High-resolution Nuclear Magnetic Resonance and Mass spectrometry methodology for the analysis of complex mixtures

用于分析复杂混合物的高分辨率核磁共振和质谱方法

• 批准号: 2424276
• 金额: --
• 依托单位: University of Edinburgh
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2020
• 资助国家: 英国
• 起止时间: 2020 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2424276
• 关键词: resolution; Nuclear; Magnetic; Resonance; Mass

Background behind the proposed research. Complex mixtures are all around us and have a greatimpact on our daily lives. Natural organic matter of soils, rivers, oceans or aerosols, food andbeverages, bio-fluids or biologic medical products are all examples of very complex mixtures. Thestatus quo in compound identification is to expend lots of energy combating the second law ofthermodynamics to try to isolate individual compounds from a mixture. However, wouldn't it bewonderful if we did not have to go through such an arduous process and were able to simply bypassthe customary purification step? This is particularly relevant, as the separation of individualcompounds from a mixture of thousands of molecules is beyond the capability of today'schromatographic methods.2The methodology I aim to develop will be relevant to environmental issues, food and medicineproduction and regulation.Methodology. NMR spectroscopy and mass spectrometry are the two state-of-the-art highresolutiontechniques that have the potential to tackle the analysis of complex mixtures at amolecular level.3,4 The hardware and software capabilities of NMR and MS spectrometers areconstantly improving, opening doors for the development of new methodology. The School ofChemistry of the University of Edinburgh is one of only two UK universities that houses both cuttingedge NMR and MS spectrometers (800 MHz NMR cryoprobe instrument and 12 T FT-ICR massspectrometer). Researchers here also have access to the world-leading NMR and MS equipment ofthe Pacific Northwest National Laboratory (PNNL), USA.An overarching aim of my research thus is to advance NMR and MS methodology for theanalysis of complex mixtures by developing new methods for data acquisition, processingand analysis.My objectives. To apply the developed methodology to answer important questions concerning reallife complex mixtures:(i) Disinfection by-products (DBPs) in drinking water(ii) Scotch whisky(iii) Biological medicinesResearch questions and hypotheses. Each of the above objectives poses a unique researchquestion that is briefly elaborated on in the following paragraphs.(i) Characterisation of DBPs generated during the production of potable water. Extensive physicaland chemical treatment is required to reduce the levels of dissolved organic matter (DOM) below 2mg/l when microbial disinfectant can be applied. In Scotland, this involves chlorination/chloramination. In addition to dealing with microbes, radical reactions involving DOM moleculesproduce hundreds of chlorinated molecules that become part of potable water.5 At present only ahandful of these is regulated, as the structures of a vast majority of DBPs are unknown. Knowingstructures of DBPs is essential if we are to determine their potential effects on human health.Hypothesis. A single fluorine atom used as a tag on DOM constituent molecules (representingdifferent classes of DOM molecules) will allow structure determination of DBPs through newlydeveloped NMR and MS methodology. This approach is necessary since Cl is not "a NMR friendlynucleus", which is in complete contrast to 19F that has 100% natural abundance, high sensitivity,large chemical shift range and far reaching couplings with 1H and 13C, facilitating structuredetermination. Chlorine isotopes on the other hand a

拟议研究背后的背景。复杂的混合物无处不在，对我们的日常生活有很大的影响。土壤、河流、海洋或气溶胶、食品和饮料、生物液体或生物医疗产品等天然有机物都是非常复杂的混合物的例子。化合物鉴定的现状是花费大量的精力来对抗热力学第二定律，试图从混合物中分离出单独的化合物。然而，如果我们不需要经历这样一个艰苦的过程，能够简单地绕过惯常的提纯步骤，那不是很好吗？这一点特别重要，因为从数千个分子的混合物中分离单个化合物超出了今天的层析方法的能力。2我的目标是开发与环境问题、食品和药品生产和监管相关的方法学。核磁共振光谱和质谱仪是两种最先进的高分辨率技术，有可能在分子水平上处理复杂混合物的分析。3、4核磁共振和质谱仪的硬件和软件能力不断提高，为新方法的发展打开了大门。爱丁堡大学化学学院是英国仅有的两所同时拥有尖端核磁共振和质谱仪(800 MHz核磁共振冷冻探针仪和12T FT-ICR质谱仪)的大学之一。这里的研究人员还可以接触到美国太平洋西北国家实验室(PNNL)世界领先的核磁共振和质谱学设备。因此，我研究的一个总体目标是通过开发新的数据采集、处理和分析方法来推进复杂混合物的核磁共振和质谱学分析方法。应用开发的方法学回答与现实生活中复杂混合物有关的重要问题：(I)饮用水中的消毒副产品(DBPs)(Ii)苏格兰威士忌(Iii)生物药物研究问题和假设。上述目标中的每一个都提出了一个独特的研究问题，以下各段将对此作简要阐述：(1)饮用水生产过程中产生的DBPs的特征。当可以使用微生物消毒剂时，需要进行广泛的物理和化学处理，以使溶解有机物(DOM)水平降至2 mg/L以下。在苏格兰，这涉及氯化/氯胺化。除了与微生物打交道外，涉及DOM分子的自由基反应还会产生数百个氯化分子，成为饮用水的一部分。5目前只有一小部分氯化分子受到管制，因为绝大多数DBPs的结构尚不清楚。如果我们要确定DBPs对人类健康的潜在影响，了解DBPs的结构是必不可少的。在DOM组成分子(代表不同类别的DOM分子)上使用单个氟原子作为标记，可以通过新开发的核磁共振和MS方法来确定DBPs的结构。这种方法是必要的，因为氯不是“核磁共振友好核”，这与19F完全相反，后者具有100%的自然丰度、高灵敏度、大的化学位移范围和与1H和13C的深远偶合，便于结构确定。另一方面，氯同位素是一种