Predicting pKa values from EEM atomic charges

Vařeková, Radka Svobodová; Geidl, Stanislav; Ionescu, Crina-Maria; Skřehota, Ondřej; Bouchal, Tomáš; Sehnal, David; Abagyan, Ruben; Koča, Jaroslav
June 2013
Journal of Cheminformatics;2013, Vol. 5 Issue 1, p1
Academic Journal
The acid dissociation constant pKa is a very important molecular property, and there is a strong interest in the development of reliable and fast methods for pKa prediction. We have evaluated the pKa prediction capabilities of QSPR models based on empirical atomic charges calculated by the Electronegativity Equalization Method (EEM). Specifically, we collected 18 EEM parameter sets created for 8 different quantum mechanical (QM) charge calculation schemes. Afterwards, we prepared a training set of 74 substituted phenols. Additionally, for each molecule we generated its dissociated form by removing the phenolic hydrogen. For all the molecules in the training set, we then calculated EEM charges using the 18 parameter sets, and the QM charges using the 8 above mentioned charge calculation schemes. For each type of QM and EEM charges, we created one QSPR model employing charges from the non-dissociated molecules (three descriptor QSPR models), and one QSPR model based on charges from both dissociated and non-dissociated molecules (QSPR models with five descriptors). Afterwards, we calculated the quality criteria and evaluated all the QSPR models obtained. We found that QSPR models employing the EEM charges proved as a good approach for the prediction of pKa (63% of these models had R2 > 0.9, while the best had R2 = 0.924). As expected, QM QSPR models provided more accurate pKa predictions than the EEM QSPR models but the differences were not significant. Furthermore, a big advantage of the EEM QSPR models is that their descriptors (i.e., EEM atomic charges) can be calculated markedly faster than the QM charge descriptors. Moreover, we found that the EEM QSPR models are not so strongly influenced by the selection of the charge calculation approach as the QM QSPR models. The robustness of the EEM QSPR models was subsequently confirmed by cross-validation. The applicability of EEM QSPR models for other chemical classes was illustrated by a case study focused on carboxylic acids. In summary, EEM QSPR models constitute a fast and accurate pKa prediction approach that can be used in virtual screening


Related Articles

  • Mechanism of phenol degradation processes induced by direct-current atmospheric-pressure discharge in air. Bobkova, E.; Sungurova, A.; Rybkin, V. // High Energy Chemistry;Jul2013, Vol. 47 Issue 4, p198 

    The phenol degradation kinetics and the buildup kinetics of the products hydroxyphenols, nitrophenols, carboxylic acids, and formaldehyde in electrolytic-cathode direct-current discharge have been studied, as well as the formation of nitric acid. On the basis of the results, a scheme of the...

  • QM quality atomic charges for proteins. Geidl, Stanislav; Ionescu, Crina-Maria; Vařeková, Radka Svobodová; Koča, Jaroslav // Journal of Cheminformatics;2014, Vol. 6 Issue Suppl 1, p1 

    An abstract of the article "QM quality atomic charges for proteins" by Stanislav Geidl, Crina-Maria Ionescu and colleagues is presented.

  • High-quality and universal empirical atomic charges for chemoinformatics applications. Geidl, Stanislav; Bouchal, Tomáš; Raèek, Tomáš; Vaøeková, Radka Svobodová; Hejret, Václav; Křenek, Aleš; Abagyan, Ruben; Koèa, Jaroslav // Journal of Cheminformatics;12/2/2015, Vol. 7, p1 

    Background: Partial atomic charges describe the distribution of electron density in a molecule and therefore provide clues to the chemical behaviour of molecules. Recently, these charges have become popular in chemoinformatics, as they are informative descriptors that can be utilised in...

  • Enhanced phenol bioavailability by means of photocatalysis. Wang, Jiewei; Zhang, Yongming; Yan, Ning; Chen, Jiwei; Rittmann, Bruce // Biodegradation;Sep2013, Vol. 24 Issue 5, p597 

    Phenol was investigated for the ability of TiO photocatalysis to increase its bioavailability as an electron donor for denitrification. The rate of nitrate removal by denitrification was increased by up to 2.6-fold by exposing phenol to photocatalysis for 30 min, although the rate decreased with...

  • Biobleaching chemistry of laccase-mediator systems on high-lignin-content kraft pulps. Chakar, Fadi S.; Ragauskas, Arthur J. // Canadian Journal of Chemistry;Feb2004, Vol. 82 Issue 2, p344 

    A high-lignin-content softwood kraft pulp was reacted with laccase in the presence of 1-hydroxybenzotriazole (HBT), N-acetyl-N-phenylhydroxylamine (NHA), and violuric acid (VA). The biodelignification response with violuric acid was superior to both 1-hydroxybenzotriazole and...

  • A Comparative Study of the Volatile Constituents of Southeast Asian Coffea arabica, Coffea liberica and Coffea robusta Green Beans and their Antioxidant Activities. Saw, Alex Keng-Chee; Wan-Sinn Yam; Keng-Chong Wong; Choon-Sheen Lai // Journal of Essential Oil-Bearing Plants;Jan2015, Vol. 18 Issue 1, p64 

    A comparative study on the volatile constituents of green beans of three commercially grown coffees in Southeast Asia, namely Coffea arabica, Coffea robusta and Coffea liberica, and their antioxidant properties was carried out. Volatile constituents of the green beans were isolated by...

  • Properties of bio-oil generated by a pyrolysis of forest cedar residuals with the movable Auger-type reactor. Shun Nishimura; Akio Miyazato; Kohki Ebitani // AIP Conference Proceedings;2016, Vol. 1709, p020026-1 

    Our research project has developed the new movable reactor for bio-oil production in 2013 on the basis of Augertype system. This package would be a great impact due to the concept of local production for local consumption in the hilly and mountainous area in not only Japan but also in the world....

  • Novel, simple method for the preparation of 7-hydroxy-4-phenylquinoline-2-carboxylic acid. Kozminykh, V. O.; Kirillova, E. A.; Nozdrin, I. N.; Dvorskaya, O. N.; Kozminykh, E. N. // Chemistry of Heterocyclic Compounds;Mar2010, Vol. 46 Issue 3, p358 

    The article presents information on the methodology for the preparation of the 7-hydroxy-4-phenylquinoline-2-carboxylic acid. It states that Derivatives of quinoline-2-carboxylic (quinaldic) acid are used as model structures of natural antibiotics and biologically active protein molecules. It...

  • The Raman-active O–H and O–D stretching vibrations and Raman spectra of gaseous formic acid-d1 and -OD. Bertie, John E.; Michaelian, Kirk H.; Eysel, Hans H.; Hager, Darcy // Journal of Chemical Physics;11/1/1986, Vol. 85 Issue 9, p4779 

    In keeping with current theoretical activity concerning the OH and OD stretching bands of the carboxylic acids, we report the Raman spectra of gaseous formic acid-OD and formic acid-d1 for the first time. We emphasize the OH and OD stretching bands, which can be studied cleanly in these...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics