Single-conformation spectroscopy of hydrogen bonding networks: Solvation, synthetic foldamers, and neurodegenerative diseases
The hydrogen bond is one of the most important interactions in natural processes ranging from protein folding to chemical reactions. Two complementary methodologies are applied to understanding this important interaction: top-down and bottom-up. Top-down methods use large molecules, such as proteins, revealing secondary structure information. Bottom-up experiments are performed on small molecules, utilizing high-resolution spectroscopy to reveal underlying quantum mechanical effects. The complexity gap is formed between these two experimental regimes; between large and small molecules; between bulk and individual solvent molecules; between classical mechanics calculations and quantum chemical calculations. This dissertation will focus on the application of gas phase, single-conformation ultraviolet (UV) and infrared (IR) spectroscopies to the study of molecules and clusters in the size and solvation complexity gap, with the goal of bridging the gulf between the two experimental approaches. Single-conformation spectroscopy is perfectly suited to study solvation. Solvent molecules, in many instances water, can be frozen onto the solute in a stepwise manner. Here, we solvate a prototypical flexible bichromophore—1,2-diphenoxyethane (DPOE)—by stepwise addition of water molecules. Single-conformation spectroscopy reveals both the structural perturbations associated with water molecule addition and their effect on DPOE’s pair of closely spaced excited electronic states. These experimental studies provide excellent insight into solvent effects on vibronic and excitonic coupling, and can be used to further develop the models used to describe such processes. Similarly, single-conformation spectroscopy can reveal the effects of conformational flexibility on the innate conformational preferences and hydrogen bonding motifs in peptides. Results obtained from a study of a cyclically constrained γ peptide, γACHC, reveal that increased conformational flexibility can be controlled by synthetic chemists in order to direct folding into pre-programmed secondary structures and that these structures are stabilized with intramolecular rather than intermolecular hydrogen bonds. This theme of conformational flexibility is continued in studies of glutamine containing peptides. Glutamine—with its flexible, hydrogen bond forming sidechain—is intimately involved with neurodegenerative diseases such as Huntington’s disease. Single-conformation studies help reveal the delicate interplay between three different types of hydrogen bonds within the molecule: backbone-backbone, sidechain-backbone, and sidechain-sidechain hydrogen bonds. The importance of these competing hydrogen bonds on the conformational preferences will be discussed both locally and within the larger context of disease pathogenesis.
Zwier, Purdue University.
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