Calculations of pKa Values of Selected Pyridinium and Its N-Oxide Ions in Water and Acetonitrile.

Pyridine, its N-oxide, and their derivatives are exciting classes of organic bases. These compounds show widespread biological activity, and they are often used in synthesis. In this work results on theoretical calculations of acid dissociation constants as pKa of pyridine, its N-oxide, and their derivatives were done based on the thermodynamic cycle in water and acetonitrile. Additionally, gas-phase basicity (GB) and proton affinity (PA) values were computed for systems studied. All pKa values were obtained using B3LYP, M06-2X, and G4MP2 methods in the gas phase, which were combined with the PCM model calculations (at the Hartree-Fock method) and with the use of four different scale factors alpha. Theoretical GB, PA, and pKa values were then compared with the available experimental ones. Results obtained from B3LYP and M06-2X methods are quite similar and compatible with experimental ones in terms of quality with correlation coefficients values R2 higher than 0.9, whereas results received from G4MP2 deviate strongly. The calculated pKa values are highly sensitive to the scale factors alpha used in the computational procedure. Root-mean-square deviations (RMSD) between both theoretically and experimentally available pKa values of systems studied were also computed. The RMSD values are lower than 0.8 for the best results, suggesting that the theoretical model presented in this work is promising for applications for pKa calculations of different classes of compounds.