CAREER: Differentiation of Metabolic Isomers via Gas-phase Reactions

With support from the Chemical Measurement and Imaging Program in the Division of Chemistry, Professor Boone Prentice's group at the University of Florida is working to devise means of identifying subtle differences in the chemical structures of lipids and metabolites - biomolecules that play vital roles in cellular functions. Changes in the structures of these molecules can signal changes in health and biology, but these differences can be difficult to characterize. The Prentice group is developing experimental and computational methods that are better able than existing approaches to identify chemical changes in these biomolecules, potentially enabling new biological discoveries and benefiting societal health. As part of this project, the team is developing a 2-day, hands-on, laboratory-based Gainesville Emerging Scientist Training (GEST) workshop for high school students in the local community. These outreach efforts are designed to promote careers in STEM disciplines, increase public scientific literacy and engagement, improve educator development at the graduate and undergraduate student levels, and develop a more competitive scientific workforce. Tandem mass spectrometry (MS/MS) has become an important resource in biological research (e.g., in proteomics, lipidomics, and metabolomics) due to the high level of specificity afforded by fragmenting compounds of interest and then analyzing the product masses. However, severe deficiencies remain in the ability to identify and differentiate small molecules and their isomers. Work in the Prentice laboratory aims to develop gas-phase reactions to enable rapid differentiation of metabolic isomers in complex biological samples. The approach entails novel use of gas-phase kinetics to determine and exploit the unique thermochemical properties of each isomer. Dissociation kinetics of analyte/reagent ion complexes generated using either ion/ion or ion/molecule gas-phase reaction chemistries are probed using infrared multiphoton dissociation (IRMPD) to measure isomer activation energies (Ea). These workflows are being tested for applicability to multiple analyte classes, including isomers of sugars, glycolipids, gangliosides, and glycerophospholipids. The experimental data is complemented with computational experiments to improve understanding of the fundamental energy surfaces, chemical structures, and dissociation kinetics responsible for the observed gas-phase behaviors. 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.