The study of proton and metal ion interactions with biomolecules by tandem mass spectrometry

This dissertation examines the so far unknown intrinsic thermochemistry of protonation and sodium ion attachment to selected bio- and functional molecules. The bond energies and entropies of the resulting cations are correlated to the corresponding structures and conformations. Fast atom bombardment tandem mass spectrometry (FAB-MS/MS) and the kinetic method are used to determine the thermochemical data based on the competitive unimolecular dissociations of proton-and sodium ion-bound heterodimer complexes containing the molecules of interest.; The extended version of the kinetic method is used to determine the proton affinity (PA) of β-alanine and four other difunctional molecules (α-alanine and three α,ω-diaminoalkanes) that can develop intramolecular hydrogen bonds after protonation. This method probes any difference in the activation entropies of the above mentioned competitive dissociation reactions, Δ(ΔS ‡), which is assumed to be negligible in the classical kinetic method, thereby deriving more accurate PA data. The measurements attest that the Δ(ΔS‡) obtained by the extended kinetic method is a relative entropy between the dissociation transition states at the actual, non-Boltzmann energy distribution of the dissociating proton-bound heterodimers.; Selected Na+-bound heterodimer pairs of nineteen dipeptides (AA; A represents an amino acid residue) are also generated in the gas phase. The dissociation kinetics of these complexes are determined via the classical kinetic method and converted into a scale of relative Na+ affinities. Absolute Na+ binding energies are obtained by anchoring the relative scale to the Na+ affinity of AlaAla, which was re-measured by the extended kinetic method using Na+bound heterodimers of AlaAla and a series of amino acids as reference bases. The Na+ affinity of AlaAla deduced from such heterodimers is found to be significantly higher than the affinity deduced from heterodimers with nucleobases. The thermochemical data obtained for the Na+-bound dipeptides reflect Lewis acid/base chemistry. Functional side chains generally enhance the metal ion binding energies by either providing more ligands to the metal ion (multidentate chelation) or promoting the formation of salt bridges (zwitterionic structures). Substantial increases in the metal ion binding energies are observed with aromatic and carbonyl functional substituents in the side chian, such as electron-rich (N-containing) aromatic and amide groups.