Determining the Structures and Properties of Biologically-relevant Ions

Abstract

Gas phase studies of biologically relevant ions are increasing in popularity due to the possibility of high throughput analysis requiring minimum sample concentrations. This thesis explores the potential of differential mobility spectrometry-mass spectrometry (DMS-MS) in combination with quantum chemical calculation methods to probe the structures, energetics, and dynamics of three distinct classes of biomolecules. The first project outlines the use of DMS-MS to separate and identify protonated forms of methylated and unmethylated nucleobases to gain a fundamental understanding of their gas phase properties in relation to their role in nucleic acids. Next, DMS-MS and calculations were conducted for a large RNA system, the Varkud Satellite ribozyme active site loop VI, to study differences between its active and inactive conformations, especially through the use of negative mode hydrogen-deuterium exchange. Finally, DMS-MS was used to identify transformation products of trimethoprim, an antibiotic often found in environmental wastewaters in a reliable and efficient method. Ultimately, DMS-MS and quantum calculations have been shown to be a powerful analytical tool to investigate structures and properties of biomolecules. The methodologies described herein can have an impact in a wide variety of industries, from drug discovery to environmental wastewater cleanup.