QSPR Prediction of pK_a for Benzoic Acids in Different Solvents

Abstract

A Computational Neural Network (CNN) derived model is proposed for the pK a prediction of benzoic acids in different solvents. The system studied contains 519 pK a values corresponding to 136 benzoic acids determined in water and in 8 organic solvents. The benzoic acids were described by the usual molecular descriptors and the solvents by a number of physical properties and by several parameters of the most widely used polarity solvent scales. The model is composed of seven descriptors -five of them corresponding to the solute and the other two to the solvents -and was validated by an external prediction set. The three sets of values needed in the analysis, training, prediction, and cross-validation, have the same squared correlation coefficient (0.998) and Root-Mean Square Error (RMSE) (0.21) values. The robustness of the model is also given for the statistical results for small subsets, such as ortho-and non-ortho-substituted acids, those obtained in protic or aprotic solvents, those obtained in each solvent, and even those for the set of pK a values of one specific acid in several solvents. The descriptors encode information about the chemical nature of the solutes and the solvents that is clearly related to the interactions present in the dissociation process in solution. The derived model also has the ability to predict pK a values of a larger set of aromatic neutral acids, containing both phenols and benzoic acids.

Analysis of phenolic acids by non-aqueous capillary electrophoresis after electrokinetic supercharging

“…This range is highly relevant given that it is well known that the pK a of weak acids in MeOH increases by approximately 5 pH units, meaning that the pK a values for the weak acids used in this work are likely to fall near this range. A thorough search through the literature reveals pK a values in MeOH for 2,4-dihydroxybenzoic acid of 8.48 (pK a H 2 O of 3.29, pK a 5.19) [50], 2,5-dihydroxybenzoic acid of 8.04 (pK a H 2 O of 2.97, pK a 5.07) [50] and 4-hydroxybenzoic acid of 9.99 (pK a H 2 O of 4.55, pK a 5.44) [51]. No values in MeOH have been reported for the remaining phenolic acids.…”

QSPR Prediction of pK for Aliphatic Carboxylic Acids and Anilines in Different Solvents

“…The CNNs used are three-layer, fully connected, feed-forward networks, that were employed in our previous papers on the pK a estimation of phenols [4] and benzoic acids [5], and have been described in detail by Jurs and coworkers [60,61]. The number of neurons of the input layer corresponds to the number of descriptors in the model.…”

“…More recently, we have applied this approach to predict the acidity in water and also in several organic solvents of phenols and benzoic acids [4,5]. In the study of these multicomponent systems, we have developed non-linear models, by means of Computational Neural Networks (CNN), that contain the habitual molecular descriptors of the solutes as well as others that characterize the solvents as a bulk.…”

Complexes of 2,6-dihydroxybenzoic acid with divalent metal ions: Synthesis, crystal structure, spectral studies, and biological activity enhancement

“…Since dissociation of the ligand at its carboxyl moiety have a pK a1 of 0.94, thus ideally pH~4 was sufficient to provide the environment for the dissociation of the ligand. The dissociation provides negative charge to the ligand thus allowed it to bind metal ion which has positive charge [16,17]. However, results on crystal structure of the complexes indicate that formation of the complex did not occur through the coordination of dissociated -O donor group of DHBA.…”