Computational Studies of the Gas-Phase Acidity and Proton Affinity of Organic Compounds

The ability of an organic compound to form ions in the gas phase depends largely on its strength as an acid or a base. This information can be used alongside mass spectrometry data to better understand ionization efficiency. Some compounds are so complex that, measurements for acidity and basicity become challenging to perform experimentally. For this reason, molecular modeling calculations are used to determine the theoretical value Lowest energy conformer of the neutral, deprotonated, and protonated molecule were obtained by conformer search using the Merck Molecular force field followed by AM1 geometry optimization using Spartan 08. Geometry and frequency calculation is at B3LYP/6-31+G(d) level of theory using Gaussian 09. The gas phase acidity/Proton affinity is calculated by an isodesmic reaction scheme with a selected reference acid/base. Computational studies were performed on 30 compounds that included alcohols, carboxylic acids, ketones, amines, and cholesterol derivatives. Most of these compounds did not have reported gas phase acidity/proton affinity data. Validation of the method was carried out and the values correlated closely with the available experimental values (\u3c 1% error). The results showed that for fatty acids, the length of the hydrocarbon chain had a minimal effect on the gas phase acidity and proton affinity. Increasing from a 6-carbon chain to a 12-carbon, the gas phase acidity values were within 1 kcal/mol of each other and the basicity values were within 6 kcal/mol. This study also included compounds that had multiple acidity and basicity sites; these compounds had unique values for each group