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Chemical Physics Letters 613 (2014) 139–145

Contents lists available at ScienceDirect

Chemical Physics Letters

jou rn al hom epage: www.elsev ier .com/ locate /cp le t t

heoretical investigation on the bond dissociation enthalpies ofhenolic compounds extracted from Artocarpus altilis usingNIOM(ROB3LYP/6-311++G(2df,2p):PM6) method

guyen Minh Thonga, Tran Duongb, Linh Thuy Phamc, Pham Cam Namd,∗

The University of Danang – Campus in Kon Tum, 704 Phan Dinh Phung, Kontum, Viet NamDepartment of Chemistry, Hue’s University College of Education, 34 Le Loi, Hue, Viet NamDepartment of Biochemistry, University of California, Los Angeles – UCLA, Los Angeles, CA 90095, United StatesDepartment of Chemistry, The University of Danang, Danang University of Science and Technology, 54 Nguyen Luong Bang, Lien Chieu, Da Nang, Viet Nam

r t i c l e i n f o

rticle history:eceived 12 June 2014

n final form 29 August 2014

a b s t r a c t

Theoretical calculations have been performed to predict the antioxidant property of phenolic com-pounds extracted from Artocarpus altilis. The O H bond dissociation enthalpy (BDE), ionization

vailable online 6 September 2014energy (IE), and proton dissociation enthalpy (PDE) of the phenolic compounds have been com-puted. The ONIOM(ROB3LYP/6-311++G(2df,2p):PM6) method is able to provide reliable evaluation forthe BDE(O H) in phenolic compounds. An important property of antioxidants is determined via theBDE(O H) of those compounds extracted from A. altilis. Based on the BDE(O H), compound 12 is con-sidered as a potential antioxidant with the estimated BDE value of 77.3 kcal/mol in the gas phase.

© 2014 Elsevier B.V. All rights reserved.

. Introduction

Natural antioxidants present in plants effectively scavengearmful free radicals from our body. Free radical is any specieshat is capable of independent existence and contains one or morenpaired electrons, which reacts with other molecules by donatingr accepting electrons and involves in many pathological conditions1].

It is possible to reduce the risk of chronic diseases and preventisease progression by either enhancing the natural antioxidantefense of the body or by supplementing with proven dietaryntioxidants. All human cells protect themselves by multipleechanisms especially by the enzymatic and the non-enzymatic

ntioxidant systems against free radical damages. However, theserotective mechanisms may not be enough for severe or con-inued oxidative stresses. Hence, certain amounts of antioxidantupplements are constantly required to maintain an adequateevel of antioxidants in order to balance the reactive oxygenpecies in human body [2]. Many natural organic compounds

xtracted from leaves, seeds, and other parts of plants are con-idered as potential antioxidants [3,4]. The great advantages ofhese compounds are in their high antioxidant activity, non-toxic

∗ Corresponding author.E-mail address: camnamp@yahoo.com (P.C. Nam).

ttp://dx.doi.org/10.1016/j.cplett.2014.08.067009-2614/© 2014 Elsevier B.V. All rights reserved.

effects on human beings, and safety to the environment [5]. Innature, Artocarpus altilis is known as a good source of pheno-lic compounds including flavonoids, stilbenoids, arylbenzofurons,and Jacalin [6–9] whose beneficial role in the digestive processin humans is well established. The leaves, roots, and root barkof this plant are used as traditional medicines for the treat-ment of antioxidant, gout, hepatitis, hypertension, fever, liverdisorders, and diabetes [10]. Therefore, the study of antioxi-dant compounds extracted from A. altilis is a matter of greatinterest to researchers in different fields. Regarding the proper-ties of its antioxidants, prenylflavones, cycloheterophyllin, andartonins A and B inhibited iron-induced lipid peroxidation inrat brain homogenate, scavenged 1,1-diphenyl-2-picrylhydrazyl(DPPH), scavenged peroxyl radicals, hydroxyl radicals that weregenerated by 2,2-azobis (2-amidinopropane) dihydrochloride andthe Fe3+–ascorbate–EDTA–H2O2 system, respectively [6]. There aremany phenolic compounds extracted from A. altilis, therefore inour restricted aim, the chosen compounds for examining theirantioxidant properties are nine geranyl flavonoids [11] and threenew geranyl aurones [9] from the leaves of A. altilis as shownin Figure 1.

The purpose of this study was to determine whether natu-

ral components from A. altilis act as antioxidants. Compounds1–12 were identified as 1-(2,4-dihydroxyphenyl)-3-[8-hydro-xy-2-methyl-2-(4-methyl-3-pentenyl)-2H-1-benzopyran-5-yl]-1-propanone (1), 1-(2,4-dihydroxyphenyl)-3-{4-hydroxy-6,6,

140 N.M. Thong et al. / Chemical Physics

OH

HO

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B 3

10 11

12

Figure 1. Structures of twelve investigated compounds extracted from Artocarpusa

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layer, respectively.

ltilis.

-trimethyl-6a,7,8,10a-tetrahydro-6H-dibenzo[b,d] pyran-5-yl}--propanone (2), 2-geranyl-2′,3,4,4′-tetrahydroxydihydrochal-one (3), 1-(2,4-dihydroxyphenyl)-3-[3,4-dihydro-3,8-dihydr-xy-2-methyl-2-(4-methyl-3-pentenyl)-2H-1-benzopyran-5-yl]--propanone (4), 1-(2,4-dihydroxyphenyl)-3-[8-hydroxy-2-ethyl-2-(3,4-epoxy-4-methyl-1-pentenyl)-2H-1-benzopyran-5-

l]-1-propanone (5), 2′-geranyl-3′,4′,7-trihydroxyflavanone (6),ycloaltilisin 6 (7), 1-(2,4-dihydroxyphenyl)-3-[8-hydroxy-2-ethyl-2-(4-hydroxy-4-methyl-2-pentenyl)-2H-1-benzopyran-

-yl]-1-propanone (8), and 2-[6-hydroxy-3,7-dimethylocta-(E),7-dienyl]-2′,3,4,4′-tetrahydroxydihydrochalcone (9), Altilisin

(10), Altilisin I (11), and Altilisin J (12) [9,11].The ethyl acetate soluble fraction of the methanol extract of the

eaves of A. altilis was subjected to repeated silica gel column chro-atography to yield compounds 1–9 [11]. Compounds 10–12 are

ew aurones, which were identified in methanol solvent. Struc-ural elucidation of new compounds has been reported with theiryrosinase and (�)-glucosidase inhibitory activities [9].

Previous researches have proposed and characterized two mainechanisms by which the antioxidants can play their protective

oles being the hydrogen atomic transfer (HAT, Eq. (1)) and theingle electron transfer–proton transfer (SET–PT, Eq. (2)). The HATechanism involves a hydrogen atom being abstracted from the

ntioxidant, ArOH, turning ArOH into a free radical. The processs dependent on the bond dissociation energy (BDE) of the O Hond in ArOH. On the other hand, the first step of the SET–PT

echanism is governed by the ionization energy (IE), which is the

lectron transfer capacity of the antioxidant to donate an electrono the free radical. As the result, the antioxidant becomes a radical

Letters 613 (2014) 139–145

cation [12]. The second step of this mechanism, where a proton istransferred to the formed ROO− anion, is governed by proton dis-sociation enthalpy (PDE) from ArOH•+ radical cation formed in thefirst step. However, low IE values also enhance the probability ofsuperoxide radical anion generation through the direct electron-transfer to surrounding O2 [12,13].

ROO• + ArOH → ROOH + ArO• (1)

ROO• + ArOH → ROO− + ArOH•+ → ROOH + ArO• (2)

Recently, Nam and coworkers studied the thiophenol, 3-pyridinethiol, phenylphosphine, toluene, benzenthioselenol, andtheir derivatives using density functional theory (DFT) with the(RO)B3LYP method to accurately determine the BDE of the S H,P H, C H, and Se H bonds [14–18]. For the larger phenolic com-pounds like vitamin E, enol curcumin, and epigallocatechin gallate,the two-layer ONIOM method [19–23] with the high layer treatedwith ROB3LYP/6-311++G(2df,2p) that consists of only the hydro-gen and oxygen atoms was used to predict the BDE(O H) with theaccuracy within 1–2 kcal/mol [24]. In the present work, we contin-ued to develop this partitioning scheme using the DFT restrictedopen-shell (RO)B3LYP/6-311++G(2df,2p) for the high layer and thesemi-empirical PM6 method for the low layer with the aim to fur-ther shed light on the electronic properties of phenolic compoundsextracted from A. altilis and their radicals. In addition, the otherreaction enthalpies such as IE and PDE were also calculated to eluci-date the radical scavenging activity of the investigated compounds.

2. Computational methods

All computations were performed using the Gaussian 09 (ver-sion A.02) suite of programs [25]. Geometry optimizations andvibrational frequency calculations were conducted using the semi-empirical PM6 method. Vibrational frequencies obtained at thePM6 level were subsequently scaled by a factor of 1.078 for esti-mating the zero-point vibrational energies (ZPE).

The reaction enthalpies values in gas phase at 298.15 K and1.00 atm for the polyphenol compound (ArOH) were calculatedfrom the following expression:

BDE(O H) = H(ArO•) + H(H•) − H(ArOH) (3)

IE = H(ArOH•+) + H(e−) − H(ArOH) (4)

PDE = H(ArO•) + H(H+)–H(ArOH•+) (5)

where H’s are the enthalpies of different species at 298.15 K.The enthalpies were estimated from the given expression:H(T) = E0 + ZPE + Htrans + Hrot + Hvib + RT. The Htrans, Hrot, and Hvib arethe translational, rotational, and vibrational contributions to theenthalpy, respectively. E0 is the total energy at 0 K and ZPE is thezero-point vibrational energy. The enthalpy value for the hydrogenatom in the gas phase was taken at its exact energy of −0.5 hartree.The calculated gas-phase enthalpies of the proton (H+) and electron(e−) were taken from the literature [26,27].

For ONIOM method, the enthalpy values at higher level methodwere evaluated from the calculated single-point electronic energybased on PM6 optimized structures. In Figure 2, we describe sevenways of choosing the layer in our proposed ONIOM scheme. In theproposed ONIOM treatment, each molecule is divided into two lay-ers: the atoms at the breaking bond are treated as a high layer whilethe leftover atoms of the molecule belong to the second layer, whichare treated as a low layer. The (RO)B3LYP/6-311++G(2df,2p) andPM6 methods are applied to the atoms in the high layer and low

In addition, we consider some different ways of selecting theONIOM model denoted as 1A, 3A and 5A. For the 1A, the modelhas only one oxygen atom and one hydrogen atom related to the

N.M. Thong et al. / Chemical Physics Letters 613 (2014) 139–145 141

OH

R5 R1

R2

R3

R4

High laye r

low laye r

MODEL 3A-1

OH

R5 R1

R2

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of two

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Figure 2. Schematic description

arget bond for estimating BDE at the higher level of theory. Theest are defined as the low layer calculated using the PM6 method.he 3A ONIOM model has three heavy atoms including oxygen andwo carbon atoms at the high layer. We have two ways to choosehree heavy atoms in the high level, namely the 3A-1 and the 3A-. Similarly, the 5A ONIOM model has five heavy atoms includingxygen and four carbon atoms at the high layer. There are fourays to build up the high layer in the 5A model, denoted as the

A-1, 5A-2, 5A-3 and 5A-4.

. Results and discussion

.1. The reliability of the two layer ONIOM model for BDEsalculation

In this part, a series of substituted phenols, X-C6H4OH with = H, F, CH3, NH2, NO2, and OH, was chosen to benchmark the cal-ulated BDE(O H) values with the experimental data and to assesshe partitioning scheme for the two-layer-ONIOM as described inigure 2. It should be noted that the substituent is in turn placed athe ortho, meta, and para positions of the aromatic ring (except for-NH2 and o-NO2). The calculated BDE(O H) of these substitutedhenol are summarized in Figure 3.

From the calculated results for a series of substituted phenolshown in Figure 3, the largest deviation between our calculatedDE(O H) using model 1A and the experimental values of the

orresponding molecules is 1.3 kcal/mol in the case of o-CH3-6H4OH. For the other substituted compounds of phenol, theifferences between the theoretical calculation and the experimen-al data of BDE(O H) are small and in the range of 0.5–1.0 kcal/mol.

MODE L 5A -4

-layer proposed ONIOM model.

However, when we apply models 3A-1 and 3A-2 with three heavyatoms (one oxygen and two carbons) at the high layer, the dif-ference between our calculated and the experimental BDE(O H)significantly increases with the averaged deviation is 5.2 kcal/mol.The largest deviation of 8 kcal/mol is observed with o-CH3-C6H4OHusing model 3A-1. For models 5A-1, 5A-2, 5A-3 and 5A-4 with fiveheavy atoms (one oxygen and four carbons) at the high layer, thedifference between our calculated and the experimental BDE(O H)is the largest. The average deviation using these models rangesbetween 5.6 and 11.2 kcal/mol.

All computed results shown in Figure 3 (see also Table S1 insupporting data) show that the BDE(O H) values obtained fromthe model 1A are reasonably accurate and comparable with the bestexperimental data. To assess the performance of this partitioningscheme in model 1A, we also performed to obtain the �S value,which is defined as the error of the ONIOM energy related to thecorrect target energy, [E(high,real)] [29]. The equation of �S is asfollowed:

�S = BDE(ONIOM) − BDE(high, real)

= [BDE(low, real) − BDE(low, model)]

− [BDE(high, real) − BDE(high, model)] = S(low) − S(high)

where S(level) = BDE(level,real) − BDE(level,model) is the “sub-stituent effect” for the dissociation energy evaluated at the given

level. If the substituent effect evaluated at the low level, S(low),is the same as that evaluated at the high level, S(high), the ONIOMerror �S is zero, and the ONIOM reproduces the exact target energy[29].

142 N.M. Thong et al. / Chemical Physics Letters 613 (2014) 139–145

ms us

mXos

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Figure 3. Comparisons of the calculated BDE(O H) values of phenolic syste

Table 1 shows the substituent effect (S) evaluated at the PM6ethod and those at the ROB3LYP/6-311++G(2df,2p) for a system ofC6H4OH. It is clear that the calculated absolute errors (|�S|) basedn a series of substituted phenols are within 0.2–2.3 kcal/mol. Thetandard deviation (�) of the ONIOM error is of 1.3 kcal/mol.

All computed results shown in Figure 3 and Table 1 emphasizehat the ONIOM(ROB3LYP/6-311++G(2df,2p):PM6) and the parti-ioning scheme of model 1A in Figure 2 are actually the reasonableNIOM combinations. Hence we choose model 1A as our methodf choice for further study of BDE(O H). However, the reliabil-ty of model 1A needs to be checked further for larger molecules,ike ubiquinol-2, ubiquinol-6, and ubiquinol-10 (ubiquinol-10 is

nown as a strong antioxidant). Figure 4 depicts the structure ofbiquinols and the chosen model 1A. The high layer is displayed inhe bond type format and the low layer is in the wire frame for-

at. The calculated BDE(O H) of ubiquinols are given in Table 2.

ing seven ONIOM models with the experimental data taken from Ref. [28].

It can be observed that our calculated BDE(O H) values are in verygood agreement with the corresponding experimental values forubiquinols, with the deviation of only ±1.0 kcal/mol.

Our calculations using two-layer ONIOM combined with thepartitioning scheme 1A described above predict the BDE(O H) ofsubstituted phenol, uniquinol-2, uniquinol-6, and ubiquinol-10 tobe stable and reliable. In the next part we will use this method tocompute the BDE(O H) of twelve phenolic compounds extractedfrom A. altilis as shown in Figure 1.

3.2. BDE(O H) values of studied compounds extracted from A.altilis

3.2.1. Finding the position of the weakest O H bondFor a compound possessing more than one phenolic hydroxyl,

its radical-scavenging activity is determined by the one with the

N.M. Thong et al. / Chemical Physics Letters 613 (2014) 139–145 143

Table 1�S values between the real and the model system at the ONIOM(ROB3LYP/6-311++G(2df,2p):PM6) for model 1A.

Molecule S valuekcal/mol

�S = S(Low) − S(High)

S(Low) S(High)

C6H5OH −44.6 −43.5 −1.1o-F-C6H4OH −45.8 −44.1 −1.7m-F-C6H4OH −42.5 −42.8 +0.3p-F-C6H4OH −45.8 −46.1 +0.3o-CH3-C6H4OH −46.8 −49.1 +2.3m-CH3-C6H4OH −44.3 −44.0 −0.3p-CH3-C6H4OH −47.1 −46.1 −1.0o-NH2-C6H4OH −54.9 −55.9 +1.0m-NH2-C6H4OH −43.0 −44.0 +1.0p-NH2-C6H4OH −51.7 −53.8 +2.1o-NO2-C6H4OH −30.1 −28.6 −1.5m-NO2-C6H4OH −41.8 −40.3 −1.5p-NO2-C6H4OH −39.1 −39.3 +0.2o-OH-C6H4OH −51.5 −52.6 +1.1m-OH-C6H4OH −41.2 −42.5 +1.3p-OH-C6H4OH −49.1 −50.2 +1.1

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Table 3The O H bond dissociation enthalpies and the proton dissociation enthalpies usingthe PM6 method, kcal/mol.

Compounds Active sitea BDEb PDEc

1 2′ (ring A) 83.8 190.94′ (ring A) 82.7 172.04 (ring B) 70.7 158.1

2 2′ (ring A) 83.4 171.84′ (ring A) 82.8 171.24 (ring B) 71.2 159.7

3 2′ (ring A) 83.8 170.74′ (ring A) 82.8 158.53 (ring B) 68.9 156.04 (ring B) 83.8 169.7

4 2′ (ring A) 101.9 189.14′ (ring A) 83.1 170.24 (ring B) 71.8 158.92′′ (ring C) 100.2 187.3

5 2′ (ring A) 84.3 169.54′ (ring A) 82.3 167.44 (ring B) 70.6 155.9

6 4′ (ring A) 80.2 156.73 (ring B) 71.9 148.44 (ring B) 67.7 144.2

7 2′ (ring A) 85.1 171.84′ (ring A) 81.6 168.43 (ring B) 70.9 157.84 (ring B) 66.7 153.62′(ring A′) 81.2 167.94′ (ring A′) 81.9 168.73 (ring B′) 68.9 155.84 (ring B′) 71.8 158.7

8 2′ (ring A) 83.2 166.74′ (ring A) 82.6 166.14 (ring B) 70.4 153.97′′ 100.6 184.1

9 2′ (ring A) 83.8 174.04′ (ring A) 82.7 172.83 (ring B) 68.4 158.74 (ring B) 70.5 160.76′′ 99.9 190.2

10 6′ (ring A) 79.3 174.98 (ring B) 66.8 162.6

11 6′ (ring A) 79.9 167.08 (ring B) 69.2 156.3

12 6′ (ring A) 79.9 160.52 (ring B) 65.0 145.73 (ring B) 71.2 151.8

a See Figure 1 for definition of atom numbering.b BDE(O H) for the phenolic compounds.c PDE for the radical cations of phenolic compounds.

Table 4ONIOM(ROB3LYP/6-311++G(2df,2p):PM6)-computed BDE(O H) of twelve pheno-lic compounds extracted from Artocarpus altilis.

Compounds O H position BDE(O H)kcal/mol

Gas phase Methanol Water

igure 4. Structures and two layer ONIOM model of ubiquinol-n (n = 2, 6, 10).

owest BDE(O H). To reduce computation time, we used the PM6ethod to calculate preliminarily the BDE(O H) at any position to

nd out the weakest bond. Then, the weakest bond was continuedo be calculated at higher level of calculation using model 1A. Thealculated results are given in Table 3. In compound 12, 2-OH hadhe lowest BDE value, 65.0 kcal/mol. The lowest BDE(O H) is atosition 3 of ring B for compounds 3 and 9, which are estimatedo be about 68.9 and 68.4 kcal/mol, respectively. The BDE valuesf 4-OH for compounds 1, 2, 4, 5, 6, 7, 8, which are lower thanther positions are estimated to be about 70.7, 71.2, 71.8, 70.6, 67.7,6.7 and 70.4 kcal/mol, respectively. Similarly, in compound 10 and1, the BDE values of 8-OH are the lowest BDE values, 66.8 and9.2 kcal/mol, respectively.

able 2alculated BDE(O H) of ubiquinols (data are in kcal/mol).

Molecule BDE(O H) Experimental valuea �BDE(O H)b

Ubiquinol-2 81.9 82.3 −0.4Ubiquinol-6 81.9 82.3 −0.4Ubiquinol-10 77.8 78.5 −0.7

a Experimental values from Ref. [28].b �BDE(O H) = BDE(O H)calc − BDE(O H)expt.

1 4-OH (ring B) 83.2 83.5 82.82 4-OH (ring B) 84.5 83.2 83.13 3-OH (ring B) 80.8 82.4 82.24 4-OH (ring B) 85.1 83.7 83.15 4-OH (ring B) 83.9 83.8 83.16 4-OH (ring B) 80.3 83.9 83.17 4-OH (ring B) 79.3 82.9 82.18 4-OH (ring B) 83.7 82.8 81.49 3-OH (ring B) 79.3 81.3 80.510 8-OH (ring B) 80.3 82.7 81.611 8-OH (ring B) 82.5 83.9 83.212 2-OH (ring B) 77.3 79.0 78.3

144 N.M. Thong et al. / Chemical Physics Letters 613 (2014) 139–145

Table 5The calculated ionization energies (eV) using the PM6 method and the available experimental value of some phenolic compounds and twelve compounds extracted fromArtocarpus altilis.

Compound IE �IEb Compounds from Artocarpus altilis IE

Calc. Expt.a

Phenol 8.38 (8.61) 8.49 ± 0.02 (8.70) 0.11 (0.09) 1 7.30 (7.87)1,4-Benzenediol 8.00 (8.28) 7.94 ± 0.01 (8.44) −0.06 (0.16) 2 7.36 (7.77)1,3-Benzenediol 8.29 (8.56) 8.20 (8.63) −0.09 (0.07) 3 7.45 (8.03)1,2-Benzenediol 8.10 (8.44) 8.15 (8.56) 0.05 (0.12) 4 7.41 (8.06)BHT 7.39 (7.74) N/A (7.80) N/A (0.06) 5 7.50 (7.98)

6 7.87 (8.20)7 7.44 (7.80)8 7.57 (7.98)9 7.28 (7.83)

10 7.04 (7.56)11 7.42 (7.85)12 7.66 (8.08)

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ata in parentheses are vertical values.a Experimental values are taken from the NIST Chemistry web book, number 69,

b �IE = IEexpt − IEcalc.

.2.2. BDE(O H) of twelve phenolic compounds extracted from A.ltilis using ONIOM and the influence of solvents

The abilities of donating a hydrogen and forming the radicalorm of a wide class of phenolic compounds are characterized byhe BDE values. The BDE corresponds to the O H bond breakinghydrogen abstraction), thus this parameter describes the stabilityf the hydroxyl bonds. The molecules with lower values of BDEre endowed with higher antioxidant activity. Table 4 presentshe calculated BDE values in the gas phase and in the solventsmethanol and water) using ONIOM with our partitioning model.n the basis of the calculated BDE(O H) values in Table 4, theydrogen donating ability of phenolic compounds follows therder: 12 > 9 ≈ 7 > 10 ≈ 6 > 3 > 11 > 1 > 8 > 5 > 2 > 4. Moreover, amonghe phenolic hydroxyls at different positions, the hydroxyl at posi-ion 2 in compound 12 has the lowest BDE(O H), 77.3, 79.0 and8.3 kcal/mol in the gas phase, methanol, and water, respectively.

From Table 4, it can be seen that the BDE values of each ofhe O H groups present in all radicals of phenolic compoundsre smaller than those of phenols calculated at the same level ofheory. This indicates that most of the phenolic hydroxyls havetronger hydrogen donating ability than phenols. It can also beeen from Table 4 that the BDE of the 2-OH group in compound 1277.3 kcal/mol in gas phase) is similar to that of the ubiquinol-1078.5 kcal/mol).

.3. Ionization energy (IE) of studied compounds extracted from

. altilis

As discussed in the electron transfer–proton transfer mech-nism (Eq. (2)), the IE is also the important parameter to beonsidered while studying the antioxidant activity of a compound.n this part, we first evaluated the accuracy of PM6 method foralculating the IE value. The IE values of the following speciesere calculated and compared with the experimental values: phe-ol (C6H5OH), 1,4-benzenediol (pOH-C6H4OH), 1,3-benzenediolmOH-C6H4OH), 1,2-benzenediol (oOH-C6H4OH), and butylatedydroxyl toluene (BHT, C15H24O).

The calculated IE values given in Table 5 show that the PM6ethod can predict the adiabatic IE values within an error margin

ess than 0.11 eV. In the case of butylated hydroxyl toluene (BHT),hich does not have the available experimental adiabatic IE value,

he vertical IE value indicates the deviation between the calculated

nd experimental data being only 0.06 eV. The calculated adiabaticnd vertical IE values of twelve phenolic compounds extracted from. altilis are also presented in Table 5. The sequence of IE values inas-phase is 10 < 9 < 1 < 2 < 4 < 11 < 7 < 3 < 5 < 8 < 12 < 6.

/webbook.nist.gov/chemistry/.

3.4. Proton dissociation enthalpy (PDE) of radical cation fromstudied compounds

The calculated proton dissociation enthalpies of the radicalcation species formed in the first step of the SET-PT mechanismare also given in Table 3. Each radical cation species may haveseveral positions for the deprotonization. On the basis of data inTable 3, lowest gas-phase PDEs increase in the following order:6 < 12 < 7 < 8 < 5 < 3 < 11 < 1 < 9 < 4 < 2 < 10.

However, in the SET–PT mechanism, the preferred site of antiox-idant action may be estimated from the minimal sum of enthalpiesinvolved in a particular free radical scavenging mechanism [30].This sum includes the adiabatic IE plus the PDE from Tables 3 and 5.These values given in Table S2 of supporting information show thatthe minimal energy requirements for the HAT and SET–PT mecha-nism are associated with the same O H group of twelve studiedcompounds and the final product of all free radical scavengingmechanisms is the same. This indicates that the BDE and (IE + PDE)are perfectly correlated. From data in Table S2, the sequence oflowest gas-phase minimal sum of ionization energy and protondissociation enthalpies is 12 < 10 ≈ 7 < 6 < 9 < 3 < 11 < 1 < 8 < 5 < 2 < 4.

Therefore, it is concluded that formation of phenoxy radicalfrom a phenolic radical cation and a corresponding neutral phe-nolic molecule is favored at the same position. It turned out thatthe first mechanism has a greater impact on terminating the oxi-dation process. Hence, the BDE is the key parameter to evaluate theactivity of antioxidants.

4. Conclusions

In this article, the ONIOM(ROB3LYP/6-311++G(2df,2p):PM6)and partitioning model 1A, in which the core layer has only oneoxygen atom and one hydrogen atom related to the target bondfor estimating the BDE at the high level are actually the reason-able ONIOM combinations for accurately predicting the BDE(O H)values of a series of substituted phenols, ubiquinols, and twelveselective gernaryl flavanoids extract from A. altilis. The BDE(O H)sof compounds 3, 6, 7, 9, 10, and 12 amount to 80.8, 80.3, 79.3,79.3, 80.3, and 77.3 kcal/mol, respectively and they are consid-ered as the antioxidants. Compound 12 is a genaryl flavanoid withBDE(O H) of 77.3, 79.0 and 78.3 kcal/mol in gas phase, methanoland water, respectively. The adiabatic ionization energy of pheno-

lic compounds can be predicted using the PM6 method with theaccuracy within 0.11 eV. Formation of phenoxy radical from a phe-nolic radical cation and a corresponding neutral phenolic moleculeis favored at the same position. On the basis of the results obtained,

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onclusions can be drawn regarding the potency of the BDE as major physicochemical parameter that correlates with the freeadical scavenging activity of phenolic compounds.

To sum up, this study will contribute to the ongoing interest onhe antioxidant activity of phenolic compounds from A. altilis andheir future exploitation for food or pharmaceutical applications.

cknowledgements

This research is funded by Vietnam National Foundation forcience and Technology Development (NAFOSTED) under grantumber 104.06-2013.21. We would also like to thank the Institute

or Computational Science and Technology at HoChiMinh City, Vietam for permission to use computing systems for calculations in

his research.

ppendix A. Supplementary data

Supplementary data associated with this article can be found, inhe online version, at doi:10.1016/j.cplett.2014.08.067.

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