Heravi, M., Sabahi, Y., Ardalan, T. (2015). DFT Study of Substituent Effects on Antioxidant Activity of Kaempferol in the Gas Phase. Physical Chemistry & Electrochemistry, 3(1), 21-25.
Mohammad Momen Heravi; Yalda Sabahi; Touran Ardalan. "DFT Study of Substituent Effects on Antioxidant Activity of Kaempferol in the Gas Phase". Physical Chemistry & Electrochemistry, 3, 1, 2015, 21-25.
Heravi, M., Sabahi, Y., Ardalan, T. (2015). 'DFT Study of Substituent Effects on Antioxidant Activity of Kaempferol in the Gas Phase', Physical Chemistry & Electrochemistry, 3(1), pp. 21-25.
Heravi, M., Sabahi, Y., Ardalan, T. DFT Study of Substituent Effects on Antioxidant Activity of Kaempferol in the Gas Phase. Physical Chemistry & Electrochemistry, 2015; 3(1): 21-25.
DFT Study of Substituent Effects on Antioxidant Activity of Kaempferol in the Gas Phase
1Department of Chemistry, Mashhad Branch, Islamic Azad University, Mashhad, Iran
2Young Researchers and Elite Club, Mashhad Branch, Islamic Azad University, Mashhad, Iran
Abstract
In this work, the study of various substituted Kaempferol derivatives is presented. The bond dissociation energies (BDE) have been calculated using B3LYP level and different basis sets in gas-phase. Calculated results show that the BDE values of substituted Kaempferol range from about 77 to100 kcal/mol, demonstrating that Kaempferol is an effective chain-breaking antioxidant that prevents lipid peroxidation. Also we can seen, Cl, OH, CN, NH2 and CH3 groups in C3′ position, CH3, OH and NH2 groups in C5′ position and NH2 and CN groups in C6′ position destabilize the parent Kaempferol molecule and stabilize the radical; hence, it decreases the O-H BDE.
Journal of Physical Chemistry and Electrochemistry Journal homepage: http://journals.miau.ac.ir/jpe Journal of Physical Chemistry and Electrochemistry Vol.2 No.1(2013) 21-25 Islamic Azad University Marvdasht Branch *Correspondig Author E-mail address: drmh@mshdiau.ac.ir 1. Introduction Oxidation reactions are the major cause of the irreversible deterioration of biological systems and synthetic polymers. Oxidation generally corresponds to a free radical chain reaction [1]. The most important reactive radical intermediates formed during oxidation reactions are hydroxyl (HO•), alkoxyl (RO•) and peroxyl (ROO•) radicals [1, 2]. Owing to the presence of at least one paired electron, free radicals will constantly seek to react with other cellular structures, altering DNA and destroying membranes through lipid per-oxidation. And there is strong evidence that free radicals could induce oxidative damage in bio-molecules and play an important role in many diseases associated with old age, notably Alzheimer's disease, Parkinson disease, cardiovascular disease and cancer. Recently, there has been growing interest in finding efficient and novel antioxidants from natural compound, such as flavonoids and phenols [3-5], to meet the requirements of pharmaceuticals, chemical and food industries. Flavonoids are a group of plant secondary metabolites characterized by a diphenylpropane structure. They are widely distributed in the plant kingdom and are common constituents of fruits, vegetables and some beverages. Flavonoids may play a role in the decreased risk of chronic diseases associated with a diet rich in plant-derived foods. A positive relationship between the ingestion of foods containing flavonoids and a reduced risk of developing cancer and cardiovascular diseases has indeed been observed in some epidemiological studies [6-10]. In vitro and DFT Study of Substituent Effects on Antioxidant Activity of Kaempferol in the Gas Phase Mohammad Momen Heravia,*, Yalda Sabahia and Touran Ardalanb aDepartment of Chemistry, Mashhad Branch, Islamic Azad University, Mashhad, Iran bYoung Researchers and Elite Club, Mashhad Branch, Islamic Azad University, Mashhad, Iran Abstract In this work, the study of various substituted Kaempferol derivatives is presented. The bond dissociation energies (BDE) have been calculated using B3LYP level and different basis sets in gas-phase. Calculated results show that the BDE values of substituted Kaempferol range from about 77 to100 kcal/mol, demonstrating that Kaempferol is an effective chain-breaking antioxidant that prevents lipid peroxidation. Also we can seen, Cl, OH, CN, NH2 and CH3 groups in C3′ position, CH3, OH and NH2 groups in C5′ position and NH2 and CN groups in C6′ position destabilize the parent Kaempferol molecule and stabilize the radical; hence, it decreases the O-H BDE. Keywords: Kaempferol; Antioxidant Activity; BDE; Free Radical in vivo investigations have shown plausible mechanisms by which flavonoids may confer cancer and cardiovascular protection [11]. Evidence also suggests that certain flavonoids may be useful in the treatment of several diseases [12-17]. Some of this evidence comes from the study of plants used in traditional medicine to treat a wide range of pathologies, which has revealed that flavonoids are common bioactive constituents of these plants. The flavonoid Kaempferol (3, 5, 7-trihydroxy-2-(4- hydroxyphenyl)-4H-1-and in plants used in traditional medicine. 7658432O1'6'5'4''3'2OHHOOHOHOACBX Fig1. Kaempferol structureAlthough there are over two thousand articles in PubMed reporting the isolation and/or biological properties of this flavonoid, there is not any report summarizing or analyzing all this information. Our aim is to provide a theoretical explanation to the relationship between the antioxidant activity of Kaempferol and the molecularstructure or O-H bond dissociation energy. Fig2. Optimized structures of Kaempferol and corresponding radicals (yellow balls: Carbon atom, Blue balls: Hydrogen atom and red balls: Oxygen atom) 22 M.M. Heravi et al. / Journal of Physical Chemistry and Electrochemistry Vol.2 No.1 (2013) 21-25 2.Computational Details The geometries of the molecules and respective radicals were optimized using DFT method with B3LYP functional [ 18-20] and the 6–31G, 6–311G, 6–311G** basis set [18,19] in the gas-phase. The ground-state geometries of molecules were optimized at restricted B3LYP level and the geometry of the radicals were optimized at the unrestricted B3LYP open shell (half electron) level. Optimized structures and corresponding radicals are shown in Fig. 1 and Fig. 2. All calculations were performed using Gaussian 03 program package [21]. The hydroxyl bond dissociation energies of each corresponding hydroxyl group of radicals were calculated. In the HAT mechanism, the bond dissociation enthalpy (BDE) of the phenolic O-H bond is one of the important parameters in evaluating the antioxidant action; the lower the BDE, the easier the dissociation of the phenolic O-H bond. Bond dissociation energy, BDE, is defined as: BDE= E (R˚) + E (H˚) – E(R–H) 3. Results And Discussion 3. 1 Bond Dissociation Energy (Bde) of Kaempferol In this study the relationship between the antioxidant activity of Kaempferol and substituted Kaempferol with the molecular structure and O-H bond dissociation energy was investigated. Calculated BEDs for Kaempferol were listed in table 1. The hydroxyl bond dissociation energies of each corresponding hydroxyl group of Kaempferol were calculated. It can be seen that the BDE values of Kaempferol range from about 74 to106 kcal/mol[22], demonstrating that Kaempferol is an effective chain-breaking antioxidant that prevents lipid peroxidation. Moreover, the molecules are observed to have the possibility of generating radicals at positions 3-OH, 4׳-OH, 5-OH and 7-OH because of the lower values of BDE. Comparison between BDE and antioxidant activity are defined as below: BDE values C3-OH> C4׳-OH> C7-OH> C5-OH Antioxidant activity C3-OH> C4׳-OH> C7-OH> C5-OH 3. 2 Calculation of Bond Dissociation Energy (Bde) for Substituted Kaempferol BDE for substituted Kaempferol in different position with H, Cl, NO2, NH2, CN, CH3 and OH groups were calculated. The results are listed in table 2. Table2. Calculated BDEs and ΔBDEs for Kaempferol and substituted Kaempferol in gas-phase by using B3LYP/6-311G** method X C2′ C3′ C5′ C6′ BDE (kcal/mol) ΔBDE (kcal/mol) BDE (kcal/mol) ΔBDE (kcal/mol) BDE (kcal/mol) ΔBDE (kcal/mol) BDE (kcal/mol) ΔBDE (kcal/mol) H 88.81289 0 88.81289 0 88.81289 0 88.81289 0 NO2 90.98750 2.174602 89.29325 0.48035 100.14900 11.33611 92.24250 3.42960 Cl 91.30125 2.48835 86.97150 -1.84139 89.92075 1.10785 90.67375 1.86085 CN 90.61100 1.79810 88.60300 -0.20989 91.17575 2.36285 81.88875 -6.92414 NH2 90.54825 1.73535 78.12375 -10.68914 77.81000 -11.00289 87.53625 -1.27664 CH3 90.36000 1.54710 86.90875 -1.90414 86.21850 -2.59439 90.79925 1.98635 OH 90.79925 1.98635 79.44150 -9.37139 79.25325 -9.55964 100.7765 11.96361 Table1. Calculated BDEs for Kaempferol in gas-phase Levels and Basis Sets BDE (kcal/mol) 3-OH 4׳-OH 5-OH 7-OH B3LYP/6-31G 74.21649 86.17037 105.06715 90.48393 B3LYP/6-311G 75.31104 86.68648 105.30140 90.851583 B3LYP/6-311G** 77.75302 88.81289 106.16296 93.78966 M.M. Heravi et al. / Journal of Physical Chemistry and Electrochemistry Vol.2 No.1 (2013) 21-25 23 Comparison of BDE values for substituted Kaempferol C2'-CL > C2' -NO2 > C2'-OH > C2'-CN > C2'-NH2 > C2'-CH3 > C2'-H C3'-NO2 > C3'-H > C3'-CN > C3'-CL > C3'-CH3 > C3'-OH> C3'-NH2 C5'-NO2 > C5'-CN > C5'- CL > C5'-H > C5'-CH3 > C5'-OH > C5'-NH2 : C6'-OH > C6'-NO2 > C6'-CH3 > C6'-CL > C6'-H > C6'-NH2 > C6'-CN For substituent's placed on C2′ (Fig 3(A)) the O-H BDE of structure with Cl substituent was higher in comparison to BDE value of other substituent. For C3′substituted Kaempferol (Fig 3B) with CN, Cl, CH3, OH and NH2 the BDE values are lower in comparison to the Kaempferol. For C5′substituted Kaempferol (Fig 3C) with NO2, Cl and CN the BDE values are higher in comparison to the Kaempferol and For C5′substituted Kaempferol with CH3, OH and NO2 the BDE values are lower in comparison to the Kaempferol. For C6′ 7658432O1'6'5'4''32'OHHOOHOHOX 7658432O1'6'5'4'3''2OHHOOHOHOACBX substituted Kaempferol (Fig 3D) with OH, NO2, CH3 and Cl the BDE values are 11.96, 3.42, 1.98 and1.86 kcal/mol higher than BDE value of Kaempferol, respectively. The O-H BDE of structure with NH2 and CN substituent in C6′position were lower 1.27664 and 6.92414 kcal/mol in comparison to BDE value of Kaempferol, respectively. Obtained results can be interpreted that Cl, NO2, OH, CN, NH2 and CH3 groups in C2′ position, NO2 group in C3′ position, NO2, CN and Cl groups in C5′ position and OH, NO2, CH3 and Cl groups in C6′ position stabilize the parent molecule and destabilize the radical; hence, it increases the O-H BDE. However, Cl, OH, CN, NH2 and CH3 groups in C3′ position, CH3, OH and NH2 groups in C5′ position and NH2 and CN groups in C6′ position destabilize the parent Kaempferol molecule and stabilize the radical; hence, it decreases the O-H BDE. Generally the donating capacity of hydrogen atom depends on charge on oxygen and hydrogen atoms. This is confirmed by the obtained results. Low BDE values are often attributed to the higher positive charge on hydrogen atom and the high antioxidant potential. 7658432O1'6'5'4''3'2OHHOOHOHOACBX Fig3. Substituted Kaempferol on A) C2′ , B) C3′ , C) C5′, D) C6′ ( X=H, Cl,NO2 , NH2, CN, CH3 and OH) A B C D 24 M.M. Heravi et al. / Journal of Physical Chemistry and Electrochemistry Vol.2 No.1 (2013) 21-25 4. Conclusions In this article, the bond dissociation energies of O-H for various substituted Kaempferol were calculated in gas-phase. It can be seen that the BDE values of Kaempferol range from about 74 to106 kcal/mol, demonstrating that Kaempferol is an effective chain-breaking antioxidant that prevents lipid peroxidation. For substituent’s placed Cl, OH, CN, NH2 and CH3 groups in C3′ position, CH3, OH and NH2 groups in C5′ position and NH2 and CN groups in C6′ position destabilize the parent Kaempferol molecule and stabilize the radical; hence, it decreases the O-H BDE. References [1] F. Gugumus. Oxidation inhibition in organic materials, Vol. 1. CRC Press, Boca Raton. 1990. [2] Q. Zhu, XM. Zhang, AJ. Fry, Polym. Degrad. Stab. 57 (1997) 43. [3] M. Meyer, Int. J. Quantum Chem. 76 (2000) 724. [4] J. Wright, E. R. Johnson, G. A. DiLabio, J. Am. Chem. Soc. 123 (2001), 1173. [5] V. B. Luzhkov, Chem. Phys. 314 (2005) 211. [6] M. G. Hertog, E. J. Feskens, P. C. Hollman, M. B. Katan, D. Kromhout, Lancet, 342 (1993) 1011. [7] M. L. Neuhouser, Nutr. Cancer. 50 ( 2004) 7. [8] L. Le Marchand, Biomed. Pharmacother, 56 (2002) 301. [9] D. Maron, Curr. Atheroscler. Rep. 6 (2004) 73. [10] R. Garcia-Closas, C. A. Gonzalez, A. Agudo, E. Riboli, Cancer Causes Control. 10 (1999) 71. [11] E. Middleton, C. Kandaswami, T. Theoharides, Pharmacol. Rev. 52 (2000), 673. [12] H. K. Wang, Expert. Opin. Investig. Drugs. 9 (2000) 2103. [13] M. Lopez-Lazaro, Curr. Med. Chem. Anticancer Agents. 2 (2002) 691. [14] Y. Li, H. Fang, W. Xu, Mini Rev. Med. Chem. 7 (2007) 663. [15] M. Lopez-Lazaro, Mini Rev. Med. Chem. 9 (2009)31. [16] W. Ren, Z. Qiao, H. Wang, L. Zhu, L. Zhang, Med. Res. Rev. 23(2003) 519. [17] H. P. Hoensch, W. Kirch, Int. J Gastrointest. Cancer. 35 (2005)187. [18] A. D. Becke, J. Chem. Phys. 98 (1993) 5648. [19] A. D. Becke, Phys. Rev. A. 38 (1988) 3098. [20] C. Lee, W. Yang, R. Parr, Phys. Rev. B. 37 (1988) 785. [21] Frisch MJ, Trucks GW, Schlegel HB, Scuseria GE, Robb MA, Cheeseman JR, Montgomery JA, Jr., Vreven T, Kudin KN, Burant JC, Millam JM, Iyengar SS, Tomasi J, Barone, B. Mennucci, M. Cossi, G. Scalmani, N. Rega, G.A. Petersson, H. Nakatsuji, M. Hada V, Ehara M, Toyota K, Fukuda R, Hasegawa J, Ishida M, Nakajima T, Honda Y, Kitao O, Nakai H, Klene M, Li X, Knox JE, Hratchian HP, Cross JB, Adamo C, Jaramillo J, Gomperts R, Stratmann RE, Yazyev O, Austin AJ, Cammi R, Pomelli C, Ochterski JW, Ayala PY, Morokuma K, Voth GA, Salvador P, Dannenberg JJ, Zakrzewski VG, Dapprich S, Daniels AD, Strain M-C, Farkas O, Malick DK, Rabuck AD, Raghavachari K, Foresman JB, Ortiz JV, Cui Q, Baboul AG, Clifford S, Cioslowski J, Stefanov BB, Liu G, Liashenko A, Piskorz P, Komaromi I, Martin RL, Fox DJ, Keith T, Al-Laham MA, Peng CY, Nanayakkara A, Challacombe M, Gill PMW, Johnson B, Chen W, Wong MW, Gonzalez C, Pople JA (2003) GAUSSIAN 03, Revision A.1, Gaussian, Inc., Pittsburgh. [22] M. Leopoldini, T. Marino, N. Russo, M. Toscano, J. Phys. Chem B. 108 (2004) 4922. M.M. Heravi et al. / Journal of Physical Chemistry and Electr ochemistry Vol.2 No.1 (2013) 21-25 25
References
[1] F. Gugumus. Oxidation inhibition in organic materials, Vol. 1. CRC Press, Boca Raton. 1990. [2] Q. Zhu, XM. Zhang, AJ. Fry, Polym. Degrad. Stab. 57 (1997) 43. [3] M. Meyer, Int. J. Quantum Chem. 76 (2000) 724. [4] J. Wright, E. R. Johnson, G. A. DiLabio, J. Am. Chem. Soc. 123 (2001), 1173. [5] V. B. Luzhkov, Chem. Phys. 314 (2005) 211. [6] M. G. Hertog, E. J. Feskens, P. C. Hollman, M. B. Katan, D. Kromhout, Lancet, 342 (1993) 1011. [7] M. L. Neuhouser, Nutr. Cancer. 50 ( 2004) 7. [8] L. Le Marchand, Biomed. Pharmacother, 56 (2002) 301. [9] D. Maron, Curr. Atheroscler. Rep. 6 (2004) 73. [10] R. Garcia-Closas, C. A. Gonzalez, A. Agudo, E. Riboli, Cancer Causes Control. 10 (1999) 71. [11] E. Middleton, C. Kandaswami, T. Theoharides, Pharmacol. Rev. 52 (2000), 673. [12] H. K. Wang, Expert. Opin. Investig. Drugs. 9 (2000) 2103. [13] M. Lopez-Lazaro, Curr. Med. Chem. Anticancer Agents. 2 (2002) 691. [14] Y. Li, H. Fang, W. Xu, Mini Rev. Med. Chem. 7 (2007) 663. [15] M. Lopez-Lazaro, Mini Rev. Med. Chem. 9 (2009)31. [16] W. Ren, Z. Qiao, H. Wang, L. Zhu, L. Zhang, Med. Res. Rev. 23(2003) 519. [17] H. P. Hoensch, W. Kirch, Int. J Gastrointest. Cancer. 35 (2005)187. [18] A. D. Becke, J. Chem. Phys. 98 (1993) 5648. [19] A. D. Becke, Phys. Rev. A. 38 (1988) 3098. [20] C. Lee, W. Yang, R. Parr, Phys. Rev. B. 37 (1988) 785. [21] Frisch MJ, Trucks GW, Schlegel HB, Scuseria GE, Robb MA, Cheeseman JR, Montgomery JA, Jr., Vreven T, Kudin KN, Burant JC, Millam JM, Iyengar SS, Tomasi J, Barone, B. Mennucci, M. Cossi, G. Scalmani, N. Rega, G.A. Petersson, H. Nakatsuji, M. Hada V, Ehara M, Toyota K, Fukuda R, Hasegawa J, Ishida M, Nakajima T, Honda Y, Kitao O, Nakai H, Klene M, Li X, Knox JE, Hratchian HP, Cross JB, Adamo C, Jaramillo J, Gomperts R, Stratmann RE, Yazyev O, Austin AJ, Cammi R, Pomelli C, Ochterski JW, Ayala PY, Morokuma K, Voth GA, Salvador P, Dannenberg JJ, Zakrzewski VG, Dapprich S, Daniels AD, Strain M-C, Farkas O, Malick DK, Rabuck AD, Raghavachari K, Foresman JB, Ortiz JV, Cui Q, Baboul AG, Clifford S, Cioslowski J, Stefanov BB, Liu G, Liashenko A, Piskorz P, Komaromi I, Martin RL, Fox DJ, Keith T, Al-Laham MA, Peng CY, Nanayakkara A, Challacombe M, Gill PMW, Johnson B, Chen W, Wong MW, Gonzalez C, Pople JA (2003) GAUSSIAN 03, Revision A.1, Gaussian, Inc., Pittsburgh. [22] M. Leopoldini, T. Marino, N. Russo, M. Toscano, J. Phys. Chem B. 108 (2004) 4922. M.M. Heravi et al. / Journal of Physical Chemistry and Electr ochemistry Vol.2 No.1 (2013) 21-25 25