Computational Determination of Aqueous pKa Values of Protonated Benzimidazoles (Part 1)
- 20 April 2006
- journal article
- research article
- Published by American Chemical Society (ACS) in The Journal of Physical Chemistry B
- Vol. 110 (18), 9270-9279
- https://doi.org/10.1021/jp055084i
Abstract
Benzimidazoles are the organic compounds investigated in this work. The experimental determination of the pKa values of protonated benzimidazoles in water is a challenge because of their low solubility. In addition, some derivatives are involved in tautomeric equilibria which increase the complexity of the theoretical pKa determinations. In the present study, different approaches are considered to develop a methodology for the accurate prediction of aqueous pKa values of protonated benzimidazoles at 298.15 K. We have considered different reaction schemes for approximating the acid dissociation equilibrium; two distinct equations are used for the calculation of pKa values, and a number of levels of theory and empirical corrections are applied in the process of working toward this aim. The best correlations between the experimental and calculated data are obtained at the B3LYP/6-31+G(d,p)-PCM(opt) level of theory. The predictive capabilities of the methodologies attempted are tested with two compounds that were not included in the set of benzimidazoles initially investigated. The direct calculations differ significantly from the expected values, but the pKa values calculated using the correlation equations are very similar and in reasonable agreement with the expected pKa values.Keywords
This publication has 31 references indexed in Scilit:
- pKaValues of Guanine in Water: Density Functional Theory Calculations Combined with Poisson−Boltzmann Continuum−Solvation ModelThe Journal of Physical Chemistry B, 2002
- A new integral equation formalism for the polarizable continuum model: Theoretical background and applications to isotropic and anisotropic dielectricsThe Journal of Chemical Physics, 1997
- Determination of thermodynamic aqueous acid-base stability constants for several benzimidazole derivativesJournal of Chemical & Engineering Data, 1993
- Acid and base dissociation constants of water and its associated ionsJournal of Chemical Education, 1991
- The Ka values of water and the hydronium ion for comparison with other acidsJournal of Chemical Education, 1990
- Basicity and acidity of azoles: the annelation effect in azolesJournal of the American Chemical Society, 1988
- Development of the Colle-Salvetti correlation-energy formula into a functional of the electron densityPhysical Review B, 1988
- Who knows the Ka values of water and the hydronium ion?Journal of Chemical Education, 1986
- Development and use of quantum mechanical molecular models. 76. AM1: a new general purpose quantum mechanical molecular modelJournal of the American Chemical Society, 1985
- Note on an Approximation Treatment for Many-Electron SystemsPhysical Review B, 1934