Date of Award
2025
Degree Type
Dissertation
Degree Name
Doctor of Philosophy in Chemistry
Department
Chemistry
First Advisor
Daniel Thomas
Abstract
Biomolecular structure is supported by a network of inter- and intramolecular interactions, which can be inherently complex in the condensed phase. Isolating biomolecules from the condensed phase to vacuum, via electrospray ionization (ESI), can afford precise control over experimental conditions, yielding additional structural insight. However, the loss of solvation inherent to the ESI process can drive structural rearrangement, particularly at charge sites.
Microsolvation reagents can be used to partially mimic the solvation of charged moieties in solution as they are brought into the gas phase through complexation. This serves two primary functions: 1) reducing propensity for structural rearrangement of systems with well-defined solution phase structures and 2) and probing the conformational landscape of biomolecules upon adduction to better understand the interplay of intra- and intermolecular interactions in higher order structure. Chapter 1 and 2 of this work detail the design and synthesis of a novel microsolvation agent, diserinol isophthalamide, (DIP), which non-covalently binds to anionic phosphate and carboxylate sites of small peptides.
A complementary objective of this work is to utilize helium nanodroplet isolation infrared (HENDI IR) action spectroscopy to characterize these complexed species. This technique combines the selectivity of mass spectrometry and the high resolution of cryogenic ion spectroscopy to allow for a detailed characterization of these isolated species. Chapter 3 describes the application of a HENDI IR instrument at the Fritz Haber Institute in Berlin to study the effect of DIP complexation on a model pentapeptide species, leucine enkephalin (YGGFL). By comparing the infrared spectrum of the complexed species to that of the free anion, we are able to probe the balance of inter- and intramolecular interactions.
Lastly, chapter 4 describes the construction of novel HENDI IR instrumentation at the University of Rhode Island. This instrument couples ESI to a continuous wave tabletop laser system capable of measuring the hydrogen stretching region, namely the vibrational modes of hydrogen bound to carbon, nitrogen, and oxygen atoms.
Recommended Citation
Schultz, Madeline, "PROBING BIOMOLECULAR STRUCTURE AND DYNAMICS VIA INFRARED ACTION SPECTROSCOPY" (2025). Open Access Dissertations. Paper 4476.
https://digitalcommons.uri.edu/oa_diss/4476