SEMI-EMPIRICAL MODEL FOR PREDICTING PHENOL CARBOXYLIC ACIDS ANTIRADICAL ACTIVITY
Abstract
Using the spectral method, the rate constants of natural phenolcarboxylic acids reaction with the radical 2,2'-diphenyl-1-picrylhydrazyl in benzene at a temperature of 293±2 K were determined. It is established that the reaction corresponds to the second-order kinetic equation and proceeds by the mechanism of the hydrogen atom transfer. This confirmed by the presence of the deuterium isotope effect. The parameter, affecting the proceed of this mechanism in a non-polar medium, is the energy of the homolytic rupture of the weakest phenolic O–H bond in the phenolcarboxylic acid molecule, calculated using the quantum-chemical methods. Changes in the strength of phenolic O–H bonds in an acid molecule lead to corresponding changes in their reactivity with respect to the hydrazyl radical. It is seen that the compounds with low bond strengths of functional groups – 3 pyrogallolcarboxylic and gallic acids, methyl- and ethyl- gallate – showed the most antiradical activity. According to the calculated and experimental data, a semiempirical linear single-factor equation is proposed. This equation describes the relationship between the antiradical activity of phenolic acids and the descriptor of their structure and allows to predict the reactivity of the antioxidant in lipid-like media. The applicability of the proposed model was proved by studying the control group of hydroxyacetophenones which belong to plant phenol compounds. According to the forecast, 3,4- and 2,5-hydroxyacetophenones can be recommended as potential effective antioxidants in non-polar environments. The unit relative deviations of the predicted rate constants from their experimental values vary from 2 to 9% with an average approximation error equals to 7.9%, which indicates a good selection of the linear model.
References
Chen Y., Xiao H., Zheng J., Liang G. Structure-Thermodynamics-Antioxidant Activity Relationships of Selected Natural Phenolic Acids and Derivatives: An Experimental and Theoretical Evaluation. PLoS ONE. 2015. V. 10. N 3. P. 1-20. DOI: 10.1371/journal.pone.0121276.
Zou T., He T., Li H., Tang H., Xia E. The structure-activity relationship of the antioxidant peptides from natural proteins. Molecules. 2016. V. 21. N 1. P. 1-14. DOI: 10.3390/molecules21010072.
Filipović M., Marković Z., Dorović J., Marković J., Lučić B., Amić D. QSAR of the free radical scavenging potency of selected hydroxybenzoic acids and simple phenolics. Comptes Rendus Chimie. 2015. V. 18. N 5. P. 492-498. DOI: 10.1016/j.crci.2014.09.001.
Das S., Mitra I., Batuta S., Niharul Alam M., Roy K., Begum N. Design, synthesis and exploring the quantitative structure-activity relationship of some antioxidant flavonoid analogues. Bioorg. Med. Chem. Lett. 2014. V. 24. N 21. P. 5050-5054. DOI: 10.1016/j.bmcl.2014.09.028.
Sarkar A., Middya T., Jana A. A QSAR study of radical scavenging antioxidant activity of a series of flavonoids using DFT based quantum chemical descriptors - The importance of group frontier electron density. J. Molec. Model. 2012. V. 18. N 6. P. 2621-2631. DOI: 10.1007/s00894-011-1274-2.
Mladenović M., Mihailović M., Bogojević D., Matić S., Nićiforović N., Mihailović V., Vuković N., Sukdolak S., Solujić S. In vitro antioxidant activity of selected 4-hydroxy-chromene-2-one derivatives-SAR, QSAR and DFT studies. Internat. J. Molec. Sci. 2011. V. 12. N 5. P. 2822-2841. DOI: 10.3390/ijms12052822.
Amić D., Lučić B. Reliability of bond dissociation enthalpy calculated by the PM6 method and experimental TEAC values in antiradical QSAR of flavonoids. Bioorg. Med. Chem. 2010. V. 18. N 1. P. 28-35. DOI: 10.1016/j.bmc.2009.11.015.
Khanam U., Oba S., Yanase E., Murakami Y. Phenolic acids, flavonoids and total antioxidant capacity of selected leafy vegetables. J. Funct. Food. 2012. V. 4. N P. 979-987. DOI: 10.1016/j.jff.2012.07.006.
Vermerris W., Nicholson R. Phenolic Compound Biochemistry. Dodrecht: Springer. 2006. 275 p.
Pérez-González A., Galano A., Alvarez-Idaboya J.R. Dihydroxybenzoic acids as free radical scavengers: mechanisms, kinetics, and trends in activity. New J. Chem. 2014. V. 38. P. 2639-2652. DOI: 10.1039/c4nj00071d.
Villaño D., Fernández-Pachón M., Moyá M., Troncoso A., García-Parrilla M. Radical scavenging ability of polyphenolic compounds towards DPPH free radical. Talanta. 2007. V. 71. N 1. P. 230-235. DOI: 10.1016/j.talanta.2006.03.050.
Kedare S.B., Singh R.P. Genesis and development of DPPH method of antioxidant assay. J. Food Sci. Technol. 2011. V. 48. N 4. P. 412-422. DOI: 10.1007/s13197-011-0251-1.
Fadda A., Serra M., Molinu M. G., Azara E., Barberis A., Sanna D. Reaction time and DPPH concentration influence antioxidant activity and kinetic parameters of bioactive molecules and plant extracts in the reaction with the DPPH radical. J. Food Composit. Anal. 2014. V. 35. N 2. P. 112–119. DOI: 10.1016/j.jfca.2014.06.006.
Marinova G., Batchvarov V. Evaluation of the methods for determination of the free radical scavenging activity by DPPH. Bulg. J. Agric. Sci. 2011. V. 17. N 1. P. 11-24.
Alam Md.N., Bristi N.J., Rafiquzzama Md. Review on in vivo and in vitro methods evaluation of antioxidant activity. Saud. Pharmaceut. J. 2013. V. 21. P. 143–152. DOI: 10.1016/j.jsps.2012.05.002.
Belaya N.I., Belyi A.V., Zarechnaya O.M., Shcherbakov I.N., Doroshkevich V.S. Transition State Structure and Mechanism of the Reaction of Hydroxybenzenes with N-Centered Radical in Non-Ionizing Media. Russ. J. Gen. Chem. 2018. V. 88. N 7. P. 1351-1362. DOI: 10.1134/S013434751807001X.
Belaya N., Belyj A., Zarechnaya O., Shcherbakov I., Mikhalchuk V., Doroshkevich V. The effect of the medium polarity on the mechanism of the reaction of hydroxybenzenes with hydrazyl radical in aprotic solvents. Russ. J. Gen. Chem. 2017. V. 87. N 4. P. 690-697. DOI: 10.1134/S1070363217040053.
Aliaga C., Almodovar I., Rezende M.C. A single theoretical descriptor for the bond-dissociation energy of substituted phenols. J. Mol. Model. 2015. V. 21. N 1. P. 1-12. DOI: 10.1007/s00894-015-2572-x.
Frisch M.J., Trucks G.W., Schlegel H.B., Scuseria G.E., Robb M.A., Cheeseman J.R., Scalmani G., Barone V., Mennucci B., Petersson G.A., Nakatsuji H., Caricato M., X.Li, Hratchian H.P., Izmaylov A.F., Bloino J., Zheng G., Sonnenberg J.L., Hada M., Ehara M., Toyota K., Fukuda R., Hasegawa J., Ishida M., Nakajima T., Honda Y., Kitao O., Nakai H., Vreven T., Montgomery J.A., Jr., Peralta J.E., Ogliaro F., Bearpark M., Heyd J.J., Brothers E., Kudin K.N., Staroverov V.N., Keith T., Kobayashi R., Normand J., Raghavachari K., Ren-dell A., Burant J.C., Iyengar S.S., Tomasi J., Cossi M., Rega N., Millam J.M., Klene M., Knox J.E., Cross J.B., Bakken V., Adamo C., Jaramillo J., Gomperts R., Stratmann R.E., Yazyev O., Austin A.J., Cammi R., Pomelli C., Ochterski J.W., Martin R.L., Morokuma K., Zakrzewski V.G., Voth G.A., Salvador P., Dannenberg J.J., Dapprich S., Daniels A.D., Farkas O., Foresman J.B., Ortiz J.V., Cioslowski J., Fox D.J. Gaussian 09, Revision B.01 Gaussian, Inc., Wallingford CT, 2010.
Tomasi J., Mennucci B., Cammi R. Quantum mechanical continuum solvation models. Chem. Rev. 2005. V. 105. N 8. P. 2999-3093. DOI: 10.1021/cr9904009.
