Structurally Specific Isotopic Shifts Across Analytical Separations

在化学系化学测量和成像(CMI)计划的支持和生物基础设施部(DBI)的部分共同资助下，威奇托州立大学的Alexandre Shvartsburg正在开发基于天然同位素-一个或多个原子具有不同同位素(元素形式)的物种-的分子结构表征的全新分析方法。Shvartsburg团队结合了复杂的分析方法，包括质谱仪(MS)、离子迁移率光谱(IMS)和高级色谱，以评估同位素替代对不同介质中同位素化合物分离的影响，以确定其分子几何形状。由此产生的新方法预计将能够识别广泛的分子，如生物样品中的代谢物、环境污染物以及与局部法医和安全应用相关的爆炸物和化学制剂。这项研究项目将通过IMS和MS方法和应用的课程和独立讲座，为下一代科学家提供实践培训，并通过IMS和MS方法和应用的课程和独立讲座，为WSU和地区性大学的本科生和研究生提供广泛的教育机会。这项研究依赖于离子或分子的运输对其结构组成的具体依赖。测量的天然同位素之间分离参数的变化可以反映分析物的几何形状，从而能够识别异构体并解开它们的混合物。同位素包络长期以来一直用于MS，但不用于有限分辨率的分析分离。出于这个原因，观察到的作为同位素取代函数的液相色谱(LC)洗脱时间的变化通常被认为是质量效应，而没有结构上的意义。最近，IMS在分辨率方面的重大进展使得能够在线性IMS(基于绝对迁移率)和差分IMS(捕捉强电场中的迁移率增量)中检测到同位素位移。分离后的MS选择与重复统计相结合，将允许Shvartsburg团队利用非同分异构体同位素之间的微小位移。施瓦茨伯格博士和他的团队正在探索这一能力，并通过仪器升级来扩展这一能力，利用超高分辨率的Orbitrap MS来解开标称等压素，以提取关于准确同位素的信息。该项目将把这一方法扩展到一系列有机化合物类别、形态和元素组成的研究，包括合成类固醇和具有转位双键的脂肪酸。如果在这些努力中取得成功，施瓦茨堡团队从分离科学中提取结构信息的能力有望在分离科学中得到广泛应用。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

With support from the Chemical Measurement and Imaging (CMI) Program in the Division of Chemistry and partial co-funding from the Division of Biological Infrastructure (DBI), Alexandre Shvartsburg at Wichita State University is developing fundamentally new analytical approaches to molecular structure characterization based on separations of natural isotopologues - species with different isotopes (elemental forms) for one or more atoms. The Shvartsburg group combines sophisticated analytical methods including mass spectrometry (MS), ion mobility spectrometry (IMS), and advanced chromatography to assess the impact of isotope substitution on the separations of isotopologues in various media to determine their molecular geometries. The resulting new methods are expected to enable identification of a wide range of molecules, such as metabolites in biological samples, environmental contaminants, and explosives and chemical agents relevant to topical forensic and security applications. This research project will provide hands-on training for next-generation scientists, as well as broad educational opportunities for undergraduate and graduate students at WSU and regional universities through courses and stand-alone lectures on IMS and MS methods and applications.This research relies on the dependence of the transport of ions or molecules on their isotopic composition in a structurally specific manner. Measured shifts of separation parameters between natural isotopologues can reflect analyte geometry, enabling identification of isomers and disentangling their mixtures. Isotopic envelopes have long been used in MS, but not in analytical separations limited resolution. For this reason, observed shifts in liquid chromatography (LC) elution times as a function of isotopic substitution have generally been treated mass effects without structural significance. Recently, the major gains in resolving power of IMS have enabled detection of isotopic shifts in both linear IMS--based on absolute mobility--and differential IMS--capturing the mobility increment in strong electric fields. MS selection after separation combined with replicate statistics will allow the Shvartsburg team to exploit the small shifts between non-isomeric isotopologues. Dr. Shvartsburg and his group are exploring this capability and extending it with instrumental upgrades utilizing ultrahigh-resolution Orbitrap MS to disentangle nominal isobars to extract information about exact isotopologues. This project will expand this methodology to the study of a range of organic compound classes, morphologies, and elemental compositions, including anabolic steroids and fatty acids with transposed double bonds. If successful in these endeavors, the Shvartsburg team's ability to extract structural information from the splitting of isotopic envelopes is expected to find broad application in separation science.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.