NSF Award
2105182
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.<br/><br/>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.<br/><br/>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.
