LC-Mass Spectrometer for Intramolecular Isotope Ratios at Natural Isotopic Abundance

LC 质谱仪测定天然同位素丰度下的分子内同位素比率

• 批准号: 527844764
• 金额: --
• 依托单位: Technische Universität München (TUM)
• 依托单位国家: 德国
• 项目类别: Major Research Instrumentation
• 财政年份: 2023
• 资助国家: 德国
• 起止时间: 2022-12-31 至 无数据
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/527844764?language=en
• 关键词: LC; Mass; Spectrometer; Intramolecular; Isotope

Compound-specific isotope analysis (CSIA) has revolutionized the detection and characterization of organic contaminant degradation in the environment. Gas- or liquid-chromatography (GC, LC) in sequence with online conversion and subsequent isotope ratio mass spectrometry (IRMS) has allowed accessing a previously untapped source of information: the ratio of naturally occurring stable isotopes (13C/12C, 15N/14N, etc.) within molecules. Isotopic fingerprinting can elucidate the different origins of organic chemicals in cases of groundwater contamination. Gradual changes in contaminant isotope ratios over time and space can detect natural contaminant degradation, and even underlying transformation mechanisms. However, research in Environmental Chemistry has moved on from the foundation of CSIA’s success story (i.e., non-polar highly concentrated legacy contaminants of low molecular weight) to explore the behavior of more polar chemicals of high molecular weight and at low concentrations (e.g. pesticides or pharmaceuticals). This narrows the window of opportunity for CSIA. First, polar compounds of high molecular weight are often not compatible with GC and require liquid-chromatography involving organic eluents. This presently precludes CSIA of these target compounds. Second, isotope effects of degradation typically occur in only one molecular position and are “diluted out” when molecular size increases. This puts an intrinsic limit to assessing larger compounds based on compound-average isotope fractionation. Third, molecules of higher molecular weight offer more distinguishable molecular positions for isotopic fingerprinting. This powerful source of information remains untapped when only the compound average is analyzed. We, therefore, apply for instrument funding to explore fragment- or even position-specific isotope analysis in polar organic molecules by liquid injection MS. This will allow us to tap the potential that (i) fragmentation and high mass resolution can access element-specific isotopic information in defined molecular fragments or positions and (ii) that the approach is compatible with polar compounds of higher molecular weight. In recent work, the approach has been demonstrated for comparatively simple compounds such as oxyanions (e.g., nitrate), or taking advantage of the fortuitous existence of standards of known intramolecular isotope distribution (e.g., methionine). With the requested instrument we want to spearhead the approach for important environmental pollutants and biomolecules: (i) synthesize standards with known intramolecular isotopic composition for calibration; (ii) explore isotopic fingerprinting to distinguish sources and biosynthetic fluxes; (iii) access position-specific isotope effects to study transformation reactions; (iv) explore lower limits of precise isotope analysis in environmental samples and (v) spearhead applications to characterize metabolism in biology and medicine.

化合物特异性同位素分析（CSIA）为环境中有机污染物降解的检测和表征带来了革命性的变化。气相或液相色谱（GC，LC）与在线转换和随后的同位素比质谱（IRMS）的顺序允许访问以前未开发的信息源：天然存在的稳定同位素（13 C/12 C，15 N/14 N等）的比率。在分子中。同位素指纹法可以阐明地下水污染中有机化学品的不同来源。污染物同位素比值随时间和空间的逐渐变化可以检测自然污染物降解，甚至潜在的转化机制。然而，环境化学的研究已经从CSIA成功故事的基础（即，低分子量的非极性高浓度遗留污染物），以探索高分子量和低浓度的极性更强的化学品（例如农药或药物）的行为。这缩小了CSIA的机会之窗。首先，高分子量的极性化合物通常与GC不相容，并且需要涉及有机洗脱剂的液相色谱法。这目前排除了这些目标化合物的CSIA。第二，降解的同位素效应通常仅发生在一个分子位置，并且当分子大小增加时被“稀释”。这使得基于化合物平均同位素分馏来评估较大的化合物受到固有限制。第三，较高分子量的分子为同位素指纹提供了更可区分的分子位置。当只分析复合平均数时，这种强大的信息源仍然没有得到利用。因此，我们申请仪器资金，通过液体注射MS探索极性有机分子中的片段甚至位置特异性同位素分析。这将使我们能够挖掘以下潜力：（i）片段化和高质量分辨率可以在定义的分子片段或位置中获得元素特异性同位素信息，以及（ii）该方法与更高分子量的极性化合物兼容。在最近的工作中，该方法已被证明用于相对简单的化合物，如含氧阴离子（例如，硝酸盐），或利用已知分子内同位素分布的标准品的偶然存在（例如，甲硫氨酸）。利用所要求的仪器，我们希望率先对重要的环境污染物和生物分子采取以下方法：㈠合成具有已知分子内同位素组成的标准品，以供校准; ㈡探索同位素指纹，以区分来源和生物合成通量; ㈢利用特定位置的同位素效应，以研究转化反应;（iv）探索环境样品中精确同位素分析的下限;（v）率先应用于生物学和医学中的新陈代谢特性。