Peptides, Diamines, and Nucleobases: Investigations in Ion Chemistry

Gas-phase ion chemistry offers a variety of experimental tools that can assist in determining the structure and properties of molecules that are difficult to purify and isolate or available in only small concentrations. This thesis highlights three areas where ion chemistry has been successfully used to give new insight into the structures and properties of various peptides, diamines, and nucleobases.;Peptides. Peptide biosynthesis incorporates only L-isomers of the chiral amino acids, however, D-isomers can result from post-translational modifications performed by epimerase enzymes or through spontaneous racemization. Sequential mass spectrometry can be used to measure quantitative differences in the fragmentation patterns of peptides containing a single D-amino acid. This thesis describes the differences in the collsionally activated dissociation (CAD) patterns of the diastereomers of the tripeptide Gly-Ser-Lys (GSK) and the tetrapeptide Gly-Leu-Ser-Lys (GLSK). The latter is among the tryptic fragments expected from the digest of alpha-synuclein, a protein found in Lewy bodies implicated in Parkinsonism and other neurological disorders. The differences between the CAD fragmentation patterns is used to develop a method to quantitate the amount of the GLdSK diastereomer in a mixture of GLSK.;Diamines Vibrational spectra of the conjugate acid of the linear diamine N,N,N',N'-tetramethylputrescine has been recorded in the gas-phase with infrared multiple photon dissociation (IRMPD) and solid-phase by inelastic neutron scattering (INS). A band near 550 cm-1 is observed in both spectra and is assigned as the asymmetric stretch of a proton between two nitrogens based on deuterium substitution. The position of this band agrees with the value predicted from a 2-dimensional potential energy surface. The reduced dimensionality of the potential energy surface, which treats the ion as though it has a linear geometry, predicts the zero-point energy level to be slightly above the calculated barrier to proton transit suggesting that this is a low-barrier hydrogen bond and the proton is equally shared between the two nitrogens. The cyclic diamine N,N,N',N'-tetramethyl-cis-1,5-diaminocyclooctane was synthesized and its 1-dimensional potential energy surface predicted the zero-point energy to be below the calculated barrier to proton transit suggesting that it is not a low-barrier hydrogen bond. The IRMPD and INS spectra will be recorded to determine if the value of the N-H-N asymmetric stretch matches with theory.;Nucleobases. The vibrational spectrum of proton-bound dimers consisting of 1-methylcytosine, 1,5-dimethylcytosine, and 5-fluoro-1-methylcytosine has been recorded and the structure of the dimers as well as the location of the band corresponding to the N-H-N asymmetric stretch were determined based upon comparisons with theoretical spectra and isotopic substitution. The proton between the two nucleobases prefers to be situated on one side of the dimer and is not equally shared between the two nitrogens based upon the presence of two IR bands in the spectrum of the proton-bound dimer formed between 1-methylcytosine and 1,5-dimethylcytosine that correspond to the N-H-N asymmetric stretches of the two tautomers of the dimer.