Ultraviolet and Infrared Spectroscopy of Synthetic Peptides and Natural Products in the Gas Phase

Abstract

The hydrogen bond is one of nature’s ubiquitous molecular interactions. Its role ranges from that of a static provider of structural integrity in proteins to that of a dynamic coordinate, along which excited state deactivation in sunscreen molecules is achieved. The work in this dissertation employs a supersonic expansion to collisionally cool peptide oligomers and a sunscreen chromophore to the zero-point vibrational level of their low lying conformational minima. These species are interrogated using high-resolution, conformer-specific ultraviolet and infrared laser spectroscopic techniques with the aim of elucidating their intrinsic conformational preferences, hydrogen bonding networks, and excited state deactivation mechanisms.Synthetic foldamers are oligomers composed of non-natural building blocks, such as b- and g-amino acids. Incorporation of such residues into a peptide backbone results in secondary and tertiary structures that are distinct from those found in nature. Herein, the folding propensity of a series of mixed a/b and pure b-peptides is presented. In each case, both the left- and right-handed emergence of mixed-helical secondary structures, the 11/9- and the 12/10-helix, are observed. Next, the intrinsic conformational preferences of a series of increasingly complex asparagine-containing peptides are characterized. Asparagine, with its flexible carboxamide sidechain, is omnipresent within the prion forming domain of the misfolded proteins associated with several neurodegenerative diseases. Asparagine’s propensity for b-turn structures is discussed and compared with that of analogous peptide sequences found in nature.Methyl anthranilate is a natural product that contains an identical electronic chromophore to the sunscreen agent, meradimate. The excited state deactivation mechanism of methyl anthranilate and its water complex is determined with extensive ultraviolet spectroscopic characterization, and is discussed within the broader context of its role as a sunscreen agent. Vibronic analysis coupled with computational results indicate extensive heavy-atom rearrangement leading to hydrogen atom dislocation, rather than full transfer, on the S1 surface. This phenomenon is further characterized with infrared spectroscopy and theoretical modeling, in which the NH stretch is adiabatically separated from other internal coordinates. Extensive dilution of the dislocated NH stretch oscillator strength over many transitions and ~1,300 cm-1 is predicted. These results may have implications for similar molecules, such as salicylic acid and its derivatives.