Structure-radical scavenging activity relationships of hydroxytoluene derivatives

Authors

Department of Pharmaceutical Chemistry, School of Pharmacy, Addis Ababa University, Addis Ababa 1176, Ethiopia

Abstract

Research works proposed that radical scavenging activity of flavonoids is due to ring B, and
the remaining part of the molecule can be disregarded. Thus the objective of this work is to
observe whether hydroxytoluenes account the radical scavenging activity of flavonoid and to
establish structural requirements for their activity (as they showed appreciable activity) and
elucidate a comprehensive mechanism that can explain their activity and termination. Thus, the
radical-scavenging activity of nine hydroxytoluene derivatives against 2,2-diphenyl-1-
picrylhydrazyl, DPPH was determined. The relative change in energy (ΔHf) associated with the
formation of phenolic radicals and the spin distributions in these radicals were determined using
computational programs (Density function theory and Hartree Fock). By correlating
experimental data with ΔHf, the most active compounds and structural features that are
responsible for their activities were identified. Reaction product of 4-methyl catechol with 2,2-
diphenyl-1-picrylhydrazyl, DPPH was isolated and characterized in order to unravel the
mechanism of termination of most active hydroxytoluenes. Termination enthalpy (ΔH2) of
methyl-catechols and methyl-hydroquinone, once the termination mechanism explained, was
calculated to understand its role in the radical scavenging activity.

Keywords


[1] H.Y. Zhang, Cur. CADD 1 (2005) 257-272.
[2] S.H. Pine, Organic chemistry. 5th edition, Tata-McGram –Hill Publishing Company Ltd., New Delhi,
India, 2006.
[3] http://en.wikipedia.org/wiki/Radical_(chemistry) /accessed on Nov.2, 2009.
[4] V. Butkovicä, L. Klasinc, W. Bors, J. Agric. Food Chem. 52 (2004) 2816-2820.
[5] C. Guohua, S. Emin, L. Ronald, Free Radic. Biol. Med. 22 (1997) 749-760.
[6] D.I. Tsimogiannis, V. Oreopoulou, Innov. Food Sci. Emerg. Tech. 7 (2006) 140-146.
[7] D. Amić, S. Davidovi, N.Trinajsti, Chem. Acta, 76 (2003) 55-65.
[8] W. Bors, C. Michel, K. Stettmaier, Biofactors 6 (1997) 399-402.
[9] B. Stanislaw, O. Wieslaw, J. Agric. Food Chem. 49 (2001) 2774-2779.
[10] A. Francisco, M. Silva, B. Fernanda, G. Carla, J. Agric. Food Chem. 48 (2000) 122-126.
[11] C.G.M. Heijnen, J.A.J.M. Haenen, Environ. Toxicol. Pharmacol. 10 (2001) 199-206.
[12] H. Yu Zhang, Y. Min Sun, D. Zhang, Chin. Chem. Lett. 13 (2002) 531-534.
[13] T.A. Kennedy, D.C. Liebler, J. Biol. Chem. 267 (1992) 4658-4663.
[14] A. Seyoum, K. Asres, F.K. El-Fiky, Photochemistry 67 (2006) 2058-2070.
[15] M. Bruits, K. Asres, F. Bucar, Phytother. Res. 15 (2001) 103-108.
[16] J. Vaya, S. Mahmood, A. Goldblum, M. Aviram, N. Volkova, A. Shaalan, R. Musa, S. Tamir,
Phytochemistry 62 (2003) 89-99.
[17] J.P. Jones, M. Mysinger, K.R. Korzekwa, Drug Metab. Dispos. 30 (2002) 7-12.
[18] H. Hussain, G. Babic, T. Durst, S. James, M. Flueraru, A. Chichirau, C. Leonid, J. Org. Chem. 68
(2003) 7023-7032.
[19] D.I. Tsimogiannis, V. Oreopoulou, Innov. Food Sci. Emerg. Tech. 5 (2004) 523-528.
[20] K. Ikihir, D. Boureima, B. Dabkoulodo, Int. J. Pharmacog. 4 (1992) 251-262.
[21] R. Gažák, P. Sedmera, M. Vrbacký, J. Vostálová, Z. Drahota, P. Marhol, D. Walterová, K. Vladimír,
Free Radi. Biol. Med. (2009) 745-752.
[22] G. Glässer, E.U. Graefe, F. Struck, M. Veit, R. Gebhardt, Phytomedicine 9 (2002) 33-40.
[23] G. Litwinienko, K. Ingold, J. Org. Chem. 68 (2005) 7023-7032.
[24] P. Molyneux, Songklanakarin J. Sci. Technol. 26 (2004) 211-219.
[25] D. Huang, O. Boxin, L. Ronald, J. Agric. Food Chem. 53 (2005) 1841-1856.
[26] C.G. Heijnen, G.R. Haenen, F.A. van Acker, W.J. van der Vijgh, A. Bast, Toxicol. In Vitro 15
(2001) 3-6.
[27] E. Middleton, C. Kandaswami, T.C. Theoharides, Pharmacol. Rev. 52 (2000) 673-684.
[28] L.F. Wang, H.Y. Zhang, Bioorg. Med. Chem. Lett. 14 (2004) 2609-2611.
[29] S.A. Van Acker, M.J. de Groot, D.J. van den Berg, M.N. Tromp, G. Donne´-Op den Kelder, W.J.
van der Vijgh, A. Bast, Chem. Res. Toxicol 9 (1996) 1305-1312.
[30] O. Dangles, G. Fargeix, C. Dufour, J. Chem. Soc. Perkin Trans. 2 (2000) 1653-1663, K.
Ramachandran, G. Deepa, K. Namboori, Computational Chemistry and Molecular Modeling:
Principles and Applications, 1st edition, Springer, India, 2008, B. Rasulev, N. Abdullaevb, V. Syrovb,
J. Leszczynskia, Qsarcomb. Sci. 24 (2005) 1056-1065.
[31] J. Foresm, A. Fris, Exploring Chemistry with Electronic Structure Method, 2nd edition, Gaussian
Publisher, Gaussian Publisher,USA, 2004.
[32] V. Thavasi, L.P. Leong, R.P. Bettens, J. Phys. Chem. 110 (2006) 4918-4923.
[33] M. Foti, G. Ruberto, J. Agric. Food Chem. 49 (2001) 342-345.
B. Akele & et al. / J. Iran. Chem. Res. 3 (2010) 141-153
153
[34] H.Y. Zhang, Y.M. Sun, L.F. Wang, Chin. Chem. Lett. 14 (2003) 209-221.
[35] K. Lemanska, W. Vander, H. Szymusiak, M. Boersma, A. Gliszczynska, M.Rietjens, B. Tyrakowska,
Free Radic.Res., 38 (2004) 639-647.
[36] O. Dangles, G. Fargeix, C. Dufour, J. Chem. Soc. Perkin Trans. 65 (1999) 1387-1395.
[37] S. Terauchi, N, Tomihiro, T. Yamamura, K. Nishiwaki, Y. Tanigakin, Bull. Chem. Soc. Jpn. 68
(2006) 2955-2960.
[38] C. Henriquez, C. Aliaga, E. Lissi, J. Chil. Chem. Soc. 49 (2004) 225-265.
[39] C. Sa´nchez-Moreno, Food Sci.Tech. Int. 8 (2002) 121-137.
[40] D. Amić, D. Davidović-Amić, D. Bešlo, V. Rastija, B. Lučić, N. Trinajstić, Current Med. Chem. 14
(2007) 827-845.
[41] A.S. Pannala, T.S. Chan, P.J. O’Brien, C.A. Rice-Evans, Biochem. Biophys. Res. Commun. 282
(2001) 1161-1168.