Empirically Fitted Parameters for Calculating pKa Values with Small Deviations from Experiments Using a Simple Computational Strategy

• Published in: Journal of chemical information and modeling Vol. 56; no. 9; pp. 1714 - 1724
• Main Authors: Galano, Annia, Pérez-González, Adriana, Castañeda-Arriaga, Romina, Muñoz-Rugeles, Leonardo, Mendoza-Sarmiento, Gabriela, Romero-Silva, Antonio, Ibarra-Escutia, Agustin, Rebollar-Zepeda, Aida Mariana, León-Carmona, Jorge Rafael, Hernández-Olivares, Manuel Alejandro, Alvarez-Idaboy, Juan Raúl
• Format: Journal Article
• Language: English
• Published: United States 26.09.2016
• Subjects: Amines - chemistry; Carboxylic Acids - chemistry; Hydrogen-Ion Concentration; Informatics - methods; Phenols - chemistry; Statistics as Topic; Thermodynamics; Water - chemistry
• ISSN: 1549-960X
• DOI: 10.1021/acs.jcim.6b00310

Two empirically fitted parameters have been derived for 74 levels of theory. They allow fast and reliable pKa calculations using only the Gibbs energy difference between an acid and its conjugated base in aqueous solution (ΔGs(BA)). The parameters were obtained by least-squares fits of ΔGs(BA) vs experimental pKa values for phenols, carboxylic acids, and amines using training sets of 20 molecules for each chemical family. Test sets of 10 molecules per family-completely independent from the training set-were used to verify the reliability of the fitting parameters method. It was found that, except for MP2, deviations from experiments are lower than 0.5 pKa units. Moreover, mean unsigned errors lower than 0.35 pKa units were found for the 98.6%, 98.6%, and 94.6% of the tested levels of theory for phenols, carboxylic acids and amines, respectively. The parameters estimated here are expected to facilitate computationally based estimations of pKa values of species for which this magnitude is still unknown, with uncertainties similar to the experimental ones. However, the present study deals only with molecules of modest complexity, thus the reliability of the FP method for more complex systems remains to be tested.