- Email: [email protected]
Theoretical exploration on quenching mechanisms of triplet state riboflavin by xanthone derivatives
Journal of Molecular Structure: THEOCHEM 854 (2008) 106–109 www.elsevier.com/locate/theochem
Theoretical exploration on quenching mechanisms of triplet state riboflavin by xanthone derivatives Liang Shen, Hong-Fang Ji * Shandong Provincial Research Center for Bioinformatic Engineering and Technique, Center for Advanced Study, Shandong University of Technology, Zibo 255049, PR China Received 4 September 2007; received in revised form 12 December 2007; accepted 12 December 2007 Available online 23 December 2007
Abstract Riboflavin (RF), also known as vitamin B2, is an endogenous photosensitizer and much effort has been devoted to finding chemopreventive agents to alleviate the photosensitizing damage of RF. In this communication, the quenching mechanisms of triplet state RF by xanthone derivatives (XD) were explored by means of theoretical calculations. The results indicate that H-atom transfer-based pathway is more probable than direct energy transfer and direct electron transfer pathways to be involved in the triplet state RF quenching by XD, which may be responsible for the chemopreventive activities of XD on RF induced photosensitizing damage. Ó 2008 Elsevier B.V. All rights reserved. Keywords: Riboflavin; Xanthone derivatives; Triplet state; Quenching mechanism; Density functional theory
1. Introduction
2. Calculation methods
Various endogenous compounds may act as photosensitizers, among which, riboflavin (RF), also known as vitamin B2 (Fig. 1), has attracted much attention. Numerous studies indicated that RF can cause photosensitized DNA damage [1,2]. In a recent attempt to find chemopreventive agents, it was revealed that the DNA damage caused by photoexcited RF can be inhibited by some naturally occurring xanthone derivatives (XD), such as gentiacaulein and norswertianin (Fig. 1) [3]. However, the underlying chemopreventive mechanisms are not well understood. Considering the successful use of theoretical methods in exploring the photosensitizing characters of various photosensitizers [4–8], we attempt to gain some deeper insights into the quenching behaviors of XD through density functional theory (DFT) calculations.
The molecular structures of RF and XD were first fully optimized by hybrid density functional theory (DFT) [9,10] and B3LYP functional [11–13] with 6-31G(d,p) Gaussian basis set in vacuo. Then, the lowest T1 excitation energies (ET1) of the molecules studied were estimated by TDDFT formalism [14–17] with the same basis set in an implicit water model. Moreover, as the diffusion functions are essential for treatment of anion and cation radicals, to ensure the accuracy of the calculation, the vertical electron affinities (VEA) and vertical ionization potentials (VIP) of RF or XD in aqueous solution were calculated using a combined DFT method labeled as B3LYP/6-31+G(d,p)// B3LYP/6-31G(d,p)/B3LYP/6-31G(d,p), which means that B3LYP/6-31+G(d,p) was used to perform a single-point calculation on the basis of B3LYP/6-31G(d,p)-optimized structures [4]. The O–H bond dissociation enthalpy (BDEs) of XD and H-atom affinity (HAA) of RF were calculated by a hybrid method combining density functional theory (DFT) and semiempirical method AM1, labeled as (RO)B3LYP/6-311+G(2d,2p)//AM1/AM1, which takes
*
Corresponding author. Tel./fax: +86 533 278 0271. E-mail address: [email protected] (H.-F. Ji).
0166-1280/$ - see front matter Ó 2008 Elsevier B.V. All rights reserved. doi:10.1016/j.theochem.2007.12.010
L. Shen, H.-F. Ji / Journal of Molecular Structure: THEOCHEM 854 (2008) 106–109
107
CH2OH (CHOH)3 OH
CH2
5
H3C
4
7
6 N
N
O
O
OCH3
7
6
5 4
8
8
NH
3
H3C
2
N
1
9
10
H3CO
3
O
9
O
2
O
riboflavin OH
OH
10
1
gentiacaulein OH OH
HO
O
norswertianin Fig. 1. Molecular structures of riboflavin and xanthone derivatives (gentiacaulein and norswertianin).
advantages of accuracy and economy [18]. During the single point calculations, the solvent (water) effect was taken into consideration by employing the self-consistent reaction field (SCRF) method with polarizable continuum model (PCM) of Tomasi and coworkers [19–21]. All of the calculations were completed with Gaussian 03 package of programs [22].
Table 1 Theoretically estimated lowest triplet excitation energies (ET1, in eV), vertical electron affinities (VEA, in eV) and vertical ionization potentials (VIP, in eV) of riboflavin and xanthone derivatives in an implicit water model b
Riboflavin Gentiacaulein Norswertianin a
3. Results and discussion
b
As we know, during the photosensitization, S0 state RF is initially excited to the singlet excited state (S1) and then intersystem cross to the triplet excited state (T1), which may react with DNA bases directly through electron transfer (Type I, Eq. (1)), or react with 3O2 to generate 1 O2 (Eq. (2)), an important intermediate of DNA photodamage (Type II, Eq. (2)) [8]. Thus, quenching of triplet state RF will inhibit the photosensitized DNA damage [3]. RFðT1 Þ þ D ! RF þ Dþ 3
ð1Þ 1
RFðT1 Þ þ O2 ! RFðS0 Þ þ O2
ð2Þ
ET
VEAS0
VEAT1a
VIPS0
2.09 2.67 2.55
3.32 2.39 2.42
5.41 5.06 4.97
6.33 5.94 5.81
VEAT1 = VEAS0 ET1. Data from ref [8].
Table 2 Theoretically estimated O–H bond dissociation enthalpies (BDE, in kcal/ mol) of xanthone derivatives in an implicit water model at 298.15 K Quenchers
O–H BDE
Gentiacaulein (8)a Gentiacaulein (5)a Norswertianin (8)a Norswertianin (3)a
83.45 94.23 81.47 87.21
a The number in parenthesis indicates the position of hydroxyl group readily to donate a H-atom.
Therefore, the lowest triplet excitation energy (ET1) and selected electronic parameters of XD as well as RF were calculated and listed in Table 1, by which, the mechanisms of triplet state RF quenching by XD were explored. The first quenching pathway may involve direct energy transfer between triplet state RF and XD (Eq. (3)). However, the theoretical ET1 of XD are higher than that of RF (Table 1), implying that this pathway is not favorable on thermodynamic grounds.
The second important quenching pathway may occur through the electron transfer between the triplet state RF and XD (Eq. (4)) with the precondition that the total energy of the reaction is negative. However, the summation of the VEA of T1 state RF (VEAT1) and VIP of XD is positive, indicating that the electron transfer-based triplet state RF quenching by XD is also not permitted on thermodynamic grounds.
RFðT1 Þ þ XD ! RF þ XDðT1 Þ
RFðT1 Þ þ XD ! RF þ XDþ
ð3Þ
ð4Þ
108
L. Shen, H.-F. Ji / Journal of Molecular Structure: THEOCHEM 854 (2008) 106–109 CH 2OH
CH2OH
(CHOH)3
(CHOH)3
CH 2 H 3C
N
H 3C
N
CH2 N
O
H 3C
N
H 3C
N
N
.
NH
O
NH
O
O
H
+H -H OH
O
OCH3
OH
O
OCH 3
OH
H 3CO
O
O
H3 CO
.
O
Fig. 2. Proposed H-atom transfer-based quenching mechanisms of triplet state riboflavin by gentiacaulein.
Thus, it is expected that there exist other quenching pathways. Recently, it was reported that the deactivation of the triplet state RF by some compounds, e.g. a-tocopherol, proceeded through H-atom transfer reaction [23]. Considering the facts that: (i) XD possesses similar Hatom-donating potential with a-tocopherol [24] and the phenolic hydroxyl at position 8 for XD shows relatively lower O–H BDE (Table 2), an appropriate parameter to characterize the H-atom-donating ability; (ii) N1 is the thermodynamically favorable position to accept an H-atom for RF [23], and theoretically estimated HAA, a theoretical parameter successfully used to measure the molecular H-atom-abstracting ability, of T1 state RF (106.19 kcal/mol) is larger than the BDE of XD (Table 2), a new possible H-atom transfer-based triplet state RF quenching mechanism by XD is proposed and schemed in Fig. 2. In summary, the present study indicates that both direct energy transfer and electron transfer pathways are not favored on thermodynamic grounds during the triplet state RF quenching by XD. Other possible pathways, e.g. Hatom transfer-based mechanism is proposed to account for the chemopreventive activities of XD on the RF induced photosensitizing damage, which provides some new clues to screen and design new ideal chemopreventive agents. Acknowledgments This work was supported by the National Basic Research Program of China (2003CB114400) and the National Natural Science Foundation of China (Grant No. 30700113).
Appendix A. Supplementary data Supplementary data associated with this article can be found, in the online version, at doi:10.1016/j.theochem. 2007.12.010. References [1] K. Ito, S. Inoue, K. Yamamoto, S. Kawanishi, J. Biol. Chem. 268 (1993) 13221. [2] P.C. Joshi, Toxicol. Lett. 26 (1985) 211. [3] K. Hirakawa, M. Yoshida, A. Nagatsu, H. Mizukami, V. Rana, M.S. Rawat, S. Oikawa, S. Kawanishi, Photochem. Photobiol. 81 (2005) 314. [4] J. Llano, J. Raber, L.A. Eriksson, J. Photochem. Photobiol. A: Chem. 154 (2003) 235. [5] L. Shen, H.-F. Ji, H.-Y. Zhang, Bioorg. Med. Chem. Lett. 16 (2006) 1414. [6] L. Shen, H.-F. Ji, H.-Y. Zhang, Photochem. Photobiol. 82 (2006) 798. [7] L. Shen, H.-F. Ji, H.-Y. Zhang, Chem. Phys. Lett. 409 (2005) 300. [8] L. Shen, H.-F. Ji, H.-Y. Zhang, J. Mol. Struct. (Theochem) 821 (2007) 171. [9] P. Hohenberg, W. Kohn, Phys. Rev. 136 (1964) B864. [10] W. Kohn, L. Sham, J. Phys. Rev. 140 (1965) A1133. [11] C. Lee, W. Yang, R.G. Parr, Phys. Rev. B. 37 (1988) 785. [12] A.D. Becke, J. Chem. Phys. 98 (1993) 1372. [13] P.J. Stephens, F.J. Devlin, C.F. Chabalowski, M.J. Frisch, J. Phys. Chem. 98 (1994) 11623. [14] R.E. Stratmann, G.E. Scuseria, M.J. Frisch, J. Chem. Phys. 109 (1998) 8218. [15] R. Bauernschmitt, R. Ahlrichs, Chem. Phys. Lett. 256 (1996) 454. [16] M.E. Casida, C. Jamorski, K.C. Casida, D.R. Salahub, J. Chem. Phys. 108 (1998) 4439. [17] E. Sikorska, J.R. Herance, J.L. Bourdelande, I.V. Khmelinskii, S.L. Williams, D.R. Worrall, G. Nowacka, A. Komasae, M. Sikorski, J. Photochem. Photobiol. A: Chem. 170 (2005) 267. [18] H.-F. Ji, H.-Y. Zhang, L. Shen, Bioorg. Med. Chem. Lett. 16 (2006) 4095.
L. Shen, H.-F. Ji / Journal of Molecular Structure: THEOCHEM 854 (2008) 106–109 [19] [20] [21] [22]
S. Miertus, E. Scrocco, J. Tomasi, Chem. Phys. 55 (1981) 117. S. Miertus, J. Tomasi, Chem. Phys. 65 (1982) 239. M. Cossi, V. Barone, J. Cammi, Chem. Phys. Lett. 255 (1996) 327. M.J. Frisch, G.W. Trucks, H.B. Schlegel, G.E. Scuseria, M.A. Robb, J.R. Cheeseman, J.A. Montgomery Jr., T. Vreven, K.N. Kudin, J.C. Burant, J.M. Millam, S.S. Iyengar, J. Tomasi, V. Barone, B. Mennucci, M. Cossi, G. Scalmani, N. Rega, G.A. Petersson, H. Nakatsuji, M. Hada, M. Ehara, K. Toyota, R. Fukuda, J. Hasegawa, M. Ishida, T. Nakajima, Y. Honda, O. Kitao, H. Nakai, M. Klene, X. Li, J.E. Knox, H.P. Hratchian, J.B. Cross, C. Adamo, J. Jaramillo, R. Gomperts, R.E. Stratmann, O. Yazyev, A.J. Austin, R. Cammi, C. Pomelli, J.W. Ochterski, P.Y. Ayala, K. Morokuma, G.A. Voth, P.
109
Salvador, J.J. Dannenberg, V.G. Zakrzewski, S. Dapprich, A.D. Daniels, M.C. Strain, O. Farkas, D.K. Malick, A.D. Rabuck, K. Raghavachari, J.B. Foresman, J.V. Ortiz, Q. Cui, A.G. Baboul, S. Clifford, J. Cioslowski, B.B. Stefanov, G. Liu, A. Liashenko, P. Piskorz, I. Komaromi, R.L. Martin, D.J. Fox, T. Keith, M.A. AlLaham, C.Y. Peng, A. Nanayakkara, M. Challacombe, P.M.W. Gill, B. Johnson, W. Chen, M.W. Wong, C. Gonzalez, J.A. Pople, Gaussian 03, Revision A.1, Gaussian, Inc., Pittsburgh, PA, 2003. [23] D.R. Cardoso, K. Olsen, L.H. Skibsted, J. Agric. Food Chem. 55 (2007) 6285. [24] H.-F. Ji, G.-Y. Tang, H.-Y. Zhang, QSAR Combin. Sci. 24 (2005) 826.
Theoretical exploration on quenching mechanisms of triplet state riboflavin by xanthone derivatives Liang Shen, Hong-Fang Ji * Shandong Provincial Research Center for Bioinformatic Engineering and Technique, Center for Advanced Study, Shandong University of Technology, Zibo 255049, PR China Received 4 September 2007; received in revised form 12 December 2007; accepted 12 December 2007 Available online 23 December 2007
Abstract Riboflavin (RF), also known as vitamin B2, is an endogenous photosensitizer and much effort has been devoted to finding chemopreventive agents to alleviate the photosensitizing damage of RF. In this communication, the quenching mechanisms of triplet state RF by xanthone derivatives (XD) were explored by means of theoretical calculations. The results indicate that H-atom transfer-based pathway is more probable than direct energy transfer and direct electron transfer pathways to be involved in the triplet state RF quenching by XD, which may be responsible for the chemopreventive activities of XD on RF induced photosensitizing damage. Ó 2008 Elsevier B.V. All rights reserved. Keywords: Riboflavin; Xanthone derivatives; Triplet state; Quenching mechanism; Density functional theory
1. Introduction
2. Calculation methods
Various endogenous compounds may act as photosensitizers, among which, riboflavin (RF), also known as vitamin B2 (Fig. 1), has attracted much attention. Numerous studies indicated that RF can cause photosensitized DNA damage [1,2]. In a recent attempt to find chemopreventive agents, it was revealed that the DNA damage caused by photoexcited RF can be inhibited by some naturally occurring xanthone derivatives (XD), such as gentiacaulein and norswertianin (Fig. 1) [3]. However, the underlying chemopreventive mechanisms are not well understood. Considering the successful use of theoretical methods in exploring the photosensitizing characters of various photosensitizers [4–8], we attempt to gain some deeper insights into the quenching behaviors of XD through density functional theory (DFT) calculations.
The molecular structures of RF and XD were first fully optimized by hybrid density functional theory (DFT) [9,10] and B3LYP functional [11–13] with 6-31G(d,p) Gaussian basis set in vacuo. Then, the lowest T1 excitation energies (ET1) of the molecules studied were estimated by TDDFT formalism [14–17] with the same basis set in an implicit water model. Moreover, as the diffusion functions are essential for treatment of anion and cation radicals, to ensure the accuracy of the calculation, the vertical electron affinities (VEA) and vertical ionization potentials (VIP) of RF or XD in aqueous solution were calculated using a combined DFT method labeled as B3LYP/6-31+G(d,p)// B3LYP/6-31G(d,p)/B3LYP/6-31G(d,p), which means that B3LYP/6-31+G(d,p) was used to perform a single-point calculation on the basis of B3LYP/6-31G(d,p)-optimized structures [4]. The O–H bond dissociation enthalpy (BDEs) of XD and H-atom affinity (HAA) of RF were calculated by a hybrid method combining density functional theory (DFT) and semiempirical method AM1, labeled as (RO)B3LYP/6-311+G(2d,2p)//AM1/AM1, which takes
*
Corresponding author. Tel./fax: +86 533 278 0271. E-mail address: [email protected] (H.-F. Ji).
0166-1280/$ - see front matter Ó 2008 Elsevier B.V. All rights reserved. doi:10.1016/j.theochem.2007.12.010
L. Shen, H.-F. Ji / Journal of Molecular Structure: THEOCHEM 854 (2008) 106–109
107
CH2OH (CHOH)3 OH
CH2
5
H3C
4
7
6 N
N
O
O
OCH3
7
6
5 4
8
8
NH
3
H3C
2
N
1
9
10
H3CO
3
O
9
O
2
O
riboflavin OH
OH
10
1
gentiacaulein OH OH
HO
O
norswertianin Fig. 1. Molecular structures of riboflavin and xanthone derivatives (gentiacaulein and norswertianin).
advantages of accuracy and economy [18]. During the single point calculations, the solvent (water) effect was taken into consideration by employing the self-consistent reaction field (SCRF) method with polarizable continuum model (PCM) of Tomasi and coworkers [19–21]. All of the calculations were completed with Gaussian 03 package of programs [22].
Table 1 Theoretically estimated lowest triplet excitation energies (ET1, in eV), vertical electron affinities (VEA, in eV) and vertical ionization potentials (VIP, in eV) of riboflavin and xanthone derivatives in an implicit water model b
Riboflavin Gentiacaulein Norswertianin a
3. Results and discussion
b
As we know, during the photosensitization, S0 state RF is initially excited to the singlet excited state (S1) and then intersystem cross to the triplet excited state (T1), which may react with DNA bases directly through electron transfer (Type I, Eq. (1)), or react with 3O2 to generate 1 O2 (Eq. (2)), an important intermediate of DNA photodamage (Type II, Eq. (2)) [8]. Thus, quenching of triplet state RF will inhibit the photosensitized DNA damage [3]. RFðT1 Þ þ D ! RF þ Dþ 3
ð1Þ 1
RFðT1 Þ þ O2 ! RFðS0 Þ þ O2
ð2Þ
ET
VEAS0
VEAT1a
VIPS0
2.09 2.67 2.55
3.32 2.39 2.42
5.41 5.06 4.97
6.33 5.94 5.81
VEAT1 = VEAS0 ET1. Data from ref [8].
Table 2 Theoretically estimated O–H bond dissociation enthalpies (BDE, in kcal/ mol) of xanthone derivatives in an implicit water model at 298.15 K Quenchers
O–H BDE
Gentiacaulein (8)a Gentiacaulein (5)a Norswertianin (8)a Norswertianin (3)a
83.45 94.23 81.47 87.21
a The number in parenthesis indicates the position of hydroxyl group readily to donate a H-atom.
Therefore, the lowest triplet excitation energy (ET1) and selected electronic parameters of XD as well as RF were calculated and listed in Table 1, by which, the mechanisms of triplet state RF quenching by XD were explored. The first quenching pathway may involve direct energy transfer between triplet state RF and XD (Eq. (3)). However, the theoretical ET1 of XD are higher than that of RF (Table 1), implying that this pathway is not favorable on thermodynamic grounds.
The second important quenching pathway may occur through the electron transfer between the triplet state RF and XD (Eq. (4)) with the precondition that the total energy of the reaction is negative. However, the summation of the VEA of T1 state RF (VEAT1) and VIP of XD is positive, indicating that the electron transfer-based triplet state RF quenching by XD is also not permitted on thermodynamic grounds.
RFðT1 Þ þ XD ! RF þ XDðT1 Þ
RFðT1 Þ þ XD ! RF þ XDþ
ð3Þ
ð4Þ
108
L. Shen, H.-F. Ji / Journal of Molecular Structure: THEOCHEM 854 (2008) 106–109 CH 2OH
CH2OH
(CHOH)3
(CHOH)3
CH 2 H 3C
N
H 3C
N
CH2 N
O
H 3C
N
H 3C
N
N
.
NH
O
NH
O
O
H
+H -H OH
O
OCH3
OH
O
OCH 3
OH
H 3CO
O
O
H3 CO
.
O
Fig. 2. Proposed H-atom transfer-based quenching mechanisms of triplet state riboflavin by gentiacaulein.
Thus, it is expected that there exist other quenching pathways. Recently, it was reported that the deactivation of the triplet state RF by some compounds, e.g. a-tocopherol, proceeded through H-atom transfer reaction [23]. Considering the facts that: (i) XD possesses similar Hatom-donating potential with a-tocopherol [24] and the phenolic hydroxyl at position 8 for XD shows relatively lower O–H BDE (Table 2), an appropriate parameter to characterize the H-atom-donating ability; (ii) N1 is the thermodynamically favorable position to accept an H-atom for RF [23], and theoretically estimated HAA, a theoretical parameter successfully used to measure the molecular H-atom-abstracting ability, of T1 state RF (106.19 kcal/mol) is larger than the BDE of XD (Table 2), a new possible H-atom transfer-based triplet state RF quenching mechanism by XD is proposed and schemed in Fig. 2. In summary, the present study indicates that both direct energy transfer and electron transfer pathways are not favored on thermodynamic grounds during the triplet state RF quenching by XD. Other possible pathways, e.g. Hatom transfer-based mechanism is proposed to account for the chemopreventive activities of XD on the RF induced photosensitizing damage, which provides some new clues to screen and design new ideal chemopreventive agents. Acknowledgments This work was supported by the National Basic Research Program of China (2003CB114400) and the National Natural Science Foundation of China (Grant No. 30700113).
Appendix A. Supplementary data Supplementary data associated with this article can be found, in the online version, at doi:10.1016/j.theochem. 2007.12.010. References [1] K. Ito, S. Inoue, K. Yamamoto, S. Kawanishi, J. Biol. Chem. 268 (1993) 13221. [2] P.C. Joshi, Toxicol. Lett. 26 (1985) 211. [3] K. Hirakawa, M. Yoshida, A. Nagatsu, H. Mizukami, V. Rana, M.S. Rawat, S. Oikawa, S. Kawanishi, Photochem. Photobiol. 81 (2005) 314. [4] J. Llano, J. Raber, L.A. Eriksson, J. Photochem. Photobiol. A: Chem. 154 (2003) 235. [5] L. Shen, H.-F. Ji, H.-Y. Zhang, Bioorg. Med. Chem. Lett. 16 (2006) 1414. [6] L. Shen, H.-F. Ji, H.-Y. Zhang, Photochem. Photobiol. 82 (2006) 798. [7] L. Shen, H.-F. Ji, H.-Y. Zhang, Chem. Phys. Lett. 409 (2005) 300. [8] L. Shen, H.-F. Ji, H.-Y. Zhang, J. Mol. Struct. (Theochem) 821 (2007) 171. [9] P. Hohenberg, W. Kohn, Phys. Rev. 136 (1964) B864. [10] W. Kohn, L. Sham, J. Phys. Rev. 140 (1965) A1133. [11] C. Lee, W. Yang, R.G. Parr, Phys. Rev. B. 37 (1988) 785. [12] A.D. Becke, J. Chem. Phys. 98 (1993) 1372. [13] P.J. Stephens, F.J. Devlin, C.F. Chabalowski, M.J. Frisch, J. Phys. Chem. 98 (1994) 11623. [14] R.E. Stratmann, G.E. Scuseria, M.J. Frisch, J. Chem. Phys. 109 (1998) 8218. [15] R. Bauernschmitt, R. Ahlrichs, Chem. Phys. Lett. 256 (1996) 454. [16] M.E. Casida, C. Jamorski, K.C. Casida, D.R. Salahub, J. Chem. Phys. 108 (1998) 4439. [17] E. Sikorska, J.R. Herance, J.L. Bourdelande, I.V. Khmelinskii, S.L. Williams, D.R. Worrall, G. Nowacka, A. Komasae, M. Sikorski, J. Photochem. Photobiol. A: Chem. 170 (2005) 267. [18] H.-F. Ji, H.-Y. Zhang, L. Shen, Bioorg. Med. Chem. Lett. 16 (2006) 4095.
L. Shen, H.-F. Ji / Journal of Molecular Structure: THEOCHEM 854 (2008) 106–109 [19] [20] [21] [22]
S. Miertus, E. Scrocco, J. Tomasi, Chem. Phys. 55 (1981) 117. S. Miertus, J. Tomasi, Chem. Phys. 65 (1982) 239. M. Cossi, V. Barone, J. Cammi, Chem. Phys. Lett. 255 (1996) 327. M.J. Frisch, G.W. Trucks, H.B. Schlegel, G.E. Scuseria, M.A. Robb, J.R. Cheeseman, J.A. Montgomery Jr., T. Vreven, K.N. Kudin, J.C. Burant, J.M. Millam, S.S. Iyengar, J. Tomasi, V. Barone, B. Mennucci, M. Cossi, G. Scalmani, N. Rega, G.A. Petersson, H. Nakatsuji, M. Hada, M. Ehara, K. Toyota, R. Fukuda, J. Hasegawa, M. Ishida, T. Nakajima, Y. Honda, O. Kitao, H. Nakai, M. Klene, X. Li, J.E. Knox, H.P. Hratchian, J.B. Cross, C. Adamo, J. Jaramillo, R. Gomperts, R.E. Stratmann, O. Yazyev, A.J. Austin, R. Cammi, C. Pomelli, J.W. Ochterski, P.Y. Ayala, K. Morokuma, G.A. Voth, P.
109
Salvador, J.J. Dannenberg, V.G. Zakrzewski, S. Dapprich, A.D. Daniels, M.C. Strain, O. Farkas, D.K. Malick, A.D. Rabuck, K. Raghavachari, J.B. Foresman, J.V. Ortiz, Q. Cui, A.G. Baboul, S. Clifford, J. Cioslowski, B.B. Stefanov, G. Liu, A. Liashenko, P. Piskorz, I. Komaromi, R.L. Martin, D.J. Fox, T. Keith, M.A. AlLaham, C.Y. Peng, A. Nanayakkara, M. Challacombe, P.M.W. Gill, B. Johnson, W. Chen, M.W. Wong, C. Gonzalez, J.A. Pople, Gaussian 03, Revision A.1, Gaussian, Inc., Pittsburgh, PA, 2003. [23] D.R. Cardoso, K. Olsen, L.H. Skibsted, J. Agric. Food Chem. 55 (2007) 6285. [24] H.-F. Ji, G.-Y. Tang, H.-Y. Zhang, QSAR Combin. Sci. 24 (2005) 826.