丰富的 H 极化，并以一种反映异核化学位移或四极偏移的光谱强度的方式实现这种 H 信号的耗竭。为此，PROSPR 使用循环交叉极化方案，该方案反复耗尽 H-H 局部偶极顺序，然后通过自旋扩散过程将这种饱和传递到整个 H 储层，自旋扩散过程充当 CEST 实验中化学交换的模拟。重复此交叉极化/自旋扩散过程多次，会导致每个异核响应的有效放大，当以频率步进的方式重复时，会间接映射它们的 NMR 谱，作为丰富的 H NMR 信号的可观衰减。实验 PROSPR 示例表明，以这种方式，可以获得忠实的宽线 NMR 谱。与针对低自然丰度的不易接受核的优化直接检测实验相比，使用适度的硬件要求和常规 NMR 设备在室温下，这些基于 H 检测的异核 NMR 谱的灵敏度可以提高几个数量级。
