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

Abstract

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 pK a 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 pK a 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 pK a 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 R 2 higher than 0.9, whereas results received from G4MP2 deviate strongly. The calculated pK a 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 pK a 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 pK a calculations of different classes of compounds.

Charge-State Dependence of Proton Uptake in Polyoxovanadate-alkoxide Clusters

“…To quantify the strength of the acid required for surface activation of 1-V IV 6 O 7 2– , we explored the reactivity of the reduced assembly with a series of organic acids, all of which possess acid dissociation constants that have been reported in MeCN ( Table S1 ). 45 , 52 − 55 As discussed above, the 1 H NMR spectrum of the crude reaction mixture of 1-V IV 6 O 7 2– with [HNEt 3 ][BF 4 ] reveals four paramagnetically shifted and broadened resonances ( Figure S1 ); three of these signals correspond to the oxygen-deficient assembly 2-V III V IV 5 O 6 1 – (δ = 25.3, 23.9, and −15.6 ppm), while the fourth signal corresponds to the fully oxygenated species 3-V IV 5 V V O 7 1– (δ = 23.4 ppm). It is important to note that the signal assigned to the protons of the methoxide substituents of the starting material, 1-V IV 6 O 7 2– , is observed at a similar chemical shift (δ = 23.9 ppm).…”

When biomolecules meet 2-hydrazinopyrazine: from theory through experiment to molecular levels using a wide spectrum of techniques

“…48 It was assumed that the Gibbs free energy of a proton is À6.28 kcal mol À1 in vacuo and À265.9 kcal mol À1 in water, and the correction for the change in the Gibbs free energy arising from the conversion of the standard states (1 M to 1 atm) is 1.89 kcal mol À1 . 34,49 Partition coefficient studies were performed in a water/noctanol system. Gas phase minima geometries were optimized at the PCM/B3LYP/6-311+G** and SMD/M06-2X/6-311+G** levels in water and n-octanol.…”

Low-Molecular Pyrazine-Based DNA Binders: Physicochemical and Antimicrobial Properties

“…The analyses of structure, conformation, and tautomerism of the studied compounds were conducted with B3LYP (Becke's three-parameter Lee-Yang-Parr) [59] functional and the split-valence 6-311+G** basis set in vacuo. It has been shown previously that the use of such a type of basis set reproduces experimental results reasonably well and is not expensive in terms of computational time [60]. The molecular structures of the compounds were fully optimized, and the total Gibbs free energies were determined at the same level of theory, along with vibration frequencies and their IR spectra.…”

“…The free energy of the proton was assumed as −6.28 kcal/mol in a vacuum and −265.9 kcal/mol in water. The correction of the Gibbs free energy change resulting from the conversion of standard states (1 M to 1 atm) was also applied and was assumed to be 1.89 kcal/mol [30,60].…”