Comparative assessment of the direct and isodesmic methods for pKa calculation of monocarboxylic acids using density functional theory

Author(s)

Dutra, Felipe Ribeiro ; Custodio, Rogerio

• Document type: Journal article
• Source: COMPUTATIONAL AND THEORETICAL CHEMISTRY; v. 1237, p. 10-pg., 2024-05-07.

Abstract

This study utilizes direct and isodesmic methods to determine the pKa of monocarboxylic acids. Twenty-four density functionals are tested using Dunning's aug-cc-pVDZ and aug-cc-pVTZ basis sets, incorporating the SMD model for implicit solvent effects and two explicit water molecules near the carboxyl group. Both methods achieve mean absolute errors below 0.5 pKa units, with hybrid functionals showing superior performance, while local density functionals also yield significant results. The comparative effectiveness of aug-cc-pVTZ and aug-ccpVDZ is assessed. The selection of appropriate training sets for the direct method and reference acids for the isodesmic method is crucial, with diverse acids in the training set reducing errors in the direct method and closely related reference acids enhancing precision in the isodesmic method. B3PW91 exhibited particularly outstanding performance, proving to be the most reliable for accurate pKa predictions across different setups. (AU)

• FAPESP's process: 13/08293-7 - CCES - Center for Computational Engineering and Sciences
• Grantee: Munir Salomao Skaf
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 17/11485-6 - Computational and theoretical developments based on ab initio methods and the Density Functional Theory
• Grantee: Rogério Custodio
• Support Opportunities: Regular Research Grants
• FAPESP's process: 21/03201-3 - Study of the direct method for calculating pKa for different multiprotic species from quantum calculations
• Grantee: Felipe Ribeiro Dutra
• Support Opportunities: Scholarships in Brazil - Doctorate