Computational Studies of the Gas-Phase Acidity and Basicity of Organic Molecules

The gas-phase acidities and basicities, or proton affinities, for many organic molecules are unknown. Yet this information can be an important reference tool in the study of bioorganic reaction mechanisms. Due to the complexity of some of the compounds, experimental measurements for acidity and basicity are not feasible. In those cases, reliance on quantum mechanical modeling data to determine theoretical values is necessary. This research focuses on selected organic acids, cholesterol derivatives, fatty acids, and amine containing compounds. The ionization ability of these organic molecules is largely dependent on the intrinsic acid-base properties of the molecule and can alter both their structure and function. Molecular modeling software (Gaussian and Gaussview) was used to predict molecular structures, to calculate energies associated with the structures, and to visualize three-dimensional shapes of the molecules. . The gas-phase acidity and proton affinity of these molecules (unknowns) were obtained by incorporating the calculated energetic values into a proton transfer reaction between the unknown molecule and a reference compound. These theoretically obtained acidity and proton affinity values were compared to available experimental data determined using mass spectrometry techniques. Good correlation was observed between theoretical values and experimental data. Our results showed that chain length had an effect on acidity and proton affinity of fatty acids, and compounds containing multiple ionizable groups displayed different acidity/basicity values for each group