New methods for mixture analysis by liquid state NMR

液态核磁共振混合物分析新方法

• 批准号: EP/E05899X/1
• 负责人: Mathias Nilsson
• 金额: $ 88.07万
• 依托单位: University of Manchester
• 依托单位国家: 英国
• 项目类别: Fellowship
• 财政年份: 2007
• 资助国家: 英国
• 起止时间: 2007 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FE05899X%2F1
• 关键词: New; methods; mixture; analysis; liquid

Nuclear magnetic resonance (NMR) spectroscopy is the best tool we have for determining the chemical structures of unknown compounds. Hundreds of thousands of structures are identified by NMR each year, but almost all as dilute solutions of pure compounds: NMR struggles to analyse mixtures because it is very difficult, often impossible, to tell which signals in the spectrum come from which species. At the same time, mixtures lie at the heart of chemistry and biochemistry, for example in the search for drugs in plant extracts, in understanding chemical reactions - or simply in finding out what makes one wine taste better than another. One big challenge in mixture analysis is the field of metabolomics, which studies the effects of genetic makeup, disease, drugs etc. on the occurrence of metabolites in biofluids. The ability to disentangle structural information from different molecules in complex mixtures is the key to exploiting this and many other fields. Isolation, purification and concentration of individual components are tedious, expensive and time-consuming; what is needed are ways of determining the structures of individual species without separating a mixture into its individual components. By combining NMR with separation methods, spectral information can be obtained directly from mixtures. The most common example of this is LC-NMR, in which an NMR spectrometer is used as the detector for liquid chromatography (LC). A sample of a mixture flows through a column containing a fine powder, and thence into an NMR instrument. Different species stick to the column material to different extents so they emerge at different times, and the NMR spectrum of each species in turn is measured. Such methods are powerful, but they are expensive in instrumentation, in materials, and in expertise, and they struggle to deal with small amounts of material or very complex mixtures. The most potent method in current use for NMR studies of intact mixtures is diffusion-ordered spectroscopy (DOSY), which separate the signals of different species according to how rapidly they diffuse. DOSY has proven its worth in many areas of analysis, including food chemistry, biofluids, binding studies etc., but its use is limited because it only works well where the NMR signals of different species do not overlap. I propose to try to enhance significantly the power of NMR in studying mixtures by developing a new technique and by using powerful mathematical methods so far largely unexploited for NMR data. I will apply techniques currently used to measure blood flow in magnetic resonance imaging to measure directly how the rates at which different molecules flow through a chromatography column are affected by their interactions with the contents of the column. Because this method measures mean flow velocity rather than retention time, the mixture can be pumped continuously through the column in a closed cycle so, in contrast to LC-NMR, we can make repeated measurements on the same sample for as long as it takes to get a clear result with good signal-to-noise ratio. Because the motion that we measure here is coherent, as opposed to the incoherent diffusion measured in DOSY, analysis of the experimental results is straightforward and avoids the difficulties that DOSY encounters when signals overlap. The basic DOSY experiment gives data which vary in two different ways; in contrast experiments that give results which vary in sympathy as a function of three different variables - trilinear data - have special advantages when it comes to analysis. I will investigate using DOSY to allow trilinear data analysis of the NMR spectra of complex mixtures (e.g. those found in metabolomics). The prize here is to be able to extract the complete NMR spectrum of a compound of interest from a background potentially containing many hundreds of such spectra, exploiting the added resolution gained by combining diffusion and chromatographic information

核磁共振（NMR）光谱是我们确定未知化合物化学结构的最佳工具。每年有数十万种结构被NMR鉴定出来，但几乎都是纯化合物的稀溶液：NMR很难分析混合物，因为很难，甚至不可能分辨光谱中的哪些信号来自哪个物种。与此同时，混合物是化学和生物化学的核心，例如在植物提取物中寻找药物，了解化学反应-或者只是找出一种葡萄酒比另一种更好的味道。混合物分析中的一个巨大挑战是代谢组学领域，该领域研究基因组成，疾病，药物等对生物流体中代谢物发生的影响。从复杂混合物中的不同分子中解开结构信息的能力是开发这一领域和许多其他领域的关键。单个组分的分离、纯化和浓缩是繁琐、昂贵和耗时的;需要的是在不将混合物分离成其单个组分的情况下确定单个物质的结构的方法。通过将NMR与分离方法相结合，可以直接从混合物中获得光谱信息。最常见的例子是LC-NMR，其中NMR光谱仪用作液相色谱（LC）的检测器。混合物的样品流过含有细粉末的柱，然后进入NMR仪器。不同的物质以不同的程度粘附在柱材料上，因此它们在不同的时间出现，并且依次测量每个物质的NMR光谱。这些方法是强大的，但它们在仪器，材料和专业知识方面都很昂贵，而且它们很难处理少量材料或非常复杂的混合物。目前用于完整混合物的NMR研究的最有效方法是扩散有序光谱（DOSY），它根据不同物质扩散的速度分离它们的信号。DOSY已在许多分析领域证明了其价值，包括食品化学，生物流体，结合研究等，但其用途是有限的，因为它仅在不同物质的NMR信号不重叠的情况下才能很好地工作。我建议尝试通过开发一种新的技术和使用强大的数学方法，到目前为止，主要是未开发的NMR数据，以显着提高NMR在研究混合物的权力。我将应用目前用于测量磁共振成像中血流的技术，直接测量不同分子流过色谱柱的速率如何受到它们与色谱柱内容物相互作用的影响。由于该方法测量的是平均流速而不是保留时间，因此混合物可以在封闭循环中连续泵送通过色谱柱，因此与LC-NMR相比，我们可以对同一样品进行重复测量，只要能够获得具有良好信噪比的清晰结果即可。因为我们在这里测量的运动是相干的，而不是在DOSY中测量的非相干扩散，所以实验结果的分析是直接的，避免了DOSY在信号重叠时遇到的困难。基本的DOSY实验给出了以两种不同方式变化的数据;相比之下，实验给出了作为三个不同变量的函数而变化的结果-三线性数据-在分析方面具有特殊的优势。我将研究使用DOSY允许复杂混合物的NMR光谱的三线性数据分析（例如，代谢组学中发现的那些）。这里的奖励是能够从可能包含数百个这样的光谱的背景中提取感兴趣的化合物的完整NMR光谱，利用通过结合扩散和色谱信息获得的增加的分辨率

项目成果

Effect of pre-extraction alkali treatment on the chemical structure and gelling properties of extracted hybrid carrageenan from Chondrus crispus and Ahnfeltiopsis devoniensis

• DOI: 10.1016/j.foodhyd.2015.03.029
• 发表时间: 2015-08-01
• 期刊: FOOD HYDROCOLLOIDS
• 影响因子: 10.7
• 作者: Azevedo, G.;Torres, M. D.;Hilliou, L.
• 通讯作者: Hilliou, L.

Decoupling Two-Dimensional NMR Spectroscopy in Both Dimensions: Pure Shift NOESY and COSY

• DOI: 10.1002/anie.201108888
• 发表时间: 2012-01-01
• 期刊: ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
• 影响因子: 16.6
• 作者: Aguilar, Juan A.;Colbourne, Adam A.;Morris, Gareth A.
• 通讯作者: Morris, Gareth A.

Pure Shift 1H NMR: A Resolution of the Resolution Problem?

• DOI: 10.1002/anie.201001107
• 发表时间: 2010-01-01
• 期刊: ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
• 影响因子: 16.6
• 作者: Aguilar, Juan A.;Faulkner, Stephen;Morris, Gareth A.
• 通讯作者: Morris, Gareth A.

Tailoring kappa/iota-hybrid carrageenan from Mastocarpus stellatus with desired gel quality through pre-extraction alkali treatment

• DOI: 10.1016/j.foodhyd.2012.10.010
• 发表时间: 2013-05-01
• 期刊: FOOD HYDROCOLLOIDS
• 影响因子: 10.7
• 作者: Azevedo, Gabriela;Hilliou, Loic;Villanueva, Ronald D.
• 通讯作者: Villanueva, Ronald D.