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一维和二维的奥弗豪泽增强液态核磁共振光谱学

Overhauser enhanced liquid state nuclear magnetic resonance spectroscopy in one and two dimensions.

作者信息

Levien Marcel, Yang Luming, van der Ham Alex, Reinhard Maik, John Michael, Purea Armin, Ganz Jürgen, Marquardsen Thorsten, Tkach Igor, Orlando Tomas, Bennati Marina

机构信息

Electron-Spin Resonance Spectroscopy, Max Planck Institute for Multidisciplinary Sciences, Am Fassberg 11, 37077, Göttingen, Germany.

Institute of Physical Chemistry, Department of Chemistry, Georg-August-University, Tammannstr. 6, 37077, Göttingen, Germany.

出版信息

Nat Commun. 2024 Jul 13;15(1):5904. doi: 10.1038/s41467-024-50265-5.

Abstract

Nuclear magnetic resonance (NMR) is fundamental in the natural sciences, from chemical analysis and structural biology, to medicine and physics. Despite its enormous achievements, one of its most severe limitations is the low sensitivity, which arises from the small population difference of nuclear spin states. Methods such as dissolution dynamic nuclear polarization and parahydrogen induced hyperpolarization can enhance the NMR signal by several orders of magnitude, however, their intrinsic limitations render multidimensional hyperpolarized liquid-state NMR a challenge. Here, we report an instrumental design for 9.4 Tesla liquid-state dynamic nuclear polarization that enabled enhanced high-resolution NMR spectra in one and two-dimensions for small molecules, including drugs and metabolites. Achieved enhancements of up to two orders of magnitude translate to signal acquisition gains up to a factor of 10,000. We show that hyperpolarization can be transferred between nuclei, allowing DNP-enhanced two-dimensional C-C correlation experiments at C natural abundance. The enhanced sensitivity opens up perspectives for structural determination of natural products or characterization of drugs, available in small quantities. The results provide a starting point for a broader implementation of DNP in liquid-state NMR.

摘要

核磁共振(NMR)在自然科学领域至关重要,涵盖化学分析、结构生物学、医学和物理学等多个方面。尽管取得了巨大成就,但其最严重的局限性之一是灵敏度低,这是由核自旋态的微小种群差异导致的。诸如溶解动态核极化和仲氢诱导超极化等方法可以将NMR信号增强几个数量级,然而,它们固有的局限性使得多维超极化液态NMR成为一项挑战。在此,我们报告了一种用于9.4特斯拉液态动态核极化的仪器设计,该设计能够为小分子(包括药物和代谢物)提供增强的一维和二维高分辨率NMR光谱。实现了高达两个数量级的增强,转化为信号采集增益高达10000倍。我们表明超极化可以在原子核之间转移,从而允许在碳自然丰度下进行DNP增强的二维碳 - 碳相关实验。增强的灵敏度为天然产物的结构测定或少量可用药物的表征开辟了前景。这些结果为在液态NMR中更广泛地实施DNP提供了一个起点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bee1/11246421/772e5a6f33bf/41467_2024_50265_Fig1_HTML.jpg

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