Correlations of lone pair ionization energies with proton affinities of amino acids and related compounds. Site specificity of protonation

The gas phase proton affinities of amino acids are compared with their adiabatic ionization energies obtained from photoelectron spectra. Using primary aliphatic amines as reference species, a linear correlation is found between the proton affinities and the adiabatic nitrogen lone pair ionization energies for those amino acids which protonate on the amine group, even in cases where the nitrogen lone pair is not the highest occupied molecular orbital. Many of the amino acids fit the correlation well, which confirms the prediction of amine protonation from earlier studies and also corroborates the assignment of the bands in the complex photoelectron spectra of these species. Proline and safcosine, amino acids with a secondary nitrogen, deviate from this correlation and instead fit a correlation using secondary aliphatic amines as reference species. Deviations from the correlation exist for molecules, such as lysine, methionine and tryptophan, which contain an intramolecular hydrogen bond between the basic side-chain and the amine site. The gas phase proton affinities of these species are larger than predicted by the correlation. Deviations from the correlation are also predicted for very basic amino acids, such as histidine and arginine, which protonate preferentially on the side-chain instead of the amine group.