Isodesmic reaction for pK a calculations of common organic molecules

The DFT calculations of pKa values of the cationic acids of aniline and pyridine derivatives in common solvents

“…RMS error in other solvents are lower, however due to lack of some of the experimental values, it cannot be compared with calculations of water and THF solutions in this work. The accuracy of results obtained for pyridinium ions in water are similar to those presented in the work of Sastre et al (Sastre et al 2013), however the mean absolute deviation (MAD) in our work is 1.01 pK a units in water and 1.50 pK a units in THF comparing to their value 0.75 pK a units. While in their work the same functional and basis set were used, they have applied conductor-like polarizable continuum model (CPCM) with the UAKS (Frisch et al 2003) cavities instead.…”

“…For mono-substituted phenols, thiophenols and anilines, it has been found that B3LYP functional provided the energetics of both the homolytic and heterolytic bond cleavage in very good accordance with available experimental and/or theoretical results (Klein et al 2006, Klein and Lukeš 2006a, 2006b, 2006c, Vagánek et al 2011, 2013, Najafi et al 2012). The pK a values of carboxylic acids calculated using the same functional are also in acceptable accordance with experiment (Charif et al 2007, Namazian et al 2004, Dissanayake and Senthilnithy 2009, Sastre et al 2013. Calculations were performed in the 6-311++G** (Krishnan et al 1980, McLean and Chandler 1980, Curtiss et al 1995 basis set.…”

“…Since continuum solvent models do not reproduce the solvent structure around the solute, it is not possible to model the steric effects on the solvation of the amino group caused by its substituents (Sastre et al 2013). Thus the structural difference of 2,4,6-trimethylpyridine and its conjugate acid could be considered as the source of the highest absolute deviation, since the nitrogen lone electron pair is sterically hindered.…”

“…The solute-solvent boundary was defined by the Van der Waals surface. Gibbs free energies of all structures were calculated for 298.15 K. Applying an isodesmic reaction for the pK a calculation requires an experimental value of similar molecule in the same solvent (Sastre et al 2013). In our work, we have choosen anilinium and pyridinium ions as a reference species for their derivatives.…”

“…The use of such cycles is due to the fact that it is not rigorously correct to obtain the free energy of deprotonation in solution (ΔG solv ) by calculating the free energies of the involved species according to the rigid rotor-harmonic approximation in the continuum solvent. In fact, the rigorous calculation would require costly simulation methods in which the solvent is explicitly considered, together with a free energy calculation procedure (Sastre et al 2013). The use of thermodynamic cycles shows problems for those species that are gas-phase unstable or undergoes major conformational changes between gas-phase and solution-phase.…”