Campbell, Sherrie A. (1995) FT-ICR studies of the structures, energetics and reaction dynamics of biological molecules in the gas phase. Dissertation (Ph.D.), California Institute of Technology. http://resolver.caltech.edu/CaltechETD:etd-05122005-160230
Fourier transform ion cyclotron resonance (FT-ICR) mass spectroscopy has been used to investigate the energetics and reaction dynamics of biological molecules in the gas phase. Experimental results aid in predicting gas phase protonation sites and molecular conformations of peptides and amino acids. Correlations of proton affinities with adiabatic lone-pair ionization energies indicate that amino acids lacking basic side chains protonate on the amine nitrogen, while more basic amino acids protonate on their side chain. These results have been similarly applied to small peptides, with protonation predicted on the N-terminus for peptides lacking basic amino acid residues.
Two novel experimental methods have been developed for measuring gas phase proton affinities, which utilize infrared multiphoton dissociation and collision induced dissociation techniques to cleave proton-bound dimers of reagent gases. The dimers fragment into two products with the more basic reagent retaining the proton. A simplified RRKM analysis is used to determine proton affinities from product ion abundances.
Isotopic hydrogen exchange reactions of protonated glycine oligomers with a series of reagent bases have been performed, and the exchange mechanisms and energetics identified. Although it is not the sole determining factor, the extent and rates of H/D exchange increase with reagent basicity, with ND3 being the most efficient exchange gas studied. Exchange of the N-terminus hydrogens occurs via an onium ion mechanism in which an endothermic proton transfer is rendered energetically favorable by simultaneous solvation of the ammonium ion. Exchange of the C-terminus occurs via a salt bridge intermediate, in which the carboxylate and ammonium ion is stabilized by interactions with the nearby protonated N-terminus.
Finally, the H/D exchange reactions of several peptides possessing basic residues with ND3 have been investigated. The results indicate that basic amino acids hinder exchange processes as protonation energetics and molecular folding become more important. Calculations using semiempirical AM1 and PM3 methods were performed to identify the gas phase configurations of the protonated peptides and determine if stable salt bridge structures are possible. Potential energy surfaces were also calculated for all exchange processes.
|Item Type:||Thesis (Dissertation (Ph.D.))|
|Degree Grantor:||California Institute of Technology|
|Division:||Chemistry and Chemical Engineering|
|Thesis Availability:||Restricted to Caltech community only|
|Defense Date:||23 September 1994|
|Default Usage Policy:||No commercial reproduction, distribution, display or performance rights in this work are provided.|
|Deposited By:||Imported from ETD-db|
|Deposited On:||13 May 2005|
|Last Modified:||26 Dec 2012 02:41|
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