Dramatic medium effects on reactivity. The ionization sites of pyrrole andindole carboxylic acids

The intrinsic (gas phase) acidities of pyrrole- and indole-2- and 3-carboxy lic acids as well as those of methyl indole-3-carboxylate and 1-methyl indo le-3-carboxylic acid have been measured by means of Fourier Transform Ion C yclotron Resonance (FT-ICR) mass spectrometry. Ab initio molecular orbital and DFT calculations were performed at several levels of theory on all the relevant species. This study was extended to the same species in aqueous so lution by means of the continuum model implemented in the SCRFPAC program. The calculated acidities, both in the gas phase and in solution, are in ver y good agreement with the experimental data and conclusively show that (i) pyrrole- and indole-3-carboxylic acids behave as NH acids in the gas phase, (ii) in the gas phase, pyrrole- and indole-2-carboxylic acids are deproton ated at the COOH group, although competing ionizations possibly take place, and (iii) these four compounds behave in aqueous solution as OH acids.