Evaluation of metal binding interactions in host-guest chemistry using quadrupole ion trap mass spectrometry

Metal binding interactions were investigated in host-guest complexes using quadrupole ion trap mass spectrometry. A series of polyamine ligands were first analyzed to determine their gas-phase basicities. The proton-binding affinities of the polyamines correlated with the number of nitrogen donor atoms as well as the ability to form favorable intramolecular hydrogen bonds. These ligands were then complexed with alkali metal ions in solution, and the behaviors of singly protonated, doubly protonated, and alkali metal cationized species were compared via hydrogen/deuterium exchange in the gas-phase. Both protonated species underwent noticeable exchange, however exchange for the alkali metal cationized species was effectively quenched. A kinetic analysis revealed that the first rate constant for exchange of the alkali metal cationized species was at least 3600 times lower than the analogous rate constant for the singly protonated species for one polyamine ligand. Another gas-phase study was undertaken involving pyridyl ligands as hosts and monopositive transition metal ions as guests. The ability of larger, chelating ligands to displace smaller ligands from dimer or trimer ligand/metal complexes was evaluated, and in many cases evidence of stepwise displacement was found. However, displacement was greatly reduced when the metal ion was fully solvated by smaller, chelating ligands due to steric effects and ligand repulsions.; In conjunction with electrospray ionization, mass spectrometry was also used to evaluate metal binding interactions in solution in two cases. First the alkali metal binding selectivities of a group of caged crown ligands was evaluated in comparison to non-caged reference crown ethers. In these experiments, the mass spectral intensities of the metal complexes were used to determine the equilibrium distribution of the complexes in solution. Differences in the selectivities between the reference hosts and the caged hosts were attributed to the presence of the cage moiety. Finally, the binding interactions of metal mediated DNA binding drugs to DNA oligomers were examined. The presence and identity of the metal ion and the base-pair sequence of the oligomer affected the binding of the drugs to the different aligomers studied.