不均匀场下单扫描空间编码技术获取高分辨多核NMR谱

High-resolution multi-nuclear nuclear magnetic resonance (NMR) spectroscopy has been widely used in studying structure and dynamics of organic molecules and biomacromolecules. However, the application of NMR spectroscopy is limited by its resolution and signal to noise ratio (SNR) because they are affected by the inhomogeneous fields due to the environment and the discontinuities of magnetic susceptibility. We would like to build a series of methods to obtain high-resolution multi-nuclear NMR spectroscopy based on spatially encoded single scan technique. We will draw on world-class research results and focus on two aspects to obtain high-resolution multi-nuclear NMR spectroscopy. Firstly, the characteristics of spatially encoded single scan technique and heternuclear iMQC (intermolecular Multiple Quantum Coherence) signal will be studied. We will look for the methods to enhance the SNR (Signal to Noise Ratio) of the spatially encoded heternuclear iMQC spectroscopy. The brand-new pulse sequences to obtain high-resolution and better SNR heternuclear iMQC spectroscopy in the inhomogeneous field will be designed. They will be verified and optimized by the simulations and experiments. Secondly, the characteristics of spatially encoded single scan signal obtained in the inhomogeneous fields will be analyzed systematically. The internal and external factors to affect the resolution will be considered. The methods to obtain high-resolution spectroscopy, including nutation echoes and total spin coherence transfer echoes, will be introduced. The physical model of spatially encoded single scan method to obtain high-resolution multi-nuclear single quantum coherence and multiple quantum coherence NMR spectroscopy will be built. The brand-new pulse sequences to obtain high-resolution spectroscopy in the inhomogeneous field will be designed. They will be verified and optimized by the simulations and experiments.

高分辨多核核磁共振(NMR)波谱广泛应用于有机化合物与生物大分子的结构与反应动力学的研究。然而，其分辨率和信噪比受到环境或样品磁化率不均匀的影响，从而其应用领域受到严重限制。本课题旨在建立一套基于单扫描空间编码技术的高分辨多核NMR谱方法，拟在我们已达到国际水平的研究基础上开展如下两方面的研究：(1)研究单扫描空间编码技术的编解码特点和异核iMQC信号特点，寻找提高单扫描空间编码获取异核iMQC谱图信噪比的方法，设计全新的脉冲序列实现不均匀场下超快速获取高分辨和较高信噪比异核iMQC谱方法。(2)深入研究不均匀磁场下单扫描空间编码NMR信号的演化特点，分析影响谱图分辨率内在因素和外在条件，引入章动回波和全相干转移回波高分辨谱方法，建立不均匀磁场下单扫描获取高分辨多核单量子相干和多量子相干谱的物理模型。设计全新的脉冲用于不均匀场下采集多核高分辨谱，并利用计算机模拟和实验验证及优化新脉冲序列。

高分辨多核核磁共振(NMR)波谱广泛应用于有机化合物与生物大分子的结构与反应动力学的研究。通常情况下要获取谱图的精细结构需要高度均匀的静磁场，其空间变化率一般应低于10^(-9)。然而在许多情况下由于环境的原因或样品磁化率的差异不可避免地导致磁场的不均匀，这种不均匀性通常难以通过匀场等方法消除。本课题首先建立一套基于单扫描空间编码技术的高分辨分子间多量子相干NMR谱方法：(1) 不均匀场下利用单扫描空间编码技术获取高分辨分子间单量子相干信号。(2) 不均匀不稳定场下利用单扫描空间编码技术获取高分辨分子间零量子相干信号。利用单扫描空间编码技术获取高分辨分子间单量子相干信号的序列已应用于粘稠样品和组织样品的检测，能用于研究鲑鱼的肌肉组织，多春鱼的卵以及整条斑马鱼从新鲜到腐烂化学成份的变化。单扫描空间编码技术获取高分辨分子间零量子相干信号方法不仅适用于短时磁场漂移环境也适用于长时磁场漂移场环境下样品的检测。. 单扫描空间编码技术在演化期将传统的串行时间演化用并行的空间演化来代替，实现单扫描获取多维核磁共振(NMR)谱，大幅缩短了二维(2D)及多维NMR谱实验时间。然而这种方法获得的谱F1维谱线展宽比较严重。本课题利用协方差和模式识别方法改进单扫描空间编码谱高分辨，使F1维具有F2维的分辨率。另外，为了提高快速采样谱的灵敏度，本课题还尝试利用异核自旋-自旋偶合相位调制快速获取多维核磁共振谱方法。该方法已能够二次扫描成功获得简单化学样品的异核相关谱(HSQC)，且信噪比强于传统HSQC谱。