Protonation energies and the Laplacian of the electron density: A criticalexamination

The success and limitations of the Laplacian of the electron density in pre dicting protonation energies is systematically discussed for a selection of molecules, including aldehydes, amines, amides and diglycine. We address f our questions related to (a) the preference between competing protonation s ites, (b) correlations between the Laplacian and the protonation energy in substituted homologous series and (c) upon conformational change and (d) th e Laplacian's uniqueness in using information stored in the unprotonated mo lecule. This study forms a solid basis to investigate the use of the Laplac ian in the rationalisation of mass spectrometric fragmentation patterns of peptides.