Proton affinity and zwitterion stability: new results from infrared spectroscopy and theory of cationized lysine and analogues in the gas phase.

The gas-phase structures of alkali metal cationized lysine (Lys), alpha-N-methyllysine (NMeLys), and epsilon-N,N-dimethyllysine (Lys(Me)(2)) are investigated using infrared multiple photon dissociation (IRMPD) spectroscopy utilizing light generated by a free electron laser and ab initio calculations. The proton affinities of the compounds span a range of approximately 20 kJ/mol. For NMeLys x M(+), experiment and theory indicate that NMeLys is nonzwitterionic for M = Li and zwitterionic for M = Na and K. For Lys(Me)(2) x M(+), experiment and theory indicate that Lys(Me)(2) is zwitterionic for M = Li, Na, and K. This is the first spectroscopic observation of the zwitterionic form of an amino acid complexed with Li(+). The results are compared with IRMPD spectra reported previously for Lys and -N-methyllysine (Lys(Me)) complexed with Li, Na, and K, and new calculations performed at higher levels of theory for those ions. The combined experimental and theoretical results indicate that protonation in the zwitterionic forms of the these amino acids is favored at the more basic methylated amine site, but that any relationship between the proton affinity of the amino acid and the relative zwitterion stability of the alkali metal cationized amino acid is only indirect. These results provide additional evidence that proton affinities are not a reliable indicator of zwitterion stability for cationized amino acids because side chains can have very different effects on the stability of different conformers in the neutral, protonated, and metal cationized forms.