First-Principles Calculation of pK_a for Cocaine, Nicotine, Neurotransmitters, and Anilines in Aqueous Solution

Abstract

The absolute pK a values of 24 representative amine compounds, including cocaine, nicotine, 10 neurotransmitters, and 12 anilines, in aqueous solution were calculated by performing first-principles electronic structure calculations that account for the solvent effects using four different solvation models, i.e. the surface and volume polarization for electrostatic interaction (SVPE) model, the standard polarizable continuum model (PCM), the integral equation formalism for the polarizable continuum model (IEFPCM), and the conductor-like screening solvation model (COSMO). Within the examined computational methods, the calculations using the SVPE model lead to the absolute pK a values with the smallest root-mean-square-deviation (RMSD) value (1.18). When the SVPE model was replaced by the PCM, IEFPCM, and COSMO, the RMSD value of the calculated absolute pK a values became 3.21, 2.72, and 3.08, respectively. All types of calculated pK a values linearly correlate with the experimental pK a values very well. With the empirical corrections using the linear correlation relationships, the theoretical pK a values are much closer to the corresponding experimental data and the RMSD values become 0.51 to 0.83. The smallest RMSD value (0.51) is also associated with the SVPE model. All of the results suggest that the first-principles electronic structure calculations using the SVPE model are a reliable approach to the pK a prediction for the amine compounds.

Bimodal Concentration-Response of Nicotine Involves the Nicotinic Acetylcholine Receptor, Transient Receptor Potential Vanilloid Type 1, and Transient Receptor Potential Ankyrin 1 Channels in Mouse Trachea and Sensory Neurons

“…4A). Although these deficits were evident at pH 7.4 of the extracellular nicotine solution, they were much more prominent at pH 9.0 when the alkaloid is largely uncharged (pK a 8.02; Lu, Chen, Zhan, 2007) and, thus, well membrane-permeable. This is most likely due to the fact that both TRP receptor-channels have their binding sites for most agonists at the intracellular site of the transmembrane proteins (Vriens et al, 2009).…”

Theoretical calculations of the relative pKa values of some selected aromatic arsonic acids in water using density functional theory

“…Accordingly, many researchers are tending to calculation of pKa values using theoretical and computational approaches. 21,[24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41] Recently quantum chemical calculations, using thermodynamical parameters such as Gibbs free energy, have reported good correlations between calculated and experimental acidities of a wide range of organic and inorganic acids. 18,[42][43][44][45][46][47][48][49][50] For example, gas phase and solution phase acidities of some organic compounds investigated by Namazian et al and Kheirjou et al reported good correlation between ab initio calculations of pKa values with the experimental data.…”

Prediction of acidity in acetonitrile solution with COSMO‐RS

“…Of the different quantum chemical methodologies available for the computation of pK a values the dielectric continuum solvation methods (DCSMs 9 ) have become quite popular in the recent years [10][11][12][13][14][15][16][17] since they are able to describe accurately long range electrostatic interactions of solutes at moderate computational cost in the context of quantum chemical programs. Despite the well-known deficiencies of DCSM methods, (i.e.…”