不均匀场下空间编码超快速高分辨NMR研究进展

二维核磁共振(2D NMR)的提出和发展,为NMR技术的研究和应用提供了广阔的空间. 然而当样品或磁场本身不均匀时,高分辨的2D NMR谱难以获得. 此外,常规2D NMR实验通常需要长的采样时间. 空间编码超快速采样方法利用空间编码技术,只需单次扫描即可获得2D甚至多维NMR谱,极大地缩短了采样时间. 目前相位补偿、相干转移和分子间多量子相干等技术与空间编码技术相结合,已成功实现不均匀场下超快速获得高分辨NMR谱. 该文对不均匀场下空间编码超快速NMR方法进行了介绍,对其未来发展进行了展望.     

核磁共振技术在生物组织中的应用

在生物组织内部存在大量的生化、生理反应以及分子的扩散运动,它们相互独立, 又相互关联,共同构成一个生化反应网络. 在病理条件下,某些生化反应过程会发生改变,代谢中间体可能会出现质和量的变化. 核磁共振 (NMR)可以对这些过程的研究提供非常有用的信息. 目前,有3种核磁共振波谱技术可以用于生物组织的研究：① 活体组织定域波谱技术;② 生物组织提取物的液体高分辨核磁共振技术;③ 离体组织的高分辨魔角旋转技术. 这些方法各有优劣,互为补充. 介绍了在生物组织的NMR研究方面的最新进展.     

不均匀不稳定磁场下高分辨液体核磁共振新技术的研究进展

高分辨核磁共振（Nuclear Magnetic Resonance,NMR）谱的获得通常需要高度稳定且均匀的强静磁场. 阻抗磁体或阻抗－超导混合磁体可获得比超导磁体高得多的磁场, 但它们的磁场的稳定性与均匀性比较差;另一方面, 在活体定域波谱研究中,样品内部组分的磁化率差异,运动或生理活动等作用将不可避免地导致磁场的不均匀不稳定,并且这些不稳定不均匀性无法通过锁场匀场等传统的方法消除. 基于分子间零量子相干的方法、空间编码单扫描快速方法、反卷积技术等日渐成为在不均匀不稳定磁场下获取高分辨率的NMR谱的研究热点.     

磁共振技术在食品质量与安全研究中的应用

食品质量与安全的检测分析关乎人们生命健康,高效可靠的检测手段是该领域研究的必需条件.磁共振技术,包括核磁共振（NMR）和磁共振成像（MRI）,是20世纪的新兴的食品检测技术．由于该技术对样品几乎无破坏性,且具有可实时快速测量、可同时检测多成分、可获得样品内部图像等优点,因此在食品检测领域的应用越来越多．为了促进该技术在食品科学领域更为深入的应用,该文对磁共振技术在国内外食品质量和安全研究领域的应用现状进行了总结．     

基于自主研发的500 MHz NMR谱仪的紫杉醇结构解析

中国科学院武汉物理与数学研究所（WIPM）于2010年成功研制了500 MHz（WIPM-I 500）高分辨超导核磁共振（NMR）谱仪,并将其投入实际应用中.然而,关于其二维核磁共振（2D NMR）谱图的准确性及在此基础上对复杂物质的结构解析尚无系统完整的数据报道.该文利用WIPM-I 500型NMR谱仪,对紫杉醇样品进行了1D NMR及2D NMR（包括¹H-¹H COSY、¹H-¹H TOCSY、J-Res、¹H-¹³C HMQC和¹H-¹³C HMBC）实验,将谱图分析结果与进口仪器进行了对比.结果表明：利用WIPM-I 500型NMR谱仪能够采集准确的2D NMR谱图,为紫杉醇的正确归属提供了实验基础;而且该文也纠正了文献中对紫杉醇的错误归属.     

高磁场中纳升(Nanoliter)生物组织固态氢谱及代谢研究

在高磁场21.1 T（900 MHz ¹H NMR)的快速魔角旋转条件下,采用商业化的1.6 mm探头, 生物样品可以在≤1 μL(150 nL,约0.15 mg）和较短的时间（数分钟）内获得满意的代谢产物的固体高分辨氢谱,且仅需对1.6 mm样品管稍作改进. 防止生物样品的泄漏和污染是实验成功的关键因素,因此对于生物样品的封装进行了讨论, 同时对于微量生物样品在高磁场下信噪比的优化策略也进行了理论和实验的探讨. 该文介绍了生物样品的高磁场固体NMR谱学方法在代谢组学的应用,并总结了此领域里的最新研究进展.     

基于哈德曼编码的新型高分辨定域谱

核磁共振（NMR）技术作为一种非植入无损伤的检测技术，已经广泛应用于化学、生物和医学等领域.本文基于哈德曼（Hadamard）编码的分子间单量子相干（iSQC）技术提出了一种新的序列，首先从理论上对该序列进行了简要的分析并阐明其原理，然后用套管模型实验和脑模型实验验证该序列在不均匀磁场下准确定域和快速获取高分辨谱的能力.实验表明，该序列在不均匀磁场下可以快速获取高分辨定域谱，同时抑制溶剂峰信号，具备一定的应用价值.     

液体核磁共振 HSQC 实验的量子化学计算与模拟

核磁共振（NMR）异核单量子相干（HSQC）实验因具有较高的灵敏度和分辨率而被广泛用于液体大分子化合物的结构鉴定和研究．然而由于HSQC脉冲的复杂性,需要严格控制实验参数和实验条件才能得到高质量的谱图．本文基于量子力学原理对HSQC实验进行数学建模,通过理论推导、数值计算求解自旋1/2的IS双核体系在每个脉冲节点作用后的密度矩阵,然后结合二维NMR信号采样方法,使用计算机程序完成了该体系HSQC谱图的模拟,同时,还实现了乙醇分子的HSQC谱图模拟． HSQC实验的成功模拟基于对复杂演化过程的精确计算,可用于预测谱图以及实验参数改变对NMR谱图的影响,指导高质量HSQC实验谱图的采集．     

超强磁场中核磁共振信号与屏蔽效应的理论研究

研究了超强磁场对于核磁共振样品中双原子分子中电子系统的哈密顿量的影响,并且给出了磁共振信号中由于外磁场与氢原子电子系统相互作用所产生的含有B02的修正项.基于核磁共振原理,获得了利用氢的NMR谱对超强磁场进行精确测量的理论依据,推导出了一种基于核磁共振技术的超强磁场测量公式,从而在理论上证明了对超强磁场进行精确测量是可行的.     

NMR在α-synuclein的结构及相互作用研究中的应用

α-synuclein(AS)是一种和帕金森病(PD)密切相关的天然无结构蛋白,是PD标志物路易小体(LB)的主要成分.AS异常聚集和纤维化被认为是引起PD的主要原因之一,因而针对其结构、聚集和功能的研究一直是国际上的热点.核磁共振(NMR)技术能获得具有原子分辨率的蛋白质结构和动态信息,尤其适合研究其它生物物理方法难以研究的天然无结构蛋白.该综述主要讨论NMR技术结合其他技术手段在AS的结构、聚集机制、以及与生物膜、金属离子和其它蛋白质相互作用研究中的应用.这些研究结果为探索PD的发病机制提供了有益的线索.     

Fast high-resolution nuclear magnetic resonance spectroscopy through indirect zero-quantum coherence detection in inhomogeneous fields

In many cases, high-resolution nuclear magnetic resonance （NMR） spectra are virtually impossible to obtain by con- ventional nuclear magnetic resonance methods because of inhomogeneity of magnetic field and inherent heterogeneity of sample. Although conventional intramolecular zero-quantum coherence （ZQC） can be used to obtain high-resolution spectrum in inhomogeneous field, the acquisition takes rather long time. In this paper, a spatially encoded intramolecular ZQC technique is proposed to fast acquire high-resolution NMR spectrum in inhomogeneous field. For the first time, the gradient-driven decoding technique is employed to selectively acquire intramolecular ZQC signals. Theoretical analyses and experimental observations demonstrate that high-resolution NMR spectral information can be retrieved within several scans even when the field inhomogeneity is severe enough to erase most spectral information. This work provides a new way to enhance the acquisition efficiency of high-resolution intramolecular ZQC spectroscopy in inhomogeneous fields.     

High-resolution heteronuclear correlation spectroscopy based on spatial encoding and coherence transfer in inhomogeneous fields

Two-dimensional (2D) nuclear magnetic resonance (NMR) spectroscopy has been proven to be a powerful technique for chemical, biological, and medical studies. Heteronuclear single quantum correlation (HSQC) and heteronuclear multiple bond correlation (HMBC) are two frequently used 2D NMR methods. In combination with spatially encoded techniques, a heteronuclear 2D NMR spectrum can be acquired in several seconds and may be applied to monitoring chemical reactions. However, it is difficult to obtain high-resolution NMR spectra in inhomogeneous fields. Inspired by the idea of tracing the difference of precession frequencies between two different spins to yield high-resolution spectra, we propose a method with correlation acquisition option and J-resolved-like acquisition option to ultrafast obtain high-resolution HSQC/HMBC spectra and heteronuclear J-resolved-like spectra in inhomogeneous fields.     

Advances in high-resolution nuclear magnetic resonance methods in inhomogeneous magnetic fields using intermolecular multiple quantum coherences

Strong and extremely homogeneous static magnetic field is usually required for high-resolution nu-clear magnetic resonance (NMR). However, in the cases of in vivo and so on, the magnetic field inho-mogeneity owing to magnetic susceptibility variation in samples is unavoidable and hard to eliminate by conventional methods such as shimming. Recently, intermolecular multiple quantum coherences (iMQCs) have been employed to eliminate inhomogeneous broadening and obtain high-resolution NMR spectra, especially for in vivo samples. Compared to other high-resolution NMR methods, iMQC method exhibits its unique feature and advantage. It simultaneously holds information of chemical shifts, multiplet structures, coupling constants, and relative peak areas. All the information is often used to analyze and characterize molecular structures in conventional one-dimensional NMR spec-troscopy. In this work, recent technical developments including our results in this field are summarized; the high-resolution mechanism is analyzed and comparison with other methods based on interactions between spins is made; comments on the current situation and outlook on the research directions are also made.     

High-resolution NMR spectra in inhomogeneous and unstable fields via the three-pulse method

In modern solution nuclear magnetic resonance (NMR), the spectral resolution is mainly dependent on the spatial homogeneity and temporal stability of the magnetic field. The spectral linewidths are usually proportional to the overall field homogeneity and the stability experienced by the sample. Many high-resolution NMR methods have been developed, but few are applicable in inhomogeneous and unstable fields. In this paper, a high-resolution three-pulse method based on intermolecular zero-quantum coherences (iZQCs) is proposed. Since this method is insensitive to field inhomogeneity and instability, spectral information such as the chemical shift can be retained in the resulting spectra. In comparison with the CPMG-HOMOGENIZED method, the new method provides almost pure solvent–solute iZQC signals.     

High-resolution absorptive intermolecular multiple-quantum coherence NMR spectroscopy under inhomogeneous fields

Intermolecular multiple-quantum coherence (iMQC) is capable of improving NMR spectral resolution using a 2D shearing manipulation method. A pulse sequence termed CT-iDH, which combines intermolecular double-quantum filter (iDQF) with a modified constant-time (CT) scheme, is designed to achieve fast acquisition of high-resolution intermolecular zero-quantum coherences (iZQCs) and intermolecular double-quantum coherences (iDQCs) spectra without strong coupling artifacts. Furthermore, double-absorption lineshapes are first realized in 2D intermolecular multi-quantum coherences (iMQCs) spectra under inhomogeneous fields through a combination of iZQC and iDQC signals to double the resolution without loss of sensitivity. Theoretically the spectral linewidth can be further reduced by half compared to original iMQC high-resolution spectra. Several experiments were performed to test the feasibility of the new method and the improvements are evaluated quantitatively. The study suggests potential applications for in vivo spectroscopy.     

Two-dimensional high-resolution NMR spectra in matched B(0) and B(1) field gradients

In a recent publication we presented a method to obtain highly resolved NMR spectra in the presence of an inhomogeneous B(0) field with the help of a matched RF gradient. If RF gradient pulses are combined with "ideal" 90 degrees pulses to form inhomogeneous z rotation pulses, the line broadening caused by the B(0) gradient can be refocused, while the full chemical shift information is maintained. This approach is of potential use for NMR spectroscopy in an inhomogeneous magnetic field produced by an "ex-situ" surface spectrometer. In this contribution, we extend this method toward two-dimensional spectroscopy with high resolution in one or both dimensions. Line narrowing in the indirect dimension can be achieved by two types of nutation echoes, thus leading to depth-sensitive NMR spectra with full chemical shift information. If the nutation echo in the indirect dimension is combined with a stroboscopic acquisition using inhomogeneous z-rotation pulses, highly resolved two-dimensional correlation spectra can be obtained in matched field gradients. Finally, we demonstrate that an INEPT coherence transfer from proton to carbon spins is possible in inhomogeneous B(0) fields. Thus, it is possible to obtain one-dimensional (13)C NMR spectra with increased sensitivity and two-dimensional HETCOR spectra in the presence of B(0) gradients of 0.4 mT/cm. These schemes may be of some value for ex-situ NMR analysis of materials and biological systems.     

Numerical studies of intermolecular multiple quantum coherences: high-resolution NMR in inhomogeneous fields and contrast enhancement in MRI

A fast, efficient numerical algorithm is used to study intermolecular zero-quantum coherences (iZQCs) and double-quantum coherences (iDQCs) in two applications where the three-dimensional structure of the magnetization is important: high-resolution NMR in inhomogeneous fields and contrast enhancement in MRI. Simulations with up to 2 million coupled volume elements (256 x 256 x 32) show that iZQCs can significantly narrow linewidths in the indirectly detected dimension of systems with inhomogeneous fields and explore the effects of shape and orientation of the inhomogeneities. In addition, this study shows that MR images from iZQC and iDQC CRAZED pulse sequences contain fundamentally new contrast, and a modified CRAZED pulse sequence (modCRAZED) can isolate the contrast from chemically inequivalent spins.