Research ArticleIsoflavones and Isoflavone Glycosides Structural-ElectronicProperties and Antioxidant RelationsmdashA Case of DFT Study

Son Ninh The 1 Thanh Do Minh2 and Trang Nguyen Van 2

1Institute of Natural Products Chemistry Vietnam Academy of Science and Technology (VAST) 18 Hoang Quoc Viet CaugiayHanoi Vietnam2Institute for Tropical Technology Vietnam Academy of Science and Technology (VAST) 18 Hoang Quoc Viet CaugiayHanoi Vietnam

Correspondence should be addressed to Son Ninh e yamantsongmailcom and Trang Nguyen Vannguyenvantrangsphn1909gmailcom

Received 8 January 2019 Revised 13 February 2019 Accepted 24 February 2019 Published 24 June 2019

Academic Editor Artur M S Silva

Copyright copy 2019 Son Ninhe et al is is an open access article distributed under the Creative Commons Attribution Licensewhich permits unrestricted use distribution and reproduction in any medium provided the original work is properly cited

Isoflavonoids and isoflavonoid glycosides have drawnmuch attention because of their antioxidant radical-scavenging capacity Basedon computational methods we now present the antioxidant potential results of genistein (1) biochanin A (2) ambocin (3) andtectorigenin 7-O-[β-D-apiofuranosyl-(1-6)-β-D-glucopyranoside] (4)e optimized structures of the neutral and radical forms havebeen determined by the DFT-B3LYP method with the 6-311G(d) basis set From the findings and thermodynamic point of view thering B system of isoflavones is considered as an active center in facilitating antioxidant reactions Antioxidant activities are mostlydriven by O-H bond dissociation enthalpy (BDE) following hydrogen atom transfer (HAT) mechanism Antioxidant ability can bearranged in the following order compounds (4)gt (3)gt (2)gt (1) Of comprehensive structural analysis flavonoids with 4prime-meth-ylation and 6-methoxylation especially 7-glycosylation would claim responsibility for antioxidant enhancement

1 Introduction

Naturally occurring isoflavone compounds fall into the class offlavonoid phenolic compounds which consists of a molecularstructure of 3-phenylchromen-4-one backbone and are widelydistributed in the plant kingdom particularly in Fabaceaefamily [1] Isoflavone derivatives were found to involve invarious biological experiments and have been employed inpharmacological drugs to treat cancer Alzheimerrsquos diseaseatherosclerosis and so on [2] Basically the reactive oxygenradicals such as hydroxyls (middotOH) presenting in living organ-isms can be seen as the reason for the changes in the body andone of the main causes of various diseases [3] Numerousevidence suggests that either flavonoids or typical isoflavoneshave been shown to be associated with good antioxidantcapacities due to their radical-scavenging activities

Of computational compounds 1ndash4 we herein select the bestisoflavones and their 7-glycosylation principally based on thegood results in their biological experiments including genistein(1) biochanin A (2) ambocin (3) and tectorigenin 7-O-[β-D-

apiofuranosyl-(1-6)-β-D-glucopyranoside] (4) (Figure 1) [4 5]A vast data showed that the substitutions at C-5 C-7 and C-4primein isoflavonoid rings have been playing a key role in structuralfeatures of bioactive isoflavones especially in terms of anti-oxidants [4] For instance genistein (1) revealed much moresignificance in the powerful antioxidant when compared toother isoflavones like daidzein and glycitein due to the de-pendence on its functional hydroxyl groups [5] Likewise asurvey conducted by Dowling et al proposed that with regardsto DPPH (22-diphenyl-1-picrylhydrazyl) assay both genstein(1) and its 4prime-methoxylation biochanin A (2) successfullychelated to Cu (II) and Fe (III) with a 1 2ML stoichiometry inmethanol phase whereas daidzein fails to do so [6]

Using B3LYP functional with 6-311G(d) basis set forstudied mediums gas and methanol the current DFT(density functional theory) study will provide an insight intostructural features conformational analyses and electronicproperties of the selective isoflavones 1-2 in which the resultintensively related to explaining their reactivity with freeradicals Ambocin (3) was isolated from the root of Pueraria

HindawiJournal of ChemistryVolume 2019 Article ID 4360175 12 pageshttpsdoiorg10115520194360175

mirica while its 6-methoxylation compound (4) had re-cently been identied as a new compound existing inDalbergia sissoo stem bark [4 7] To the best of ourknowledge there have been no specic theoretically usefulaccount reports on their glycosides 3-4 erefore we alsoset out a computational work on 7-glycosylated compound(3) and 6-methoxylated-7-glycosylated compound (4)within the aim of nding the eects of chemical structure onthe antioxidant capacity Hopefully the ndings will lay theground for future research

11 eoretical Parameters and Computational ProcedureDFT calculation is carried out with Gaussian 09 softwarepackage [8] In order to optimize the structure the B3LYPexchange correlation functional level without constraintshas been utilized and has been linked to 6-311G(d) basis setin the gas phase (dielectric constant ε 1) and in methanolsolvent (ε 32613) [9 10] Vibrational frequencies arecalculated at the same level to correct zero-point energy(ZPE) e result conrms the presence of ground stateswithout imaginary frequency e self-consistent reactioneld polarizable continuum model (SCRF-PCM) has beenemployed for estimating solvent eects [9]

From literature there have been three known mecha-nisms HAT (H-atom Transfer) SET-PT (Single electrontransfer-proton transfer) and SPLET (Sequential protonloss electron transfer) which concern radical-scavengingproperties of the parent molecular (Flav-OH) [11ndash17]

(1) HAT mechanical route (Equation (1)) involves inO-H bond breaking of Flav-OH then transfers toradicals and is often controlled by homolytic bonddissociation enthalpy (BDE) (Equation (2))

Flav-OH + RObull⟶ Flav-Obull + ROH (1)

BDE H Flav-Obull( ) + H Hbull( )minusH(Flav-OH)

(2)

H(Flav-Obull) H(Hbull) and H(Flav-OH) are the en-thalpies of Flav-Obull hydrogen radical atom and theparent avonoid molecule respectively

(2) SET-PT pathway was recognized by two steps(Equation (3)) In details the rst step accountedfor the process of losing an electron to form mo-lecular radical cation Flav-OHbull+ After that Flav-OHbull+ was deprotonated e rst action wasevaluated by the sum of the ionization potential(IP) whereas deprotonation was characterized byheterolytic bond dissociation enthalpy (PDE)(Equations (4) and (5))

Flav-OH + Rbull⟶ Flav-OHbull++Rminus

⟶ Flav-Obull + ROH(3)

IP H Flav-OHbull+( ) + H eminus( )minusH(Flav-OH)

(4)

PDE H Flav-Obull( ) + H H+( )minusH Flav-OHbull+( )

(5)

H(Flav-OHbull+) presents the enthalpies of avonoidradical cation Flav-OHbull+ after electron abstraction oforiginal avonoid e calculated gaseous phaseenthalpy values which are 075 kcalmol and148 kcalmol are normally used for H(endash) andH(H+) respectively [11 12]

(3) e third mechanical SPLET is briey describedwhen avonoid is deprotonated to aord a typicalanion Flav-Ondash and the sequential electron transferfrom this anion happens (Equation (6)) Protonacurrennity (PA) and the electron transfer enthalpy(ETE) are two conceptual parameters which corre-spond to deprotonation and electron transfer re-spectively (Equations (7) and (8))

Flav-OH⟶ Flav-Ominus + H+ Flav-Ominus + Rbull

⟶ Flav-Obull + Rminus Rminus + H+⟶ RH(6)

PA H Flav-Ominus( ) + H H+( )minusH(Flav-OH)

(7)

OHO

OR2

OOH

1 R = H2 R = Me

2

44a

8a

5

7

1prime

4prime

A C

B

θ2

3 2prime

(a)

2

44a5

78a

4prime

O

OHO

HOOH O

O

1Prime2Prime5Prime

6Prime

OOH

O

OHOH

HO

1primeprimeprime2primeprimeprime

4primeprimeprime5primeprimeprime

1prime

3 R = H4 R = OMe

OH

R2prime3

θ2

(b)

Figure 1 General structures of studied compounds 1ndash4 with atom numbering

2 Journal of Chemistry

ETE H Flav-Obull( 1113857 + H eminus( )

minus H Flav-Ominus( )(8)

H(Flav-Ominus) is the enthalpy of flavonoid anion afterproton abstraction of original molecule

Antioxidant activities have been explained by DFT-basedreactivity descriptors [11] including energies of highest oc-cupied molecular orbital (HOMO) and lowest unoccupiedmolecular orbital (LUMO) dipole moments atomic chargeselectron affinity A the ionization potential Io the globalhardness η the electronegativity χ the chemical potential microglobal electrophilicity indexω and Fukui chemical parameters

Based on the theoretical approach of DFT Janakrsquostheorem and the finite difference approximation thesedescriptors can be proposed by the related equations given asfollows [18]

Io asymp minusEH

A asymp minusEL

η asympIo minusA( 1113857

2asymp

EL minusEH( 1113857

2

χ asympIo + A( 1113857

2asymp

EL + EH( 1113857

2

micro asymp minusIo + A( 1113857

2asympminus EL + EH( 1113857

2

(9)

where EH and EL are energies of HOMO and LUMOrespectively

e atomic charges for neutral molecular were restrictedby Mulliken population analysis (MPA) following the sameframework of B3LYP6-311G(d)

e global electrophilicity index ω indicates the stabiliza-tion energy of a molecule system when being saturated byelectrons from outside erefore the higher value of ω+

(electron accepting) shows the significant electrophilicity whilethe lower one of ωminus (electron donating) evidently exhibits thebetter nucleophilicity of a compound ese chemical indiceswere expressed following the functions as follows [19]

ω micro2

2ηasymp

Io + A( 11138572

4 Io minusA( 11138571113858 1113859asymp

EL + EH( 11138572

4 EL minusEH( 11138571113858 1113859

ωminus 3Io + A( 1113857

2

16 Io minusA( 11138571113858 1113859

ω+

Io + 3A( 11138572

16 Io minusA( 11138571113858 1113859

(10)

As a general conceptual comprehension the condensedFukui parameters evidently provide information on a se-lective property in a chemical reaction e atom coupledwith the high electronic population displays as the mostreactive site when compared to the surrounding atoms in amolecule [20] Briefly Fukui descriptors have been shown to

associate with nucleophilic (f+k ) electrophilic (fminusk ) andor

radical attacks (f0k) and were possibly described by the

following equilibriums [20]

f+k qk(N + 1)minus qk(N)

fminusk qk(N)minus qk(Nminus 1)

f0k

qk(N + 1)minus qk(Nminus 1)1113858 1113859

2

(11)

where qk(N) electronic population of atom k in a neutralmolecule qk(N+ 1) electronic population of atom k in ananionic molecule and qk(Nminus 1) electronic population ofatom k in a cationic molecule

2 Results and Discussion

21 Geometrical Analysis e comprehension of isoflavoneconformational analysis is an important method to prove therelationship between the antioxidant activities and structuralaspects since the HAT SET-PT and SPLETpathways closelydepend on the behaviors of differential hydroxyl groups andthe geometric features From Figures 2 and S1 and Table 1we reported the optimized structures with patterns ofintramolecular hydrogen bonds (IHBs) between 5-OH and4-CO along with selective characters of bonds bond anglesand dihedral angles As of local minimum energies there isno distinction in each compound between gaseous state andmethanol (Table 2) e first feature observed from theoptimized molecular structures of 1ndash4 is that π-electron isdelocalized in the whole aglycone especially B towards Cthrough 23-double and the coplanar between chromenering and phenyl unit is lost In agreement with findings ofIHBs in many previous flavonoid DFT calculated researches[21] IHBs lengths are found to be 1721 A for 1-2 1726 A for3 and 1733 A for 4 in gas When compared to 5-OH and 7-OH the longer bond lengths of 4prime-OH and O-CPrime1 at 7-po-sition evidently reinforces that as a matter of fact hydrolysisreactions occurred in flavone glycosides at aglycone-glyconelinkage or antioxidant activations facilitated at 4prime-OH forflavonoids [22 23] As shown in Table 1 bond angles θ1 (4prime-O-H) and θ1 (7-O-H) demonstrate larger 2-3deg than θ1 (5-O-H) obviously caused by effective IHBs

Regarding the effects of environmental researches es-pecially polar solvents we now select methanol as a goodagent because it promotes many biological processes [24] Sofar flavonoids are recognized as weak polar compounds andthat it is not easy to dilute them in water [25] In comparisonwith gaseous circumstance methanol directly induces thereduction of IHBs lengths and the elongation of 5-OH bondlengths Also 6-OCH3 can be seen as the main reason thatmakes a slight difference in IHBs between compounds 3 and4 in the procedures of both gas and methanol Dihedralangles θ1 (C2-C3-C1prime-C2prime) among all structures 1ndash4 show notmuch change and reach 415deg in gas and 44deg in methanolFrom previous literature data utilizing the RHF6-311 +G(d) ab initio method compounds 1-2 have beenlinked to θ1 numbers of 40deg and 45deg in environmentalacetonitrile or regarding to employment of UB3LYP6-

Journal of Chemistry 3

31++G (dp) in gas phase and θ1 value of 393deg was recordedfor genistein (1) [22 26] but no manuscript associates withan insight into relationships between conformations andtheir energies

To confirm the results mentioned above potential en-ergy curves for all considered compounds 1ndash4 are obtainedlike the functions of torsional angle θ2 (C2-C3-C1prime-C2prime)

between the rings B and C linkage in the gaseous state In thiscase θ2 has been explored by scanning in the characteristicsteps of 15deg values from 0deg to 360deg at theoretical level B3LYP6-311G(d) (Table S1) An attempt to accurate without anyconstraints the structures of these four isoflavones is thenoptimized around each conformational potential minimumand the results are drawn in Figure 3 It can generally be

1721

(a)

1721

(b)

(c)

1726

(d)

Figure 2 State forms of studied structures 1ndash4 in gas medium (a) Compound 1 (b) Compound 2 (c) Compound 3 (d) Compound 4

Table 1 Optimized bond distances bond angles (θ1) and dihedral angles (θ2) of studied compounds with B3LYP6-311G(d) in gas andmethanol mediums

No Bond lengths5 (O-H) 7 (O-H) 7 (O-C1Prime) 6 (O-CH3) 4prime (O-H) 4prime (O-CH3) Hydrogen bonds

1 Gas 1337 1357 1364 1721Methanol 1343 1354 1364 1714

2 Gas 1337 1357 1362 1721Methanol 1343 1354 1361 1714

3 Gas 1338 1365 1365 1733Methanol 1343 1365 1364 1720

4 Gas 1338 1365 1364 1365 1726Methanol 1343 1362 1370 1364 1716

No Bond angles Dihedral anglesθ1 (C5-O-H) θ1 (C7-O-H) θ1 (C4prime-O-H) θ1 (C2-C3-C1prime) θ2 (C2-C3-C1prime-C2prime)

1 Gas 107450 109900 109748 120378 41491Methanol 107122 110640 110240 120286 44364

2 Gas 107459 109886 120342 41492Methanol 107106 110620 120273 44440

3 Gas 107631 109726 120316 41531Methanol 107791 110207 120214 43576

4 Gas 107631 109726 120642 41531Methanol 106792 110241 120189 44128

4 Journal of Chemistry

noted that the dependence of conformational states ontorsional angle θ2 is similar among all isoavonoids 1ndash4including two conformers I-II lying at 415deg (conformer I)

and 135deg (conformer II) for each molecule ese twoconformers arise from the potential energy versus torsionalangles obtained as a good agreement with the previous

Table 2 Chemical reactivity indices obtained using the DFT method in gas and methanol mediums

No Medium η (eV) χ (eV) micro (eV) Io (eV) A (eV)ω (eV)

ω ωminus ω+

1 Gas 2125 3835 minus3835 5960 1710 3461 5644 1809Methanol 2124 3932 minus3932 6056 1808 3639 5871 1939

2 Gas 2107 3789 minus3789 5897 1682 3407 5565 1776Methanol 2109 3915 minus3915 6024 1806 3633 5854 1940

3 Gas 2134 3758 minus3758 5891 1624 3309 5455 1697Methanol 2115 3967 minus3967 6081 1852 3720 5968 2001

4 Gas 2086 3710 minus3710 5796 1624 3299 5415 1705Methanol 2093 3956 minus3956 6049 1863 3740 5979 2023

No Medium Dipole moment (debye) Polarizability (au) Energy (kcalmol) EHOMO (eV) ELUMO (eV)

1 Gas 3036 187118104 minus59860814 minus5960 minus1710Methanol 4455 247343170 minus59861859 minus6056 minus1808

2 Gas 2862 202392352 minus62327698 minus5897 minus1682Methanol 4231 264841735 minus62328597 minus6024 minus1806

3 Gas 10227 347615084 minus129339488 minus5891 minus1624Methanol 13200 440126098 minus129341513 minus6081 minus1852

4 Gas 10069 365799666 minus136526747 minus5796 minus1624Methanol 13537 461553236 minus136528945 minus6049 minus1863

30 60 90 120 150 180 210 240 270 300 330 3600Dihedral angle (degree)

ndash598608

ndash598607

ndash598606

ndash598605

ndash598604

ndash598603

ndash598602

Ener

gy (k

calm

ol)

(a)

30 60 90 120 150 180 210 240 270 300 330 3600Dihedral angle (degree)

ndash623277

ndash623276

ndash623275

ndash623274

ndash623273

Ener

gy (k

calm

ol)

(b)

30 60 90 120 150 180 210 240 270 300 330 3600Dihedral angle (degree)

ndash1293395

ndash1293394

ndash1293393

ndash1293392

ndash1293391

Ener

gy (k

calm

ol)

(c)

30 60 90 120 150 180 210 240 270 300 330 3600Dihedral angle (degree)

ndash1365268

ndash1365267

ndash1365266

ndash1365265

ndash1365264

ndash1365263

Ener

gy (k

calm

ol)

(d)

Figure 3 Potential energy curves versus torsional angle of studied structures 1ndash4 in gas medium (a) Compound 1 (b) Compound 2(c) Compound 3 (d) Compound 4

Journal of Chemistry 5

publication on several isoflavones [11] e absolute mini-mum I is more stable than the conformational relativeminimum II by 198 kcalmol for genistein (1) however thisone for compounds 2ndash4 has smaller values of 040 kcalmol029 kcalmol and 026 kcalmol respectively Parallel withthis there are several potential energy barriers that rangefrom I to II in compound 1 the first interconversion energybarrierrsquos value of 355 kcalmol is recognized at the per-pendicular conformation (θ2 90deg) and the second energybarrier accounts for 494 kcalmol and peaks at anti(θ2 180deg) conformation meanwhile the maximum in-terchangeable barrier reaches 541 kcalmol at syn (θ2 360degor 0deg) shape In the same manner with torsional angles θ1 of90deg 180deg and 360deg (or 0deg) these potential energy barriers arefound at the values of 215 kcalmol 378 kcalmol and402 kcalmol 215 kcalmol 377 kcalmol and 400 kcalmol and 211 kcalmol 381 kcalmol and 403 kcalmol forcompounds 2ndash4 respectively e dramatic difference ob-tained from energies between two minima together with thedistinction from the interchangeable energy barriers of 1 andgroups 2ndash4 can be explained by the symmetric property of 1the phenomena of 4prime-methylation in 2 7-glycosylation in 3and 6-methoxylation-7-glycosylation in 4

22 Frontier Molecular Orbital eory and Spin DensityTaking π-electron delocalization into consideration it in-volves in the stabilization of parent molecular and radicalsafter H abstractions [27] e frontier orbital theoreticalcalculation seems to be a significant tool for explaining therelationship between neutral and radical forms especially interms of the electron delocalization At the level of B3LYP6-311G(d) in both mediums of gas and methanol HOMO andLUMO of neutral and radical visual images and frontierorbital energies of 1ndash4 are shown in Figures 4ndash6 and Table 2HOMO neutral images show that the electron distribution isconcentrated in the entire aglycone especially ring B and23-double bond while LUMO neutral is delocalized oversystematic rings A and C Sugar units are not a suitable sitefor radical reactions e same result has been found inpreviously studied isoflavones glycitein pratensein andprunetin [11] When hydrogen atom abstraction takes placein four isoflavones it is worth noting that 4prime-OH HOMOradical species in compounds 1 and 3-4 which correspondto the small BDE values consist of high electron density inring B and slightly less in ring A 5-OH andor 7-OHHOMO radical shapes which concern the high BDE valuesdid not differ from neutral composition except for the lesselectron distribution in ring C for 5-OH radical site ofcompound 4 LUMO radical forms mostly focus on chro-mene systems but slightly view in ring B in the case of 5-OH7-OH of compounds 1-2 and 5-OH of compounds 3-4 ehigher EHOMO (the lower ionization potential Io) and thelower ELUMO (the higher electron affinity A) mean the bettercapacity of electrons donating and the better sensitivity toreceive electrons respectively whereas the easier electrontransfer indicates the lower Egap ELUMOminusEHOMO andthus the better antioxidant reactivity From Table 2 thegaseous phase would lay a better ground for decreasing

EHOMO values when compared with using methanol butmethanol solution should be a suitable tool to scale downELUMO values Paying attention to the gaseous medium thehighest EHOMO which can be claimed responsible for ad-vantageous radical reactions here facilitates compound 4(minus5796 eV) in preference to the others 3 (minus5891 eV) 2(minus5897 eV) and 1 (minus5960 eV) e numbers of 4250 eV4215 eV 4267 eV and 4172 eV are assignable to the re-spective Egap values of compounds 1ndash4 in the environmentalgas e most striking feature is that 4prime-methylated

4250 4215 4267 4172

ndash9ndash8ndash7ndash6ndash5ndash4ndash3ndash2ndash1

01

Fron

tier m

olec

ular

orb

ital e

nerg

y (e

V)

Com

poun

d 4

Com

poun

d 3

Com

poun

d 2

Com

poun

d 1

Compound

HOMOLUMO

Figure 4 Neutral HOMO and LUMO images and Egap of struc-tures 1ndash4 in gas medium

4248 4218 4229 4185

Com

poun

d 1

Com

poun

d 3

Com

poun

d 4

Com

poun

d 2

Compound

HOMOLUMO

ndash9ndash8ndash7ndash6ndash5ndash4ndash3ndash2ndash1

01

Fron

tier m

olec

ular

orb

ital e

nerg

y (e

V)

Figure 5 Neutral HOMO and LUMO images and Egap of struc-tures 1ndash4 in MeOH medium

6 Journal of Chemistry

(a) (b) (c)

(d) (e) (f)

(g) (h) (i)

(j) (k) (l)

(m) (n) (o)

(p) (q) (r)

Figure 6 HOMO and LUMO of structural radicals 1ndash4 (a) HOMO-5-OH radical (1) (b) HOMO-7-OH radical (1) (c) HOMO-4prime-OHradical (1) (d) LUMO-5-OH radical (1) (e) LUMO-7-OH radical (1) (f ) LUMO-4prime-OH radical (1) (g) HOMO-5-OH radical (2)(h) HOMO-7-OH radical (2) (i) HOMO-5-OH radical (3) (j) LUMO-5-OH radical (2) (k) LUMO-7-OH radical (2) (l) LUMO-5-OHradical (3) (m) HOMO-4prime-OH radical (3) (n) HOMO-5-OH radical (4) (o) HOMO-4prime-OH radical (4) (p) LUMO-4prime-OH radical (3) (q)LUMO-5-OH radical (4) (r) LUMO-4prime-OH radical (4)

Journal of Chemistry 7

compound 2 and 6-methoxylated compound 4 evidentlygenerate better Egap values when compared to respectivecompounds 1 and 3 in both of the phases Emphasizing onthe change of gas phase into methanol a remarkable reversecan be observed in the Egap values between 1 and 3 due tothe 7-glycosylated phenomenon Among four compounds1ndash4 we primarily assumed that tectorigenin 7-O-[β-D-apiofuranosyl-(1-6)-β-D-glucopyranoside] (4) is the bestcandidate employable for antioxidant targets not mentionthe fact that 4prime-methylation 6-methoxylation and 7-gly-cosylation facilitate the antioxidant ability

Calculation of the atomic spin density population ofvarious radicals after H-abstraction from four consideredisoflavones 1ndash4 is given in Figure 7 It should be kept inmindthat the higher the spin density delocalized in radicals theeasier the radical formation hence lower BDE values [28]As a general view the computed results reveal that strongspin distributions remain on oxygen atoms of phenolicgroups carbons C-1prime C-3prime and C-5prime of the ring B andcarbons C-6 and C-8 in ring A and also C4a In all fourcompounds 1ndash4 C-1prime C-3prime and C-5prime are centers of positivespin density C-2prime C-4prime and C-6prime bear negative one whilstatomic carbons in ring A fail to do so [11] It suggests thatphenyl unit ring B with more delocalized spin is significantlysuitable for radical formation e spin density values ofO-atommake an order as 0432ndash0433 (7-OH in compounds1-2)gt 0381ndash0382 (4prime-OH in compounds 1 3-4)gt 0310ndash0376 (5-OH in compounds 1ndash4) As of a normal rule thehigher spin density means higher BDE values Nonethelessthe number of spin in O-atom is found in the oppositedirection with predictable BDE values among 5-OH and 4prime-OH radicals which can be explained by the fact thatH-removal needs to have suitable energy to break the hy-drogen bonds between 5-OH and 4-CO [29]

23 ElectronicProperties e global hardness η has emergedas a measurement of resistance to charge transfer [29] 7-Glycosylated compound (3) accounts for the maximumchemical hardness η value of 2134 eV in the gaseous phase ithas been confirmed that this compound is much more stablethan the remainder particularly in comparison with theunstable 6-methoxylated-7-glycosylated compound 4(2086 eV in gas 2093 eV in methanol) By comparingcompounds 1 and 2 4prime-OCH3 mainly causes a decrease of ηin both phases erefore it can be concluded that meth-ylations and methoxylations in isoflavones and their gly-cosides induce a trend in transferring from ldquohigh oxidationstate and low polarizabilityrdquo to ldquolow oxidation state and highpolarizabilityrdquo

e electronegativity χ measures a trend to attract elec-trons along with the chemical potential micro which will beproportional to this parameter of a negative signal [30] Fol-lowing Sandersonrsquos principle a compound exerting the highelectronegativitymight quickly reach equalization and establishlow reactivity [31] erefore the low value of this one forantioxidant reactions is expected Compound 4 with low χvalue of 3710 eV in the gaseous state participates in antioxidantreactivity better than the range of 3758ndash3835 eV for

compounds 1ndash3 Nevertheless using solvents if solvents likemedium methanol are used the results are greatly influencedIndeed it is opposite to the tendency of genistein (1) andbiochanin A (2) whose glycosides 3-4 tend to go from a lowerelectronegativity in gas to a higher one in methanol (Table 2)

Apart from descriptors such as the electron affinity theionization potential the global hardness and the globalelectronegativity the global electrophilicity index ω ωminusand ω+ values have so far been increased when methanol istaken into account e ωminus values of all considered com-pounds 1ndash4 are 2-3-folds higher than those of ω+ in eithergas or methanol method is one is identical with theprevious literature data [11] in which isoflavones and theirsugar derivatives tend to donate electrons rather thancapturing

Within a molecule the dipole moment is an availablemethod to estimate the separation of positive and negativeelectrical charges e high magnitudes of the dipole mo-ment accompany with the high charge densities and highpolarity in bonds [21] In our current account glycosylatedcompounds 3-4 is 3-folds higher than isoflavones 1-2 in bothstates gas and methanol because of the effects of sugar unitsand solvents However focusing on the comparison between1 and 2 and 3 and 4 4prime-methylation and 6-methoxylation aresuitable for slightly reducing this property Han and hispartners pointed out that the more symmetric property instructures the lower dipole moment and its antioxidantefficiency is better than that of the asymmetric molecule ofthe same size [22] We found that the symmetric genistein(1) and its 4prime-methylation (2) with the low dipole momentvalues of 3036D and 2862D have resulted in good anti-oxidant ability in many real experiments [5 6] Polariz-ability may be justified considering the soluble nature ofmolecules in polar solvents [21] Compounds containingsugars and isoflavones 3-4 have generally shown to asso-ciate with the higher dipole moment as well as higherpolarizability (Table 2) Followed on 4prime-methylations and 6-methoxylations the polarizability is also in accordancewith chemical hardness as mentioned above

Mulliken population analysis (MPA) has resulted in netcharges of a chemical ring system which also appears to bean effective tool to assess a chemical reactivity e Mul-liken atomic charges values using the DFT method arepresented in Table S2 Generally the heteroatom oxygensin flavonoids 1ndash4 remark the significant negative chargeswhich are active sites of donating their electrons In themeantime the maximum of positive charge which is thepreferential site for the nucleophilic reaction has occurredin carbon C-4 e high number of positive (negative)charges of atoms oxygens carbon and hydrogen arisingfrom 5-OH and 4-CO is caused by internal hydrogenbonds thereby stabilizing the structure e fact is thatantioxidant activities of flavonoids further depend onnegative centers whereby hydroxyl groups in ring B arefound to act as active sites of radical reactions [20] As aconsequence considering flavonoid aglycones of studied 3-4 and compound 1 the high values of negative chargesoccur in 4prime-OH in both gas and methanol agreeing with thesmallest BDE outcome

8 Journal of Chemistry

Besides frontier molecular orbital considerations andanalysis of electronic structure Fukui parameters alsoprovide important information and quick solutions to justifythe powerful reactive site of each atom Fukui indices fromTable S3 are calculated in gaseous medium based on the-oretical HSAB principle [31] It seemed that oxygen ofcarbonyl group 4-CO of all studiedmembers 1ndash4 and carbonC-2 in compounds 2 and 4 should have opted as good sitesfor both electrophilic and radical attacks but carbon C-2 isthe only suitable site of electrophilic scope for metabolites 1and 3 4prime-OH in compound 1 and carbon C-6 bears OCH3 incompound 4 adapted for nucleophilic attractive types Mostimportantly the f o condensed Fukui values advocate otherpreferential radical sites that are found in hydroxyl groups

Numerous atoms in β-D-apiofuranosyl-(1-6)-β-D-glu-copyranosyl parts of compounds 3-4 show the signicantMulliken electronic charges 4Prime-OH of glycoside 3 is nowexpected as electrophilic tendencies but for further cor-roboration with HOMO-LUMO analysis above Fukui de-scriptors research indicates that sugar units did not showfavorability for the antioxidant reactive types resembling inthe computational results in a avone glycoside rutin orresearch on pryoanthocyanin [17 28 32]

24 Antioxidant Mechanisms In the same condition of298K and environmental gas our BDE results in genistein(1) and biochanin A (2) dier from the B3LYP6-31 +G(dp) andor B3LYP6-311++G(dp) previously cal-culated publications within usually 40 kcalmol [33 34] Inaddition our PDE PA and ETE numbers show good

accordance with B3LYP6-311++G(dp) level in the lastaccount performed by Lengyel and partners particularly thedeviation just only found to be 2 kcalmol in PA calculationbut largely dierent from the work of Zhang and co-authors[33 34]

e favorable mechanisms of antiradical activity ofisoavones might possibly be discussed via thermodynam-ically preferential BDE of HAT IP of SET-PT and PA ofSPLET actions [35] From genistein (1) in gaseous statereaction in Table 3 BDE values (7709ndash9426 kcalmol) aresignicantly lower than those of IP (16830 kcalmol) and PA(32968ndash34707 kcalmol) is behavior is also similarlyestablished from the remainders like 2ndash4 erefore HATpathway is probable for isoavones and isoavone glycosidesin gas

From a thermodynamic point of view relating to threewell-known mechanisms the active sites of antioxidantaction have also been proposed throughout theminimal sumof enthalpies including BDEmin in HAT (IP + PDE)min inSET-PT and (PA+ETE)min in SPLET [35] e lowestrank of BDE values ranges from 7685 to 7709 kcalmol isdominated by 4prime-OH radical in gas for all isoavones 1ndash4compared with those of 7-OH radical (8376ndash8384 kcalmol) and 5-OH radical (8511ndash9426 kcalmol) A similarinstance arises from enthalpies of SET-PT and SPLETpathways that either isoavones 1-2 or their glycosides 3-4also encompasses the minimum values of IP + PDE andPA+ETE at 4prime-OH Once again it can be seen that ring B ofisoavones and 4prime-OH are active centers involving in an-tioxidant activity Although electron transfer enthalpy (ETE)shows the lowest amount in all radical cases of 1ndash4 minimal

OO

OHOOH

0295

0388

0226

0433

(a)

OHO

OHOO

0202

0354

0366

0459

(b)

OHO

OOOH

03820284

0381

(c)

OO

OOOH

0295

0432 0389

(d)

OHO

OOO

0202

0353

0459

0366

(e)

OO

OHOO

sugar

0376

0407

0436

(f )OO

OOOH

0380

sugar

0286

03810283

(g)

OO

OHOO

sugar

O

0310

0224

0359

(h)

OO

OOOH

0380

sugar

O 0285

02830381

(i)

Figure 7 Spin density distribution of structural radicals 1ndash4 obtained after H-atom abstraction (a) Compound 1 7-OH radical(b) Compound 1 5-OH radical (c) Compound 1 4prime-OH radical (d) Compound 2 7-OH radical (e) Compound 2 5-OH radical(f ) Compound 3 5-OH radical (g) Compound 3 4prime-OH radical (h) Compound 4 5-OH radical (i) Compound 4 4prime-OH radical

Journal of Chemistry 9

total energies of PA+ETE and IP + PDE establish 4 timesmore potency than those of BDEis is sequential evidenceto deeply vindicate that HATmechanism gets more favor ingas Here we can make an arrangement in the followingorder of favorable HATgt SET-PTasymp SPLET and impor-tantly conclude that in the environmental gas and antiox-idant mechanisms have been becoming dependent on theprocesses of proton disruptions rather than the effects ofelectron actions

In terms of comparing among radicals 5-OH 7-OH and4prime-OH in each metabolite O-H homolytic bond dissociationenthalpy (BDE) O-H heterolytic bond dissociation enthalpy(PDE) and proton affinity (PA) are realistic evidence wouldsince have been proved that energies of 5-OH bond breakingalways overcome due to IHBs (Table 3)

Antioxidant-structural relationships can be highlightedthrough the differences in enthalpies calculations Whenspontaneously compared two isoflavone glycosides 3-4 5-OH radical enthalpy parameters BDE IP PDE PA andETE the courses of IP + PDE and PA+ETE of compound 4are less than those of 5-OH radical in compound 3 from 2 to9 kcalmol It therefore remarks that 6-OCH3 has greatlyinfluenced 5-OH and IHBs so that the 6-methoxylationwould help increase antioxidant In the same assessment forcompounds 1-2 4prime-methylation did not significantly con-tribute to the effect itself on 5-OH and 7-OH radicals but thereverse trends are observed 5-OH radical BDE in genstein(1)gt biochanin A (2) 5-OH and 7-OH radicals PDE ingenistein (1)lt biochanin A (2) As mentioned above β-D-apiofuranosyl-(1-6)-β-D-glucopyranosyl unit should not bethe suitable sites for radical scavenging but they have greatlyaffected isoflavone core Indeed 7-glycosylation (meta po-sition) in ambocin (3) has two sides On the one hand itshows a decrease in the amount of energy in 5-OH bondbreaking in terms of BDE IP IP + PDE ETE and PA+ETEwhile on the other hand it induces an increase pattern inthose in PDE and PA as compared with 7-hydroxylation ingenistein (1)

Last but not least among 1 and 3-4 4prime-OH radicalBDE leads to the introduction of an actively antioxidantarrangement tectorigenin 7-O-[β-D-apiofuranosyl-(1-6)-β-D-glucopyranoside] (4) gt ambocin (3) gt genistein (1)while no change is observed in 7-OH radical BDE values

and 5-OH radical one with the order genistein (1)lt biochanin A (2)

3 Conclusion

Naturally occurring isoflavones and their glycosides havesuccessfully been investigated by the density theory-basedmethod Actually the prospective outcome points out thatHAT pathway is preferentially closely related to the anti-oxidant action of all studied polyphenolic compounds inthe gaseous state Numerous parameters such as ionizationpotential (IP) proton affinity (PA) the sum of energies ofSET-PT andor SPLETmechanisms especially in terms ofBDE values provide supportive information to confirm theradical-scavenging process that takes place throughoutO-H breaking bond in isoflavones is current resultcorresponds to many previous studies in which structuralconformations π-electrons delocalization potential po-larizability hydroxyl groups distributed in ring B andfunctional groups are major reasons for antioxidant ac-tivities of general flavonoids Antioxidant isoflavone gly-cosides ambocin and tectorigenin 7-O-[β-D-apiofuranosyl-(1-6)-β-D-glucopyranoside] are more significant thanisoflavone genistein and biochanin A deducing from 7-glycosylation and 6-methoxylation is account providesnecessary guidelines for future research

Abbreviations

DFT Density functional theoryHOMO Highest occupied molecular orbitalLUMO Lowest unoccupied molecular orbitalIHBs Intramolecular hydrogen bondsBDE Homolytic bond dissociation enthalpyPDE Heterolytic bond dissociation enthalpyIP Ionization potentialPA Proton affinityETE Electron transfer enthalpyHAT Hydrogen atom transferSET-PT Single electron transfer-proton transferSPLET Sequential proton loss electron transferDPPH 22-Diphenyl-1-picrylhydrazyl

Table 3 Gas phase reaction enthalpies at 298 K for radicals of the studied compounds at B3LYP6-311G(d) level of theory (in kcalmol)

Compounds HAT BDE IP PDE SET-PT (IP + PDE) PA ETE SPLET (PA+ETE)1 168305-OH 9426 24166 40996 34707 6289 409967-OH 8384 23136 39966 32968 7002 399704prime-OH 7709 22449 39279 33790 5589 393792 165795-OH 9426 24419 40998 34740 6257 409977-OH 8376 23368 39947 33000 6962 399623 164765-OH 9414 24509 40985 34802 6183 409854prime-OH 7689 22784 39260 33811 5449 392604 157175-OH 8511 24372 40089 34563 5519 400824prime-OH 7685 23542 39269 33822 5429 39251

10 Journal of Chemistry

Data Availability

All data used for this project are publicly available andaccessible online e authors have pronounced the entiredata building process and empirical techniques presented inthe paper

Conflicts of Interest

e authors declare that they have no conflicts of interest

Acknowledgments

is work was supported by a grant (no VASTCTG0117-19) from Vietnam Academy of Science and Technology(VAST) 18 Hoang Quoc Viet Caugiay Hanoi Vietnam

Supplementary Materials

Figure S1 the state forms of studied structures in MeOHmedium Table S1 the collective energies depended ontorsional angles θ2 (C2-C3-C1prime-C2prime) Table S2 Mullikenatomic charges at theoretical level B3LYP6-311G(d) ofstudied compounds in gas and methanol mediums Table S3condensed Fukui indices at B3LYP6-311G(d) of studiedcompounds in gas medium (Supplementary Materials)

References

[1] E Miadokova ldquoIsoflavonoids-an overview of their biologicalactivities and potential health benefitsrdquo InterdisciplinaryToxicology vol 2 no 4 pp 211ndash218 2009

[2] A N Panche A D Diwan and S R Chandra ldquoFlavonoidsan overviewrdquo Journal of Nutritional Science vol 5 p e472016

[3] Z Dhaouadi M Nsangou N Garrab E H AnouarK Marakchi and S Lahmar ldquoDFT study of the reaction ofquercetin with and radicalsrdquo Journal of Molecular StructureTHEOCHEM vol 904 no 1-3 pp 35ndash42 2009

[4] P Dixit R Chillara V Khedgikar et al ldquoConstituents ofDalbergia sissoo Roxb leaves with osteogenic activityrdquo Bio-organic amp Medicinal Chemistry Letters vol 22 no 2pp 890ndash897 2012

[5] J N Choi K Dockyu K C Hyung M Y Kyung K Jiyoungand H L Choong ldquo2prime-Hydroxyaltion of genistein enhancedantioxidant and antiproliferative activities in MCF-7 humanbreast cancer cellsrdquo Journal of Microbiology and Bio-technology vol 19 pp 1348ndash1354 2009

[6] S Dowling F Regan and H Hughes ldquoe characterisation ofstructural and antioxidant properties of isoflavone metalchelatesrdquo Journal of Inorganic Biochemistry vol 104 no 10pp 1091ndash1098 2010

[7] J-G Cho H-J Park G-W Huh et al ldquoFlavonoids fromPueraria mirifica roots and quantitative analysis usingHPLCrdquo Food Science and Biotechnology vol 23 no 6pp 1815ndash1820 2014

[8] Y Zhang and Y Sun ldquoeoretical investigation on atmo-spheric reaction of O(3P) with CH 2 CNrdquo Journal of PhysicalOrganic Chemistry vol 32 no 4 article e3913 2018

[9] E M Kamel A M Mahmoud S A Ahmed andA M Lamsabhi ldquoA phytochemical and computational studyon flavonoids isolated from Trifolium resupinatum L and

their novel hepatoprotective activityrdquo Food amp Function vol 7no 4 pp 2094ndash2106 2016

[10] R A Mendes S K C Almeida I N Soares et al ldquoAcomputational investigation on the antioxidant potential ofmyricetin 34prime-di-O-α-L-rhamnopyranosiderdquo Journal ofMolecular Modeling vol 24 no 6 p 133 2018

[11] K S Kumar and R Kumarresan ldquoA DFT study on thestructural electronic properties and radical scavengingmechanisms of calycosin glycitein pratensein and prunetinrdquoComputational andeoretical Chemistry vol 985 pp 14ndash222012

[12] A Vaganek J Rimarcik V Lukes L Rottmannova andE Klein ldquoDFTB3LYP study of the enthalpies of Homolyticand Heterolytic O-H Bond dissociation in sterically hinderedphenolsrdquo Acta Chimica Slovenica vol 4 pp 55ndash71 2011

[13] M Leopoldini T Marino N Russo and M Toscano ldquoAn-tioxidant properties of phenolic compounds H-atom versuselectron transfer mechanismrdquo Journal of Physical ChemistryA vol 108 no 22 pp 4916ndash4922 2004

[14] R A Mendes B L S Silva R Takeara R G Freitas A Brownand G L C de Souza ldquoProbing the antioxidant potential ofphloretin and phlorizin through a computational investigationrdquoJournal of Molecular Modeling vol 24 no 4 p 101 2018

[15] E N Maciel S K C Almeida S C da Silva andG L C de Souza ldquoExamining the reaction between anti-oxidant compounds and 22-diphenyl-1-picrylhydrazyl(DPPH) through a computational investigationrdquo Journal ofMolecular Modeling vol 24 no 8 p 218 2018

[16] A Galano G Mazzone R A Diduk T MarinoJ R A Idaboy and N Russo ldquoFood antioxidants chemicalInsights at the Molecular Levelrdquo Annual Review of FoodScience and Technology vol 7 no 1 pp 335ndash352 2016

[17] V B Luzhkov ldquoMechanisms of antioxidant activity the DFTstudy of hydrogen abstraction from phenol and toluene by thehydroperoxyl radicalrdquo Chemical Physics vol 314 no 1-3pp 211ndash217 2005

[18] S A P Gomez N F Holguin A P HernandezM P Miramontes and D G Mitnik ldquoComputational mo-lecular characterization of the flavonoid rutinrdquo ChemistryCentral Journal vol 4 no 1 p 12 2010

[19] D G Mitnik ldquoComputational chemistry of natural productsa comparison of the chemical reactivity of isonaringin cal-culated with the M06 family of density functionalsrdquo Journal ofMolecular Modeling vol 20 no 7 p 2316 2014

[20] H Djeradi A Rahmouni and A Cheriti ldquoAntioxidant ac-tivity of flavonoids a QSAR modeling using Fukui indicesdescriptorsrdquo Journal of Molecular Modeling vol 20 no 10p 2476 2014

[21] K Sadasivam and R Kumaresan ldquoAntioxidant behavior ofmearnsetin and myricetin flavonoid compounds-a DFTstudyrdquo Spectrochimica Acta Part A Molecular and Bio-molecular Spectroscopy vol 79 no 1 pp 282ndash293 2011

[22] R-M Han Y-X Tian Y Liu et al ldquoComparison of flavo-noids and isoflavonoids as antioxidantsrdquo Journal of Agri-cultural and Food Chemistry vol 57 no 9 pp 3780ndash37852009

[23] S F Farag A S Ahmed K Terashima Y Takaya andM Niwa ldquoIsoflavonoid glycosides from Dalbergia sissoordquoPhytochemistry vol 57 pp 1263ndash1268 2001

[24] S T Ninh ldquoA Review on the medicinal plant Dalbergiaodorifera species phytochemistry and biological activityrdquoEvidence-Based Complementary and Alternative Medicinevol 2017 Article ID 7142370 27 pages 2017

Journal of Chemistry 11

ETE H Flav-Obull( 1113857 + H eminus( )

minus H Flav-Ominus( )(8)

H(Flav-Ominus) is the enthalpy of flavonoid anion afterproton abstraction of original molecule

Antioxidant activities have been explained by DFT-basedreactivity descriptors [11] including energies of highest oc-cupied molecular orbital (HOMO) and lowest unoccupiedmolecular orbital (LUMO) dipole moments atomic chargeselectron affinity A the ionization potential Io the globalhardness η the electronegativity χ the chemical potential microglobal electrophilicity indexω and Fukui chemical parameters

Based on the theoretical approach of DFT Janakrsquostheorem and the finite difference approximation thesedescriptors can be proposed by the related equations given asfollows [18]

Io asymp minusEH

A asymp minusEL

η asympIo minusA( 1113857

2asymp

EL minusEH( 1113857

2

χ asympIo + A( 1113857

2asymp

EL + EH( 1113857

2

micro asymp minusIo + A( 1113857

2asympminus EL + EH( 1113857

2

(9)

where EH and EL are energies of HOMO and LUMOrespectively

e atomic charges for neutral molecular were restrictedby Mulliken population analysis (MPA) following the sameframework of B3LYP6-311G(d)

e global electrophilicity index ω indicates the stabiliza-tion energy of a molecule system when being saturated byelectrons from outside erefore the higher value of ω+

(electron accepting) shows the significant electrophilicity whilethe lower one of ωminus (electron donating) evidently exhibits thebetter nucleophilicity of a compound ese chemical indiceswere expressed following the functions as follows [19]

ω micro2

2ηasymp

Io + A( 11138572

4 Io minusA( 11138571113858 1113859asymp

EL + EH( 11138572

4 EL minusEH( 11138571113858 1113859

ωminus 3Io + A( 1113857

2

16 Io minusA( 11138571113858 1113859

ω+

Io + 3A( 11138572

16 Io minusA( 11138571113858 1113859

(10)

As a general conceptual comprehension the condensedFukui parameters evidently provide information on a se-lective property in a chemical reaction e atom coupledwith the high electronic population displays as the mostreactive site when compared to the surrounding atoms in amolecule [20] Briefly Fukui descriptors have been shown to

associate with nucleophilic (f+k ) electrophilic (fminusk ) andor

radical attacks (f0k) and were possibly described by the

following equilibriums [20]

f+k qk(N + 1)minus qk(N)

fminusk qk(N)minus qk(Nminus 1)

f0k

qk(N + 1)minus qk(Nminus 1)1113858 1113859

2

(11)

where qk(N) electronic population of atom k in a neutralmolecule qk(N+ 1) electronic population of atom k in ananionic molecule and qk(Nminus 1) electronic population ofatom k in a cationic molecule

2 Results and Discussion

21 Geometrical Analysis e comprehension of isoflavoneconformational analysis is an important method to prove therelationship between the antioxidant activities and structuralaspects since the HAT SET-PT and SPLETpathways closelydepend on the behaviors of differential hydroxyl groups andthe geometric features From Figures 2 and S1 and Table 1we reported the optimized structures with patterns ofintramolecular hydrogen bonds (IHBs) between 5-OH and4-CO along with selective characters of bonds bond anglesand dihedral angles As of local minimum energies there isno distinction in each compound between gaseous state andmethanol (Table 2) e first feature observed from theoptimized molecular structures of 1ndash4 is that π-electron isdelocalized in the whole aglycone especially B towards Cthrough 23-double and the coplanar between chromenering and phenyl unit is lost In agreement with findings ofIHBs in many previous flavonoid DFT calculated researches[21] IHBs lengths are found to be 1721 A for 1-2 1726 A for3 and 1733 A for 4 in gas When compared to 5-OH and 7-OH the longer bond lengths of 4prime-OH and O-CPrime1 at 7-po-sition evidently reinforces that as a matter of fact hydrolysisreactions occurred in flavone glycosides at aglycone-glyconelinkage or antioxidant activations facilitated at 4prime-OH forflavonoids [22 23] As shown in Table 1 bond angles θ1 (4prime-O-H) and θ1 (7-O-H) demonstrate larger 2-3deg than θ1 (5-O-H) obviously caused by effective IHBs

Regarding the effects of environmental researches es-pecially polar solvents we now select methanol as a goodagent because it promotes many biological processes [24] Sofar flavonoids are recognized as weak polar compounds andthat it is not easy to dilute them in water [25] In comparisonwith gaseous circumstance methanol directly induces thereduction of IHBs lengths and the elongation of 5-OH bondlengths Also 6-OCH3 can be seen as the main reason thatmakes a slight difference in IHBs between compounds 3 and4 in the procedures of both gas and methanol Dihedralangles θ1 (C2-C3-C1prime-C2prime) among all structures 1ndash4 show notmuch change and reach 415deg in gas and 44deg in methanolFrom previous literature data utilizing the RHF6-311 +G(d) ab initio method compounds 1-2 have beenlinked to θ1 numbers of 40deg and 45deg in environmentalacetonitrile or regarding to employment of UB3LYP6-

Journal of Chemistry 3

31++G (dp) in gas phase and θ1 value of 393deg was recordedfor genistein (1) [22 26] but no manuscript associates withan insight into relationships between conformations andtheir energies

To confirm the results mentioned above potential en-ergy curves for all considered compounds 1ndash4 are obtainedlike the functions of torsional angle θ2 (C2-C3-C1prime-C2prime)

between the rings B and C linkage in the gaseous state In thiscase θ2 has been explored by scanning in the characteristicsteps of 15deg values from 0deg to 360deg at theoretical level B3LYP6-311G(d) (Table S1) An attempt to accurate without anyconstraints the structures of these four isoflavones is thenoptimized around each conformational potential minimumand the results are drawn in Figure 3 It can generally be

1721

(a)

1721

(b)

(c)

1726

(d)

Figure 2 State forms of studied structures 1ndash4 in gas medium (a) Compound 1 (b) Compound 2 (c) Compound 3 (d) Compound 4

Table 1 Optimized bond distances bond angles (θ1) and dihedral angles (θ2) of studied compounds with B3LYP6-311G(d) in gas andmethanol mediums

No Bond lengths5 (O-H) 7 (O-H) 7 (O-C1Prime) 6 (O-CH3) 4prime (O-H) 4prime (O-CH3) Hydrogen bonds

1 Gas 1337 1357 1364 1721Methanol 1343 1354 1364 1714

2 Gas 1337 1357 1362 1721Methanol 1343 1354 1361 1714

3 Gas 1338 1365 1365 1733Methanol 1343 1365 1364 1720

4 Gas 1338 1365 1364 1365 1726Methanol 1343 1362 1370 1364 1716

No Bond angles Dihedral anglesθ1 (C5-O-H) θ1 (C7-O-H) θ1 (C4prime-O-H) θ1 (C2-C3-C1prime) θ2 (C2-C3-C1prime-C2prime)

1 Gas 107450 109900 109748 120378 41491Methanol 107122 110640 110240 120286 44364

2 Gas 107459 109886 120342 41492Methanol 107106 110620 120273 44440

3 Gas 107631 109726 120316 41531Methanol 107791 110207 120214 43576

4 Gas 107631 109726 120642 41531Methanol 106792 110241 120189 44128

4 Journal of Chemistry

noted that the dependence of conformational states ontorsional angle θ2 is similar among all isoavonoids 1ndash4including two conformers I-II lying at 415deg (conformer I)

and 135deg (conformer II) for each molecule ese twoconformers arise from the potential energy versus torsionalangles obtained as a good agreement with the previous

Table 2 Chemical reactivity indices obtained using the DFT method in gas and methanol mediums

No Medium η (eV) χ (eV) micro (eV) Io (eV) A (eV)ω (eV)

ω ωminus ω+

1 Gas 2125 3835 minus3835 5960 1710 3461 5644 1809Methanol 2124 3932 minus3932 6056 1808 3639 5871 1939

2 Gas 2107 3789 minus3789 5897 1682 3407 5565 1776Methanol 2109 3915 minus3915 6024 1806 3633 5854 1940

3 Gas 2134 3758 minus3758 5891 1624 3309 5455 1697Methanol 2115 3967 minus3967 6081 1852 3720 5968 2001

4 Gas 2086 3710 minus3710 5796 1624 3299 5415 1705Methanol 2093 3956 minus3956 6049 1863 3740 5979 2023

No Medium Dipole moment (debye) Polarizability (au) Energy (kcalmol) EHOMO (eV) ELUMO (eV)

1 Gas 3036 187118104 minus59860814 minus5960 minus1710Methanol 4455 247343170 minus59861859 minus6056 minus1808

2 Gas 2862 202392352 minus62327698 minus5897 minus1682Methanol 4231 264841735 minus62328597 minus6024 minus1806

3 Gas 10227 347615084 minus129339488 minus5891 minus1624Methanol 13200 440126098 minus129341513 minus6081 minus1852

4 Gas 10069 365799666 minus136526747 minus5796 minus1624Methanol 13537 461553236 minus136528945 minus6049 minus1863

30 60 90 120 150 180 210 240 270 300 330 3600Dihedral angle (degree)

ndash598608

ndash598607

ndash598606

ndash598605

ndash598604

ndash598603

ndash598602

Ener

gy (k

calm

ol)

(a)

30 60 90 120 150 180 210 240 270 300 330 3600Dihedral angle (degree)

ndash623277

ndash623276

ndash623275

ndash623274

ndash623273

Ener

gy (k

calm

ol)

(b)

30 60 90 120 150 180 210 240 270 300 330 3600Dihedral angle (degree)

ndash1293395

ndash1293394

ndash1293393

ndash1293392

ndash1293391

Ener

gy (k

calm

ol)

(c)

30 60 90 120 150 180 210 240 270 300 330 3600Dihedral angle (degree)

ndash1365268

ndash1365267

ndash1365266

ndash1365265

ndash1365264

ndash1365263

Ener

gy (k

calm

ol)

(d)

Figure 3 Potential energy curves versus torsional angle of studied structures 1ndash4 in gas medium (a) Compound 1 (b) Compound 2(c) Compound 3 (d) Compound 4

Journal of Chemistry 5

publication on several isoflavones [11] e absolute mini-mum I is more stable than the conformational relativeminimum II by 198 kcalmol for genistein (1) however thisone for compounds 2ndash4 has smaller values of 040 kcalmol029 kcalmol and 026 kcalmol respectively Parallel withthis there are several potential energy barriers that rangefrom I to II in compound 1 the first interconversion energybarrierrsquos value of 355 kcalmol is recognized at the per-pendicular conformation (θ2 90deg) and the second energybarrier accounts for 494 kcalmol and peaks at anti(θ2 180deg) conformation meanwhile the maximum in-terchangeable barrier reaches 541 kcalmol at syn (θ2 360degor 0deg) shape In the same manner with torsional angles θ1 of90deg 180deg and 360deg (or 0deg) these potential energy barriers arefound at the values of 215 kcalmol 378 kcalmol and402 kcalmol 215 kcalmol 377 kcalmol and 400 kcalmol and 211 kcalmol 381 kcalmol and 403 kcalmol forcompounds 2ndash4 respectively e dramatic difference ob-tained from energies between two minima together with thedistinction from the interchangeable energy barriers of 1 andgroups 2ndash4 can be explained by the symmetric property of 1the phenomena of 4prime-methylation in 2 7-glycosylation in 3and 6-methoxylation-7-glycosylation in 4

22 Frontier Molecular Orbital eory and Spin DensityTaking π-electron delocalization into consideration it in-volves in the stabilization of parent molecular and radicalsafter H abstractions [27] e frontier orbital theoreticalcalculation seems to be a significant tool for explaining therelationship between neutral and radical forms especially interms of the electron delocalization At the level of B3LYP6-311G(d) in both mediums of gas and methanol HOMO andLUMO of neutral and radical visual images and frontierorbital energies of 1ndash4 are shown in Figures 4ndash6 and Table 2HOMO neutral images show that the electron distribution isconcentrated in the entire aglycone especially ring B and23-double bond while LUMO neutral is delocalized oversystematic rings A and C Sugar units are not a suitable sitefor radical reactions e same result has been found inpreviously studied isoflavones glycitein pratensein andprunetin [11] When hydrogen atom abstraction takes placein four isoflavones it is worth noting that 4prime-OH HOMOradical species in compounds 1 and 3-4 which correspondto the small BDE values consist of high electron density inring B and slightly less in ring A 5-OH andor 7-OHHOMO radical shapes which concern the high BDE valuesdid not differ from neutral composition except for the lesselectron distribution in ring C for 5-OH radical site ofcompound 4 LUMO radical forms mostly focus on chro-mene systems but slightly view in ring B in the case of 5-OH7-OH of compounds 1-2 and 5-OH of compounds 3-4 ehigher EHOMO (the lower ionization potential Io) and thelower ELUMO (the higher electron affinity A) mean the bettercapacity of electrons donating and the better sensitivity toreceive electrons respectively whereas the easier electrontransfer indicates the lower Egap ELUMOminusEHOMO andthus the better antioxidant reactivity From Table 2 thegaseous phase would lay a better ground for decreasing

EHOMO values when compared with using methanol butmethanol solution should be a suitable tool to scale downELUMO values Paying attention to the gaseous medium thehighest EHOMO which can be claimed responsible for ad-vantageous radical reactions here facilitates compound 4(minus5796 eV) in preference to the others 3 (minus5891 eV) 2(minus5897 eV) and 1 (minus5960 eV) e numbers of 4250 eV4215 eV 4267 eV and 4172 eV are assignable to the re-spective Egap values of compounds 1ndash4 in the environmentalgas e most striking feature is that 4prime-methylated

4250 4215 4267 4172

ndash9ndash8ndash7ndash6ndash5ndash4ndash3ndash2ndash1

01

Fron

tier m

olec

ular

orb

ital e

nerg

y (e

V)

Com

poun

d 4

Com

poun

d 3

Com

poun

d 2

Com

poun

d 1

Compound

HOMOLUMO

Figure 4 Neutral HOMO and LUMO images and Egap of struc-tures 1ndash4 in gas medium

4248 4218 4229 4185

Com

poun

d 1

Com

poun

d 3

Com

poun

d 4

Com

poun

d 2

Compound

HOMOLUMO

ndash9ndash8ndash7ndash6ndash5ndash4ndash3ndash2ndash1

01

Fron

tier m

olec

ular

orb

ital e

nerg

y (e

V)

Figure 5 Neutral HOMO and LUMO images and Egap of struc-tures 1ndash4 in MeOH medium

6 Journal of Chemistry

(a) (b) (c)

(d) (e) (f)

(g) (h) (i)

(j) (k) (l)

(m) (n) (o)

(p) (q) (r)

Figure 6 HOMO and LUMO of structural radicals 1ndash4 (a) HOMO-5-OH radical (1) (b) HOMO-7-OH radical (1) (c) HOMO-4prime-OHradical (1) (d) LUMO-5-OH radical (1) (e) LUMO-7-OH radical (1) (f ) LUMO-4prime-OH radical (1) (g) HOMO-5-OH radical (2)(h) HOMO-7-OH radical (2) (i) HOMO-5-OH radical (3) (j) LUMO-5-OH radical (2) (k) LUMO-7-OH radical (2) (l) LUMO-5-OHradical (3) (m) HOMO-4prime-OH radical (3) (n) HOMO-5-OH radical (4) (o) HOMO-4prime-OH radical (4) (p) LUMO-4prime-OH radical (3) (q)LUMO-5-OH radical (4) (r) LUMO-4prime-OH radical (4)

Journal of Chemistry 7

compound 2 and 6-methoxylated compound 4 evidentlygenerate better Egap values when compared to respectivecompounds 1 and 3 in both of the phases Emphasizing onthe change of gas phase into methanol a remarkable reversecan be observed in the Egap values between 1 and 3 due tothe 7-glycosylated phenomenon Among four compounds1ndash4 we primarily assumed that tectorigenin 7-O-[β-D-apiofuranosyl-(1-6)-β-D-glucopyranoside] (4) is the bestcandidate employable for antioxidant targets not mentionthe fact that 4prime-methylation 6-methoxylation and 7-gly-cosylation facilitate the antioxidant ability

Calculation of the atomic spin density population ofvarious radicals after H-abstraction from four consideredisoflavones 1ndash4 is given in Figure 7 It should be kept inmindthat the higher the spin density delocalized in radicals theeasier the radical formation hence lower BDE values [28]As a general view the computed results reveal that strongspin distributions remain on oxygen atoms of phenolicgroups carbons C-1prime C-3prime and C-5prime of the ring B andcarbons C-6 and C-8 in ring A and also C4a In all fourcompounds 1ndash4 C-1prime C-3prime and C-5prime are centers of positivespin density C-2prime C-4prime and C-6prime bear negative one whilstatomic carbons in ring A fail to do so [11] It suggests thatphenyl unit ring B with more delocalized spin is significantlysuitable for radical formation e spin density values ofO-atommake an order as 0432ndash0433 (7-OH in compounds1-2)gt 0381ndash0382 (4prime-OH in compounds 1 3-4)gt 0310ndash0376 (5-OH in compounds 1ndash4) As of a normal rule thehigher spin density means higher BDE values Nonethelessthe number of spin in O-atom is found in the oppositedirection with predictable BDE values among 5-OH and 4prime-OH radicals which can be explained by the fact thatH-removal needs to have suitable energy to break the hy-drogen bonds between 5-OH and 4-CO [29]

23 ElectronicProperties e global hardness η has emergedas a measurement of resistance to charge transfer [29] 7-Glycosylated compound (3) accounts for the maximumchemical hardness η value of 2134 eV in the gaseous phase ithas been confirmed that this compound is much more stablethan the remainder particularly in comparison with theunstable 6-methoxylated-7-glycosylated compound 4(2086 eV in gas 2093 eV in methanol) By comparingcompounds 1 and 2 4prime-OCH3 mainly causes a decrease of ηin both phases erefore it can be concluded that meth-ylations and methoxylations in isoflavones and their gly-cosides induce a trend in transferring from ldquohigh oxidationstate and low polarizabilityrdquo to ldquolow oxidation state and highpolarizabilityrdquo

e electronegativity χ measures a trend to attract elec-trons along with the chemical potential micro which will beproportional to this parameter of a negative signal [30] Fol-lowing Sandersonrsquos principle a compound exerting the highelectronegativitymight quickly reach equalization and establishlow reactivity [31] erefore the low value of this one forantioxidant reactions is expected Compound 4 with low χvalue of 3710 eV in the gaseous state participates in antioxidantreactivity better than the range of 3758ndash3835 eV for

compounds 1ndash3 Nevertheless using solvents if solvents likemedium methanol are used the results are greatly influencedIndeed it is opposite to the tendency of genistein (1) andbiochanin A (2) whose glycosides 3-4 tend to go from a lowerelectronegativity in gas to a higher one in methanol (Table 2)

Apart from descriptors such as the electron affinity theionization potential the global hardness and the globalelectronegativity the global electrophilicity index ω ωminusand ω+ values have so far been increased when methanol istaken into account e ωminus values of all considered com-pounds 1ndash4 are 2-3-folds higher than those of ω+ in eithergas or methanol method is one is identical with theprevious literature data [11] in which isoflavones and theirsugar derivatives tend to donate electrons rather thancapturing

Within a molecule the dipole moment is an availablemethod to estimate the separation of positive and negativeelectrical charges e high magnitudes of the dipole mo-ment accompany with the high charge densities and highpolarity in bonds [21] In our current account glycosylatedcompounds 3-4 is 3-folds higher than isoflavones 1-2 in bothstates gas and methanol because of the effects of sugar unitsand solvents However focusing on the comparison between1 and 2 and 3 and 4 4prime-methylation and 6-methoxylation aresuitable for slightly reducing this property Han and hispartners pointed out that the more symmetric property instructures the lower dipole moment and its antioxidantefficiency is better than that of the asymmetric molecule ofthe same size [22] We found that the symmetric genistein(1) and its 4prime-methylation (2) with the low dipole momentvalues of 3036D and 2862D have resulted in good anti-oxidant ability in many real experiments [5 6] Polariz-ability may be justified considering the soluble nature ofmolecules in polar solvents [21] Compounds containingsugars and isoflavones 3-4 have generally shown to asso-ciate with the higher dipole moment as well as higherpolarizability (Table 2) Followed on 4prime-methylations and 6-methoxylations the polarizability is also in accordancewith chemical hardness as mentioned above

Mulliken population analysis (MPA) has resulted in netcharges of a chemical ring system which also appears to bean effective tool to assess a chemical reactivity e Mul-liken atomic charges values using the DFT method arepresented in Table S2 Generally the heteroatom oxygensin flavonoids 1ndash4 remark the significant negative chargeswhich are active sites of donating their electrons In themeantime the maximum of positive charge which is thepreferential site for the nucleophilic reaction has occurredin carbon C-4 e high number of positive (negative)charges of atoms oxygens carbon and hydrogen arisingfrom 5-OH and 4-CO is caused by internal hydrogenbonds thereby stabilizing the structure e fact is thatantioxidant activities of flavonoids further depend onnegative centers whereby hydroxyl groups in ring B arefound to act as active sites of radical reactions [20] As aconsequence considering flavonoid aglycones of studied 3-4 and compound 1 the high values of negative chargesoccur in 4prime-OH in both gas and methanol agreeing with thesmallest BDE outcome

8 Journal of Chemistry

Besides frontier molecular orbital considerations andanalysis of electronic structure Fukui parameters alsoprovide important information and quick solutions to justifythe powerful reactive site of each atom Fukui indices fromTable S3 are calculated in gaseous medium based on the-oretical HSAB principle [31] It seemed that oxygen ofcarbonyl group 4-CO of all studiedmembers 1ndash4 and carbonC-2 in compounds 2 and 4 should have opted as good sitesfor both electrophilic and radical attacks but carbon C-2 isthe only suitable site of electrophilic scope for metabolites 1and 3 4prime-OH in compound 1 and carbon C-6 bears OCH3 incompound 4 adapted for nucleophilic attractive types Mostimportantly the f o condensed Fukui values advocate otherpreferential radical sites that are found in hydroxyl groups

Numerous atoms in β-D-apiofuranosyl-(1-6)-β-D-glu-copyranosyl parts of compounds 3-4 show the signicantMulliken electronic charges 4Prime-OH of glycoside 3 is nowexpected as electrophilic tendencies but for further cor-roboration with HOMO-LUMO analysis above Fukui de-scriptors research indicates that sugar units did not showfavorability for the antioxidant reactive types resembling inthe computational results in a avone glycoside rutin orresearch on pryoanthocyanin [17 28 32]

24 Antioxidant Mechanisms In the same condition of298K and environmental gas our BDE results in genistein(1) and biochanin A (2) dier from the B3LYP6-31 +G(dp) andor B3LYP6-311++G(dp) previously cal-culated publications within usually 40 kcalmol [33 34] Inaddition our PDE PA and ETE numbers show good

accordance with B3LYP6-311++G(dp) level in the lastaccount performed by Lengyel and partners particularly thedeviation just only found to be 2 kcalmol in PA calculationbut largely dierent from the work of Zhang and co-authors[33 34]

e favorable mechanisms of antiradical activity ofisoavones might possibly be discussed via thermodynam-ically preferential BDE of HAT IP of SET-PT and PA ofSPLET actions [35] From genistein (1) in gaseous statereaction in Table 3 BDE values (7709ndash9426 kcalmol) aresignicantly lower than those of IP (16830 kcalmol) and PA(32968ndash34707 kcalmol) is behavior is also similarlyestablished from the remainders like 2ndash4 erefore HATpathway is probable for isoavones and isoavone glycosidesin gas

From a thermodynamic point of view relating to threewell-known mechanisms the active sites of antioxidantaction have also been proposed throughout theminimal sumof enthalpies including BDEmin in HAT (IP + PDE)min inSET-PT and (PA+ETE)min in SPLET [35] e lowestrank of BDE values ranges from 7685 to 7709 kcalmol isdominated by 4prime-OH radical in gas for all isoavones 1ndash4compared with those of 7-OH radical (8376ndash8384 kcalmol) and 5-OH radical (8511ndash9426 kcalmol) A similarinstance arises from enthalpies of SET-PT and SPLETpathways that either isoavones 1-2 or their glycosides 3-4also encompasses the minimum values of IP + PDE andPA+ETE at 4prime-OH Once again it can be seen that ring B ofisoavones and 4prime-OH are active centers involving in an-tioxidant activity Although electron transfer enthalpy (ETE)shows the lowest amount in all radical cases of 1ndash4 minimal

OO

OHOOH

0295

0388

0226

0433

(a)

OHO

OHOO

0202

0354

0366

0459

(b)

OHO

OOOH

03820284

0381

(c)

OO

OOOH

0295

0432 0389

(d)

OHO

OOO

0202

0353

0459

0366

(e)

OO

OHOO

sugar

0376

0407

0436

(f )OO

OOOH

0380

sugar

0286

03810283

(g)

OO

OHOO

sugar

O

0310

0224

0359

(h)

OO

OOOH

0380

sugar

O 0285

02830381

(i)

Figure 7 Spin density distribution of structural radicals 1ndash4 obtained after H-atom abstraction (a) Compound 1 7-OH radical(b) Compound 1 5-OH radical (c) Compound 1 4prime-OH radical (d) Compound 2 7-OH radical (e) Compound 2 5-OH radical(f ) Compound 3 5-OH radical (g) Compound 3 4prime-OH radical (h) Compound 4 5-OH radical (i) Compound 4 4prime-OH radical

Journal of Chemistry 9

total energies of PA+ETE and IP + PDE establish 4 timesmore potency than those of BDEis is sequential evidenceto deeply vindicate that HATmechanism gets more favor ingas Here we can make an arrangement in the followingorder of favorable HATgt SET-PTasymp SPLET and impor-tantly conclude that in the environmental gas and antiox-idant mechanisms have been becoming dependent on theprocesses of proton disruptions rather than the effects ofelectron actions

In terms of comparing among radicals 5-OH 7-OH and4prime-OH in each metabolite O-H homolytic bond dissociationenthalpy (BDE) O-H heterolytic bond dissociation enthalpy(PDE) and proton affinity (PA) are realistic evidence wouldsince have been proved that energies of 5-OH bond breakingalways overcome due to IHBs (Table 3)

Antioxidant-structural relationships can be highlightedthrough the differences in enthalpies calculations Whenspontaneously compared two isoflavone glycosides 3-4 5-OH radical enthalpy parameters BDE IP PDE PA andETE the courses of IP + PDE and PA+ETE of compound 4are less than those of 5-OH radical in compound 3 from 2 to9 kcalmol It therefore remarks that 6-OCH3 has greatlyinfluenced 5-OH and IHBs so that the 6-methoxylationwould help increase antioxidant In the same assessment forcompounds 1-2 4prime-methylation did not significantly con-tribute to the effect itself on 5-OH and 7-OH radicals but thereverse trends are observed 5-OH radical BDE in genstein(1)gt biochanin A (2) 5-OH and 7-OH radicals PDE ingenistein (1)lt biochanin A (2) As mentioned above β-D-apiofuranosyl-(1-6)-β-D-glucopyranosyl unit should not bethe suitable sites for radical scavenging but they have greatlyaffected isoflavone core Indeed 7-glycosylation (meta po-sition) in ambocin (3) has two sides On the one hand itshows a decrease in the amount of energy in 5-OH bondbreaking in terms of BDE IP IP + PDE ETE and PA+ETEwhile on the other hand it induces an increase pattern inthose in PDE and PA as compared with 7-hydroxylation ingenistein (1)

Last but not least among 1 and 3-4 4prime-OH radicalBDE leads to the introduction of an actively antioxidantarrangement tectorigenin 7-O-[β-D-apiofuranosyl-(1-6)-β-D-glucopyranoside] (4) gt ambocin (3) gt genistein (1)while no change is observed in 7-OH radical BDE values

and 5-OH radical one with the order genistein (1)lt biochanin A (2)

3 Conclusion

Naturally occurring isoflavones and their glycosides havesuccessfully been investigated by the density theory-basedmethod Actually the prospective outcome points out thatHAT pathway is preferentially closely related to the anti-oxidant action of all studied polyphenolic compounds inthe gaseous state Numerous parameters such as ionizationpotential (IP) proton affinity (PA) the sum of energies ofSET-PT andor SPLETmechanisms especially in terms ofBDE values provide supportive information to confirm theradical-scavenging process that takes place throughoutO-H breaking bond in isoflavones is current resultcorresponds to many previous studies in which structuralconformations π-electrons delocalization potential po-larizability hydroxyl groups distributed in ring B andfunctional groups are major reasons for antioxidant ac-tivities of general flavonoids Antioxidant isoflavone gly-cosides ambocin and tectorigenin 7-O-[β-D-apiofuranosyl-(1-6)-β-D-glucopyranoside] are more significant thanisoflavone genistein and biochanin A deducing from 7-glycosylation and 6-methoxylation is account providesnecessary guidelines for future research

Abbreviations

DFT Density functional theoryHOMO Highest occupied molecular orbitalLUMO Lowest unoccupied molecular orbitalIHBs Intramolecular hydrogen bondsBDE Homolytic bond dissociation enthalpyPDE Heterolytic bond dissociation enthalpyIP Ionization potentialPA Proton affinityETE Electron transfer enthalpyHAT Hydrogen atom transferSET-PT Single electron transfer-proton transferSPLET Sequential proton loss electron transferDPPH 22-Diphenyl-1-picrylhydrazyl

Table 3 Gas phase reaction enthalpies at 298 K for radicals of the studied compounds at B3LYP6-311G(d) level of theory (in kcalmol)

Compounds HAT BDE IP PDE SET-PT (IP + PDE) PA ETE SPLET (PA+ETE)1 168305-OH 9426 24166 40996 34707 6289 409967-OH 8384 23136 39966 32968 7002 399704prime-OH 7709 22449 39279 33790 5589 393792 165795-OH 9426 24419 40998 34740 6257 409977-OH 8376 23368 39947 33000 6962 399623 164765-OH 9414 24509 40985 34802 6183 409854prime-OH 7689 22784 39260 33811 5449 392604 157175-OH 8511 24372 40089 34563 5519 400824prime-OH 7685 23542 39269 33822 5429 39251

10 Journal of Chemistry

Data Availability

All data used for this project are publicly available andaccessible online e authors have pronounced the entiredata building process and empirical techniques presented inthe paper

Conflicts of Interest

e authors declare that they have no conflicts of interest

Acknowledgments

is work was supported by a grant (no VASTCTG0117-19) from Vietnam Academy of Science and Technology(VAST) 18 Hoang Quoc Viet Caugiay Hanoi Vietnam

Supplementary Materials

Figure S1 the state forms of studied structures in MeOHmedium Table S1 the collective energies depended ontorsional angles θ2 (C2-C3-C1prime-C2prime) Table S2 Mullikenatomic charges at theoretical level B3LYP6-311G(d) ofstudied compounds in gas and methanol mediums Table S3condensed Fukui indices at B3LYP6-311G(d) of studiedcompounds in gas medium (Supplementary Materials)

References

[1] E Miadokova ldquoIsoflavonoids-an overview of their biologicalactivities and potential health benefitsrdquo InterdisciplinaryToxicology vol 2 no 4 pp 211ndash218 2009

[2] A N Panche A D Diwan and S R Chandra ldquoFlavonoidsan overviewrdquo Journal of Nutritional Science vol 5 p e472016

[3] Z Dhaouadi M Nsangou N Garrab E H AnouarK Marakchi and S Lahmar ldquoDFT study of the reaction ofquercetin with and radicalsrdquo Journal of Molecular StructureTHEOCHEM vol 904 no 1-3 pp 35ndash42 2009

[4] P Dixit R Chillara V Khedgikar et al ldquoConstituents ofDalbergia sissoo Roxb leaves with osteogenic activityrdquo Bio-organic amp Medicinal Chemistry Letters vol 22 no 2pp 890ndash897 2012

[5] J N Choi K Dockyu K C Hyung M Y Kyung K Jiyoungand H L Choong ldquo2prime-Hydroxyaltion of genistein enhancedantioxidant and antiproliferative activities in MCF-7 humanbreast cancer cellsrdquo Journal of Microbiology and Bio-technology vol 19 pp 1348ndash1354 2009

[6] S Dowling F Regan and H Hughes ldquoe characterisation ofstructural and antioxidant properties of isoflavone metalchelatesrdquo Journal of Inorganic Biochemistry vol 104 no 10pp 1091ndash1098 2010

[7] J-G Cho H-J Park G-W Huh et al ldquoFlavonoids fromPueraria mirifica roots and quantitative analysis usingHPLCrdquo Food Science and Biotechnology vol 23 no 6pp 1815ndash1820 2014

[8] Y Zhang and Y Sun ldquoeoretical investigation on atmo-spheric reaction of O(3P) with CH 2 CNrdquo Journal of PhysicalOrganic Chemistry vol 32 no 4 article e3913 2018

[9] E M Kamel A M Mahmoud S A Ahmed andA M Lamsabhi ldquoA phytochemical and computational studyon flavonoids isolated from Trifolium resupinatum L and

their novel hepatoprotective activityrdquo Food amp Function vol 7no 4 pp 2094ndash2106 2016

[10] R A Mendes S K C Almeida I N Soares et al ldquoAcomputational investigation on the antioxidant potential ofmyricetin 34prime-di-O-α-L-rhamnopyranosiderdquo Journal ofMolecular Modeling vol 24 no 6 p 133 2018

[11] K S Kumar and R Kumarresan ldquoA DFT study on thestructural electronic properties and radical scavengingmechanisms of calycosin glycitein pratensein and prunetinrdquoComputational andeoretical Chemistry vol 985 pp 14ndash222012

[12] A Vaganek J Rimarcik V Lukes L Rottmannova andE Klein ldquoDFTB3LYP study of the enthalpies of Homolyticand Heterolytic O-H Bond dissociation in sterically hinderedphenolsrdquo Acta Chimica Slovenica vol 4 pp 55ndash71 2011

[13] M Leopoldini T Marino N Russo and M Toscano ldquoAn-tioxidant properties of phenolic compounds H-atom versuselectron transfer mechanismrdquo Journal of Physical ChemistryA vol 108 no 22 pp 4916ndash4922 2004

[14] R A Mendes B L S Silva R Takeara R G Freitas A Brownand G L C de Souza ldquoProbing the antioxidant potential ofphloretin and phlorizin through a computational investigationrdquoJournal of Molecular Modeling vol 24 no 4 p 101 2018

[15] E N Maciel S K C Almeida S C da Silva andG L C de Souza ldquoExamining the reaction between anti-oxidant compounds and 22-diphenyl-1-picrylhydrazyl(DPPH) through a computational investigationrdquo Journal ofMolecular Modeling vol 24 no 8 p 218 2018

[16] A Galano G Mazzone R A Diduk T MarinoJ R A Idaboy and N Russo ldquoFood antioxidants chemicalInsights at the Molecular Levelrdquo Annual Review of FoodScience and Technology vol 7 no 1 pp 335ndash352 2016

[17] V B Luzhkov ldquoMechanisms of antioxidant activity the DFTstudy of hydrogen abstraction from phenol and toluene by thehydroperoxyl radicalrdquo Chemical Physics vol 314 no 1-3pp 211ndash217 2005

[18] S A P Gomez N F Holguin A P HernandezM P Miramontes and D G Mitnik ldquoComputational mo-lecular characterization of the flavonoid rutinrdquo ChemistryCentral Journal vol 4 no 1 p 12 2010

[19] D G Mitnik ldquoComputational chemistry of natural productsa comparison of the chemical reactivity of isonaringin cal-culated with the M06 family of density functionalsrdquo Journal ofMolecular Modeling vol 20 no 7 p 2316 2014

[20] H Djeradi A Rahmouni and A Cheriti ldquoAntioxidant ac-tivity of flavonoids a QSAR modeling using Fukui indicesdescriptorsrdquo Journal of Molecular Modeling vol 20 no 10p 2476 2014

[21] K Sadasivam and R Kumaresan ldquoAntioxidant behavior ofmearnsetin and myricetin flavonoid compounds-a DFTstudyrdquo Spectrochimica Acta Part A Molecular and Bio-molecular Spectroscopy vol 79 no 1 pp 282ndash293 2011

[22] R-M Han Y-X Tian Y Liu et al ldquoComparison of flavo-noids and isoflavonoids as antioxidantsrdquo Journal of Agri-cultural and Food Chemistry vol 57 no 9 pp 3780ndash37852009

[23] S F Farag A S Ahmed K Terashima Y Takaya andM Niwa ldquoIsoflavonoid glycosides from Dalbergia sissoordquoPhytochemistry vol 57 pp 1263ndash1268 2001

[24] S T Ninh ldquoA Review on the medicinal plant Dalbergiaodorifera species phytochemistry and biological activityrdquoEvidence-Based Complementary and Alternative Medicinevol 2017 Article ID 7142370 27 pages 2017

Journal of Chemistry 11

31++G (dp) in gas phase and θ1 value of 393deg was recordedfor genistein (1) [22 26] but no manuscript associates withan insight into relationships between conformations andtheir energies

To confirm the results mentioned above potential en-ergy curves for all considered compounds 1ndash4 are obtainedlike the functions of torsional angle θ2 (C2-C3-C1prime-C2prime)

between the rings B and C linkage in the gaseous state In thiscase θ2 has been explored by scanning in the characteristicsteps of 15deg values from 0deg to 360deg at theoretical level B3LYP6-311G(d) (Table S1) An attempt to accurate without anyconstraints the structures of these four isoflavones is thenoptimized around each conformational potential minimumand the results are drawn in Figure 3 It can generally be

1721

(a)

1721

(b)

(c)

1726

(d)

Figure 2 State forms of studied structures 1ndash4 in gas medium (a) Compound 1 (b) Compound 2 (c) Compound 3 (d) Compound 4

Table 1 Optimized bond distances bond angles (θ1) and dihedral angles (θ2) of studied compounds with B3LYP6-311G(d) in gas andmethanol mediums

No Bond lengths5 (O-H) 7 (O-H) 7 (O-C1Prime) 6 (O-CH3) 4prime (O-H) 4prime (O-CH3) Hydrogen bonds

1 Gas 1337 1357 1364 1721Methanol 1343 1354 1364 1714

2 Gas 1337 1357 1362 1721Methanol 1343 1354 1361 1714

3 Gas 1338 1365 1365 1733Methanol 1343 1365 1364 1720

4 Gas 1338 1365 1364 1365 1726Methanol 1343 1362 1370 1364 1716

No Bond angles Dihedral anglesθ1 (C5-O-H) θ1 (C7-O-H) θ1 (C4prime-O-H) θ1 (C2-C3-C1prime) θ2 (C2-C3-C1prime-C2prime)

1 Gas 107450 109900 109748 120378 41491Methanol 107122 110640 110240 120286 44364

2 Gas 107459 109886 120342 41492Methanol 107106 110620 120273 44440

3 Gas 107631 109726 120316 41531Methanol 107791 110207 120214 43576

4 Gas 107631 109726 120642 41531Methanol 106792 110241 120189 44128

4 Journal of Chemistry

noted that the dependence of conformational states ontorsional angle θ2 is similar among all isoavonoids 1ndash4including two conformers I-II lying at 415deg (conformer I)

and 135deg (conformer II) for each molecule ese twoconformers arise from the potential energy versus torsionalangles obtained as a good agreement with the previous

Table 2 Chemical reactivity indices obtained using the DFT method in gas and methanol mediums

No Medium η (eV) χ (eV) micro (eV) Io (eV) A (eV)ω (eV)

ω ωminus ω+

1 Gas 2125 3835 minus3835 5960 1710 3461 5644 1809Methanol 2124 3932 minus3932 6056 1808 3639 5871 1939

2 Gas 2107 3789 minus3789 5897 1682 3407 5565 1776Methanol 2109 3915 minus3915 6024 1806 3633 5854 1940

3 Gas 2134 3758 minus3758 5891 1624 3309 5455 1697Methanol 2115 3967 minus3967 6081 1852 3720 5968 2001

4 Gas 2086 3710 minus3710 5796 1624 3299 5415 1705Methanol 2093 3956 minus3956 6049 1863 3740 5979 2023

No Medium Dipole moment (debye) Polarizability (au) Energy (kcalmol) EHOMO (eV) ELUMO (eV)

1 Gas 3036 187118104 minus59860814 minus5960 minus1710Methanol 4455 247343170 minus59861859 minus6056 minus1808

2 Gas 2862 202392352 minus62327698 minus5897 minus1682Methanol 4231 264841735 minus62328597 minus6024 minus1806

3 Gas 10227 347615084 minus129339488 minus5891 minus1624Methanol 13200 440126098 minus129341513 minus6081 minus1852

4 Gas 10069 365799666 minus136526747 minus5796 minus1624Methanol 13537 461553236 minus136528945 minus6049 minus1863

30 60 90 120 150 180 210 240 270 300 330 3600Dihedral angle (degree)

ndash598608

ndash598607

ndash598606

ndash598605

ndash598604

ndash598603

ndash598602

Ener

gy (k

calm

ol)

(a)

30 60 90 120 150 180 210 240 270 300 330 3600Dihedral angle (degree)

ndash623277

ndash623276

ndash623275

ndash623274

ndash623273

Ener

gy (k

calm

ol)

(b)

30 60 90 120 150 180 210 240 270 300 330 3600Dihedral angle (degree)

ndash1293395

ndash1293394

ndash1293393

ndash1293392

ndash1293391

Ener

gy (k

calm

ol)

(c)

30 60 90 120 150 180 210 240 270 300 330 3600Dihedral angle (degree)

ndash1365268

ndash1365267

ndash1365266

ndash1365265

ndash1365264

ndash1365263

Ener

gy (k

calm

ol)

(d)

Figure 3 Potential energy curves versus torsional angle of studied structures 1ndash4 in gas medium (a) Compound 1 (b) Compound 2(c) Compound 3 (d) Compound 4

Journal of Chemistry 5

publication on several isoflavones [11] e absolute mini-mum I is more stable than the conformational relativeminimum II by 198 kcalmol for genistein (1) however thisone for compounds 2ndash4 has smaller values of 040 kcalmol029 kcalmol and 026 kcalmol respectively Parallel withthis there are several potential energy barriers that rangefrom I to II in compound 1 the first interconversion energybarrierrsquos value of 355 kcalmol is recognized at the per-pendicular conformation (θ2 90deg) and the second energybarrier accounts for 494 kcalmol and peaks at anti(θ2 180deg) conformation meanwhile the maximum in-terchangeable barrier reaches 541 kcalmol at syn (θ2 360degor 0deg) shape In the same manner with torsional angles θ1 of90deg 180deg and 360deg (or 0deg) these potential energy barriers arefound at the values of 215 kcalmol 378 kcalmol and402 kcalmol 215 kcalmol 377 kcalmol and 400 kcalmol and 211 kcalmol 381 kcalmol and 403 kcalmol forcompounds 2ndash4 respectively e dramatic difference ob-tained from energies between two minima together with thedistinction from the interchangeable energy barriers of 1 andgroups 2ndash4 can be explained by the symmetric property of 1the phenomena of 4prime-methylation in 2 7-glycosylation in 3and 6-methoxylation-7-glycosylation in 4

22 Frontier Molecular Orbital eory and Spin DensityTaking π-electron delocalization into consideration it in-volves in the stabilization of parent molecular and radicalsafter H abstractions [27] e frontier orbital theoreticalcalculation seems to be a significant tool for explaining therelationship between neutral and radical forms especially interms of the electron delocalization At the level of B3LYP6-311G(d) in both mediums of gas and methanol HOMO andLUMO of neutral and radical visual images and frontierorbital energies of 1ndash4 are shown in Figures 4ndash6 and Table 2HOMO neutral images show that the electron distribution isconcentrated in the entire aglycone especially ring B and23-double bond while LUMO neutral is delocalized oversystematic rings A and C Sugar units are not a suitable sitefor radical reactions e same result has been found inpreviously studied isoflavones glycitein pratensein andprunetin [11] When hydrogen atom abstraction takes placein four isoflavones it is worth noting that 4prime-OH HOMOradical species in compounds 1 and 3-4 which correspondto the small BDE values consist of high electron density inring B and slightly less in ring A 5-OH andor 7-OHHOMO radical shapes which concern the high BDE valuesdid not differ from neutral composition except for the lesselectron distribution in ring C for 5-OH radical site ofcompound 4 LUMO radical forms mostly focus on chro-mene systems but slightly view in ring B in the case of 5-OH7-OH of compounds 1-2 and 5-OH of compounds 3-4 ehigher EHOMO (the lower ionization potential Io) and thelower ELUMO (the higher electron affinity A) mean the bettercapacity of electrons donating and the better sensitivity toreceive electrons respectively whereas the easier electrontransfer indicates the lower Egap ELUMOminusEHOMO andthus the better antioxidant reactivity From Table 2 thegaseous phase would lay a better ground for decreasing

EHOMO values when compared with using methanol butmethanol solution should be a suitable tool to scale downELUMO values Paying attention to the gaseous medium thehighest EHOMO which can be claimed responsible for ad-vantageous radical reactions here facilitates compound 4(minus5796 eV) in preference to the others 3 (minus5891 eV) 2(minus5897 eV) and 1 (minus5960 eV) e numbers of 4250 eV4215 eV 4267 eV and 4172 eV are assignable to the re-spective Egap values of compounds 1ndash4 in the environmentalgas e most striking feature is that 4prime-methylated

4250 4215 4267 4172

ndash9ndash8ndash7ndash6ndash5ndash4ndash3ndash2ndash1

01

Fron

tier m

olec

ular

orb

ital e

nerg

y (e

V)

Com

poun

d 4

Com

poun

d 3

Com

poun

d 2

Com

poun

d 1

Compound

HOMOLUMO

Figure 4 Neutral HOMO and LUMO images and Egap of struc-tures 1ndash4 in gas medium

4248 4218 4229 4185

Com

poun

d 1

Com

poun

d 3

Com

poun

d 4

Com

poun

d 2

Compound

HOMOLUMO

ndash9ndash8ndash7ndash6ndash5ndash4ndash3ndash2ndash1

01

Fron

tier m

olec

ular

orb

ital e

nerg

y (e

V)

Figure 5 Neutral HOMO and LUMO images and Egap of struc-tures 1ndash4 in MeOH medium

6 Journal of Chemistry

(a) (b) (c)

(d) (e) (f)

(g) (h) (i)

(j) (k) (l)

(m) (n) (o)

(p) (q) (r)

Figure 6 HOMO and LUMO of structural radicals 1ndash4 (a) HOMO-5-OH radical (1) (b) HOMO-7-OH radical (1) (c) HOMO-4prime-OHradical (1) (d) LUMO-5-OH radical (1) (e) LUMO-7-OH radical (1) (f ) LUMO-4prime-OH radical (1) (g) HOMO-5-OH radical (2)(h) HOMO-7-OH radical (2) (i) HOMO-5-OH radical (3) (j) LUMO-5-OH radical (2) (k) LUMO-7-OH radical (2) (l) LUMO-5-OHradical (3) (m) HOMO-4prime-OH radical (3) (n) HOMO-5-OH radical (4) (o) HOMO-4prime-OH radical (4) (p) LUMO-4prime-OH radical (3) (q)LUMO-5-OH radical (4) (r) LUMO-4prime-OH radical (4)

Journal of Chemistry 7

compound 2 and 6-methoxylated compound 4 evidentlygenerate better Egap values when compared to respectivecompounds 1 and 3 in both of the phases Emphasizing onthe change of gas phase into methanol a remarkable reversecan be observed in the Egap values between 1 and 3 due tothe 7-glycosylated phenomenon Among four compounds1ndash4 we primarily assumed that tectorigenin 7-O-[β-D-apiofuranosyl-(1-6)-β-D-glucopyranoside] (4) is the bestcandidate employable for antioxidant targets not mentionthe fact that 4prime-methylation 6-methoxylation and 7-gly-cosylation facilitate the antioxidant ability

Calculation of the atomic spin density population ofvarious radicals after H-abstraction from four consideredisoflavones 1ndash4 is given in Figure 7 It should be kept inmindthat the higher the spin density delocalized in radicals theeasier the radical formation hence lower BDE values [28]As a general view the computed results reveal that strongspin distributions remain on oxygen atoms of phenolicgroups carbons C-1prime C-3prime and C-5prime of the ring B andcarbons C-6 and C-8 in ring A and also C4a In all fourcompounds 1ndash4 C-1prime C-3prime and C-5prime are centers of positivespin density C-2prime C-4prime and C-6prime bear negative one whilstatomic carbons in ring A fail to do so [11] It suggests thatphenyl unit ring B with more delocalized spin is significantlysuitable for radical formation e spin density values ofO-atommake an order as 0432ndash0433 (7-OH in compounds1-2)gt 0381ndash0382 (4prime-OH in compounds 1 3-4)gt 0310ndash0376 (5-OH in compounds 1ndash4) As of a normal rule thehigher spin density means higher BDE values Nonethelessthe number of spin in O-atom is found in the oppositedirection with predictable BDE values among 5-OH and 4prime-OH radicals which can be explained by the fact thatH-removal needs to have suitable energy to break the hy-drogen bonds between 5-OH and 4-CO [29]

23 ElectronicProperties e global hardness η has emergedas a measurement of resistance to charge transfer [29] 7-Glycosylated compound (3) accounts for the maximumchemical hardness η value of 2134 eV in the gaseous phase ithas been confirmed that this compound is much more stablethan the remainder particularly in comparison with theunstable 6-methoxylated-7-glycosylated compound 4(2086 eV in gas 2093 eV in methanol) By comparingcompounds 1 and 2 4prime-OCH3 mainly causes a decrease of ηin both phases erefore it can be concluded that meth-ylations and methoxylations in isoflavones and their gly-cosides induce a trend in transferring from ldquohigh oxidationstate and low polarizabilityrdquo to ldquolow oxidation state and highpolarizabilityrdquo

e electronegativity χ measures a trend to attract elec-trons along with the chemical potential micro which will beproportional to this parameter of a negative signal [30] Fol-lowing Sandersonrsquos principle a compound exerting the highelectronegativitymight quickly reach equalization and establishlow reactivity [31] erefore the low value of this one forantioxidant reactions is expected Compound 4 with low χvalue of 3710 eV in the gaseous state participates in antioxidantreactivity better than the range of 3758ndash3835 eV for

compounds 1ndash3 Nevertheless using solvents if solvents likemedium methanol are used the results are greatly influencedIndeed it is opposite to the tendency of genistein (1) andbiochanin A (2) whose glycosides 3-4 tend to go from a lowerelectronegativity in gas to a higher one in methanol (Table 2)

Apart from descriptors such as the electron affinity theionization potential the global hardness and the globalelectronegativity the global electrophilicity index ω ωminusand ω+ values have so far been increased when methanol istaken into account e ωminus values of all considered com-pounds 1ndash4 are 2-3-folds higher than those of ω+ in eithergas or methanol method is one is identical with theprevious literature data [11] in which isoflavones and theirsugar derivatives tend to donate electrons rather thancapturing

Within a molecule the dipole moment is an availablemethod to estimate the separation of positive and negativeelectrical charges e high magnitudes of the dipole mo-ment accompany with the high charge densities and highpolarity in bonds [21] In our current account glycosylatedcompounds 3-4 is 3-folds higher than isoflavones 1-2 in bothstates gas and methanol because of the effects of sugar unitsand solvents However focusing on the comparison between1 and 2 and 3 and 4 4prime-methylation and 6-methoxylation aresuitable for slightly reducing this property Han and hispartners pointed out that the more symmetric property instructures the lower dipole moment and its antioxidantefficiency is better than that of the asymmetric molecule ofthe same size [22] We found that the symmetric genistein(1) and its 4prime-methylation (2) with the low dipole momentvalues of 3036D and 2862D have resulted in good anti-oxidant ability in many real experiments [5 6] Polariz-ability may be justified considering the soluble nature ofmolecules in polar solvents [21] Compounds containingsugars and isoflavones 3-4 have generally shown to asso-ciate with the higher dipole moment as well as higherpolarizability (Table 2) Followed on 4prime-methylations and 6-methoxylations the polarizability is also in accordancewith chemical hardness as mentioned above

Mulliken population analysis (MPA) has resulted in netcharges of a chemical ring system which also appears to bean effective tool to assess a chemical reactivity e Mul-liken atomic charges values using the DFT method arepresented in Table S2 Generally the heteroatom oxygensin flavonoids 1ndash4 remark the significant negative chargeswhich are active sites of donating their electrons In themeantime the maximum of positive charge which is thepreferential site for the nucleophilic reaction has occurredin carbon C-4 e high number of positive (negative)charges of atoms oxygens carbon and hydrogen arisingfrom 5-OH and 4-CO is caused by internal hydrogenbonds thereby stabilizing the structure e fact is thatantioxidant activities of flavonoids further depend onnegative centers whereby hydroxyl groups in ring B arefound to act as active sites of radical reactions [20] As aconsequence considering flavonoid aglycones of studied 3-4 and compound 1 the high values of negative chargesoccur in 4prime-OH in both gas and methanol agreeing with thesmallest BDE outcome

8 Journal of Chemistry

Besides frontier molecular orbital considerations andanalysis of electronic structure Fukui parameters alsoprovide important information and quick solutions to justifythe powerful reactive site of each atom Fukui indices fromTable S3 are calculated in gaseous medium based on the-oretical HSAB principle [31] It seemed that oxygen ofcarbonyl group 4-CO of all studiedmembers 1ndash4 and carbonC-2 in compounds 2 and 4 should have opted as good sitesfor both electrophilic and radical attacks but carbon C-2 isthe only suitable site of electrophilic scope for metabolites 1and 3 4prime-OH in compound 1 and carbon C-6 bears OCH3 incompound 4 adapted for nucleophilic attractive types Mostimportantly the f o condensed Fukui values advocate otherpreferential radical sites that are found in hydroxyl groups

Numerous atoms in β-D-apiofuranosyl-(1-6)-β-D-glu-copyranosyl parts of compounds 3-4 show the signicantMulliken electronic charges 4Prime-OH of glycoside 3 is nowexpected as electrophilic tendencies but for further cor-roboration with HOMO-LUMO analysis above Fukui de-scriptors research indicates that sugar units did not showfavorability for the antioxidant reactive types resembling inthe computational results in a avone glycoside rutin orresearch on pryoanthocyanin [17 28 32]

24 Antioxidant Mechanisms In the same condition of298K and environmental gas our BDE results in genistein(1) and biochanin A (2) dier from the B3LYP6-31 +G(dp) andor B3LYP6-311++G(dp) previously cal-culated publications within usually 40 kcalmol [33 34] Inaddition our PDE PA and ETE numbers show good

accordance with B3LYP6-311++G(dp) level in the lastaccount performed by Lengyel and partners particularly thedeviation just only found to be 2 kcalmol in PA calculationbut largely dierent from the work of Zhang and co-authors[33 34]

e favorable mechanisms of antiradical activity ofisoavones might possibly be discussed via thermodynam-ically preferential BDE of HAT IP of SET-PT and PA ofSPLET actions [35] From genistein (1) in gaseous statereaction in Table 3 BDE values (7709ndash9426 kcalmol) aresignicantly lower than those of IP (16830 kcalmol) and PA(32968ndash34707 kcalmol) is behavior is also similarlyestablished from the remainders like 2ndash4 erefore HATpathway is probable for isoavones and isoavone glycosidesin gas

From a thermodynamic point of view relating to threewell-known mechanisms the active sites of antioxidantaction have also been proposed throughout theminimal sumof enthalpies including BDEmin in HAT (IP + PDE)min inSET-PT and (PA+ETE)min in SPLET [35] e lowestrank of BDE values ranges from 7685 to 7709 kcalmol isdominated by 4prime-OH radical in gas for all isoavones 1ndash4compared with those of 7-OH radical (8376ndash8384 kcalmol) and 5-OH radical (8511ndash9426 kcalmol) A similarinstance arises from enthalpies of SET-PT and SPLETpathways that either isoavones 1-2 or their glycosides 3-4also encompasses the minimum values of IP + PDE andPA+ETE at 4prime-OH Once again it can be seen that ring B ofisoavones and 4prime-OH are active centers involving in an-tioxidant activity Although electron transfer enthalpy (ETE)shows the lowest amount in all radical cases of 1ndash4 minimal

OO

OHOOH

0295

0388

0226

0433

(a)

OHO

OHOO

0202

0354

0366

0459

(b)

OHO

OOOH

03820284

0381

(c)

OO

OOOH

0295

0432 0389

(d)

OHO

OOO

0202

0353

0459

0366

(e)

OO

OHOO

sugar

0376

0407

0436

(f )OO

OOOH

0380

sugar

0286

03810283

(g)

OO

OHOO

sugar

O

0310

0224

0359

(h)

OO

OOOH

0380

sugar

O 0285

02830381

(i)

Figure 7 Spin density distribution of structural radicals 1ndash4 obtained after H-atom abstraction (a) Compound 1 7-OH radical(b) Compound 1 5-OH radical (c) Compound 1 4prime-OH radical (d) Compound 2 7-OH radical (e) Compound 2 5-OH radical(f ) Compound 3 5-OH radical (g) Compound 3 4prime-OH radical (h) Compound 4 5-OH radical (i) Compound 4 4prime-OH radical

Journal of Chemistry 9

total energies of PA+ETE and IP + PDE establish 4 timesmore potency than those of BDEis is sequential evidenceto deeply vindicate that HATmechanism gets more favor ingas Here we can make an arrangement in the followingorder of favorable HATgt SET-PTasymp SPLET and impor-tantly conclude that in the environmental gas and antiox-idant mechanisms have been becoming dependent on theprocesses of proton disruptions rather than the effects ofelectron actions

In terms of comparing among radicals 5-OH 7-OH and4prime-OH in each metabolite O-H homolytic bond dissociationenthalpy (BDE) O-H heterolytic bond dissociation enthalpy(PDE) and proton affinity (PA) are realistic evidence wouldsince have been proved that energies of 5-OH bond breakingalways overcome due to IHBs (Table 3)

Antioxidant-structural relationships can be highlightedthrough the differences in enthalpies calculations Whenspontaneously compared two isoflavone glycosides 3-4 5-OH radical enthalpy parameters BDE IP PDE PA andETE the courses of IP + PDE and PA+ETE of compound 4are less than those of 5-OH radical in compound 3 from 2 to9 kcalmol It therefore remarks that 6-OCH3 has greatlyinfluenced 5-OH and IHBs so that the 6-methoxylationwould help increase antioxidant In the same assessment forcompounds 1-2 4prime-methylation did not significantly con-tribute to the effect itself on 5-OH and 7-OH radicals but thereverse trends are observed 5-OH radical BDE in genstein(1)gt biochanin A (2) 5-OH and 7-OH radicals PDE ingenistein (1)lt biochanin A (2) As mentioned above β-D-apiofuranosyl-(1-6)-β-D-glucopyranosyl unit should not bethe suitable sites for radical scavenging but they have greatlyaffected isoflavone core Indeed 7-glycosylation (meta po-sition) in ambocin (3) has two sides On the one hand itshows a decrease in the amount of energy in 5-OH bondbreaking in terms of BDE IP IP + PDE ETE and PA+ETEwhile on the other hand it induces an increase pattern inthose in PDE and PA as compared with 7-hydroxylation ingenistein (1)

Last but not least among 1 and 3-4 4prime-OH radicalBDE leads to the introduction of an actively antioxidantarrangement tectorigenin 7-O-[β-D-apiofuranosyl-(1-6)-β-D-glucopyranoside] (4) gt ambocin (3) gt genistein (1)while no change is observed in 7-OH radical BDE values

and 5-OH radical one with the order genistein (1)lt biochanin A (2)

3 Conclusion

Naturally occurring isoflavones and their glycosides havesuccessfully been investigated by the density theory-basedmethod Actually the prospective outcome points out thatHAT pathway is preferentially closely related to the anti-oxidant action of all studied polyphenolic compounds inthe gaseous state Numerous parameters such as ionizationpotential (IP) proton affinity (PA) the sum of energies ofSET-PT andor SPLETmechanisms especially in terms ofBDE values provide supportive information to confirm theradical-scavenging process that takes place throughoutO-H breaking bond in isoflavones is current resultcorresponds to many previous studies in which structuralconformations π-electrons delocalization potential po-larizability hydroxyl groups distributed in ring B andfunctional groups are major reasons for antioxidant ac-tivities of general flavonoids Antioxidant isoflavone gly-cosides ambocin and tectorigenin 7-O-[β-D-apiofuranosyl-(1-6)-β-D-glucopyranoside] are more significant thanisoflavone genistein and biochanin A deducing from 7-glycosylation and 6-methoxylation is account providesnecessary guidelines for future research

Abbreviations

DFT Density functional theoryHOMO Highest occupied molecular orbitalLUMO Lowest unoccupied molecular orbitalIHBs Intramolecular hydrogen bondsBDE Homolytic bond dissociation enthalpyPDE Heterolytic bond dissociation enthalpyIP Ionization potentialPA Proton affinityETE Electron transfer enthalpyHAT Hydrogen atom transferSET-PT Single electron transfer-proton transferSPLET Sequential proton loss electron transferDPPH 22-Diphenyl-1-picrylhydrazyl

Table 3 Gas phase reaction enthalpies at 298 K for radicals of the studied compounds at B3LYP6-311G(d) level of theory (in kcalmol)

Compounds HAT BDE IP PDE SET-PT (IP + PDE) PA ETE SPLET (PA+ETE)1 168305-OH 9426 24166 40996 34707 6289 409967-OH 8384 23136 39966 32968 7002 399704prime-OH 7709 22449 39279 33790 5589 393792 165795-OH 9426 24419 40998 34740 6257 409977-OH 8376 23368 39947 33000 6962 399623 164765-OH 9414 24509 40985 34802 6183 409854prime-OH 7689 22784 39260 33811 5449 392604 157175-OH 8511 24372 40089 34563 5519 400824prime-OH 7685 23542 39269 33822 5429 39251

10 Journal of Chemistry

Data Availability

All data used for this project are publicly available andaccessible online e authors have pronounced the entiredata building process and empirical techniques presented inthe paper

Conflicts of Interest

e authors declare that they have no conflicts of interest

Acknowledgments

is work was supported by a grant (no VASTCTG0117-19) from Vietnam Academy of Science and Technology(VAST) 18 Hoang Quoc Viet Caugiay Hanoi Vietnam

Supplementary Materials

Figure S1 the state forms of studied structures in MeOHmedium Table S1 the collective energies depended ontorsional angles θ2 (C2-C3-C1prime-C2prime) Table S2 Mullikenatomic charges at theoretical level B3LYP6-311G(d) ofstudied compounds in gas and methanol mediums Table S3condensed Fukui indices at B3LYP6-311G(d) of studiedcompounds in gas medium (Supplementary Materials)

References

[1] E Miadokova ldquoIsoflavonoids-an overview of their biologicalactivities and potential health benefitsrdquo InterdisciplinaryToxicology vol 2 no 4 pp 211ndash218 2009

[2] A N Panche A D Diwan and S R Chandra ldquoFlavonoidsan overviewrdquo Journal of Nutritional Science vol 5 p e472016

[3] Z Dhaouadi M Nsangou N Garrab E H AnouarK Marakchi and S Lahmar ldquoDFT study of the reaction ofquercetin with and radicalsrdquo Journal of Molecular StructureTHEOCHEM vol 904 no 1-3 pp 35ndash42 2009

[4] P Dixit R Chillara V Khedgikar et al ldquoConstituents ofDalbergia sissoo Roxb leaves with osteogenic activityrdquo Bio-organic amp Medicinal Chemistry Letters vol 22 no 2pp 890ndash897 2012

[5] J N Choi K Dockyu K C Hyung M Y Kyung K Jiyoungand H L Choong ldquo2prime-Hydroxyaltion of genistein enhancedantioxidant and antiproliferative activities in MCF-7 humanbreast cancer cellsrdquo Journal of Microbiology and Bio-technology vol 19 pp 1348ndash1354 2009

[6] S Dowling F Regan and H Hughes ldquoe characterisation ofstructural and antioxidant properties of isoflavone metalchelatesrdquo Journal of Inorganic Biochemistry vol 104 no 10pp 1091ndash1098 2010

[7] J-G Cho H-J Park G-W Huh et al ldquoFlavonoids fromPueraria mirifica roots and quantitative analysis usingHPLCrdquo Food Science and Biotechnology vol 23 no 6pp 1815ndash1820 2014

[8] Y Zhang and Y Sun ldquoeoretical investigation on atmo-spheric reaction of O(3P) with CH 2 CNrdquo Journal of PhysicalOrganic Chemistry vol 32 no 4 article e3913 2018

[9] E M Kamel A M Mahmoud S A Ahmed andA M Lamsabhi ldquoA phytochemical and computational studyon flavonoids isolated from Trifolium resupinatum L and

their novel hepatoprotective activityrdquo Food amp Function vol 7no 4 pp 2094ndash2106 2016

[10] R A Mendes S K C Almeida I N Soares et al ldquoAcomputational investigation on the antioxidant potential ofmyricetin 34prime-di-O-α-L-rhamnopyranosiderdquo Journal ofMolecular Modeling vol 24 no 6 p 133 2018

[11] K S Kumar and R Kumarresan ldquoA DFT study on thestructural electronic properties and radical scavengingmechanisms of calycosin glycitein pratensein and prunetinrdquoComputational andeoretical Chemistry vol 985 pp 14ndash222012

[12] A Vaganek J Rimarcik V Lukes L Rottmannova andE Klein ldquoDFTB3LYP study of the enthalpies of Homolyticand Heterolytic O-H Bond dissociation in sterically hinderedphenolsrdquo Acta Chimica Slovenica vol 4 pp 55ndash71 2011

[13] M Leopoldini T Marino N Russo and M Toscano ldquoAn-tioxidant properties of phenolic compounds H-atom versuselectron transfer mechanismrdquo Journal of Physical ChemistryA vol 108 no 22 pp 4916ndash4922 2004

[14] R A Mendes B L S Silva R Takeara R G Freitas A Brownand G L C de Souza ldquoProbing the antioxidant potential ofphloretin and phlorizin through a computational investigationrdquoJournal of Molecular Modeling vol 24 no 4 p 101 2018

[15] E N Maciel S K C Almeida S C da Silva andG L C de Souza ldquoExamining the reaction between anti-oxidant compounds and 22-diphenyl-1-picrylhydrazyl(DPPH) through a computational investigationrdquo Journal ofMolecular Modeling vol 24 no 8 p 218 2018

[16] A Galano G Mazzone R A Diduk T MarinoJ R A Idaboy and N Russo ldquoFood antioxidants chemicalInsights at the Molecular Levelrdquo Annual Review of FoodScience and Technology vol 7 no 1 pp 335ndash352 2016

[17] V B Luzhkov ldquoMechanisms of antioxidant activity the DFTstudy of hydrogen abstraction from phenol and toluene by thehydroperoxyl radicalrdquo Chemical Physics vol 314 no 1-3pp 211ndash217 2005

[18] S A P Gomez N F Holguin A P HernandezM P Miramontes and D G Mitnik ldquoComputational mo-lecular characterization of the flavonoid rutinrdquo ChemistryCentral Journal vol 4 no 1 p 12 2010

[19] D G Mitnik ldquoComputational chemistry of natural productsa comparison of the chemical reactivity of isonaringin cal-culated with the M06 family of density functionalsrdquo Journal ofMolecular Modeling vol 20 no 7 p 2316 2014

[20] H Djeradi A Rahmouni and A Cheriti ldquoAntioxidant ac-tivity of flavonoids a QSAR modeling using Fukui indicesdescriptorsrdquo Journal of Molecular Modeling vol 20 no 10p 2476 2014

[21] K Sadasivam and R Kumaresan ldquoAntioxidant behavior ofmearnsetin and myricetin flavonoid compounds-a DFTstudyrdquo Spectrochimica Acta Part A Molecular and Bio-molecular Spectroscopy vol 79 no 1 pp 282ndash293 2011

[22] R-M Han Y-X Tian Y Liu et al ldquoComparison of flavo-noids and isoflavonoids as antioxidantsrdquo Journal of Agri-cultural and Food Chemistry vol 57 no 9 pp 3780ndash37852009

[23] S F Farag A S Ahmed K Terashima Y Takaya andM Niwa ldquoIsoflavonoid glycosides from Dalbergia sissoordquoPhytochemistry vol 57 pp 1263ndash1268 2001

[24] S T Ninh ldquoA Review on the medicinal plant Dalbergiaodorifera species phytochemistry and biological activityrdquoEvidence-Based Complementary and Alternative Medicinevol 2017 Article ID 7142370 27 pages 2017

Journal of Chemistry 11

noted that the dependence of conformational states ontorsional angle θ2 is similar among all isoavonoids 1ndash4including two conformers I-II lying at 415deg (conformer I)

and 135deg (conformer II) for each molecule ese twoconformers arise from the potential energy versus torsionalangles obtained as a good agreement with the previous

Table 2 Chemical reactivity indices obtained using the DFT method in gas and methanol mediums

No Medium η (eV) χ (eV) micro (eV) Io (eV) A (eV)ω (eV)

ω ωminus ω+

1 Gas 2125 3835 minus3835 5960 1710 3461 5644 1809Methanol 2124 3932 minus3932 6056 1808 3639 5871 1939

2 Gas 2107 3789 minus3789 5897 1682 3407 5565 1776Methanol 2109 3915 minus3915 6024 1806 3633 5854 1940

3 Gas 2134 3758 minus3758 5891 1624 3309 5455 1697Methanol 2115 3967 minus3967 6081 1852 3720 5968 2001

4 Gas 2086 3710 minus3710 5796 1624 3299 5415 1705Methanol 2093 3956 minus3956 6049 1863 3740 5979 2023

No Medium Dipole moment (debye) Polarizability (au) Energy (kcalmol) EHOMO (eV) ELUMO (eV)

1 Gas 3036 187118104 minus59860814 minus5960 minus1710Methanol 4455 247343170 minus59861859 minus6056 minus1808

2 Gas 2862 202392352 minus62327698 minus5897 minus1682Methanol 4231 264841735 minus62328597 minus6024 minus1806

3 Gas 10227 347615084 minus129339488 minus5891 minus1624Methanol 13200 440126098 minus129341513 minus6081 minus1852

4 Gas 10069 365799666 minus136526747 minus5796 minus1624Methanol 13537 461553236 minus136528945 minus6049 minus1863

30 60 90 120 150 180 210 240 270 300 330 3600Dihedral angle (degree)

ndash598608

ndash598607

ndash598606

ndash598605

ndash598604

ndash598603

ndash598602

Ener

gy (k

calm

ol)

(a)

30 60 90 120 150 180 210 240 270 300 330 3600Dihedral angle (degree)

ndash623277

ndash623276

ndash623275

ndash623274

ndash623273

Ener

gy (k

calm

ol)

(b)

30 60 90 120 150 180 210 240 270 300 330 3600Dihedral angle (degree)

ndash1293395

ndash1293394

ndash1293393

ndash1293392

ndash1293391

Ener

gy (k

calm

ol)

(c)

30 60 90 120 150 180 210 240 270 300 330 3600Dihedral angle (degree)

ndash1365268

ndash1365267

ndash1365266

ndash1365265

ndash1365264

ndash1365263

Ener

gy (k

calm

ol)

(d)

Figure 3 Potential energy curves versus torsional angle of studied structures 1ndash4 in gas medium (a) Compound 1 (b) Compound 2(c) Compound 3 (d) Compound 4

Journal of Chemistry 5

publication on several isoflavones [11] e absolute mini-mum I is more stable than the conformational relativeminimum II by 198 kcalmol for genistein (1) however thisone for compounds 2ndash4 has smaller values of 040 kcalmol029 kcalmol and 026 kcalmol respectively Parallel withthis there are several potential energy barriers that rangefrom I to II in compound 1 the first interconversion energybarrierrsquos value of 355 kcalmol is recognized at the per-pendicular conformation (θ2 90deg) and the second energybarrier accounts for 494 kcalmol and peaks at anti(θ2 180deg) conformation meanwhile the maximum in-terchangeable barrier reaches 541 kcalmol at syn (θ2 360degor 0deg) shape In the same manner with torsional angles θ1 of90deg 180deg and 360deg (or 0deg) these potential energy barriers arefound at the values of 215 kcalmol 378 kcalmol and402 kcalmol 215 kcalmol 377 kcalmol and 400 kcalmol and 211 kcalmol 381 kcalmol and 403 kcalmol forcompounds 2ndash4 respectively e dramatic difference ob-tained from energies between two minima together with thedistinction from the interchangeable energy barriers of 1 andgroups 2ndash4 can be explained by the symmetric property of 1the phenomena of 4prime-methylation in 2 7-glycosylation in 3and 6-methoxylation-7-glycosylation in 4

22 Frontier Molecular Orbital eory and Spin DensityTaking π-electron delocalization into consideration it in-volves in the stabilization of parent molecular and radicalsafter H abstractions [27] e frontier orbital theoreticalcalculation seems to be a significant tool for explaining therelationship between neutral and radical forms especially interms of the electron delocalization At the level of B3LYP6-311G(d) in both mediums of gas and methanol HOMO andLUMO of neutral and radical visual images and frontierorbital energies of 1ndash4 are shown in Figures 4ndash6 and Table 2HOMO neutral images show that the electron distribution isconcentrated in the entire aglycone especially ring B and23-double bond while LUMO neutral is delocalized oversystematic rings A and C Sugar units are not a suitable sitefor radical reactions e same result has been found inpreviously studied isoflavones glycitein pratensein andprunetin [11] When hydrogen atom abstraction takes placein four isoflavones it is worth noting that 4prime-OH HOMOradical species in compounds 1 and 3-4 which correspondto the small BDE values consist of high electron density inring B and slightly less in ring A 5-OH andor 7-OHHOMO radical shapes which concern the high BDE valuesdid not differ from neutral composition except for the lesselectron distribution in ring C for 5-OH radical site ofcompound 4 LUMO radical forms mostly focus on chro-mene systems but slightly view in ring B in the case of 5-OH7-OH of compounds 1-2 and 5-OH of compounds 3-4 ehigher EHOMO (the lower ionization potential Io) and thelower ELUMO (the higher electron affinity A) mean the bettercapacity of electrons donating and the better sensitivity toreceive electrons respectively whereas the easier electrontransfer indicates the lower Egap ELUMOminusEHOMO andthus the better antioxidant reactivity From Table 2 thegaseous phase would lay a better ground for decreasing

EHOMO values when compared with using methanol butmethanol solution should be a suitable tool to scale downELUMO values Paying attention to the gaseous medium thehighest EHOMO which can be claimed responsible for ad-vantageous radical reactions here facilitates compound 4(minus5796 eV) in preference to the others 3 (minus5891 eV) 2(minus5897 eV) and 1 (minus5960 eV) e numbers of 4250 eV4215 eV 4267 eV and 4172 eV are assignable to the re-spective Egap values of compounds 1ndash4 in the environmentalgas e most striking feature is that 4prime-methylated

4250 4215 4267 4172

ndash9ndash8ndash7ndash6ndash5ndash4ndash3ndash2ndash1

01

Fron

tier m

olec

ular

orb

ital e

nerg

y (e

V)

Com

poun

d 4

Com

poun

d 3

Com

poun

d 2

Com

poun

d 1

Compound

HOMOLUMO

Figure 4 Neutral HOMO and LUMO images and Egap of struc-tures 1ndash4 in gas medium

4248 4218 4229 4185

Com

poun

d 1

Com

poun

d 3

Com

poun

d 4

Com

poun

d 2

Compound

HOMOLUMO

ndash9ndash8ndash7ndash6ndash5ndash4ndash3ndash2ndash1

01

Fron

tier m

olec

ular

orb

ital e

nerg

y (e

V)

Figure 5 Neutral HOMO and LUMO images and Egap of struc-tures 1ndash4 in MeOH medium

6 Journal of Chemistry

(a) (b) (c)

(d) (e) (f)

(g) (h) (i)

(j) (k) (l)

(m) (n) (o)

(p) (q) (r)

Figure 6 HOMO and LUMO of structural radicals 1ndash4 (a) HOMO-5-OH radical (1) (b) HOMO-7-OH radical (1) (c) HOMO-4prime-OHradical (1) (d) LUMO-5-OH radical (1) (e) LUMO-7-OH radical (1) (f ) LUMO-4prime-OH radical (1) (g) HOMO-5-OH radical (2)(h) HOMO-7-OH radical (2) (i) HOMO-5-OH radical (3) (j) LUMO-5-OH radical (2) (k) LUMO-7-OH radical (2) (l) LUMO-5-OHradical (3) (m) HOMO-4prime-OH radical (3) (n) HOMO-5-OH radical (4) (o) HOMO-4prime-OH radical (4) (p) LUMO-4prime-OH radical (3) (q)LUMO-5-OH radical (4) (r) LUMO-4prime-OH radical (4)

Journal of Chemistry 7

compound 2 and 6-methoxylated compound 4 evidentlygenerate better Egap values when compared to respectivecompounds 1 and 3 in both of the phases Emphasizing onthe change of gas phase into methanol a remarkable reversecan be observed in the Egap values between 1 and 3 due tothe 7-glycosylated phenomenon Among four compounds1ndash4 we primarily assumed that tectorigenin 7-O-[β-D-apiofuranosyl-(1-6)-β-D-glucopyranoside] (4) is the bestcandidate employable for antioxidant targets not mentionthe fact that 4prime-methylation 6-methoxylation and 7-gly-cosylation facilitate the antioxidant ability

Calculation of the atomic spin density population ofvarious radicals after H-abstraction from four consideredisoflavones 1ndash4 is given in Figure 7 It should be kept inmindthat the higher the spin density delocalized in radicals theeasier the radical formation hence lower BDE values [28]As a general view the computed results reveal that strongspin distributions remain on oxygen atoms of phenolicgroups carbons C-1prime C-3prime and C-5prime of the ring B andcarbons C-6 and C-8 in ring A and also C4a In all fourcompounds 1ndash4 C-1prime C-3prime and C-5prime are centers of positivespin density C-2prime C-4prime and C-6prime bear negative one whilstatomic carbons in ring A fail to do so [11] It suggests thatphenyl unit ring B with more delocalized spin is significantlysuitable for radical formation e spin density values ofO-atommake an order as 0432ndash0433 (7-OH in compounds1-2)gt 0381ndash0382 (4prime-OH in compounds 1 3-4)gt 0310ndash0376 (5-OH in compounds 1ndash4) As of a normal rule thehigher spin density means higher BDE values Nonethelessthe number of spin in O-atom is found in the oppositedirection with predictable BDE values among 5-OH and 4prime-OH radicals which can be explained by the fact thatH-removal needs to have suitable energy to break the hy-drogen bonds between 5-OH and 4-CO [29]

23 ElectronicProperties e global hardness η has emergedas a measurement of resistance to charge transfer [29] 7-Glycosylated compound (3) accounts for the maximumchemical hardness η value of 2134 eV in the gaseous phase ithas been confirmed that this compound is much more stablethan the remainder particularly in comparison with theunstable 6-methoxylated-7-glycosylated compound 4(2086 eV in gas 2093 eV in methanol) By comparingcompounds 1 and 2 4prime-OCH3 mainly causes a decrease of ηin both phases erefore it can be concluded that meth-ylations and methoxylations in isoflavones and their gly-cosides induce a trend in transferring from ldquohigh oxidationstate and low polarizabilityrdquo to ldquolow oxidation state and highpolarizabilityrdquo

e electronegativity χ measures a trend to attract elec-trons along with the chemical potential micro which will beproportional to this parameter of a negative signal [30] Fol-lowing Sandersonrsquos principle a compound exerting the highelectronegativitymight quickly reach equalization and establishlow reactivity [31] erefore the low value of this one forantioxidant reactions is expected Compound 4 with low χvalue of 3710 eV in the gaseous state participates in antioxidantreactivity better than the range of 3758ndash3835 eV for

compounds 1ndash3 Nevertheless using solvents if solvents likemedium methanol are used the results are greatly influencedIndeed it is opposite to the tendency of genistein (1) andbiochanin A (2) whose glycosides 3-4 tend to go from a lowerelectronegativity in gas to a higher one in methanol (Table 2)

Apart from descriptors such as the electron affinity theionization potential the global hardness and the globalelectronegativity the global electrophilicity index ω ωminusand ω+ values have so far been increased when methanol istaken into account e ωminus values of all considered com-pounds 1ndash4 are 2-3-folds higher than those of ω+ in eithergas or methanol method is one is identical with theprevious literature data [11] in which isoflavones and theirsugar derivatives tend to donate electrons rather thancapturing

Within a molecule the dipole moment is an availablemethod to estimate the separation of positive and negativeelectrical charges e high magnitudes of the dipole mo-ment accompany with the high charge densities and highpolarity in bonds [21] In our current account glycosylatedcompounds 3-4 is 3-folds higher than isoflavones 1-2 in bothstates gas and methanol because of the effects of sugar unitsand solvents However focusing on the comparison between1 and 2 and 3 and 4 4prime-methylation and 6-methoxylation aresuitable for slightly reducing this property Han and hispartners pointed out that the more symmetric property instructures the lower dipole moment and its antioxidantefficiency is better than that of the asymmetric molecule ofthe same size [22] We found that the symmetric genistein(1) and its 4prime-methylation (2) with the low dipole momentvalues of 3036D and 2862D have resulted in good anti-oxidant ability in many real experiments [5 6] Polariz-ability may be justified considering the soluble nature ofmolecules in polar solvents [21] Compounds containingsugars and isoflavones 3-4 have generally shown to asso-ciate with the higher dipole moment as well as higherpolarizability (Table 2) Followed on 4prime-methylations and 6-methoxylations the polarizability is also in accordancewith chemical hardness as mentioned above

Mulliken population analysis (MPA) has resulted in netcharges of a chemical ring system which also appears to bean effective tool to assess a chemical reactivity e Mul-liken atomic charges values using the DFT method arepresented in Table S2 Generally the heteroatom oxygensin flavonoids 1ndash4 remark the significant negative chargeswhich are active sites of donating their electrons In themeantime the maximum of positive charge which is thepreferential site for the nucleophilic reaction has occurredin carbon C-4 e high number of positive (negative)charges of atoms oxygens carbon and hydrogen arisingfrom 5-OH and 4-CO is caused by internal hydrogenbonds thereby stabilizing the structure e fact is thatantioxidant activities of flavonoids further depend onnegative centers whereby hydroxyl groups in ring B arefound to act as active sites of radical reactions [20] As aconsequence considering flavonoid aglycones of studied 3-4 and compound 1 the high values of negative chargesoccur in 4prime-OH in both gas and methanol agreeing with thesmallest BDE outcome

8 Journal of Chemistry

Besides frontier molecular orbital considerations andanalysis of electronic structure Fukui parameters alsoprovide important information and quick solutions to justifythe powerful reactive site of each atom Fukui indices fromTable S3 are calculated in gaseous medium based on the-oretical HSAB principle [31] It seemed that oxygen ofcarbonyl group 4-CO of all studiedmembers 1ndash4 and carbonC-2 in compounds 2 and 4 should have opted as good sitesfor both electrophilic and radical attacks but carbon C-2 isthe only suitable site of electrophilic scope for metabolites 1and 3 4prime-OH in compound 1 and carbon C-6 bears OCH3 incompound 4 adapted for nucleophilic attractive types Mostimportantly the f o condensed Fukui values advocate otherpreferential radical sites that are found in hydroxyl groups

Numerous atoms in β-D-apiofuranosyl-(1-6)-β-D-glu-copyranosyl parts of compounds 3-4 show the signicantMulliken electronic charges 4Prime-OH of glycoside 3 is nowexpected as electrophilic tendencies but for further cor-roboration with HOMO-LUMO analysis above Fukui de-scriptors research indicates that sugar units did not showfavorability for the antioxidant reactive types resembling inthe computational results in a avone glycoside rutin orresearch on pryoanthocyanin [17 28 32]

24 Antioxidant Mechanisms In the same condition of298K and environmental gas our BDE results in genistein(1) and biochanin A (2) dier from the B3LYP6-31 +G(dp) andor B3LYP6-311++G(dp) previously cal-culated publications within usually 40 kcalmol [33 34] Inaddition our PDE PA and ETE numbers show good

accordance with B3LYP6-311++G(dp) level in the lastaccount performed by Lengyel and partners particularly thedeviation just only found to be 2 kcalmol in PA calculationbut largely dierent from the work of Zhang and co-authors[33 34]

e favorable mechanisms of antiradical activity ofisoavones might possibly be discussed via thermodynam-ically preferential BDE of HAT IP of SET-PT and PA ofSPLET actions [35] From genistein (1) in gaseous statereaction in Table 3 BDE values (7709ndash9426 kcalmol) aresignicantly lower than those of IP (16830 kcalmol) and PA(32968ndash34707 kcalmol) is behavior is also similarlyestablished from the remainders like 2ndash4 erefore HATpathway is probable for isoavones and isoavone glycosidesin gas

From a thermodynamic point of view relating to threewell-known mechanisms the active sites of antioxidantaction have also been proposed throughout theminimal sumof enthalpies including BDEmin in HAT (IP + PDE)min inSET-PT and (PA+ETE)min in SPLET [35] e lowestrank of BDE values ranges from 7685 to 7709 kcalmol isdominated by 4prime-OH radical in gas for all isoavones 1ndash4compared with those of 7-OH radical (8376ndash8384 kcalmol) and 5-OH radical (8511ndash9426 kcalmol) A similarinstance arises from enthalpies of SET-PT and SPLETpathways that either isoavones 1-2 or their glycosides 3-4also encompasses the minimum values of IP + PDE andPA+ETE at 4prime-OH Once again it can be seen that ring B ofisoavones and 4prime-OH are active centers involving in an-tioxidant activity Although electron transfer enthalpy (ETE)shows the lowest amount in all radical cases of 1ndash4 minimal

OO

OHOOH

0295

0388

0226

0433

(a)

OHO

OHOO

0202

0354

0366

0459

(b)

OHO

OOOH

03820284

0381

(c)

OO

OOOH

0295

0432 0389

(d)

OHO

OOO

0202

0353

0459

0366

(e)

OO

OHOO

sugar

0376

0407

0436

(f )OO

OOOH

0380

sugar

0286

03810283

(g)

OO

OHOO

sugar

O

0310

0224

0359

(h)

OO

OOOH

0380

sugar

O 0285

02830381

(i)

Figure 7 Spin density distribution of structural radicals 1ndash4 obtained after H-atom abstraction (a) Compound 1 7-OH radical(b) Compound 1 5-OH radical (c) Compound 1 4prime-OH radical (d) Compound 2 7-OH radical (e) Compound 2 5-OH radical(f ) Compound 3 5-OH radical (g) Compound 3 4prime-OH radical (h) Compound 4 5-OH radical (i) Compound 4 4prime-OH radical

Journal of Chemistry 9

total energies of PA+ETE and IP + PDE establish 4 timesmore potency than those of BDEis is sequential evidenceto deeply vindicate that HATmechanism gets more favor ingas Here we can make an arrangement in the followingorder of favorable HATgt SET-PTasymp SPLET and impor-tantly conclude that in the environmental gas and antiox-idant mechanisms have been becoming dependent on theprocesses of proton disruptions rather than the effects ofelectron actions

In terms of comparing among radicals 5-OH 7-OH and4prime-OH in each metabolite O-H homolytic bond dissociationenthalpy (BDE) O-H heterolytic bond dissociation enthalpy(PDE) and proton affinity (PA) are realistic evidence wouldsince have been proved that energies of 5-OH bond breakingalways overcome due to IHBs (Table 3)

Antioxidant-structural relationships can be highlightedthrough the differences in enthalpies calculations Whenspontaneously compared two isoflavone glycosides 3-4 5-OH radical enthalpy parameters BDE IP PDE PA andETE the courses of IP + PDE and PA+ETE of compound 4are less than those of 5-OH radical in compound 3 from 2 to9 kcalmol It therefore remarks that 6-OCH3 has greatlyinfluenced 5-OH and IHBs so that the 6-methoxylationwould help increase antioxidant In the same assessment forcompounds 1-2 4prime-methylation did not significantly con-tribute to the effect itself on 5-OH and 7-OH radicals but thereverse trends are observed 5-OH radical BDE in genstein(1)gt biochanin A (2) 5-OH and 7-OH radicals PDE ingenistein (1)lt biochanin A (2) As mentioned above β-D-apiofuranosyl-(1-6)-β-D-glucopyranosyl unit should not bethe suitable sites for radical scavenging but they have greatlyaffected isoflavone core Indeed 7-glycosylation (meta po-sition) in ambocin (3) has two sides On the one hand itshows a decrease in the amount of energy in 5-OH bondbreaking in terms of BDE IP IP + PDE ETE and PA+ETEwhile on the other hand it induces an increase pattern inthose in PDE and PA as compared with 7-hydroxylation ingenistein (1)

Last but not least among 1 and 3-4 4prime-OH radicalBDE leads to the introduction of an actively antioxidantarrangement tectorigenin 7-O-[β-D-apiofuranosyl-(1-6)-β-D-glucopyranoside] (4) gt ambocin (3) gt genistein (1)while no change is observed in 7-OH radical BDE values

and 5-OH radical one with the order genistein (1)lt biochanin A (2)

3 Conclusion

Naturally occurring isoflavones and their glycosides havesuccessfully been investigated by the density theory-basedmethod Actually the prospective outcome points out thatHAT pathway is preferentially closely related to the anti-oxidant action of all studied polyphenolic compounds inthe gaseous state Numerous parameters such as ionizationpotential (IP) proton affinity (PA) the sum of energies ofSET-PT andor SPLETmechanisms especially in terms ofBDE values provide supportive information to confirm theradical-scavenging process that takes place throughoutO-H breaking bond in isoflavones is current resultcorresponds to many previous studies in which structuralconformations π-electrons delocalization potential po-larizability hydroxyl groups distributed in ring B andfunctional groups are major reasons for antioxidant ac-tivities of general flavonoids Antioxidant isoflavone gly-cosides ambocin and tectorigenin 7-O-[β-D-apiofuranosyl-(1-6)-β-D-glucopyranoside] are more significant thanisoflavone genistein and biochanin A deducing from 7-glycosylation and 6-methoxylation is account providesnecessary guidelines for future research

Abbreviations

DFT Density functional theoryHOMO Highest occupied molecular orbitalLUMO Lowest unoccupied molecular orbitalIHBs Intramolecular hydrogen bondsBDE Homolytic bond dissociation enthalpyPDE Heterolytic bond dissociation enthalpyIP Ionization potentialPA Proton affinityETE Electron transfer enthalpyHAT Hydrogen atom transferSET-PT Single electron transfer-proton transferSPLET Sequential proton loss electron transferDPPH 22-Diphenyl-1-picrylhydrazyl

Table 3 Gas phase reaction enthalpies at 298 K for radicals of the studied compounds at B3LYP6-311G(d) level of theory (in kcalmol)

Compounds HAT BDE IP PDE SET-PT (IP + PDE) PA ETE SPLET (PA+ETE)1 168305-OH 9426 24166 40996 34707 6289 409967-OH 8384 23136 39966 32968 7002 399704prime-OH 7709 22449 39279 33790 5589 393792 165795-OH 9426 24419 40998 34740 6257 409977-OH 8376 23368 39947 33000 6962 399623 164765-OH 9414 24509 40985 34802 6183 409854prime-OH 7689 22784 39260 33811 5449 392604 157175-OH 8511 24372 40089 34563 5519 400824prime-OH 7685 23542 39269 33822 5429 39251

10 Journal of Chemistry

Data Availability

All data used for this project are publicly available andaccessible online e authors have pronounced the entiredata building process and empirical techniques presented inthe paper

Conflicts of Interest

e authors declare that they have no conflicts of interest

Acknowledgments

is work was supported by a grant (no VASTCTG0117-19) from Vietnam Academy of Science and Technology(VAST) 18 Hoang Quoc Viet Caugiay Hanoi Vietnam

Supplementary Materials

Figure S1 the state forms of studied structures in MeOHmedium Table S1 the collective energies depended ontorsional angles θ2 (C2-C3-C1prime-C2prime) Table S2 Mullikenatomic charges at theoretical level B3LYP6-311G(d) ofstudied compounds in gas and methanol mediums Table S3condensed Fukui indices at B3LYP6-311G(d) of studiedcompounds in gas medium (Supplementary Materials)

References

[1] E Miadokova ldquoIsoflavonoids-an overview of their biologicalactivities and potential health benefitsrdquo InterdisciplinaryToxicology vol 2 no 4 pp 211ndash218 2009

[2] A N Panche A D Diwan and S R Chandra ldquoFlavonoidsan overviewrdquo Journal of Nutritional Science vol 5 p e472016

[3] Z Dhaouadi M Nsangou N Garrab E H AnouarK Marakchi and S Lahmar ldquoDFT study of the reaction ofquercetin with and radicalsrdquo Journal of Molecular StructureTHEOCHEM vol 904 no 1-3 pp 35ndash42 2009

[4] P Dixit R Chillara V Khedgikar et al ldquoConstituents ofDalbergia sissoo Roxb leaves with osteogenic activityrdquo Bio-organic amp Medicinal Chemistry Letters vol 22 no 2pp 890ndash897 2012

[5] J N Choi K Dockyu K C Hyung M Y Kyung K Jiyoungand H L Choong ldquo2prime-Hydroxyaltion of genistein enhancedantioxidant and antiproliferative activities in MCF-7 humanbreast cancer cellsrdquo Journal of Microbiology and Bio-technology vol 19 pp 1348ndash1354 2009

[6] S Dowling F Regan and H Hughes ldquoe characterisation ofstructural and antioxidant properties of isoflavone metalchelatesrdquo Journal of Inorganic Biochemistry vol 104 no 10pp 1091ndash1098 2010

[7] J-G Cho H-J Park G-W Huh et al ldquoFlavonoids fromPueraria mirifica roots and quantitative analysis usingHPLCrdquo Food Science and Biotechnology vol 23 no 6pp 1815ndash1820 2014

[8] Y Zhang and Y Sun ldquoeoretical investigation on atmo-spheric reaction of O(3P) with CH 2 CNrdquo Journal of PhysicalOrganic Chemistry vol 32 no 4 article e3913 2018

[9] E M Kamel A M Mahmoud S A Ahmed andA M Lamsabhi ldquoA phytochemical and computational studyon flavonoids isolated from Trifolium resupinatum L and

their novel hepatoprotective activityrdquo Food amp Function vol 7no 4 pp 2094ndash2106 2016

[10] R A Mendes S K C Almeida I N Soares et al ldquoAcomputational investigation on the antioxidant potential ofmyricetin 34prime-di-O-α-L-rhamnopyranosiderdquo Journal ofMolecular Modeling vol 24 no 6 p 133 2018

[11] K S Kumar and R Kumarresan ldquoA DFT study on thestructural electronic properties and radical scavengingmechanisms of calycosin glycitein pratensein and prunetinrdquoComputational andeoretical Chemistry vol 985 pp 14ndash222012

[12] A Vaganek J Rimarcik V Lukes L Rottmannova andE Klein ldquoDFTB3LYP study of the enthalpies of Homolyticand Heterolytic O-H Bond dissociation in sterically hinderedphenolsrdquo Acta Chimica Slovenica vol 4 pp 55ndash71 2011

[13] M Leopoldini T Marino N Russo and M Toscano ldquoAn-tioxidant properties of phenolic compounds H-atom versuselectron transfer mechanismrdquo Journal of Physical ChemistryA vol 108 no 22 pp 4916ndash4922 2004

[14] R A Mendes B L S Silva R Takeara R G Freitas A Brownand G L C de Souza ldquoProbing the antioxidant potential ofphloretin and phlorizin through a computational investigationrdquoJournal of Molecular Modeling vol 24 no 4 p 101 2018

[15] E N Maciel S K C Almeida S C da Silva andG L C de Souza ldquoExamining the reaction between anti-oxidant compounds and 22-diphenyl-1-picrylhydrazyl(DPPH) through a computational investigationrdquo Journal ofMolecular Modeling vol 24 no 8 p 218 2018

[16] A Galano G Mazzone R A Diduk T MarinoJ R A Idaboy and N Russo ldquoFood antioxidants chemicalInsights at the Molecular Levelrdquo Annual Review of FoodScience and Technology vol 7 no 1 pp 335ndash352 2016

[17] V B Luzhkov ldquoMechanisms of antioxidant activity the DFTstudy of hydrogen abstraction from phenol and toluene by thehydroperoxyl radicalrdquo Chemical Physics vol 314 no 1-3pp 211ndash217 2005

[18] S A P Gomez N F Holguin A P HernandezM P Miramontes and D G Mitnik ldquoComputational mo-lecular characterization of the flavonoid rutinrdquo ChemistryCentral Journal vol 4 no 1 p 12 2010

[19] D G Mitnik ldquoComputational chemistry of natural productsa comparison of the chemical reactivity of isonaringin cal-culated with the M06 family of density functionalsrdquo Journal ofMolecular Modeling vol 20 no 7 p 2316 2014

[20] H Djeradi A Rahmouni and A Cheriti ldquoAntioxidant ac-tivity of flavonoids a QSAR modeling using Fukui indicesdescriptorsrdquo Journal of Molecular Modeling vol 20 no 10p 2476 2014

[21] K Sadasivam and R Kumaresan ldquoAntioxidant behavior ofmearnsetin and myricetin flavonoid compounds-a DFTstudyrdquo Spectrochimica Acta Part A Molecular and Bio-molecular Spectroscopy vol 79 no 1 pp 282ndash293 2011

[22] R-M Han Y-X Tian Y Liu et al ldquoComparison of flavo-noids and isoflavonoids as antioxidantsrdquo Journal of Agri-cultural and Food Chemistry vol 57 no 9 pp 3780ndash37852009

[23] S F Farag A S Ahmed K Terashima Y Takaya andM Niwa ldquoIsoflavonoid glycosides from Dalbergia sissoordquoPhytochemistry vol 57 pp 1263ndash1268 2001

[24] S T Ninh ldquoA Review on the medicinal plant Dalbergiaodorifera species phytochemistry and biological activityrdquoEvidence-Based Complementary and Alternative Medicinevol 2017 Article ID 7142370 27 pages 2017

Journal of Chemistry 11

publication on several isoflavones [11] e absolute mini-mum I is more stable than the conformational relativeminimum II by 198 kcalmol for genistein (1) however thisone for compounds 2ndash4 has smaller values of 040 kcalmol029 kcalmol and 026 kcalmol respectively Parallel withthis there are several potential energy barriers that rangefrom I to II in compound 1 the first interconversion energybarrierrsquos value of 355 kcalmol is recognized at the per-pendicular conformation (θ2 90deg) and the second energybarrier accounts for 494 kcalmol and peaks at anti(θ2 180deg) conformation meanwhile the maximum in-terchangeable barrier reaches 541 kcalmol at syn (θ2 360degor 0deg) shape In the same manner with torsional angles θ1 of90deg 180deg and 360deg (or 0deg) these potential energy barriers arefound at the values of 215 kcalmol 378 kcalmol and402 kcalmol 215 kcalmol 377 kcalmol and 400 kcalmol and 211 kcalmol 381 kcalmol and 403 kcalmol forcompounds 2ndash4 respectively e dramatic difference ob-tained from energies between two minima together with thedistinction from the interchangeable energy barriers of 1 andgroups 2ndash4 can be explained by the symmetric property of 1the phenomena of 4prime-methylation in 2 7-glycosylation in 3and 6-methoxylation-7-glycosylation in 4

22 Frontier Molecular Orbital eory and Spin DensityTaking π-electron delocalization into consideration it in-volves in the stabilization of parent molecular and radicalsafter H abstractions [27] e frontier orbital theoreticalcalculation seems to be a significant tool for explaining therelationship between neutral and radical forms especially interms of the electron delocalization At the level of B3LYP6-311G(d) in both mediums of gas and methanol HOMO andLUMO of neutral and radical visual images and frontierorbital energies of 1ndash4 are shown in Figures 4ndash6 and Table 2HOMO neutral images show that the electron distribution isconcentrated in the entire aglycone especially ring B and23-double bond while LUMO neutral is delocalized oversystematic rings A and C Sugar units are not a suitable sitefor radical reactions e same result has been found inpreviously studied isoflavones glycitein pratensein andprunetin [11] When hydrogen atom abstraction takes placein four isoflavones it is worth noting that 4prime-OH HOMOradical species in compounds 1 and 3-4 which correspondto the small BDE values consist of high electron density inring B and slightly less in ring A 5-OH andor 7-OHHOMO radical shapes which concern the high BDE valuesdid not differ from neutral composition except for the lesselectron distribution in ring C for 5-OH radical site ofcompound 4 LUMO radical forms mostly focus on chro-mene systems but slightly view in ring B in the case of 5-OH7-OH of compounds 1-2 and 5-OH of compounds 3-4 ehigher EHOMO (the lower ionization potential Io) and thelower ELUMO (the higher electron affinity A) mean the bettercapacity of electrons donating and the better sensitivity toreceive electrons respectively whereas the easier electrontransfer indicates the lower Egap ELUMOminusEHOMO andthus the better antioxidant reactivity From Table 2 thegaseous phase would lay a better ground for decreasing

EHOMO values when compared with using methanol butmethanol solution should be a suitable tool to scale downELUMO values Paying attention to the gaseous medium thehighest EHOMO which can be claimed responsible for ad-vantageous radical reactions here facilitates compound 4(minus5796 eV) in preference to the others 3 (minus5891 eV) 2(minus5897 eV) and 1 (minus5960 eV) e numbers of 4250 eV4215 eV 4267 eV and 4172 eV are assignable to the re-spective Egap values of compounds 1ndash4 in the environmentalgas e most striking feature is that 4prime-methylated

4250 4215 4267 4172

ndash9ndash8ndash7ndash6ndash5ndash4ndash3ndash2ndash1

01

Fron

tier m

olec

ular

orb

ital e

nerg

y (e

V)

Com

poun

d 4

Com

poun

d 3

Com

poun

d 2

Com

poun

d 1

Compound

HOMOLUMO

Figure 4 Neutral HOMO and LUMO images and Egap of struc-tures 1ndash4 in gas medium

4248 4218 4229 4185

Com

poun

d 1

Com

poun

d 3

Com

poun

d 4

Com

poun

d 2

Compound

HOMOLUMO

ndash9ndash8ndash7ndash6ndash5ndash4ndash3ndash2ndash1

01

Fron

tier m

olec

ular

orb

ital e

nerg

y (e

V)

Figure 5 Neutral HOMO and LUMO images and Egap of struc-tures 1ndash4 in MeOH medium

6 Journal of Chemistry

(a) (b) (c)

(d) (e) (f)

(g) (h) (i)

(j) (k) (l)

(m) (n) (o)

(p) (q) (r)

Figure 6 HOMO and LUMO of structural radicals 1ndash4 (a) HOMO-5-OH radical (1) (b) HOMO-7-OH radical (1) (c) HOMO-4prime-OHradical (1) (d) LUMO-5-OH radical (1) (e) LUMO-7-OH radical (1) (f ) LUMO-4prime-OH radical (1) (g) HOMO-5-OH radical (2)(h) HOMO-7-OH radical (2) (i) HOMO-5-OH radical (3) (j) LUMO-5-OH radical (2) (k) LUMO-7-OH radical (2) (l) LUMO-5-OHradical (3) (m) HOMO-4prime-OH radical (3) (n) HOMO-5-OH radical (4) (o) HOMO-4prime-OH radical (4) (p) LUMO-4prime-OH radical (3) (q)LUMO-5-OH radical (4) (r) LUMO-4prime-OH radical (4)

Journal of Chemistry 7

compound 2 and 6-methoxylated compound 4 evidentlygenerate better Egap values when compared to respectivecompounds 1 and 3 in both of the phases Emphasizing onthe change of gas phase into methanol a remarkable reversecan be observed in the Egap values between 1 and 3 due tothe 7-glycosylated phenomenon Among four compounds1ndash4 we primarily assumed that tectorigenin 7-O-[β-D-apiofuranosyl-(1-6)-β-D-glucopyranoside] (4) is the bestcandidate employable for antioxidant targets not mentionthe fact that 4prime-methylation 6-methoxylation and 7-gly-cosylation facilitate the antioxidant ability

Calculation of the atomic spin density population ofvarious radicals after H-abstraction from four consideredisoflavones 1ndash4 is given in Figure 7 It should be kept inmindthat the higher the spin density delocalized in radicals theeasier the radical formation hence lower BDE values [28]As a general view the computed results reveal that strongspin distributions remain on oxygen atoms of phenolicgroups carbons C-1prime C-3prime and C-5prime of the ring B andcarbons C-6 and C-8 in ring A and also C4a In all fourcompounds 1ndash4 C-1prime C-3prime and C-5prime are centers of positivespin density C-2prime C-4prime and C-6prime bear negative one whilstatomic carbons in ring A fail to do so [11] It suggests thatphenyl unit ring B with more delocalized spin is significantlysuitable for radical formation e spin density values ofO-atommake an order as 0432ndash0433 (7-OH in compounds1-2)gt 0381ndash0382 (4prime-OH in compounds 1 3-4)gt 0310ndash0376 (5-OH in compounds 1ndash4) As of a normal rule thehigher spin density means higher BDE values Nonethelessthe number of spin in O-atom is found in the oppositedirection with predictable BDE values among 5-OH and 4prime-OH radicals which can be explained by the fact thatH-removal needs to have suitable energy to break the hy-drogen bonds between 5-OH and 4-CO [29]

23 ElectronicProperties e global hardness η has emergedas a measurement of resistance to charge transfer [29] 7-Glycosylated compound (3) accounts for the maximumchemical hardness η value of 2134 eV in the gaseous phase ithas been confirmed that this compound is much more stablethan the remainder particularly in comparison with theunstable 6-methoxylated-7-glycosylated compound 4(2086 eV in gas 2093 eV in methanol) By comparingcompounds 1 and 2 4prime-OCH3 mainly causes a decrease of ηin both phases erefore it can be concluded that meth-ylations and methoxylations in isoflavones and their gly-cosides induce a trend in transferring from ldquohigh oxidationstate and low polarizabilityrdquo to ldquolow oxidation state and highpolarizabilityrdquo

e electronegativity χ measures a trend to attract elec-trons along with the chemical potential micro which will beproportional to this parameter of a negative signal [30] Fol-lowing Sandersonrsquos principle a compound exerting the highelectronegativitymight quickly reach equalization and establishlow reactivity [31] erefore the low value of this one forantioxidant reactions is expected Compound 4 with low χvalue of 3710 eV in the gaseous state participates in antioxidantreactivity better than the range of 3758ndash3835 eV for

compounds 1ndash3 Nevertheless using solvents if solvents likemedium methanol are used the results are greatly influencedIndeed it is opposite to the tendency of genistein (1) andbiochanin A (2) whose glycosides 3-4 tend to go from a lowerelectronegativity in gas to a higher one in methanol (Table 2)

Apart from descriptors such as the electron affinity theionization potential the global hardness and the globalelectronegativity the global electrophilicity index ω ωminusand ω+ values have so far been increased when methanol istaken into account e ωminus values of all considered com-pounds 1ndash4 are 2-3-folds higher than those of ω+ in eithergas or methanol method is one is identical with theprevious literature data [11] in which isoflavones and theirsugar derivatives tend to donate electrons rather thancapturing

Within a molecule the dipole moment is an availablemethod to estimate the separation of positive and negativeelectrical charges e high magnitudes of the dipole mo-ment accompany with the high charge densities and highpolarity in bonds [21] In our current account glycosylatedcompounds 3-4 is 3-folds higher than isoflavones 1-2 in bothstates gas and methanol because of the effects of sugar unitsand solvents However focusing on the comparison between1 and 2 and 3 and 4 4prime-methylation and 6-methoxylation aresuitable for slightly reducing this property Han and hispartners pointed out that the more symmetric property instructures the lower dipole moment and its antioxidantefficiency is better than that of the asymmetric molecule ofthe same size [22] We found that the symmetric genistein(1) and its 4prime-methylation (2) with the low dipole momentvalues of 3036D and 2862D have resulted in good anti-oxidant ability in many real experiments [5 6] Polariz-ability may be justified considering the soluble nature ofmolecules in polar solvents [21] Compounds containingsugars and isoflavones 3-4 have generally shown to asso-ciate with the higher dipole moment as well as higherpolarizability (Table 2) Followed on 4prime-methylations and 6-methoxylations the polarizability is also in accordancewith chemical hardness as mentioned above

Mulliken population analysis (MPA) has resulted in netcharges of a chemical ring system which also appears to bean effective tool to assess a chemical reactivity e Mul-liken atomic charges values using the DFT method arepresented in Table S2 Generally the heteroatom oxygensin flavonoids 1ndash4 remark the significant negative chargeswhich are active sites of donating their electrons In themeantime the maximum of positive charge which is thepreferential site for the nucleophilic reaction has occurredin carbon C-4 e high number of positive (negative)charges of atoms oxygens carbon and hydrogen arisingfrom 5-OH and 4-CO is caused by internal hydrogenbonds thereby stabilizing the structure e fact is thatantioxidant activities of flavonoids further depend onnegative centers whereby hydroxyl groups in ring B arefound to act as active sites of radical reactions [20] As aconsequence considering flavonoid aglycones of studied 3-4 and compound 1 the high values of negative chargesoccur in 4prime-OH in both gas and methanol agreeing with thesmallest BDE outcome

8 Journal of Chemistry

Besides frontier molecular orbital considerations andanalysis of electronic structure Fukui parameters alsoprovide important information and quick solutions to justifythe powerful reactive site of each atom Fukui indices fromTable S3 are calculated in gaseous medium based on the-oretical HSAB principle [31] It seemed that oxygen ofcarbonyl group 4-CO of all studiedmembers 1ndash4 and carbonC-2 in compounds 2 and 4 should have opted as good sitesfor both electrophilic and radical attacks but carbon C-2 isthe only suitable site of electrophilic scope for metabolites 1and 3 4prime-OH in compound 1 and carbon C-6 bears OCH3 incompound 4 adapted for nucleophilic attractive types Mostimportantly the f o condensed Fukui values advocate otherpreferential radical sites that are found in hydroxyl groups

Numerous atoms in β-D-apiofuranosyl-(1-6)-β-D-glu-copyranosyl parts of compounds 3-4 show the signicantMulliken electronic charges 4Prime-OH of glycoside 3 is nowexpected as electrophilic tendencies but for further cor-roboration with HOMO-LUMO analysis above Fukui de-scriptors research indicates that sugar units did not showfavorability for the antioxidant reactive types resembling inthe computational results in a avone glycoside rutin orresearch on pryoanthocyanin [17 28 32]

24 Antioxidant Mechanisms In the same condition of298K and environmental gas our BDE results in genistein(1) and biochanin A (2) dier from the B3LYP6-31 +G(dp) andor B3LYP6-311++G(dp) previously cal-culated publications within usually 40 kcalmol [33 34] Inaddition our PDE PA and ETE numbers show good

accordance with B3LYP6-311++G(dp) level in the lastaccount performed by Lengyel and partners particularly thedeviation just only found to be 2 kcalmol in PA calculationbut largely dierent from the work of Zhang and co-authors[33 34]

e favorable mechanisms of antiradical activity ofisoavones might possibly be discussed via thermodynam-ically preferential BDE of HAT IP of SET-PT and PA ofSPLET actions [35] From genistein (1) in gaseous statereaction in Table 3 BDE values (7709ndash9426 kcalmol) aresignicantly lower than those of IP (16830 kcalmol) and PA(32968ndash34707 kcalmol) is behavior is also similarlyestablished from the remainders like 2ndash4 erefore HATpathway is probable for isoavones and isoavone glycosidesin gas

From a thermodynamic point of view relating to threewell-known mechanisms the active sites of antioxidantaction have also been proposed throughout theminimal sumof enthalpies including BDEmin in HAT (IP + PDE)min inSET-PT and (PA+ETE)min in SPLET [35] e lowestrank of BDE values ranges from 7685 to 7709 kcalmol isdominated by 4prime-OH radical in gas for all isoavones 1ndash4compared with those of 7-OH radical (8376ndash8384 kcalmol) and 5-OH radical (8511ndash9426 kcalmol) A similarinstance arises from enthalpies of SET-PT and SPLETpathways that either isoavones 1-2 or their glycosides 3-4also encompasses the minimum values of IP + PDE andPA+ETE at 4prime-OH Once again it can be seen that ring B ofisoavones and 4prime-OH are active centers involving in an-tioxidant activity Although electron transfer enthalpy (ETE)shows the lowest amount in all radical cases of 1ndash4 minimal

OO

OHOOH

0295

0388

0226

0433

(a)

OHO

OHOO

0202

0354

0366

0459

(b)

OHO

OOOH

03820284

0381

(c)

OO

OOOH

0295

0432 0389

(d)

OHO

OOO

0202

0353

0459

0366

(e)

OO

OHOO

sugar

0376

0407

0436

(f )OO

OOOH

0380

sugar

0286

03810283

(g)

OO

OHOO

sugar

O

0310

0224

0359

(h)

OO

OOOH

0380

sugar

O 0285

02830381

(i)

Figure 7 Spin density distribution of structural radicals 1ndash4 obtained after H-atom abstraction (a) Compound 1 7-OH radical(b) Compound 1 5-OH radical (c) Compound 1 4prime-OH radical (d) Compound 2 7-OH radical (e) Compound 2 5-OH radical(f ) Compound 3 5-OH radical (g) Compound 3 4prime-OH radical (h) Compound 4 5-OH radical (i) Compound 4 4prime-OH radical

Journal of Chemistry 9

total energies of PA+ETE and IP + PDE establish 4 timesmore potency than those of BDEis is sequential evidenceto deeply vindicate that HATmechanism gets more favor ingas Here we can make an arrangement in the followingorder of favorable HATgt SET-PTasymp SPLET and impor-tantly conclude that in the environmental gas and antiox-idant mechanisms have been becoming dependent on theprocesses of proton disruptions rather than the effects ofelectron actions

In terms of comparing among radicals 5-OH 7-OH and4prime-OH in each metabolite O-H homolytic bond dissociationenthalpy (BDE) O-H heterolytic bond dissociation enthalpy(PDE) and proton affinity (PA) are realistic evidence wouldsince have been proved that energies of 5-OH bond breakingalways overcome due to IHBs (Table 3)

Antioxidant-structural relationships can be highlightedthrough the differences in enthalpies calculations Whenspontaneously compared two isoflavone glycosides 3-4 5-OH radical enthalpy parameters BDE IP PDE PA andETE the courses of IP + PDE and PA+ETE of compound 4are less than those of 5-OH radical in compound 3 from 2 to9 kcalmol It therefore remarks that 6-OCH3 has greatlyinfluenced 5-OH and IHBs so that the 6-methoxylationwould help increase antioxidant In the same assessment forcompounds 1-2 4prime-methylation did not significantly con-tribute to the effect itself on 5-OH and 7-OH radicals but thereverse trends are observed 5-OH radical BDE in genstein(1)gt biochanin A (2) 5-OH and 7-OH radicals PDE ingenistein (1)lt biochanin A (2) As mentioned above β-D-apiofuranosyl-(1-6)-β-D-glucopyranosyl unit should not bethe suitable sites for radical scavenging but they have greatlyaffected isoflavone core Indeed 7-glycosylation (meta po-sition) in ambocin (3) has two sides On the one hand itshows a decrease in the amount of energy in 5-OH bondbreaking in terms of BDE IP IP + PDE ETE and PA+ETEwhile on the other hand it induces an increase pattern inthose in PDE and PA as compared with 7-hydroxylation ingenistein (1)

Last but not least among 1 and 3-4 4prime-OH radicalBDE leads to the introduction of an actively antioxidantarrangement tectorigenin 7-O-[β-D-apiofuranosyl-(1-6)-β-D-glucopyranoside] (4) gt ambocin (3) gt genistein (1)while no change is observed in 7-OH radical BDE values

and 5-OH radical one with the order genistein (1)lt biochanin A (2)

3 Conclusion

Naturally occurring isoflavones and their glycosides havesuccessfully been investigated by the density theory-basedmethod Actually the prospective outcome points out thatHAT pathway is preferentially closely related to the anti-oxidant action of all studied polyphenolic compounds inthe gaseous state Numerous parameters such as ionizationpotential (IP) proton affinity (PA) the sum of energies ofSET-PT andor SPLETmechanisms especially in terms ofBDE values provide supportive information to confirm theradical-scavenging process that takes place throughoutO-H breaking bond in isoflavones is current resultcorresponds to many previous studies in which structuralconformations π-electrons delocalization potential po-larizability hydroxyl groups distributed in ring B andfunctional groups are major reasons for antioxidant ac-tivities of general flavonoids Antioxidant isoflavone gly-cosides ambocin and tectorigenin 7-O-[β-D-apiofuranosyl-(1-6)-β-D-glucopyranoside] are more significant thanisoflavone genistein and biochanin A deducing from 7-glycosylation and 6-methoxylation is account providesnecessary guidelines for future research

Abbreviations

DFT Density functional theoryHOMO Highest occupied molecular orbitalLUMO Lowest unoccupied molecular orbitalIHBs Intramolecular hydrogen bondsBDE Homolytic bond dissociation enthalpyPDE Heterolytic bond dissociation enthalpyIP Ionization potentialPA Proton affinityETE Electron transfer enthalpyHAT Hydrogen atom transferSET-PT Single electron transfer-proton transferSPLET Sequential proton loss electron transferDPPH 22-Diphenyl-1-picrylhydrazyl

Table 3 Gas phase reaction enthalpies at 298 K for radicals of the studied compounds at B3LYP6-311G(d) level of theory (in kcalmol)

Compounds HAT BDE IP PDE SET-PT (IP + PDE) PA ETE SPLET (PA+ETE)1 168305-OH 9426 24166 40996 34707 6289 409967-OH 8384 23136 39966 32968 7002 399704prime-OH 7709 22449 39279 33790 5589 393792 165795-OH 9426 24419 40998 34740 6257 409977-OH 8376 23368 39947 33000 6962 399623 164765-OH 9414 24509 40985 34802 6183 409854prime-OH 7689 22784 39260 33811 5449 392604 157175-OH 8511 24372 40089 34563 5519 400824prime-OH 7685 23542 39269 33822 5429 39251

10 Journal of Chemistry

Data Availability

All data used for this project are publicly available andaccessible online e authors have pronounced the entiredata building process and empirical techniques presented inthe paper

Conflicts of Interest

e authors declare that they have no conflicts of interest

Acknowledgments

is work was supported by a grant (no VASTCTG0117-19) from Vietnam Academy of Science and Technology(VAST) 18 Hoang Quoc Viet Caugiay Hanoi Vietnam

Supplementary Materials

Figure S1 the state forms of studied structures in MeOHmedium Table S1 the collective energies depended ontorsional angles θ2 (C2-C3-C1prime-C2prime) Table S2 Mullikenatomic charges at theoretical level B3LYP6-311G(d) ofstudied compounds in gas and methanol mediums Table S3condensed Fukui indices at B3LYP6-311G(d) of studiedcompounds in gas medium (Supplementary Materials)

References

[1] E Miadokova ldquoIsoflavonoids-an overview of their biologicalactivities and potential health benefitsrdquo InterdisciplinaryToxicology vol 2 no 4 pp 211ndash218 2009

[2] A N Panche A D Diwan and S R Chandra ldquoFlavonoidsan overviewrdquo Journal of Nutritional Science vol 5 p e472016

[3] Z Dhaouadi M Nsangou N Garrab E H AnouarK Marakchi and S Lahmar ldquoDFT study of the reaction ofquercetin with and radicalsrdquo Journal of Molecular StructureTHEOCHEM vol 904 no 1-3 pp 35ndash42 2009

[4] P Dixit R Chillara V Khedgikar et al ldquoConstituents ofDalbergia sissoo Roxb leaves with osteogenic activityrdquo Bio-organic amp Medicinal Chemistry Letters vol 22 no 2pp 890ndash897 2012

[5] J N Choi K Dockyu K C Hyung M Y Kyung K Jiyoungand H L Choong ldquo2prime-Hydroxyaltion of genistein enhancedantioxidant and antiproliferative activities in MCF-7 humanbreast cancer cellsrdquo Journal of Microbiology and Bio-technology vol 19 pp 1348ndash1354 2009

[6] S Dowling F Regan and H Hughes ldquoe characterisation ofstructural and antioxidant properties of isoflavone metalchelatesrdquo Journal of Inorganic Biochemistry vol 104 no 10pp 1091ndash1098 2010

[7] J-G Cho H-J Park G-W Huh et al ldquoFlavonoids fromPueraria mirifica roots and quantitative analysis usingHPLCrdquo Food Science and Biotechnology vol 23 no 6pp 1815ndash1820 2014

[8] Y Zhang and Y Sun ldquoeoretical investigation on atmo-spheric reaction of O(3P) with CH 2 CNrdquo Journal of PhysicalOrganic Chemistry vol 32 no 4 article e3913 2018

[9] E M Kamel A M Mahmoud S A Ahmed andA M Lamsabhi ldquoA phytochemical and computational studyon flavonoids isolated from Trifolium resupinatum L and

their novel hepatoprotective activityrdquo Food amp Function vol 7no 4 pp 2094ndash2106 2016

[10] R A Mendes S K C Almeida I N Soares et al ldquoAcomputational investigation on the antioxidant potential ofmyricetin 34prime-di-O-α-L-rhamnopyranosiderdquo Journal ofMolecular Modeling vol 24 no 6 p 133 2018

[11] K S Kumar and R Kumarresan ldquoA DFT study on thestructural electronic properties and radical scavengingmechanisms of calycosin glycitein pratensein and prunetinrdquoComputational andeoretical Chemistry vol 985 pp 14ndash222012

[12] A Vaganek J Rimarcik V Lukes L Rottmannova andE Klein ldquoDFTB3LYP study of the enthalpies of Homolyticand Heterolytic O-H Bond dissociation in sterically hinderedphenolsrdquo Acta Chimica Slovenica vol 4 pp 55ndash71 2011

[13] M Leopoldini T Marino N Russo and M Toscano ldquoAn-tioxidant properties of phenolic compounds H-atom versuselectron transfer mechanismrdquo Journal of Physical ChemistryA vol 108 no 22 pp 4916ndash4922 2004

[14] R A Mendes B L S Silva R Takeara R G Freitas A Brownand G L C de Souza ldquoProbing the antioxidant potential ofphloretin and phlorizin through a computational investigationrdquoJournal of Molecular Modeling vol 24 no 4 p 101 2018

[15] E N Maciel S K C Almeida S C da Silva andG L C de Souza ldquoExamining the reaction between anti-oxidant compounds and 22-diphenyl-1-picrylhydrazyl(DPPH) through a computational investigationrdquo Journal ofMolecular Modeling vol 24 no 8 p 218 2018

[16] A Galano G Mazzone R A Diduk T MarinoJ R A Idaboy and N Russo ldquoFood antioxidants chemicalInsights at the Molecular Levelrdquo Annual Review of FoodScience and Technology vol 7 no 1 pp 335ndash352 2016

[17] V B Luzhkov ldquoMechanisms of antioxidant activity the DFTstudy of hydrogen abstraction from phenol and toluene by thehydroperoxyl radicalrdquo Chemical Physics vol 314 no 1-3pp 211ndash217 2005

[18] S A P Gomez N F Holguin A P HernandezM P Miramontes and D G Mitnik ldquoComputational mo-lecular characterization of the flavonoid rutinrdquo ChemistryCentral Journal vol 4 no 1 p 12 2010

[19] D G Mitnik ldquoComputational chemistry of natural productsa comparison of the chemical reactivity of isonaringin cal-culated with the M06 family of density functionalsrdquo Journal ofMolecular Modeling vol 20 no 7 p 2316 2014

[20] H Djeradi A Rahmouni and A Cheriti ldquoAntioxidant ac-tivity of flavonoids a QSAR modeling using Fukui indicesdescriptorsrdquo Journal of Molecular Modeling vol 20 no 10p 2476 2014

[21] K Sadasivam and R Kumaresan ldquoAntioxidant behavior ofmearnsetin and myricetin flavonoid compounds-a DFTstudyrdquo Spectrochimica Acta Part A Molecular and Bio-molecular Spectroscopy vol 79 no 1 pp 282ndash293 2011

[22] R-M Han Y-X Tian Y Liu et al ldquoComparison of flavo-noids and isoflavonoids as antioxidantsrdquo Journal of Agri-cultural and Food Chemistry vol 57 no 9 pp 3780ndash37852009

[23] S F Farag A S Ahmed K Terashima Y Takaya andM Niwa ldquoIsoflavonoid glycosides from Dalbergia sissoordquoPhytochemistry vol 57 pp 1263ndash1268 2001

[24] S T Ninh ldquoA Review on the medicinal plant Dalbergiaodorifera species phytochemistry and biological activityrdquoEvidence-Based Complementary and Alternative Medicinevol 2017 Article ID 7142370 27 pages 2017

Journal of Chemistry 11

(a) (b) (c)

(d) (e) (f)

(g) (h) (i)

(j) (k) (l)

(m) (n) (o)

(p) (q) (r)

Figure 6 HOMO and LUMO of structural radicals 1ndash4 (a) HOMO-5-OH radical (1) (b) HOMO-7-OH radical (1) (c) HOMO-4prime-OHradical (1) (d) LUMO-5-OH radical (1) (e) LUMO-7-OH radical (1) (f ) LUMO-4prime-OH radical (1) (g) HOMO-5-OH radical (2)(h) HOMO-7-OH radical (2) (i) HOMO-5-OH radical (3) (j) LUMO-5-OH radical (2) (k) LUMO-7-OH radical (2) (l) LUMO-5-OHradical (3) (m) HOMO-4prime-OH radical (3) (n) HOMO-5-OH radical (4) (o) HOMO-4prime-OH radical (4) (p) LUMO-4prime-OH radical (3) (q)LUMO-5-OH radical (4) (r) LUMO-4prime-OH radical (4)

Journal of Chemistry 7

compound 2 and 6-methoxylated compound 4 evidentlygenerate better Egap values when compared to respectivecompounds 1 and 3 in both of the phases Emphasizing onthe change of gas phase into methanol a remarkable reversecan be observed in the Egap values between 1 and 3 due tothe 7-glycosylated phenomenon Among four compounds1ndash4 we primarily assumed that tectorigenin 7-O-[β-D-apiofuranosyl-(1-6)-β-D-glucopyranoside] (4) is the bestcandidate employable for antioxidant targets not mentionthe fact that 4prime-methylation 6-methoxylation and 7-gly-cosylation facilitate the antioxidant ability

Calculation of the atomic spin density population ofvarious radicals after H-abstraction from four consideredisoflavones 1ndash4 is given in Figure 7 It should be kept inmindthat the higher the spin density delocalized in radicals theeasier the radical formation hence lower BDE values [28]As a general view the computed results reveal that strongspin distributions remain on oxygen atoms of phenolicgroups carbons C-1prime C-3prime and C-5prime of the ring B andcarbons C-6 and C-8 in ring A and also C4a In all fourcompounds 1ndash4 C-1prime C-3prime and C-5prime are centers of positivespin density C-2prime C-4prime and C-6prime bear negative one whilstatomic carbons in ring A fail to do so [11] It suggests thatphenyl unit ring B with more delocalized spin is significantlysuitable for radical formation e spin density values ofO-atommake an order as 0432ndash0433 (7-OH in compounds1-2)gt 0381ndash0382 (4prime-OH in compounds 1 3-4)gt 0310ndash0376 (5-OH in compounds 1ndash4) As of a normal rule thehigher spin density means higher BDE values Nonethelessthe number of spin in O-atom is found in the oppositedirection with predictable BDE values among 5-OH and 4prime-OH radicals which can be explained by the fact thatH-removal needs to have suitable energy to break the hy-drogen bonds between 5-OH and 4-CO [29]

23 ElectronicProperties e global hardness η has emergedas a measurement of resistance to charge transfer [29] 7-Glycosylated compound (3) accounts for the maximumchemical hardness η value of 2134 eV in the gaseous phase ithas been confirmed that this compound is much more stablethan the remainder particularly in comparison with theunstable 6-methoxylated-7-glycosylated compound 4(2086 eV in gas 2093 eV in methanol) By comparingcompounds 1 and 2 4prime-OCH3 mainly causes a decrease of ηin both phases erefore it can be concluded that meth-ylations and methoxylations in isoflavones and their gly-cosides induce a trend in transferring from ldquohigh oxidationstate and low polarizabilityrdquo to ldquolow oxidation state and highpolarizabilityrdquo

e electronegativity χ measures a trend to attract elec-trons along with the chemical potential micro which will beproportional to this parameter of a negative signal [30] Fol-lowing Sandersonrsquos principle a compound exerting the highelectronegativitymight quickly reach equalization and establishlow reactivity [31] erefore the low value of this one forantioxidant reactions is expected Compound 4 with low χvalue of 3710 eV in the gaseous state participates in antioxidantreactivity better than the range of 3758ndash3835 eV for

compounds 1ndash3 Nevertheless using solvents if solvents likemedium methanol are used the results are greatly influencedIndeed it is opposite to the tendency of genistein (1) andbiochanin A (2) whose glycosides 3-4 tend to go from a lowerelectronegativity in gas to a higher one in methanol (Table 2)

Apart from descriptors such as the electron affinity theionization potential the global hardness and the globalelectronegativity the global electrophilicity index ω ωminusand ω+ values have so far been increased when methanol istaken into account e ωminus values of all considered com-pounds 1ndash4 are 2-3-folds higher than those of ω+ in eithergas or methanol method is one is identical with theprevious literature data [11] in which isoflavones and theirsugar derivatives tend to donate electrons rather thancapturing

Within a molecule the dipole moment is an availablemethod to estimate the separation of positive and negativeelectrical charges e high magnitudes of the dipole mo-ment accompany with the high charge densities and highpolarity in bonds [21] In our current account glycosylatedcompounds 3-4 is 3-folds higher than isoflavones 1-2 in bothstates gas and methanol because of the effects of sugar unitsand solvents However focusing on the comparison between1 and 2 and 3 and 4 4prime-methylation and 6-methoxylation aresuitable for slightly reducing this property Han and hispartners pointed out that the more symmetric property instructures the lower dipole moment and its antioxidantefficiency is better than that of the asymmetric molecule ofthe same size [22] We found that the symmetric genistein(1) and its 4prime-methylation (2) with the low dipole momentvalues of 3036D and 2862D have resulted in good anti-oxidant ability in many real experiments [5 6] Polariz-ability may be justified considering the soluble nature ofmolecules in polar solvents [21] Compounds containingsugars and isoflavones 3-4 have generally shown to asso-ciate with the higher dipole moment as well as higherpolarizability (Table 2) Followed on 4prime-methylations and 6-methoxylations the polarizability is also in accordancewith chemical hardness as mentioned above

Mulliken population analysis (MPA) has resulted in netcharges of a chemical ring system which also appears to bean effective tool to assess a chemical reactivity e Mul-liken atomic charges values using the DFT method arepresented in Table S2 Generally the heteroatom oxygensin flavonoids 1ndash4 remark the significant negative chargeswhich are active sites of donating their electrons In themeantime the maximum of positive charge which is thepreferential site for the nucleophilic reaction has occurredin carbon C-4 e high number of positive (negative)charges of atoms oxygens carbon and hydrogen arisingfrom 5-OH and 4-CO is caused by internal hydrogenbonds thereby stabilizing the structure e fact is thatantioxidant activities of flavonoids further depend onnegative centers whereby hydroxyl groups in ring B arefound to act as active sites of radical reactions [20] As aconsequence considering flavonoid aglycones of studied 3-4 and compound 1 the high values of negative chargesoccur in 4prime-OH in both gas and methanol agreeing with thesmallest BDE outcome

8 Journal of Chemistry

Besides frontier molecular orbital considerations andanalysis of electronic structure Fukui parameters alsoprovide important information and quick solutions to justifythe powerful reactive site of each atom Fukui indices fromTable S3 are calculated in gaseous medium based on the-oretical HSAB principle [31] It seemed that oxygen ofcarbonyl group 4-CO of all studiedmembers 1ndash4 and carbonC-2 in compounds 2 and 4 should have opted as good sitesfor both electrophilic and radical attacks but carbon C-2 isthe only suitable site of electrophilic scope for metabolites 1and 3 4prime-OH in compound 1 and carbon C-6 bears OCH3 incompound 4 adapted for nucleophilic attractive types Mostimportantly the f o condensed Fukui values advocate otherpreferential radical sites that are found in hydroxyl groups

Numerous atoms in β-D-apiofuranosyl-(1-6)-β-D-glu-copyranosyl parts of compounds 3-4 show the signicantMulliken electronic charges 4Prime-OH of glycoside 3 is nowexpected as electrophilic tendencies but for further cor-roboration with HOMO-LUMO analysis above Fukui de-scriptors research indicates that sugar units did not showfavorability for the antioxidant reactive types resembling inthe computational results in a avone glycoside rutin orresearch on pryoanthocyanin [17 28 32]

24 Antioxidant Mechanisms In the same condition of298K and environmental gas our BDE results in genistein(1) and biochanin A (2) dier from the B3LYP6-31 +G(dp) andor B3LYP6-311++G(dp) previously cal-culated publications within usually 40 kcalmol [33 34] Inaddition our PDE PA and ETE numbers show good

accordance with B3LYP6-311++G(dp) level in the lastaccount performed by Lengyel and partners particularly thedeviation just only found to be 2 kcalmol in PA calculationbut largely dierent from the work of Zhang and co-authors[33 34]

e favorable mechanisms of antiradical activity ofisoavones might possibly be discussed via thermodynam-ically preferential BDE of HAT IP of SET-PT and PA ofSPLET actions [35] From genistein (1) in gaseous statereaction in Table 3 BDE values (7709ndash9426 kcalmol) aresignicantly lower than those of IP (16830 kcalmol) and PA(32968ndash34707 kcalmol) is behavior is also similarlyestablished from the remainders like 2ndash4 erefore HATpathway is probable for isoavones and isoavone glycosidesin gas

From a thermodynamic point of view relating to threewell-known mechanisms the active sites of antioxidantaction have also been proposed throughout theminimal sumof enthalpies including BDEmin in HAT (IP + PDE)min inSET-PT and (PA+ETE)min in SPLET [35] e lowestrank of BDE values ranges from 7685 to 7709 kcalmol isdominated by 4prime-OH radical in gas for all isoavones 1ndash4compared with those of 7-OH radical (8376ndash8384 kcalmol) and 5-OH radical (8511ndash9426 kcalmol) A similarinstance arises from enthalpies of SET-PT and SPLETpathways that either isoavones 1-2 or their glycosides 3-4also encompasses the minimum values of IP + PDE andPA+ETE at 4prime-OH Once again it can be seen that ring B ofisoavones and 4prime-OH are active centers involving in an-tioxidant activity Although electron transfer enthalpy (ETE)shows the lowest amount in all radical cases of 1ndash4 minimal

OO

OHOOH

0295

0388

0226

0433

(a)

OHO

OHOO

0202

0354

0366

0459

(b)

OHO

OOOH

03820284

0381

(c)

OO

OOOH

0295

0432 0389

(d)

OHO

OOO

0202

0353

0459

0366

(e)

OO

OHOO

sugar

0376

0407

0436

(f )OO

OOOH

0380

sugar

0286

03810283

(g)

OO

OHOO

sugar

O

0310

0224

0359

(h)

OO

OOOH

0380

sugar

O 0285

02830381

(i)

Figure 7 Spin density distribution of structural radicals 1ndash4 obtained after H-atom abstraction (a) Compound 1 7-OH radical(b) Compound 1 5-OH radical (c) Compound 1 4prime-OH radical (d) Compound 2 7-OH radical (e) Compound 2 5-OH radical(f ) Compound 3 5-OH radical (g) Compound 3 4prime-OH radical (h) Compound 4 5-OH radical (i) Compound 4 4prime-OH radical

Journal of Chemistry 9

total energies of PA+ETE and IP + PDE establish 4 timesmore potency than those of BDEis is sequential evidenceto deeply vindicate that HATmechanism gets more favor ingas Here we can make an arrangement in the followingorder of favorable HATgt SET-PTasymp SPLET and impor-tantly conclude that in the environmental gas and antiox-idant mechanisms have been becoming dependent on theprocesses of proton disruptions rather than the effects ofelectron actions

In terms of comparing among radicals 5-OH 7-OH and4prime-OH in each metabolite O-H homolytic bond dissociationenthalpy (BDE) O-H heterolytic bond dissociation enthalpy(PDE) and proton affinity (PA) are realistic evidence wouldsince have been proved that energies of 5-OH bond breakingalways overcome due to IHBs (Table 3)

Antioxidant-structural relationships can be highlightedthrough the differences in enthalpies calculations Whenspontaneously compared two isoflavone glycosides 3-4 5-OH radical enthalpy parameters BDE IP PDE PA andETE the courses of IP + PDE and PA+ETE of compound 4are less than those of 5-OH radical in compound 3 from 2 to9 kcalmol It therefore remarks that 6-OCH3 has greatlyinfluenced 5-OH and IHBs so that the 6-methoxylationwould help increase antioxidant In the same assessment forcompounds 1-2 4prime-methylation did not significantly con-tribute to the effect itself on 5-OH and 7-OH radicals but thereverse trends are observed 5-OH radical BDE in genstein(1)gt biochanin A (2) 5-OH and 7-OH radicals PDE ingenistein (1)lt biochanin A (2) As mentioned above β-D-apiofuranosyl-(1-6)-β-D-glucopyranosyl unit should not bethe suitable sites for radical scavenging but they have greatlyaffected isoflavone core Indeed 7-glycosylation (meta po-sition) in ambocin (3) has two sides On the one hand itshows a decrease in the amount of energy in 5-OH bondbreaking in terms of BDE IP IP + PDE ETE and PA+ETEwhile on the other hand it induces an increase pattern inthose in PDE and PA as compared with 7-hydroxylation ingenistein (1)

Last but not least among 1 and 3-4 4prime-OH radicalBDE leads to the introduction of an actively antioxidantarrangement tectorigenin 7-O-[β-D-apiofuranosyl-(1-6)-β-D-glucopyranoside] (4) gt ambocin (3) gt genistein (1)while no change is observed in 7-OH radical BDE values

and 5-OH radical one with the order genistein (1)lt biochanin A (2)

3 Conclusion

Naturally occurring isoflavones and their glycosides havesuccessfully been investigated by the density theory-basedmethod Actually the prospective outcome points out thatHAT pathway is preferentially closely related to the anti-oxidant action of all studied polyphenolic compounds inthe gaseous state Numerous parameters such as ionizationpotential (IP) proton affinity (PA) the sum of energies ofSET-PT andor SPLETmechanisms especially in terms ofBDE values provide supportive information to confirm theradical-scavenging process that takes place throughoutO-H breaking bond in isoflavones is current resultcorresponds to many previous studies in which structuralconformations π-electrons delocalization potential po-larizability hydroxyl groups distributed in ring B andfunctional groups are major reasons for antioxidant ac-tivities of general flavonoids Antioxidant isoflavone gly-cosides ambocin and tectorigenin 7-O-[β-D-apiofuranosyl-(1-6)-β-D-glucopyranoside] are more significant thanisoflavone genistein and biochanin A deducing from 7-glycosylation and 6-methoxylation is account providesnecessary guidelines for future research

Abbreviations

DFT Density functional theoryHOMO Highest occupied molecular orbitalLUMO Lowest unoccupied molecular orbitalIHBs Intramolecular hydrogen bondsBDE Homolytic bond dissociation enthalpyPDE Heterolytic bond dissociation enthalpyIP Ionization potentialPA Proton affinityETE Electron transfer enthalpyHAT Hydrogen atom transferSET-PT Single electron transfer-proton transferSPLET Sequential proton loss electron transferDPPH 22-Diphenyl-1-picrylhydrazyl

Table 3 Gas phase reaction enthalpies at 298 K for radicals of the studied compounds at B3LYP6-311G(d) level of theory (in kcalmol)

Compounds HAT BDE IP PDE SET-PT (IP + PDE) PA ETE SPLET (PA+ETE)1 168305-OH 9426 24166 40996 34707 6289 409967-OH 8384 23136 39966 32968 7002 399704prime-OH 7709 22449 39279 33790 5589 393792 165795-OH 9426 24419 40998 34740 6257 409977-OH 8376 23368 39947 33000 6962 399623 164765-OH 9414 24509 40985 34802 6183 409854prime-OH 7689 22784 39260 33811 5449 392604 157175-OH 8511 24372 40089 34563 5519 400824prime-OH 7685 23542 39269 33822 5429 39251

10 Journal of Chemistry

Data Availability

All data used for this project are publicly available andaccessible online e authors have pronounced the entiredata building process and empirical techniques presented inthe paper

Conflicts of Interest

e authors declare that they have no conflicts of interest

Acknowledgments

is work was supported by a grant (no VASTCTG0117-19) from Vietnam Academy of Science and Technology(VAST) 18 Hoang Quoc Viet Caugiay Hanoi Vietnam

Supplementary Materials

Figure S1 the state forms of studied structures in MeOHmedium Table S1 the collective energies depended ontorsional angles θ2 (C2-C3-C1prime-C2prime) Table S2 Mullikenatomic charges at theoretical level B3LYP6-311G(d) ofstudied compounds in gas and methanol mediums Table S3condensed Fukui indices at B3LYP6-311G(d) of studiedcompounds in gas medium (Supplementary Materials)

References

[1] E Miadokova ldquoIsoflavonoids-an overview of their biologicalactivities and potential health benefitsrdquo InterdisciplinaryToxicology vol 2 no 4 pp 211ndash218 2009

[2] A N Panche A D Diwan and S R Chandra ldquoFlavonoidsan overviewrdquo Journal of Nutritional Science vol 5 p e472016

[3] Z Dhaouadi M Nsangou N Garrab E H AnouarK Marakchi and S Lahmar ldquoDFT study of the reaction ofquercetin with and radicalsrdquo Journal of Molecular StructureTHEOCHEM vol 904 no 1-3 pp 35ndash42 2009

[4] P Dixit R Chillara V Khedgikar et al ldquoConstituents ofDalbergia sissoo Roxb leaves with osteogenic activityrdquo Bio-organic amp Medicinal Chemistry Letters vol 22 no 2pp 890ndash897 2012

[5] J N Choi K Dockyu K C Hyung M Y Kyung K Jiyoungand H L Choong ldquo2prime-Hydroxyaltion of genistein enhancedantioxidant and antiproliferative activities in MCF-7 humanbreast cancer cellsrdquo Journal of Microbiology and Bio-technology vol 19 pp 1348ndash1354 2009

[6] S Dowling F Regan and H Hughes ldquoe characterisation ofstructural and antioxidant properties of isoflavone metalchelatesrdquo Journal of Inorganic Biochemistry vol 104 no 10pp 1091ndash1098 2010

[7] J-G Cho H-J Park G-W Huh et al ldquoFlavonoids fromPueraria mirifica roots and quantitative analysis usingHPLCrdquo Food Science and Biotechnology vol 23 no 6pp 1815ndash1820 2014

[8] Y Zhang and Y Sun ldquoeoretical investigation on atmo-spheric reaction of O(3P) with CH 2 CNrdquo Journal of PhysicalOrganic Chemistry vol 32 no 4 article e3913 2018

[9] E M Kamel A M Mahmoud S A Ahmed andA M Lamsabhi ldquoA phytochemical and computational studyon flavonoids isolated from Trifolium resupinatum L and

their novel hepatoprotective activityrdquo Food amp Function vol 7no 4 pp 2094ndash2106 2016

[10] R A Mendes S K C Almeida I N Soares et al ldquoAcomputational investigation on the antioxidant potential ofmyricetin 34prime-di-O-α-L-rhamnopyranosiderdquo Journal ofMolecular Modeling vol 24 no 6 p 133 2018

[11] K S Kumar and R Kumarresan ldquoA DFT study on thestructural electronic properties and radical scavengingmechanisms of calycosin glycitein pratensein and prunetinrdquoComputational andeoretical Chemistry vol 985 pp 14ndash222012

[12] A Vaganek J Rimarcik V Lukes L Rottmannova andE Klein ldquoDFTB3LYP study of the enthalpies of Homolyticand Heterolytic O-H Bond dissociation in sterically hinderedphenolsrdquo Acta Chimica Slovenica vol 4 pp 55ndash71 2011

[13] M Leopoldini T Marino N Russo and M Toscano ldquoAn-tioxidant properties of phenolic compounds H-atom versuselectron transfer mechanismrdquo Journal of Physical ChemistryA vol 108 no 22 pp 4916ndash4922 2004

[14] R A Mendes B L S Silva R Takeara R G Freitas A Brownand G L C de Souza ldquoProbing the antioxidant potential ofphloretin and phlorizin through a computational investigationrdquoJournal of Molecular Modeling vol 24 no 4 p 101 2018

[15] E N Maciel S K C Almeida S C da Silva andG L C de Souza ldquoExamining the reaction between anti-oxidant compounds and 22-diphenyl-1-picrylhydrazyl(DPPH) through a computational investigationrdquo Journal ofMolecular Modeling vol 24 no 8 p 218 2018

[16] A Galano G Mazzone R A Diduk T MarinoJ R A Idaboy and N Russo ldquoFood antioxidants chemicalInsights at the Molecular Levelrdquo Annual Review of FoodScience and Technology vol 7 no 1 pp 335ndash352 2016

[17] V B Luzhkov ldquoMechanisms of antioxidant activity the DFTstudy of hydrogen abstraction from phenol and toluene by thehydroperoxyl radicalrdquo Chemical Physics vol 314 no 1-3pp 211ndash217 2005

[18] S A P Gomez N F Holguin A P HernandezM P Miramontes and D G Mitnik ldquoComputational mo-lecular characterization of the flavonoid rutinrdquo ChemistryCentral Journal vol 4 no 1 p 12 2010

[19] D G Mitnik ldquoComputational chemistry of natural productsa comparison of the chemical reactivity of isonaringin cal-culated with the M06 family of density functionalsrdquo Journal ofMolecular Modeling vol 20 no 7 p 2316 2014

[20] H Djeradi A Rahmouni and A Cheriti ldquoAntioxidant ac-tivity of flavonoids a QSAR modeling using Fukui indicesdescriptorsrdquo Journal of Molecular Modeling vol 20 no 10p 2476 2014

[21] K Sadasivam and R Kumaresan ldquoAntioxidant behavior ofmearnsetin and myricetin flavonoid compounds-a DFTstudyrdquo Spectrochimica Acta Part A Molecular and Bio-molecular Spectroscopy vol 79 no 1 pp 282ndash293 2011

[22] R-M Han Y-X Tian Y Liu et al ldquoComparison of flavo-noids and isoflavonoids as antioxidantsrdquo Journal of Agri-cultural and Food Chemistry vol 57 no 9 pp 3780ndash37852009

[23] S F Farag A S Ahmed K Terashima Y Takaya andM Niwa ldquoIsoflavonoid glycosides from Dalbergia sissoordquoPhytochemistry vol 57 pp 1263ndash1268 2001

[24] S T Ninh ldquoA Review on the medicinal plant Dalbergiaodorifera species phytochemistry and biological activityrdquoEvidence-Based Complementary and Alternative Medicinevol 2017 Article ID 7142370 27 pages 2017

Journal of Chemistry 11

compound 2 and 6-methoxylated compound 4 evidentlygenerate better Egap values when compared to respectivecompounds 1 and 3 in both of the phases Emphasizing onthe change of gas phase into methanol a remarkable reversecan be observed in the Egap values between 1 and 3 due tothe 7-glycosylated phenomenon Among four compounds1ndash4 we primarily assumed that tectorigenin 7-O-[β-D-apiofuranosyl-(1-6)-β-D-glucopyranoside] (4) is the bestcandidate employable for antioxidant targets not mentionthe fact that 4prime-methylation 6-methoxylation and 7-gly-cosylation facilitate the antioxidant ability

Calculation of the atomic spin density population ofvarious radicals after H-abstraction from four consideredisoflavones 1ndash4 is given in Figure 7 It should be kept inmindthat the higher the spin density delocalized in radicals theeasier the radical formation hence lower BDE values [28]As a general view the computed results reveal that strongspin distributions remain on oxygen atoms of phenolicgroups carbons C-1prime C-3prime and C-5prime of the ring B andcarbons C-6 and C-8 in ring A and also C4a In all fourcompounds 1ndash4 C-1prime C-3prime and C-5prime are centers of positivespin density C-2prime C-4prime and C-6prime bear negative one whilstatomic carbons in ring A fail to do so [11] It suggests thatphenyl unit ring B with more delocalized spin is significantlysuitable for radical formation e spin density values ofO-atommake an order as 0432ndash0433 (7-OH in compounds1-2)gt 0381ndash0382 (4prime-OH in compounds 1 3-4)gt 0310ndash0376 (5-OH in compounds 1ndash4) As of a normal rule thehigher spin density means higher BDE values Nonethelessthe number of spin in O-atom is found in the oppositedirection with predictable BDE values among 5-OH and 4prime-OH radicals which can be explained by the fact thatH-removal needs to have suitable energy to break the hy-drogen bonds between 5-OH and 4-CO [29]

23 ElectronicProperties e global hardness η has emergedas a measurement of resistance to charge transfer [29] 7-Glycosylated compound (3) accounts for the maximumchemical hardness η value of 2134 eV in the gaseous phase ithas been confirmed that this compound is much more stablethan the remainder particularly in comparison with theunstable 6-methoxylated-7-glycosylated compound 4(2086 eV in gas 2093 eV in methanol) By comparingcompounds 1 and 2 4prime-OCH3 mainly causes a decrease of ηin both phases erefore it can be concluded that meth-ylations and methoxylations in isoflavones and their gly-cosides induce a trend in transferring from ldquohigh oxidationstate and low polarizabilityrdquo to ldquolow oxidation state and highpolarizabilityrdquo

e electronegativity χ measures a trend to attract elec-trons along with the chemical potential micro which will beproportional to this parameter of a negative signal [30] Fol-lowing Sandersonrsquos principle a compound exerting the highelectronegativitymight quickly reach equalization and establishlow reactivity [31] erefore the low value of this one forantioxidant reactions is expected Compound 4 with low χvalue of 3710 eV in the gaseous state participates in antioxidantreactivity better than the range of 3758ndash3835 eV for

compounds 1ndash3 Nevertheless using solvents if solvents likemedium methanol are used the results are greatly influencedIndeed it is opposite to the tendency of genistein (1) andbiochanin A (2) whose glycosides 3-4 tend to go from a lowerelectronegativity in gas to a higher one in methanol (Table 2)

Apart from descriptors such as the electron affinity theionization potential the global hardness and the globalelectronegativity the global electrophilicity index ω ωminusand ω+ values have so far been increased when methanol istaken into account e ωminus values of all considered com-pounds 1ndash4 are 2-3-folds higher than those of ω+ in eithergas or methanol method is one is identical with theprevious literature data [11] in which isoflavones and theirsugar derivatives tend to donate electrons rather thancapturing

Within a molecule the dipole moment is an availablemethod to estimate the separation of positive and negativeelectrical charges e high magnitudes of the dipole mo-ment accompany with the high charge densities and highpolarity in bonds [21] In our current account glycosylatedcompounds 3-4 is 3-folds higher than isoflavones 1-2 in bothstates gas and methanol because of the effects of sugar unitsand solvents However focusing on the comparison between1 and 2 and 3 and 4 4prime-methylation and 6-methoxylation aresuitable for slightly reducing this property Han and hispartners pointed out that the more symmetric property instructures the lower dipole moment and its antioxidantefficiency is better than that of the asymmetric molecule ofthe same size [22] We found that the symmetric genistein(1) and its 4prime-methylation (2) with the low dipole momentvalues of 3036D and 2862D have resulted in good anti-oxidant ability in many real experiments [5 6] Polariz-ability may be justified considering the soluble nature ofmolecules in polar solvents [21] Compounds containingsugars and isoflavones 3-4 have generally shown to asso-ciate with the higher dipole moment as well as higherpolarizability (Table 2) Followed on 4prime-methylations and 6-methoxylations the polarizability is also in accordancewith chemical hardness as mentioned above

Mulliken population analysis (MPA) has resulted in netcharges of a chemical ring system which also appears to bean effective tool to assess a chemical reactivity e Mul-liken atomic charges values using the DFT method arepresented in Table S2 Generally the heteroatom oxygensin flavonoids 1ndash4 remark the significant negative chargeswhich are active sites of donating their electrons In themeantime the maximum of positive charge which is thepreferential site for the nucleophilic reaction has occurredin carbon C-4 e high number of positive (negative)charges of atoms oxygens carbon and hydrogen arisingfrom 5-OH and 4-CO is caused by internal hydrogenbonds thereby stabilizing the structure e fact is thatantioxidant activities of flavonoids further depend onnegative centers whereby hydroxyl groups in ring B arefound to act as active sites of radical reactions [20] As aconsequence considering flavonoid aglycones of studied 3-4 and compound 1 the high values of negative chargesoccur in 4prime-OH in both gas and methanol agreeing with thesmallest BDE outcome

8 Journal of Chemistry

Besides frontier molecular orbital considerations andanalysis of electronic structure Fukui parameters alsoprovide important information and quick solutions to justifythe powerful reactive site of each atom Fukui indices fromTable S3 are calculated in gaseous medium based on the-oretical HSAB principle [31] It seemed that oxygen ofcarbonyl group 4-CO of all studiedmembers 1ndash4 and carbonC-2 in compounds 2 and 4 should have opted as good sitesfor both electrophilic and radical attacks but carbon C-2 isthe only suitable site of electrophilic scope for metabolites 1and 3 4prime-OH in compound 1 and carbon C-6 bears OCH3 incompound 4 adapted for nucleophilic attractive types Mostimportantly the f o condensed Fukui values advocate otherpreferential radical sites that are found in hydroxyl groups

Numerous atoms in β-D-apiofuranosyl-(1-6)-β-D-glu-copyranosyl parts of compounds 3-4 show the signicantMulliken electronic charges 4Prime-OH of glycoside 3 is nowexpected as electrophilic tendencies but for further cor-roboration with HOMO-LUMO analysis above Fukui de-scriptors research indicates that sugar units did not showfavorability for the antioxidant reactive types resembling inthe computational results in a avone glycoside rutin orresearch on pryoanthocyanin [17 28 32]

24 Antioxidant Mechanisms In the same condition of298K and environmental gas our BDE results in genistein(1) and biochanin A (2) dier from the B3LYP6-31 +G(dp) andor B3LYP6-311++G(dp) previously cal-culated publications within usually 40 kcalmol [33 34] Inaddition our PDE PA and ETE numbers show good

accordance with B3LYP6-311++G(dp) level in the lastaccount performed by Lengyel and partners particularly thedeviation just only found to be 2 kcalmol in PA calculationbut largely dierent from the work of Zhang and co-authors[33 34]

e favorable mechanisms of antiradical activity ofisoavones might possibly be discussed via thermodynam-ically preferential BDE of HAT IP of SET-PT and PA ofSPLET actions [35] From genistein (1) in gaseous statereaction in Table 3 BDE values (7709ndash9426 kcalmol) aresignicantly lower than those of IP (16830 kcalmol) and PA(32968ndash34707 kcalmol) is behavior is also similarlyestablished from the remainders like 2ndash4 erefore HATpathway is probable for isoavones and isoavone glycosidesin gas

From a thermodynamic point of view relating to threewell-known mechanisms the active sites of antioxidantaction have also been proposed throughout theminimal sumof enthalpies including BDEmin in HAT (IP + PDE)min inSET-PT and (PA+ETE)min in SPLET [35] e lowestrank of BDE values ranges from 7685 to 7709 kcalmol isdominated by 4prime-OH radical in gas for all isoavones 1ndash4compared with those of 7-OH radical (8376ndash8384 kcalmol) and 5-OH radical (8511ndash9426 kcalmol) A similarinstance arises from enthalpies of SET-PT and SPLETpathways that either isoavones 1-2 or their glycosides 3-4also encompasses the minimum values of IP + PDE andPA+ETE at 4prime-OH Once again it can be seen that ring B ofisoavones and 4prime-OH are active centers involving in an-tioxidant activity Although electron transfer enthalpy (ETE)shows the lowest amount in all radical cases of 1ndash4 minimal

OO

OHOOH

0295

0388

0226

0433

(a)

OHO

OHOO

0202

0354

0366

0459

(b)

OHO

OOOH

03820284

0381

(c)

OO

OOOH

0295

0432 0389

(d)

OHO

OOO

0202

0353

0459

0366

(e)

OO

OHOO

sugar

0376

0407

0436

(f )OO

OOOH

0380

sugar

0286

03810283

(g)

OO

OHOO

sugar

O

0310

0224

0359

(h)

OO

OOOH

0380

sugar

O 0285

02830381

(i)

Figure 7 Spin density distribution of structural radicals 1ndash4 obtained after H-atom abstraction (a) Compound 1 7-OH radical(b) Compound 1 5-OH radical (c) Compound 1 4prime-OH radical (d) Compound 2 7-OH radical (e) Compound 2 5-OH radical(f ) Compound 3 5-OH radical (g) Compound 3 4prime-OH radical (h) Compound 4 5-OH radical (i) Compound 4 4prime-OH radical

Journal of Chemistry 9

total energies of PA+ETE and IP + PDE establish 4 timesmore potency than those of BDEis is sequential evidenceto deeply vindicate that HATmechanism gets more favor ingas Here we can make an arrangement in the followingorder of favorable HATgt SET-PTasymp SPLET and impor-tantly conclude that in the environmental gas and antiox-idant mechanisms have been becoming dependent on theprocesses of proton disruptions rather than the effects ofelectron actions

In terms of comparing among radicals 5-OH 7-OH and4prime-OH in each metabolite O-H homolytic bond dissociationenthalpy (BDE) O-H heterolytic bond dissociation enthalpy(PDE) and proton affinity (PA) are realistic evidence wouldsince have been proved that energies of 5-OH bond breakingalways overcome due to IHBs (Table 3)

Antioxidant-structural relationships can be highlightedthrough the differences in enthalpies calculations Whenspontaneously compared two isoflavone glycosides 3-4 5-OH radical enthalpy parameters BDE IP PDE PA andETE the courses of IP + PDE and PA+ETE of compound 4are less than those of 5-OH radical in compound 3 from 2 to9 kcalmol It therefore remarks that 6-OCH3 has greatlyinfluenced 5-OH and IHBs so that the 6-methoxylationwould help increase antioxidant In the same assessment forcompounds 1-2 4prime-methylation did not significantly con-tribute to the effect itself on 5-OH and 7-OH radicals but thereverse trends are observed 5-OH radical BDE in genstein(1)gt biochanin A (2) 5-OH and 7-OH radicals PDE ingenistein (1)lt biochanin A (2) As mentioned above β-D-apiofuranosyl-(1-6)-β-D-glucopyranosyl unit should not bethe suitable sites for radical scavenging but they have greatlyaffected isoflavone core Indeed 7-glycosylation (meta po-sition) in ambocin (3) has two sides On the one hand itshows a decrease in the amount of energy in 5-OH bondbreaking in terms of BDE IP IP + PDE ETE and PA+ETEwhile on the other hand it induces an increase pattern inthose in PDE and PA as compared with 7-hydroxylation ingenistein (1)

Last but not least among 1 and 3-4 4prime-OH radicalBDE leads to the introduction of an actively antioxidantarrangement tectorigenin 7-O-[β-D-apiofuranosyl-(1-6)-β-D-glucopyranoside] (4) gt ambocin (3) gt genistein (1)while no change is observed in 7-OH radical BDE values

and 5-OH radical one with the order genistein (1)lt biochanin A (2)

3 Conclusion

Naturally occurring isoflavones and their glycosides havesuccessfully been investigated by the density theory-basedmethod Actually the prospective outcome points out thatHAT pathway is preferentially closely related to the anti-oxidant action of all studied polyphenolic compounds inthe gaseous state Numerous parameters such as ionizationpotential (IP) proton affinity (PA) the sum of energies ofSET-PT andor SPLETmechanisms especially in terms ofBDE values provide supportive information to confirm theradical-scavenging process that takes place throughoutO-H breaking bond in isoflavones is current resultcorresponds to many previous studies in which structuralconformations π-electrons delocalization potential po-larizability hydroxyl groups distributed in ring B andfunctional groups are major reasons for antioxidant ac-tivities of general flavonoids Antioxidant isoflavone gly-cosides ambocin and tectorigenin 7-O-[β-D-apiofuranosyl-(1-6)-β-D-glucopyranoside] are more significant thanisoflavone genistein and biochanin A deducing from 7-glycosylation and 6-methoxylation is account providesnecessary guidelines for future research

Abbreviations

DFT Density functional theoryHOMO Highest occupied molecular orbitalLUMO Lowest unoccupied molecular orbitalIHBs Intramolecular hydrogen bondsBDE Homolytic bond dissociation enthalpyPDE Heterolytic bond dissociation enthalpyIP Ionization potentialPA Proton affinityETE Electron transfer enthalpyHAT Hydrogen atom transferSET-PT Single electron transfer-proton transferSPLET Sequential proton loss electron transferDPPH 22-Diphenyl-1-picrylhydrazyl

Table 3 Gas phase reaction enthalpies at 298 K for radicals of the studied compounds at B3LYP6-311G(d) level of theory (in kcalmol)

Compounds HAT BDE IP PDE SET-PT (IP + PDE) PA ETE SPLET (PA+ETE)1 168305-OH 9426 24166 40996 34707 6289 409967-OH 8384 23136 39966 32968 7002 399704prime-OH 7709 22449 39279 33790 5589 393792 165795-OH 9426 24419 40998 34740 6257 409977-OH 8376 23368 39947 33000 6962 399623 164765-OH 9414 24509 40985 34802 6183 409854prime-OH 7689 22784 39260 33811 5449 392604 157175-OH 8511 24372 40089 34563 5519 400824prime-OH 7685 23542 39269 33822 5429 39251

10 Journal of Chemistry

Data Availability

All data used for this project are publicly available andaccessible online e authors have pronounced the entiredata building process and empirical techniques presented inthe paper

Conflicts of Interest

e authors declare that they have no conflicts of interest

Acknowledgments

is work was supported by a grant (no VASTCTG0117-19) from Vietnam Academy of Science and Technology(VAST) 18 Hoang Quoc Viet Caugiay Hanoi Vietnam

Supplementary Materials

Figure S1 the state forms of studied structures in MeOHmedium Table S1 the collective energies depended ontorsional angles θ2 (C2-C3-C1prime-C2prime) Table S2 Mullikenatomic charges at theoretical level B3LYP6-311G(d) ofstudied compounds in gas and methanol mediums Table S3condensed Fukui indices at B3LYP6-311G(d) of studiedcompounds in gas medium (Supplementary Materials)

References

[1] E Miadokova ldquoIsoflavonoids-an overview of their biologicalactivities and potential health benefitsrdquo InterdisciplinaryToxicology vol 2 no 4 pp 211ndash218 2009

[2] A N Panche A D Diwan and S R Chandra ldquoFlavonoidsan overviewrdquo Journal of Nutritional Science vol 5 p e472016

[3] Z Dhaouadi M Nsangou N Garrab E H AnouarK Marakchi and S Lahmar ldquoDFT study of the reaction ofquercetin with and radicalsrdquo Journal of Molecular StructureTHEOCHEM vol 904 no 1-3 pp 35ndash42 2009

[4] P Dixit R Chillara V Khedgikar et al ldquoConstituents ofDalbergia sissoo Roxb leaves with osteogenic activityrdquo Bio-organic amp Medicinal Chemistry Letters vol 22 no 2pp 890ndash897 2012

[5] J N Choi K Dockyu K C Hyung M Y Kyung K Jiyoungand H L Choong ldquo2prime-Hydroxyaltion of genistein enhancedantioxidant and antiproliferative activities in MCF-7 humanbreast cancer cellsrdquo Journal of Microbiology and Bio-technology vol 19 pp 1348ndash1354 2009

[6] S Dowling F Regan and H Hughes ldquoe characterisation ofstructural and antioxidant properties of isoflavone metalchelatesrdquo Journal of Inorganic Biochemistry vol 104 no 10pp 1091ndash1098 2010

[7] J-G Cho H-J Park G-W Huh et al ldquoFlavonoids fromPueraria mirifica roots and quantitative analysis usingHPLCrdquo Food Science and Biotechnology vol 23 no 6pp 1815ndash1820 2014

[8] Y Zhang and Y Sun ldquoeoretical investigation on atmo-spheric reaction of O(3P) with CH 2 CNrdquo Journal of PhysicalOrganic Chemistry vol 32 no 4 article e3913 2018

[9] E M Kamel A M Mahmoud S A Ahmed andA M Lamsabhi ldquoA phytochemical and computational studyon flavonoids isolated from Trifolium resupinatum L and

their novel hepatoprotective activityrdquo Food amp Function vol 7no 4 pp 2094ndash2106 2016

[10] R A Mendes S K C Almeida I N Soares et al ldquoAcomputational investigation on the antioxidant potential ofmyricetin 34prime-di-O-α-L-rhamnopyranosiderdquo Journal ofMolecular Modeling vol 24 no 6 p 133 2018

[11] K S Kumar and R Kumarresan ldquoA DFT study on thestructural electronic properties and radical scavengingmechanisms of calycosin glycitein pratensein and prunetinrdquoComputational andeoretical Chemistry vol 985 pp 14ndash222012

[12] A Vaganek J Rimarcik V Lukes L Rottmannova andE Klein ldquoDFTB3LYP study of the enthalpies of Homolyticand Heterolytic O-H Bond dissociation in sterically hinderedphenolsrdquo Acta Chimica Slovenica vol 4 pp 55ndash71 2011

[13] M Leopoldini T Marino N Russo and M Toscano ldquoAn-tioxidant properties of phenolic compounds H-atom versuselectron transfer mechanismrdquo Journal of Physical ChemistryA vol 108 no 22 pp 4916ndash4922 2004

[14] R A Mendes B L S Silva R Takeara R G Freitas A Brownand G L C de Souza ldquoProbing the antioxidant potential ofphloretin and phlorizin through a computational investigationrdquoJournal of Molecular Modeling vol 24 no 4 p 101 2018

[15] E N Maciel S K C Almeida S C da Silva andG L C de Souza ldquoExamining the reaction between anti-oxidant compounds and 22-diphenyl-1-picrylhydrazyl(DPPH) through a computational investigationrdquo Journal ofMolecular Modeling vol 24 no 8 p 218 2018

[16] A Galano G Mazzone R A Diduk T MarinoJ R A Idaboy and N Russo ldquoFood antioxidants chemicalInsights at the Molecular Levelrdquo Annual Review of FoodScience and Technology vol 7 no 1 pp 335ndash352 2016

[17] V B Luzhkov ldquoMechanisms of antioxidant activity the DFTstudy of hydrogen abstraction from phenol and toluene by thehydroperoxyl radicalrdquo Chemical Physics vol 314 no 1-3pp 211ndash217 2005

[18] S A P Gomez N F Holguin A P HernandezM P Miramontes and D G Mitnik ldquoComputational mo-lecular characterization of the flavonoid rutinrdquo ChemistryCentral Journal vol 4 no 1 p 12 2010

[19] D G Mitnik ldquoComputational chemistry of natural productsa comparison of the chemical reactivity of isonaringin cal-culated with the M06 family of density functionalsrdquo Journal ofMolecular Modeling vol 20 no 7 p 2316 2014

[20] H Djeradi A Rahmouni and A Cheriti ldquoAntioxidant ac-tivity of flavonoids a QSAR modeling using Fukui indicesdescriptorsrdquo Journal of Molecular Modeling vol 20 no 10p 2476 2014

[21] K Sadasivam and R Kumaresan ldquoAntioxidant behavior ofmearnsetin and myricetin flavonoid compounds-a DFTstudyrdquo Spectrochimica Acta Part A Molecular and Bio-molecular Spectroscopy vol 79 no 1 pp 282ndash293 2011

[22] R-M Han Y-X Tian Y Liu et al ldquoComparison of flavo-noids and isoflavonoids as antioxidantsrdquo Journal of Agri-cultural and Food Chemistry vol 57 no 9 pp 3780ndash37852009

[23] S F Farag A S Ahmed K Terashima Y Takaya andM Niwa ldquoIsoflavonoid glycosides from Dalbergia sissoordquoPhytochemistry vol 57 pp 1263ndash1268 2001

[24] S T Ninh ldquoA Review on the medicinal plant Dalbergiaodorifera species phytochemistry and biological activityrdquoEvidence-Based Complementary and Alternative Medicinevol 2017 Article ID 7142370 27 pages 2017

Journal of Chemistry 11

Besides frontier molecular orbital considerations andanalysis of electronic structure Fukui parameters alsoprovide important information and quick solutions to justifythe powerful reactive site of each atom Fukui indices fromTable S3 are calculated in gaseous medium based on the-oretical HSAB principle [31] It seemed that oxygen ofcarbonyl group 4-CO of all studiedmembers 1ndash4 and carbonC-2 in compounds 2 and 4 should have opted as good sitesfor both electrophilic and radical attacks but carbon C-2 isthe only suitable site of electrophilic scope for metabolites 1and 3 4prime-OH in compound 1 and carbon C-6 bears OCH3 incompound 4 adapted for nucleophilic attractive types Mostimportantly the f o condensed Fukui values advocate otherpreferential radical sites that are found in hydroxyl groups

Numerous atoms in β-D-apiofuranosyl-(1-6)-β-D-glu-copyranosyl parts of compounds 3-4 show the signicantMulliken electronic charges 4Prime-OH of glycoside 3 is nowexpected as electrophilic tendencies but for further cor-roboration with HOMO-LUMO analysis above Fukui de-scriptors research indicates that sugar units did not showfavorability for the antioxidant reactive types resembling inthe computational results in a avone glycoside rutin orresearch on pryoanthocyanin [17 28 32]

24 Antioxidant Mechanisms In the same condition of298K and environmental gas our BDE results in genistein(1) and biochanin A (2) dier from the B3LYP6-31 +G(dp) andor B3LYP6-311++G(dp) previously cal-culated publications within usually 40 kcalmol [33 34] Inaddition our PDE PA and ETE numbers show good

accordance with B3LYP6-311++G(dp) level in the lastaccount performed by Lengyel and partners particularly thedeviation just only found to be 2 kcalmol in PA calculationbut largely dierent from the work of Zhang and co-authors[33 34]

e favorable mechanisms of antiradical activity ofisoavones might possibly be discussed via thermodynam-ically preferential BDE of HAT IP of SET-PT and PA ofSPLET actions [35] From genistein (1) in gaseous statereaction in Table 3 BDE values (7709ndash9426 kcalmol) aresignicantly lower than those of IP (16830 kcalmol) and PA(32968ndash34707 kcalmol) is behavior is also similarlyestablished from the remainders like 2ndash4 erefore HATpathway is probable for isoavones and isoavone glycosidesin gas

From a thermodynamic point of view relating to threewell-known mechanisms the active sites of antioxidantaction have also been proposed throughout theminimal sumof enthalpies including BDEmin in HAT (IP + PDE)min inSET-PT and (PA+ETE)min in SPLET [35] e lowestrank of BDE values ranges from 7685 to 7709 kcalmol isdominated by 4prime-OH radical in gas for all isoavones 1ndash4compared with those of 7-OH radical (8376ndash8384 kcalmol) and 5-OH radical (8511ndash9426 kcalmol) A similarinstance arises from enthalpies of SET-PT and SPLETpathways that either isoavones 1-2 or their glycosides 3-4also encompasses the minimum values of IP + PDE andPA+ETE at 4prime-OH Once again it can be seen that ring B ofisoavones and 4prime-OH are active centers involving in an-tioxidant activity Although electron transfer enthalpy (ETE)shows the lowest amount in all radical cases of 1ndash4 minimal

OO

OHOOH

0295

0388

0226

0433

(a)

OHO

OHOO

0202

0354

0366

0459

(b)

OHO

OOOH

03820284

0381

(c)

OO

OOOH

0295

0432 0389

(d)

OHO

OOO

0202

0353

0459

0366

(e)

OO

OHOO

sugar

0376

0407

0436

(f )OO

OOOH

0380

sugar

0286

03810283

(g)

OO

OHOO

sugar

O

0310

0224

0359

(h)

OO

OOOH

0380

sugar

O 0285

02830381

(i)

Figure 7 Spin density distribution of structural radicals 1ndash4 obtained after H-atom abstraction (a) Compound 1 7-OH radical(b) Compound 1 5-OH radical (c) Compound 1 4prime-OH radical (d) Compound 2 7-OH radical (e) Compound 2 5-OH radical(f ) Compound 3 5-OH radical (g) Compound 3 4prime-OH radical (h) Compound 4 5-OH radical (i) Compound 4 4prime-OH radical

Journal of Chemistry 9

total energies of PA+ETE and IP + PDE establish 4 timesmore potency than those of BDEis is sequential evidenceto deeply vindicate that HATmechanism gets more favor ingas Here we can make an arrangement in the followingorder of favorable HATgt SET-PTasymp SPLET and impor-tantly conclude that in the environmental gas and antiox-idant mechanisms have been becoming dependent on theprocesses of proton disruptions rather than the effects ofelectron actions

In terms of comparing among radicals 5-OH 7-OH and4prime-OH in each metabolite O-H homolytic bond dissociationenthalpy (BDE) O-H heterolytic bond dissociation enthalpy(PDE) and proton affinity (PA) are realistic evidence wouldsince have been proved that energies of 5-OH bond breakingalways overcome due to IHBs (Table 3)

Antioxidant-structural relationships can be highlightedthrough the differences in enthalpies calculations Whenspontaneously compared two isoflavone glycosides 3-4 5-OH radical enthalpy parameters BDE IP PDE PA andETE the courses of IP + PDE and PA+ETE of compound 4are less than those of 5-OH radical in compound 3 from 2 to9 kcalmol It therefore remarks that 6-OCH3 has greatlyinfluenced 5-OH and IHBs so that the 6-methoxylationwould help increase antioxidant In the same assessment forcompounds 1-2 4prime-methylation did not significantly con-tribute to the effect itself on 5-OH and 7-OH radicals but thereverse trends are observed 5-OH radical BDE in genstein(1)gt biochanin A (2) 5-OH and 7-OH radicals PDE ingenistein (1)lt biochanin A (2) As mentioned above β-D-apiofuranosyl-(1-6)-β-D-glucopyranosyl unit should not bethe suitable sites for radical scavenging but they have greatlyaffected isoflavone core Indeed 7-glycosylation (meta po-sition) in ambocin (3) has two sides On the one hand itshows a decrease in the amount of energy in 5-OH bondbreaking in terms of BDE IP IP + PDE ETE and PA+ETEwhile on the other hand it induces an increase pattern inthose in PDE and PA as compared with 7-hydroxylation ingenistein (1)

Last but not least among 1 and 3-4 4prime-OH radicalBDE leads to the introduction of an actively antioxidantarrangement tectorigenin 7-O-[β-D-apiofuranosyl-(1-6)-β-D-glucopyranoside] (4) gt ambocin (3) gt genistein (1)while no change is observed in 7-OH radical BDE values

and 5-OH radical one with the order genistein (1)lt biochanin A (2)

3 Conclusion

Naturally occurring isoflavones and their glycosides havesuccessfully been investigated by the density theory-basedmethod Actually the prospective outcome points out thatHAT pathway is preferentially closely related to the anti-oxidant action of all studied polyphenolic compounds inthe gaseous state Numerous parameters such as ionizationpotential (IP) proton affinity (PA) the sum of energies ofSET-PT andor SPLETmechanisms especially in terms ofBDE values provide supportive information to confirm theradical-scavenging process that takes place throughoutO-H breaking bond in isoflavones is current resultcorresponds to many previous studies in which structuralconformations π-electrons delocalization potential po-larizability hydroxyl groups distributed in ring B andfunctional groups are major reasons for antioxidant ac-tivities of general flavonoids Antioxidant isoflavone gly-cosides ambocin and tectorigenin 7-O-[β-D-apiofuranosyl-(1-6)-β-D-glucopyranoside] are more significant thanisoflavone genistein and biochanin A deducing from 7-glycosylation and 6-methoxylation is account providesnecessary guidelines for future research

Abbreviations

DFT Density functional theoryHOMO Highest occupied molecular orbitalLUMO Lowest unoccupied molecular orbitalIHBs Intramolecular hydrogen bondsBDE Homolytic bond dissociation enthalpyPDE Heterolytic bond dissociation enthalpyIP Ionization potentialPA Proton affinityETE Electron transfer enthalpyHAT Hydrogen atom transferSET-PT Single electron transfer-proton transferSPLET Sequential proton loss electron transferDPPH 22-Diphenyl-1-picrylhydrazyl

Table 3 Gas phase reaction enthalpies at 298 K for radicals of the studied compounds at B3LYP6-311G(d) level of theory (in kcalmol)

Compounds HAT BDE IP PDE SET-PT (IP + PDE) PA ETE SPLET (PA+ETE)1 168305-OH 9426 24166 40996 34707 6289 409967-OH 8384 23136 39966 32968 7002 399704prime-OH 7709 22449 39279 33790 5589 393792 165795-OH 9426 24419 40998 34740 6257 409977-OH 8376 23368 39947 33000 6962 399623 164765-OH 9414 24509 40985 34802 6183 409854prime-OH 7689 22784 39260 33811 5449 392604 157175-OH 8511 24372 40089 34563 5519 400824prime-OH 7685 23542 39269 33822 5429 39251

10 Journal of Chemistry

Data Availability

All data used for this project are publicly available andaccessible online e authors have pronounced the entiredata building process and empirical techniques presented inthe paper

Conflicts of Interest

e authors declare that they have no conflicts of interest

Acknowledgments

is work was supported by a grant (no VASTCTG0117-19) from Vietnam Academy of Science and Technology(VAST) 18 Hoang Quoc Viet Caugiay Hanoi Vietnam

Supplementary Materials

Figure S1 the state forms of studied structures in MeOHmedium Table S1 the collective energies depended ontorsional angles θ2 (C2-C3-C1prime-C2prime) Table S2 Mullikenatomic charges at theoretical level B3LYP6-311G(d) ofstudied compounds in gas and methanol mediums Table S3condensed Fukui indices at B3LYP6-311G(d) of studiedcompounds in gas medium (Supplementary Materials)

References

[1] E Miadokova ldquoIsoflavonoids-an overview of their biologicalactivities and potential health benefitsrdquo InterdisciplinaryToxicology vol 2 no 4 pp 211ndash218 2009

[2] A N Panche A D Diwan and S R Chandra ldquoFlavonoidsan overviewrdquo Journal of Nutritional Science vol 5 p e472016

[3] Z Dhaouadi M Nsangou N Garrab E H AnouarK Marakchi and S Lahmar ldquoDFT study of the reaction ofquercetin with and radicalsrdquo Journal of Molecular StructureTHEOCHEM vol 904 no 1-3 pp 35ndash42 2009

[4] P Dixit R Chillara V Khedgikar et al ldquoConstituents ofDalbergia sissoo Roxb leaves with osteogenic activityrdquo Bio-organic amp Medicinal Chemistry Letters vol 22 no 2pp 890ndash897 2012

[5] J N Choi K Dockyu K C Hyung M Y Kyung K Jiyoungand H L Choong ldquo2prime-Hydroxyaltion of genistein enhancedantioxidant and antiproliferative activities in MCF-7 humanbreast cancer cellsrdquo Journal of Microbiology and Bio-technology vol 19 pp 1348ndash1354 2009

[6] S Dowling F Regan and H Hughes ldquoe characterisation ofstructural and antioxidant properties of isoflavone metalchelatesrdquo Journal of Inorganic Biochemistry vol 104 no 10pp 1091ndash1098 2010

[7] J-G Cho H-J Park G-W Huh et al ldquoFlavonoids fromPueraria mirifica roots and quantitative analysis usingHPLCrdquo Food Science and Biotechnology vol 23 no 6pp 1815ndash1820 2014

[8] Y Zhang and Y Sun ldquoeoretical investigation on atmo-spheric reaction of O(3P) with CH 2 CNrdquo Journal of PhysicalOrganic Chemistry vol 32 no 4 article e3913 2018

[9] E M Kamel A M Mahmoud S A Ahmed andA M Lamsabhi ldquoA phytochemical and computational studyon flavonoids isolated from Trifolium resupinatum L and

their novel hepatoprotective activityrdquo Food amp Function vol 7no 4 pp 2094ndash2106 2016

[10] R A Mendes S K C Almeida I N Soares et al ldquoAcomputational investigation on the antioxidant potential ofmyricetin 34prime-di-O-α-L-rhamnopyranosiderdquo Journal ofMolecular Modeling vol 24 no 6 p 133 2018

[11] K S Kumar and R Kumarresan ldquoA DFT study on thestructural electronic properties and radical scavengingmechanisms of calycosin glycitein pratensein and prunetinrdquoComputational andeoretical Chemistry vol 985 pp 14ndash222012

[12] A Vaganek J Rimarcik V Lukes L Rottmannova andE Klein ldquoDFTB3LYP study of the enthalpies of Homolyticand Heterolytic O-H Bond dissociation in sterically hinderedphenolsrdquo Acta Chimica Slovenica vol 4 pp 55ndash71 2011

[13] M Leopoldini T Marino N Russo and M Toscano ldquoAn-tioxidant properties of phenolic compounds H-atom versuselectron transfer mechanismrdquo Journal of Physical ChemistryA vol 108 no 22 pp 4916ndash4922 2004

[14] R A Mendes B L S Silva R Takeara R G Freitas A Brownand G L C de Souza ldquoProbing the antioxidant potential ofphloretin and phlorizin through a computational investigationrdquoJournal of Molecular Modeling vol 24 no 4 p 101 2018

[15] E N Maciel S K C Almeida S C da Silva andG L C de Souza ldquoExamining the reaction between anti-oxidant compounds and 22-diphenyl-1-picrylhydrazyl(DPPH) through a computational investigationrdquo Journal ofMolecular Modeling vol 24 no 8 p 218 2018

[16] A Galano G Mazzone R A Diduk T MarinoJ R A Idaboy and N Russo ldquoFood antioxidants chemicalInsights at the Molecular Levelrdquo Annual Review of FoodScience and Technology vol 7 no 1 pp 335ndash352 2016

[17] V B Luzhkov ldquoMechanisms of antioxidant activity the DFTstudy of hydrogen abstraction from phenol and toluene by thehydroperoxyl radicalrdquo Chemical Physics vol 314 no 1-3pp 211ndash217 2005

[18] S A P Gomez N F Holguin A P HernandezM P Miramontes and D G Mitnik ldquoComputational mo-lecular characterization of the flavonoid rutinrdquo ChemistryCentral Journal vol 4 no 1 p 12 2010

[19] D G Mitnik ldquoComputational chemistry of natural productsa comparison of the chemical reactivity of isonaringin cal-culated with the M06 family of density functionalsrdquo Journal ofMolecular Modeling vol 20 no 7 p 2316 2014

[20] H Djeradi A Rahmouni and A Cheriti ldquoAntioxidant ac-tivity of flavonoids a QSAR modeling using Fukui indicesdescriptorsrdquo Journal of Molecular Modeling vol 20 no 10p 2476 2014

[21] K Sadasivam and R Kumaresan ldquoAntioxidant behavior ofmearnsetin and myricetin flavonoid compounds-a DFTstudyrdquo Spectrochimica Acta Part A Molecular and Bio-molecular Spectroscopy vol 79 no 1 pp 282ndash293 2011

[22] R-M Han Y-X Tian Y Liu et al ldquoComparison of flavo-noids and isoflavonoids as antioxidantsrdquo Journal of Agri-cultural and Food Chemistry vol 57 no 9 pp 3780ndash37852009

[23] S F Farag A S Ahmed K Terashima Y Takaya andM Niwa ldquoIsoflavonoid glycosides from Dalbergia sissoordquoPhytochemistry vol 57 pp 1263ndash1268 2001

[24] S T Ninh ldquoA Review on the medicinal plant Dalbergiaodorifera species phytochemistry and biological activityrdquoEvidence-Based Complementary and Alternative Medicinevol 2017 Article ID 7142370 27 pages 2017

Journal of Chemistry 11

total energies of PA+ETE and IP + PDE establish 4 timesmore potency than those of BDEis is sequential evidenceto deeply vindicate that HATmechanism gets more favor ingas Here we can make an arrangement in the followingorder of favorable HATgt SET-PTasymp SPLET and impor-tantly conclude that in the environmental gas and antiox-idant mechanisms have been becoming dependent on theprocesses of proton disruptions rather than the effects ofelectron actions

In terms of comparing among radicals 5-OH 7-OH and4prime-OH in each metabolite O-H homolytic bond dissociationenthalpy (BDE) O-H heterolytic bond dissociation enthalpy(PDE) and proton affinity (PA) are realistic evidence wouldsince have been proved that energies of 5-OH bond breakingalways overcome due to IHBs (Table 3)

Antioxidant-structural relationships can be highlightedthrough the differences in enthalpies calculations Whenspontaneously compared two isoflavone glycosides 3-4 5-OH radical enthalpy parameters BDE IP PDE PA andETE the courses of IP + PDE and PA+ETE of compound 4are less than those of 5-OH radical in compound 3 from 2 to9 kcalmol It therefore remarks that 6-OCH3 has greatlyinfluenced 5-OH and IHBs so that the 6-methoxylationwould help increase antioxidant In the same assessment forcompounds 1-2 4prime-methylation did not significantly con-tribute to the effect itself on 5-OH and 7-OH radicals but thereverse trends are observed 5-OH radical BDE in genstein(1)gt biochanin A (2) 5-OH and 7-OH radicals PDE ingenistein (1)lt biochanin A (2) As mentioned above β-D-apiofuranosyl-(1-6)-β-D-glucopyranosyl unit should not bethe suitable sites for radical scavenging but they have greatlyaffected isoflavone core Indeed 7-glycosylation (meta po-sition) in ambocin (3) has two sides On the one hand itshows a decrease in the amount of energy in 5-OH bondbreaking in terms of BDE IP IP + PDE ETE and PA+ETEwhile on the other hand it induces an increase pattern inthose in PDE and PA as compared with 7-hydroxylation ingenistein (1)

Last but not least among 1 and 3-4 4prime-OH radicalBDE leads to the introduction of an actively antioxidantarrangement tectorigenin 7-O-[β-D-apiofuranosyl-(1-6)-β-D-glucopyranoside] (4) gt ambocin (3) gt genistein (1)while no change is observed in 7-OH radical BDE values

and 5-OH radical one with the order genistein (1)lt biochanin A (2)

3 Conclusion

Naturally occurring isoflavones and their glycosides havesuccessfully been investigated by the density theory-basedmethod Actually the prospective outcome points out thatHAT pathway is preferentially closely related to the anti-oxidant action of all studied polyphenolic compounds inthe gaseous state Numerous parameters such as ionizationpotential (IP) proton affinity (PA) the sum of energies ofSET-PT andor SPLETmechanisms especially in terms ofBDE values provide supportive information to confirm theradical-scavenging process that takes place throughoutO-H breaking bond in isoflavones is current resultcorresponds to many previous studies in which structuralconformations π-electrons delocalization potential po-larizability hydroxyl groups distributed in ring B andfunctional groups are major reasons for antioxidant ac-tivities of general flavonoids Antioxidant isoflavone gly-cosides ambocin and tectorigenin 7-O-[β-D-apiofuranosyl-(1-6)-β-D-glucopyranoside] are more significant thanisoflavone genistein and biochanin A deducing from 7-glycosylation and 6-methoxylation is account providesnecessary guidelines for future research

Abbreviations

DFT Density functional theoryHOMO Highest occupied molecular orbitalLUMO Lowest unoccupied molecular orbitalIHBs Intramolecular hydrogen bondsBDE Homolytic bond dissociation enthalpyPDE Heterolytic bond dissociation enthalpyIP Ionization potentialPA Proton affinityETE Electron transfer enthalpyHAT Hydrogen atom transferSET-PT Single electron transfer-proton transferSPLET Sequential proton loss electron transferDPPH 22-Diphenyl-1-picrylhydrazyl

Table 3 Gas phase reaction enthalpies at 298 K for radicals of the studied compounds at B3LYP6-311G(d) level of theory (in kcalmol)

Compounds HAT BDE IP PDE SET-PT (IP + PDE) PA ETE SPLET (PA+ETE)1 168305-OH 9426 24166 40996 34707 6289 409967-OH 8384 23136 39966 32968 7002 399704prime-OH 7709 22449 39279 33790 5589 393792 165795-OH 9426 24419 40998 34740 6257 409977-OH 8376 23368 39947 33000 6962 399623 164765-OH 9414 24509 40985 34802 6183 409854prime-OH 7689 22784 39260 33811 5449 392604 157175-OH 8511 24372 40089 34563 5519 400824prime-OH 7685 23542 39269 33822 5429 39251

10 Journal of Chemistry

Data Availability

All data used for this project are publicly available andaccessible online e authors have pronounced the entiredata building process and empirical techniques presented inthe paper

Conflicts of Interest

e authors declare that they have no conflicts of interest

Acknowledgments

is work was supported by a grant (no VASTCTG0117-19) from Vietnam Academy of Science and Technology(VAST) 18 Hoang Quoc Viet Caugiay Hanoi Vietnam

Supplementary Materials

Figure S1 the state forms of studied structures in MeOHmedium Table S1 the collective energies depended ontorsional angles θ2 (C2-C3-C1prime-C2prime) Table S2 Mullikenatomic charges at theoretical level B3LYP6-311G(d) ofstudied compounds in gas and methanol mediums Table S3condensed Fukui indices at B3LYP6-311G(d) of studiedcompounds in gas medium (Supplementary Materials)

References

[1] E Miadokova ldquoIsoflavonoids-an overview of their biologicalactivities and potential health benefitsrdquo InterdisciplinaryToxicology vol 2 no 4 pp 211ndash218 2009

[2] A N Panche A D Diwan and S R Chandra ldquoFlavonoidsan overviewrdquo Journal of Nutritional Science vol 5 p e472016

[3] Z Dhaouadi M Nsangou N Garrab E H AnouarK Marakchi and S Lahmar ldquoDFT study of the reaction ofquercetin with and radicalsrdquo Journal of Molecular StructureTHEOCHEM vol 904 no 1-3 pp 35ndash42 2009

[4] P Dixit R Chillara V Khedgikar et al ldquoConstituents ofDalbergia sissoo Roxb leaves with osteogenic activityrdquo Bio-organic amp Medicinal Chemistry Letters vol 22 no 2pp 890ndash897 2012

[5] J N Choi K Dockyu K C Hyung M Y Kyung K Jiyoungand H L Choong ldquo2prime-Hydroxyaltion of genistein enhancedantioxidant and antiproliferative activities in MCF-7 humanbreast cancer cellsrdquo Journal of Microbiology and Bio-technology vol 19 pp 1348ndash1354 2009

[6] S Dowling F Regan and H Hughes ldquoe characterisation ofstructural and antioxidant properties of isoflavone metalchelatesrdquo Journal of Inorganic Biochemistry vol 104 no 10pp 1091ndash1098 2010

[7] J-G Cho H-J Park G-W Huh et al ldquoFlavonoids fromPueraria mirifica roots and quantitative analysis usingHPLCrdquo Food Science and Biotechnology vol 23 no 6pp 1815ndash1820 2014

[8] Y Zhang and Y Sun ldquoeoretical investigation on atmo-spheric reaction of O(3P) with CH 2 CNrdquo Journal of PhysicalOrganic Chemistry vol 32 no 4 article e3913 2018

[9] E M Kamel A M Mahmoud S A Ahmed andA M Lamsabhi ldquoA phytochemical and computational studyon flavonoids isolated from Trifolium resupinatum L and

their novel hepatoprotective activityrdquo Food amp Function vol 7no 4 pp 2094ndash2106 2016

[10] R A Mendes S K C Almeida I N Soares et al ldquoAcomputational investigation on the antioxidant potential ofmyricetin 34prime-di-O-α-L-rhamnopyranosiderdquo Journal ofMolecular Modeling vol 24 no 6 p 133 2018

[11] K S Kumar and R Kumarresan ldquoA DFT study on thestructural electronic properties and radical scavengingmechanisms of calycosin glycitein pratensein and prunetinrdquoComputational andeoretical Chemistry vol 985 pp 14ndash222012

[12] A Vaganek J Rimarcik V Lukes L Rottmannova andE Klein ldquoDFTB3LYP study of the enthalpies of Homolyticand Heterolytic O-H Bond dissociation in sterically hinderedphenolsrdquo Acta Chimica Slovenica vol 4 pp 55ndash71 2011

[13] M Leopoldini T Marino N Russo and M Toscano ldquoAn-tioxidant properties of phenolic compounds H-atom versuselectron transfer mechanismrdquo Journal of Physical ChemistryA vol 108 no 22 pp 4916ndash4922 2004

[14] R A Mendes B L S Silva R Takeara R G Freitas A Brownand G L C de Souza ldquoProbing the antioxidant potential ofphloretin and phlorizin through a computational investigationrdquoJournal of Molecular Modeling vol 24 no 4 p 101 2018

[15] E N Maciel S K C Almeida S C da Silva andG L C de Souza ldquoExamining the reaction between anti-oxidant compounds and 22-diphenyl-1-picrylhydrazyl(DPPH) through a computational investigationrdquo Journal ofMolecular Modeling vol 24 no 8 p 218 2018

[16] A Galano G Mazzone R A Diduk T MarinoJ R A Idaboy and N Russo ldquoFood antioxidants chemicalInsights at the Molecular Levelrdquo Annual Review of FoodScience and Technology vol 7 no 1 pp 335ndash352 2016

[17] V B Luzhkov ldquoMechanisms of antioxidant activity the DFTstudy of hydrogen abstraction from phenol and toluene by thehydroperoxyl radicalrdquo Chemical Physics vol 314 no 1-3pp 211ndash217 2005

[18] S A P Gomez N F Holguin A P HernandezM P Miramontes and D G Mitnik ldquoComputational mo-lecular characterization of the flavonoid rutinrdquo ChemistryCentral Journal vol 4 no 1 p 12 2010

[19] D G Mitnik ldquoComputational chemistry of natural productsa comparison of the chemical reactivity of isonaringin cal-culated with the M06 family of density functionalsrdquo Journal ofMolecular Modeling vol 20 no 7 p 2316 2014

[20] H Djeradi A Rahmouni and A Cheriti ldquoAntioxidant ac-tivity of flavonoids a QSAR modeling using Fukui indicesdescriptorsrdquo Journal of Molecular Modeling vol 20 no 10p 2476 2014

[21] K Sadasivam and R Kumaresan ldquoAntioxidant behavior ofmearnsetin and myricetin flavonoid compounds-a DFTstudyrdquo Spectrochimica Acta Part A Molecular and Bio-molecular Spectroscopy vol 79 no 1 pp 282ndash293 2011

[22] R-M Han Y-X Tian Y Liu et al ldquoComparison of flavo-noids and isoflavonoids as antioxidantsrdquo Journal of Agri-cultural and Food Chemistry vol 57 no 9 pp 3780ndash37852009

[23] S F Farag A S Ahmed K Terashima Y Takaya andM Niwa ldquoIsoflavonoid glycosides from Dalbergia sissoordquoPhytochemistry vol 57 pp 1263ndash1268 2001

[24] S T Ninh ldquoA Review on the medicinal plant Dalbergiaodorifera species phytochemistry and biological activityrdquoEvidence-Based Complementary and Alternative Medicinevol 2017 Article ID 7142370 27 pages 2017

Journal of Chemistry 11

Data Availability

All data used for this project are publicly available andaccessible online e authors have pronounced the entiredata building process and empirical techniques presented inthe paper

Conflicts of Interest

e authors declare that they have no conflicts of interest

Acknowledgments

is work was supported by a grant (no VASTCTG0117-19) from Vietnam Academy of Science and Technology(VAST) 18 Hoang Quoc Viet Caugiay Hanoi Vietnam

Supplementary Materials

Figure S1 the state forms of studied structures in MeOHmedium Table S1 the collective energies depended ontorsional angles θ2 (C2-C3-C1prime-C2prime) Table S2 Mullikenatomic charges at theoretical level B3LYP6-311G(d) ofstudied compounds in gas and methanol mediums Table S3condensed Fukui indices at B3LYP6-311G(d) of studiedcompounds in gas medium (Supplementary Materials)

References

[1] E Miadokova ldquoIsoflavonoids-an overview of their biologicalactivities and potential health benefitsrdquo InterdisciplinaryToxicology vol 2 no 4 pp 211ndash218 2009

[2] A N Panche A D Diwan and S R Chandra ldquoFlavonoidsan overviewrdquo Journal of Nutritional Science vol 5 p e472016

[3] Z Dhaouadi M Nsangou N Garrab E H AnouarK Marakchi and S Lahmar ldquoDFT study of the reaction ofquercetin with and radicalsrdquo Journal of Molecular StructureTHEOCHEM vol 904 no 1-3 pp 35ndash42 2009

[4] P Dixit R Chillara V Khedgikar et al ldquoConstituents ofDalbergia sissoo Roxb leaves with osteogenic activityrdquo Bio-organic amp Medicinal Chemistry Letters vol 22 no 2pp 890ndash897 2012

[5] J N Choi K Dockyu K C Hyung M Y Kyung K Jiyoungand H L Choong ldquo2prime-Hydroxyaltion of genistein enhancedantioxidant and antiproliferative activities in MCF-7 humanbreast cancer cellsrdquo Journal of Microbiology and Bio-technology vol 19 pp 1348ndash1354 2009

[6] S Dowling F Regan and H Hughes ldquoe characterisation ofstructural and antioxidant properties of isoflavone metalchelatesrdquo Journal of Inorganic Biochemistry vol 104 no 10pp 1091ndash1098 2010

[7] J-G Cho H-J Park G-W Huh et al ldquoFlavonoids fromPueraria mirifica roots and quantitative analysis usingHPLCrdquo Food Science and Biotechnology vol 23 no 6pp 1815ndash1820 2014

[8] Y Zhang and Y Sun ldquoeoretical investigation on atmo-spheric reaction of O(3P) with CH 2 CNrdquo Journal of PhysicalOrganic Chemistry vol 32 no 4 article e3913 2018

[9] E M Kamel A M Mahmoud S A Ahmed andA M Lamsabhi ldquoA phytochemical and computational studyon flavonoids isolated from Trifolium resupinatum L and

their novel hepatoprotective activityrdquo Food amp Function vol 7no 4 pp 2094ndash2106 2016

[10] R A Mendes S K C Almeida I N Soares et al ldquoAcomputational investigation on the antioxidant potential ofmyricetin 34prime-di-O-α-L-rhamnopyranosiderdquo Journal ofMolecular Modeling vol 24 no 6 p 133 2018

[11] K S Kumar and R Kumarresan ldquoA DFT study on thestructural electronic properties and radical scavengingmechanisms of calycosin glycitein pratensein and prunetinrdquoComputational andeoretical Chemistry vol 985 pp 14ndash222012

[12] A Vaganek J Rimarcik V Lukes L Rottmannova andE Klein ldquoDFTB3LYP study of the enthalpies of Homolyticand Heterolytic O-H Bond dissociation in sterically hinderedphenolsrdquo Acta Chimica Slovenica vol 4 pp 55ndash71 2011

[13] M Leopoldini T Marino N Russo and M Toscano ldquoAn-tioxidant properties of phenolic compounds H-atom versuselectron transfer mechanismrdquo Journal of Physical ChemistryA vol 108 no 22 pp 4916ndash4922 2004

[14] R A Mendes B L S Silva R Takeara R G Freitas A Brownand G L C de Souza ldquoProbing the antioxidant potential ofphloretin and phlorizin through a computational investigationrdquoJournal of Molecular Modeling vol 24 no 4 p 101 2018

[15] E N Maciel S K C Almeida S C da Silva andG L C de Souza ldquoExamining the reaction between anti-oxidant compounds and 22-diphenyl-1-picrylhydrazyl(DPPH) through a computational investigationrdquo Journal ofMolecular Modeling vol 24 no 8 p 218 2018

[16] A Galano G Mazzone R A Diduk T MarinoJ R A Idaboy and N Russo ldquoFood antioxidants chemicalInsights at the Molecular Levelrdquo Annual Review of FoodScience and Technology vol 7 no 1 pp 335ndash352 2016

[17] V B Luzhkov ldquoMechanisms of antioxidant activity the DFTstudy of hydrogen abstraction from phenol and toluene by thehydroperoxyl radicalrdquo Chemical Physics vol 314 no 1-3pp 211ndash217 2005

[18] S A P Gomez N F Holguin A P HernandezM P Miramontes and D G Mitnik ldquoComputational mo-lecular characterization of the flavonoid rutinrdquo ChemistryCentral Journal vol 4 no 1 p 12 2010

[19] D G Mitnik ldquoComputational chemistry of natural productsa comparison of the chemical reactivity of isonaringin cal-culated with the M06 family of density functionalsrdquo Journal ofMolecular Modeling vol 20 no 7 p 2316 2014

[20] H Djeradi A Rahmouni and A Cheriti ldquoAntioxidant ac-tivity of flavonoids a QSAR modeling using Fukui indicesdescriptorsrdquo Journal of Molecular Modeling vol 20 no 10p 2476 2014

[21] K Sadasivam and R Kumaresan ldquoAntioxidant behavior ofmearnsetin and myricetin flavonoid compounds-a DFTstudyrdquo Spectrochimica Acta Part A Molecular and Bio-molecular Spectroscopy vol 79 no 1 pp 282ndash293 2011

[22] R-M Han Y-X Tian Y Liu et al ldquoComparison of flavo-noids and isoflavonoids as antioxidantsrdquo Journal of Agri-cultural and Food Chemistry vol 57 no 9 pp 3780ndash37852009

[23] S F Farag A S Ahmed K Terashima Y Takaya andM Niwa ldquoIsoflavonoid glycosides from Dalbergia sissoordquoPhytochemistry vol 57 pp 1263ndash1268 2001

[24] S T Ninh ldquoA Review on the medicinal plant Dalbergiaodorifera species phytochemistry and biological activityrdquoEvidence-Based Complementary and Alternative Medicinevol 2017 Article ID 7142370 27 pages 2017

Journal of Chemistry 11

[25] A Kuzniar J Pusz and UMaciolek ldquoPotentiometric study ofPd(II) complexes of some flavonoids in water-methanol-14-dioxane-acetonitrile (MDM) mixturerdquo Acta Poloniae Phar-maceutica vol 74 pp 369ndash377 2017

[26] K Benthami S A Lyazidi M Haddad M ChoukradB Bennetau and S Shinkaruk Photophysics of Genistein andBiochanin A Isoflavones Solvent Cage and ConcentrationEffects Studied by UV Visible Spectroscopy Nova SciencePublishers Inc Hauppauge NY USA 2009 ISBN 978-1-61728-113-6

[27] P Trouillas P Marsal D Siri R Lazzaroni and J-L DurouxldquoA DFTstudy of the reactivity of OH groups in quercetin andtaxifolin antioxidants the specificity of the 3-OH siterdquo FoodChemistry vol 97 no 4 pp 679ndash688 2006

[28] M Ghiasi and M M Heravi ldquoQuantum mechanical study ofantioxidative ability and antioxidative mechanism of rutin(vitamin P) in solutionrdquo Carbohydrate Research vol 346no 6 pp 739ndash744 2011

[29] L H M Heravi C H Rios-Reyes N J Olvera-MaturanoJ Robles and J A Rodrigues ldquoChemical reactivity ofquinclorac employing the HSAB local principle-Fukuifunctionrdquo Open Chemistry vol 13 no 1 p 52 2015

[30] K Sadasivam and R Kumaresan ldquoA comparative DFT studyon the antioxidant activity of apigenin and scutellarein fla-vonoid compoundsrdquo Molecular Physics vol 109 no 6pp 839ndash852 2011

[31] K O Sulaiman and A T Onawole ldquoQuantum chemicalevaluation of the corrosion inhibition of novel aromatichydrazide derivatives on mild steel in hydrochloric acidrdquoComputational and eoretical Chemistry vol 1093 pp 73ndash80 2016

[32] M Leopoldini F Rondinelli N Russo and M ToscanoldquoPyranoanthocyanins a theoretical investigation on theirantioxidant activityrdquo Journal of Agricultural and FoodChemistry vol 58 no 15 pp 8862ndash8871 2010

[33] J Lengyel J Rimarcık A Vaganek and E Klein ldquoOn theradical scavenging activity of isoflavones thermodynamics ofO-H bond cleavagerdquo Physical Chemistry Chemical Physicsvol 15 no 26 p 10895 2013

[34] J Zhang F Du B Peng R Lu H Gao and Z ZhouldquoStructure electronic properties and radical scavengingmechanisms of daidzein genistein formononetin and bio-chanin A a density functional studyrdquo Journal of MolecularStructure THEOCHEM vol 955 no 1-3 pp 1ndash6 2010

[35] D Amic V Stepanic B Lucic Z Markovic andJ M D Markovic ldquoPM6 study of free radical scavengingmechanisms of flavonoids why does OndashH bond dissociationenthalpy effectively represent free radical scavenging activ-ityrdquo Journal of Molecular Modeling vol 19 no 6pp 2593ndash2603 2013

12 Journal of Chemistry

TribologyAdvances in

Hindawiwwwhindawicom Volume 2018

Hindawiwwwhindawicom Volume 2018

International Journal ofInternational Journal ofPhotoenergy

Hindawiwwwhindawicom Volume 2018

Journal of

Chemistry

Hindawiwwwhindawicom Volume 2018

Advances inPhysical Chemistry

Hindawiwwwhindawicom

Analytical Methods in Chemistry

Journal of

Volume 2018

Bioinorganic Chemistry and ApplicationsHindawiwwwhindawicom Volume 2018

SpectroscopyInternational Journal of

Hindawiwwwhindawicom Volume 2018

Hindawi Publishing Corporation httpwwwhindawicom Volume 2013Hindawiwwwhindawicom

The Scientific World Journal

Volume 2018

Medicinal ChemistryInternational Journal of

Hindawiwwwhindawicom Volume 2018

NanotechnologyHindawiwwwhindawicom Volume 2018

Journal of

Applied ChemistryJournal of

Hindawiwwwhindawicom Volume 2018

Hindawiwwwhindawicom Volume 2018

Biochemistry Research International

Hindawiwwwhindawicom Volume 2018

Enzyme Research

Hindawiwwwhindawicom Volume 2018

Journal of

SpectroscopyAnalytical ChemistryInternational Journal of

Hindawiwwwhindawicom Volume 2018

MaterialsJournal of

Hindawiwwwhindawicom Volume 2018

Hindawiwwwhindawicom Volume 2018

BioMed Research International Electrochemistry

International Journal of

Hindawiwwwhindawicom Volume 2018

Na

nom

ate

ria

ls

Hindawiwwwhindawicom Volume 2018

Journal ofNanomaterials

Submit your manuscripts atwwwhindawicom

TribologyAdvances in

Hindawiwwwhindawicom Volume 2018

Hindawiwwwhindawicom Volume 2018

International Journal ofInternational Journal ofPhotoenergy

Hindawiwwwhindawicom Volume 2018

Journal of

Chemistry

Hindawiwwwhindawicom Volume 2018

Advances inPhysical Chemistry

Hindawiwwwhindawicom

Analytical Methods in Chemistry

Journal of

Volume 2018

Bioinorganic Chemistry and ApplicationsHindawiwwwhindawicom Volume 2018

SpectroscopyInternational Journal of

Hindawiwwwhindawicom Volume 2018

Hindawi Publishing Corporation httpwwwhindawicom Volume 2013Hindawiwwwhindawicom

The Scientific World Journal

Volume 2018

Medicinal ChemistryInternational Journal of

Hindawiwwwhindawicom Volume 2018

NanotechnologyHindawiwwwhindawicom Volume 2018

Journal of

Applied ChemistryJournal of

Hindawiwwwhindawicom Volume 2018

Hindawiwwwhindawicom Volume 2018

Biochemistry Research International

Hindawiwwwhindawicom Volume 2018

Enzyme Research

Hindawiwwwhindawicom Volume 2018

Journal of

SpectroscopyAnalytical ChemistryInternational Journal of

Hindawiwwwhindawicom Volume 2018

MaterialsJournal of

Hindawiwwwhindawicom Volume 2018

Hindawiwwwhindawicom Volume 2018

BioMed Research International Electrochemistry

International Journal of

Hindawiwwwhindawicom Volume 2018

Na

nom

ate

ria

ls

Hindawiwwwhindawicom Volume 2018

Journal ofNanomaterials

Submit your manuscripts atwwwhindawicom