Chrysin flavonoid adsorbed on b12n12 nanocage a novel antioxidant nanomaterial

The findings demonstrated that in the vacuum phase and water, benzene, and ethanol solvents, the BDE 5O-H, PDE, PA values of CYS/B12N12 are smaller than those of CYS system.. Solvent eff

Chrysin flavonoid adsorbed on B12N12 nanocage - A novel antioxidant

nanomaterial Atefeh Khalili 1 , Mohammad T Baei 2* , Seyed Hossein Hosseini Ghaboos 1

1

Department of Food Science and Technology, Azadshahr Branch, Islamic Azad University, Azadshahr,

Golestan, Iran, postal code: 49617-89985 2

Department of Chemistry, Azadshahr Branch, Islamic Azad University, Azadshahr, Golestan, Iran

Submitted September 29, 2020; Accepted January 8, 2021

Abstract

Antioxidative activity of chrysin (CYS) on the B12N12 nanocage has been evaluated by density functional theory with B3PW91-D3 and M06-2X-D3 methods Adsorption behavior and study of topologies demonstrated that the CYS has chemisorbed to the nanocage and shows notable changes in the electronic properties of B 12 N12 The antioxidant properties of the CYS and CYS/B12N12 systems have been studied in the different environments by the M06-2X-D3 method The findings demonstrated that in the vacuum phase and water, benzene, and ethanol solvents, the BDE (5O-H), PDE, PA values of CYS/B12N12 are smaller than those of CYS system The current study implied that B12N12 nanocage can increase the antioxidative properties of the CYS

Keywords Chrysin, antioxidative activity, antiradical mechanisms, B12N12, DFT

1 INTRODUCTION

Flavonoids have been accepted as one of the largest

and most widespread bioactive materials, and subset

of phenolic compounds that can be found in

vegetables, plants, and fruits.[1] Flavonoids showed

potent scavenger activity against reactive nitrogen

and oxygen species They can transfer hydrogen’s

and electrons to RONS which stabilizes them

providing relatively permanent flavonoid radicals

Furthermore, flavonoids can chelate to metals for the

prevention of radicals generation as well as

activating antioxidant enzymes in deactivating free

radicals They are used in food products of the

packaging in order to enhance the products' shelf-life

and bioactive compound content due to their

oxygen-sensitivity as an active antioxidant

material.[2] Chrysin is a flavonoid and an analog of

apigenin included in natural products (Pleurotus

ostreatus,[3] propolis,[4] honey,[5] etc.) and many

plants (Passiflora caerulea,[6] Passiflora

incarnate,[7] Oroxylum indicum,[8] etc.) It has the

high remedial power of transferring the intestinal

membrane and also can be used to afford a wide

variety of pharmacological activities particularly

anti-inflammatory and antioxidant[8] properties

In late years, there has been an increasing

attachment in using boron nitride nanotubes and

other boron nitride nanostructures as promising

materials for therapeutic agents[9-10] with significant prominence in cancer therapy Boron nitride (BN) has distinguishing features containing substantial electrical-insulating performance, high resistance to oxidation, high Young’s modulus high thermal conductivity and stability, and high chemical inertness.[11] BN fullerenes were characterized by electron irradiation or arc-melting methods, with their chemical compositions and cage-like structures were examined by transmission electron microscopy (TEM) and time-of-flight mass spectrometry (TOFMS).[12] BNNPs have become an important topic in this field because of the wide availability of boron nitride and its inherent features of low toxicity, biodegradability and biocompatibility.[13] Also, in the last few decades, the potential of boron nitride for biomedical uses in the medic field, such

as drug delivery, imaging and cellule stimulation was increased.[14] Hence, adsorption of chrysin on appropriate surfaces can be used as an election to increase its lifetime There are several kinds of research focused on the chrysin adsorption on different substrates.[15] Moreover, boron nitride nanostructures have been widely used for the detection and sorption of drugs.[16,17] On the other hand, in late years, research into boron-including compounds has notably increased in pharmaceutical chemistry.[18] Also, it has been widely used for the detection and absorption of noble gases.[19] It

is, therefore, significant to comprehend the influence

of B12N12 nanocage on the antiradical activity of

chrysin in order to deliver new clues to the

development of antioxidants Moreover, we

evaluated the efficacy of the polar and non-polar

solvents on the antioxidative activity of the systems

2 COMPUTATIONAL METHODS

We evaluated the improvement of antiradical

activity of the CYS through the interaction with

B12N12 nanocage by DFT calculations Geometries,

charge transfer characteristics (QT) between CYS

and the nanocage, density of states (DOS),

molecular electrostatic potential (MEP), and frontier

molecular orbital (FMO) of the considered systems

are computed with B3PW91- GD3BJ and

M06-2X-D3 methods The M06-2X method[20] is usually used

to be the most appropriate one for main groups in

chemistry and noncovalent interactions.[21]

Therefore, geometry calculations and vibration

frequencies were carried out on the nanocage, all

molecules, ions, and various chrysin/B12N12 systems

by the M06-2X/6-31G*[22,23] method with an

empirical dispersion term (M06-2X-D3) in the

Gaussian 09 program.[24] Then, the vibrational

frequencies for the optimized geometries were

computed at the M06-2X-D3 level combined with

the 6-311+G* basis set for thermodynamic

parameters For the systems, the basis set

superposition error (BSSE) and the dispersion

interaction effects were calculated Solvent effects

were checked out by using the SMD continuum

solvent model on the energies of all studied

species.[25] For the relaxed systems, the adsorption

energy (E ad) of chrysin on the B12N12 surface is

obtained using the following equation:

where E CYS - B12N12 is the energy of CYS/B12N12

system E B12N12 and E CYS are the energies of the pure

B12N12 and chrysin The phenolic antioxidants show

a significant role in the oxidative process mainly

through three accepted radical scavenging

mechanisms.[26] In this research, the antioxidative

activity of the phenolic compounds were

investigated using the bond dissociation enthalpy

(BDE), ionization potential (IP), proton dissociation

enthalpy (PDE), proton affinity (PA) and electron

transfer enthalpy (ETE).[27] For the hydrogen atom

transfer (HAT), antioxidative activity of phenolic

antioxidant (ArOH) can evaluate by electron transfer

from the phenolic system to the free radical It can

be shown as follows:

ArOH + Rº → RH + ArOº (2)

The HAT in equation (2) is defined by the BDE

of the O-H bond.[28] The molecules with a lower BDE value illustrate the greater antioxidant capacity

of the systems The BDE value can be specified by the following equation:

BDE = ΔH (ArOº) + ΔH (Hº) – ΔH (ArOH) (3)

In the single electron transfer-proton transfer (SET-PT) method, an electron is transferred from the antioxidant to a free radical and forming a cation radical as computed from equation of 4:

Rº + ArOH → R− + ArOH+º (4)

The IP and PDE are related to the first and second steps of SET-PT mechanism

R− + ArOH+º → RH + ArOº (5) The IP and PDE values were determined from the following equation:

IP = ΔH (ArOH+º) + ΔH (e−) – ΔH (ArOH) (6) PDE = ΔH (ArOº) + ΔH (H+) – ΔH (ArOH+º) (7) And in the last step, sequential proton loss electron transfer (SPLET) method was calculated from the following equation:

ArOH → ArO−

+ H+ (8) ArO− + Rº → ArOº + R− (9) The PA and ETE values were calculated from the following equation:

PA = ΔH (ArO−) + ΔH (H+) – ΔH (ArOH) (10) ETE = ΔH (ArOº) + ΔH (e−) – ΔH (ArO−) (11) The calculated values of gas and solvent phase

of H (H+), H (e−) and H (H.) were determined from Refs [29] and [30]

3 RESULTS AND DISCUSSION 3.1 Adsorption behavior of Chrysin on B 12 N 12

nanocage

Figures 1 and 2 display the relaxed structures, MEP and FMO plots of the B12N12 nanocage and chrysin

in the vacuum environment The nonpolar B12N12

nanocage is the smallest stable boron nitride

fullerene with T h symmetry which is composed of six 4-membered rings (4-MR) and eight 6-membered rings (6-MR) As depicted in figure 1, the B-N bond lengths in B12N12 are calculated to be 1.44

Å (6-MR) and 1.48 Å (4-MR) in a vacuum environment by the B3PW91-D3 functional The FMO and MEP plots on B12N12 nanocage is also shown in figure 1 FMO analysis represents that the

HOMO and LUMO distributions are mostly

localized on the boron and nitrogen atoms of the

B12N12 nanocage as shown in figure 1 MEP plot of

B12N12 represents that the boron atom of nanocage is the most desirable site for the attraction of nucleophilic agent, while the oxygen atom of

Figure 1: (a) Geometrical parameters, (b) MEP and (c, d) FMO plots for the optimized structure of B12N12

obtained by the M06-2X method The distances and angles are in Å and degrees

carbonyl group in chrysin (quinolic system) with red

color can be the most susceptible site for the

electrophilic attack to boron atom of B12N12 in

comparison to phenolic system, defined by the

distribution of charge density As shown in figure 2,

the CYS has one nucleophilic site containing oxygen

atom (-0.560 |e|) because it has a negative

electrostatic potential surface The FMO analysis

illustrates that the HOMO and LUMO are mostly

localized on the carbon and oxygen atoms of the

drug The lengths of C=O, C5-O, and C7-O bonds for

the CYS molecule are computed to be 1.25, 1.33,

and 1.35 Å by the B3PW91-D3 and 1.24, 1.33, and

1.35 Å by the M06-2X-D3 method, respectively In these analyses, the results obtained at the B3PW91-D3 method are similar to the M06-2X-B3PW91-D3 method

As shown in figure 3, CYS molecule is adsorbed from its carbonyl group on boron atom of B12N12

nanocage with the interaction distances about 1.54 Å

by the B3PW91-D3 method The adsorption energy for the CYS/B12N12 system is found to be -32.16 kcal/mol in the vacuum environment As it can be seen in figure 3, the adsorption of CYS induces a local structural deformation on both the CYS and the

B12N12 nanocage The bond length of C=O of CYS is increased from 1.25 and 1.24 Å in isolated CYS to

1.29 Å in the CYS/B12N12 system by the

B3PW91-D3 and M06-2X-B3PW91-D3, respectively This behavior is

in agreement with the change in the frequency of

C=O bond in the structure The vibratory frequency

of the bond is reduced from 1767.71 and 1823.38

cm-1 in free CYS to 1614.71 and 1646 cm-1 in the

CYS/B12N12 system by the B3PW91-D3 and

M06-2X-D3, respectively.[31] A natural bond orbital

(NBO) charge about 0.12 e transfers from the CYS

to the B12N12 nanocage This can be understood by

the fact that the CYS tends to share some electron

with the LUMO site of the B12N12 nanocage The

HOMO-LUMO gap (Egap) CYS is found to be about

4.51 eV (B3PW91-D3) and 6.83 eV (M06-2X-D3) After adsorption of CYS on the surface of B12N12

nanocage, the value of Egap was reduced to 3.44 and 5.81 eV by the B3PW91-D3 and M06-2X-D3 methods, respectively (figure 4) The difference in the Egap value in the CYS/B12N12 system was 50.99 (B3PW91-D3) and 54.23 % (M06-2X-D3), respectively As expected, a significant decrement of

Egap is accompanied by the increase in the electrical conductivity of B12N12 nanocage.[32] Hence, B12N12

nanocage can exhibit an electrical noise in the presence of CYS and can be used as biosensor for medical usage

Figure 2: (a) Geometrical parameters, (b) MEP and (c, d) FMO plots for the optimized structure of Chrysin

obtained by the M06-2X method The distances and angles are in Å and degrees

3.2 Antioxidative mechanisms of CSY on B 12 N 12

nanocage

3.2.1 HAT mechanism

In the HAT mechanism, the strength of a phenolic

antioxidant to exist as stable radical species when

breaking a hydrogen atom from its phenolic OH

group was measured that can be characterized by the BDE The lower values of BDE represent an easier reaction and the greater antioxidant activity of the configuration The BDE and ΔBDE values, where ΔBDE = BDE (CYS/B12N12 system) – BDE (CSY) for the O-H of CYS and CYS/B12N12 system in vacuum environment in addition in the different solvents (water, ethanol and benzene) are computed

at the M06-2X-D3 level as listed in table 1 For

CYS, the lowest BDE is at 7O-H and the BDE value

in 7O-H in the environments is lower than that of

5O-H, because 5O-H situation taking part in inter

hydrogen bond so, 7O-H of CYS is the most

effective for OH radical attack In the previous

report,[33] for CYS in water and DMSO phases,

7O-H is also more suitable for radical attack, because

the BDE value of 7O-H in these two solvents is

lower than that of 5O-H Also, as can be showed in

table 1, the lowest BDE value for the CYS/B12N12

complex at situation 7-OH of the systems in the

vacuum and benzene environments In truth, it can

be assumed that for the systems the 7-OH group undergoes the HAT mechanism with the most possibility On the other hand, the BDE values (5O-H) of CYS/B12N12 complex in the vacuum, water, benzene, and ethanol environments are lower than BDE values of CYS Therefore, the ΔBDE values (BDE CYS/B12N12 –BDE CYS) in the environments for 5O-H are negative Nevertheless, negative value

of ΔBDE for the systems represent that CYS adsorption on B12N12 nanocage in the HAT analysis with lower BDEs may present stronger antioxidant activity in comparison to CYS in the reported structures

Figure 3: Calculated geometries (a), MEP (b), and FMO (c, d) for CSY/B12N12 system

Table 1: Bond dissociation enthalpy (BDE) and ΔBDE in kcal/mol of O-H

obtained by the M062X-D3 functional

Solvent

BDE

ΔBDE

Figure 4: Calculated TDOS plots for CSY (a), B12N12 (b), and CSY/B12N12 (c) systems

3.2.2 SET-PT mechanism analysis

In this mechanism an electron is transferred from the

antioxidant to a free radical and forming a cation

radical that is characterized by IP, then, a proton

donation carried out from the cation radical and is

governed by PDE A stronger the electron-donating

ability and the proton donation ability is expected

upon having lower values of IP and PDE The

effects of substituents (phenols and chromans),[34]

several substituted anilines[35] on the IP value were

reported in the literature In this paper, we are

reporting on the computed values for the IP, ΔIP,

PDE, and ΔPDE for the CYS and CYS/B12N12

system in the vacuum and solvent environments

through M06-2X-D3 functional (tables 2 and 3) It is

noted that the calculated IP and PDE values have an

obvious sensitivity towards the polarity changes of

the solvents where these values are computed to be

lower in polar solvents (ethanol and water)

compared to those of the nonpolar (vacuum and

benzene) solvents This shows that polar solvents

Table 2: Ionization potential (IP) and ΔIP in kcal/mol calculated by the M062X-D3 level

Solvent CYS

B12N12-CYS

enhance the electron-donating and the proton donation abilities of the CYS and CYS/B12N12

system Moreover, the ΔIP values (IP CYS/B12N12 –IP

CYS) was positive showing that the formation of a cation radical in CYS/B12N12 system is not as easy as those of the CYS and stands for the more activity of the CYS in the first step of the SET-PT mechanism The sequences of PDEs and BDEs for OH groups of the systems are similar whereas the 7−OH groups

undergo the mechanisms with the most probability

Herein, it is expected that the 7−OH group of the

CYS and CYS/B12N12 system generates the most

stable cation among the studied structures

Moreover, the ΔPDE values (PDE CYS/B12N12 –PDE

CYS) in the environments were negative This shows that the proton-donating ability of the cation radical

of the CYS/B12N12 system in the environments are stronger than that in the CYS, resulting in a higher antioxidant activity of the CYS/B12N12 system

Table 3: Proton dissociation enthalpy (PDE) and ΔPDE in kcal/mol calculated by

the M062X/6-311+G* method

Solvent

3.2.3 SPLET mechanism analysis

SPLET is known as the other significant mechanism

for the antioxidative activity of a given

molecule/system Deprotonation of a flavonoid and

forming a flavonoid anion is the first step of the

SPLET analysis PA is herein a significant

parameter indicating for the capability of proton

donation In the second step, an electron is

transferred from flavonoid anion to free radical

(ETE) The calculated PA, ΔPA, ETE, and ΔETE for

the CYS and CYS/B12N12 system in the vacuum

environment and the different solvents were

calculated and shown in tables 4 and 5 Here, the

polarity dramatically affects the PAs value obtained

by our calculations where the PA values for the CYS

and CYS/B12N12 systems are decreased drastically

from the vacuum environment to the solvent

environments The sequences of PAs for the OH

groups in the structures in these environments also

demonstrate that the 7−OH groups almost creates the most acidic hydrogens and the deprotonation of 7−OH groups forms the most stable anion in the calculated structures showing the important role that the 7−OH group of the compounds play in the first step of SPLET mechanism Moreover, ΔPA values

obtained as negative (especially in vacuum and benzene environment), showing that the PA value of the CYS/B12N12 system is smaller than that in the CYS which results in a higher antioxidant activity of the CYS/B12N12 complex These findings suggest that the interaction of CYS on the B12N12 nanocage enhances the antiradical activity of the CYS The ETE values of the CYS were obtained to be smaller than that the CYS/B12N12 complex (ΔETE is positive) meaning that the CYS is more active than the CYS/B12N12 system in the second step of the SPLET method

Table 4: Proton affinity (PA) and ΔPA in kcal/mol calculated by the M062X/6-311+G* method

Solvent

3.2.4 Thermodynamically preferred mechanism of

the investigated structures

The mechanism of this process is separated into two

steps which the first step is substantially based on

the thermodynamic aspect Normally, the

mechanisms of HAT, SET-PT and SPLET are

dependent on the BDE, IP, and PA parameters

whereas these parameters are generally implemented

in defining the thermodynamically preferred reaction pathway in the free radical scavenging reactions Tables 1, 2, and 4 of the vacuum and benzene environments represent that the lowermost BDEs are smaller than PA and the lowest IP Herein, the free radical scavenging progress of the CYS and CYS on the B12N12 nanocage preferably and most possibly

proceed through the HAT mechanism in these

mentioned environments Moreover, the order of

BDE, IP, and PA are as follows: PA < BDE < IP in

ethanol and water environments Consequently,

SPLET mechanism is the most desirable route for

the free radical scavenging progress of the CYS and,

CYS by B12N12 nanocage in these studied systems

3.2.5 The antiradical activity influenced by the

B 12 N 12 nanocage on the CYS

The result of our calculations demonstrates that in the vacuum and the solvent environments, the values

of IP and ETE for the CYS are dropped slightly than those of CYS/B12N12 system (tables 2 and 5) In other words, the obtained results represents that in the different environments, the BDE (5O-H), PDE,

PA values of CYS/B12N12 are smaller than that of CYS system Therefore, the CYS adsorption on

B12N12 surface can improve the antiradical activity

of the CYS

Table 5: Electron transfer enthalpy (ETE) and ΔETE in kcal/mol calculated by

the M062X/6-311+G* method

Solvent

4 CONCLUSIONS

In summary, the adsorption behavior and

antioxidative activities of CYS and CYS/B12N12

systems have been successfully evaluated in

vacuum, water, ethanol, and benzene environments

The result showed that CYS can chemisorbed via the

C=O bond to a boron atom of the nanocage with Eads

of -32.16 and -31.88 kcal/mol at the

B3PW91-D/6-31G* and M06-2X-D/6-B3PW91-D/6-31G* methods in vacuum

environment, respectively The results presented that

adsorption of the CYS on the B12N12 surface induces

remarkable changes in electronic properties of the

nanocage and its E gap is diminished after adsorption

process In fact, the CYS can improve the electronic

properties of the B12N12 surface by CYS adsorption

and can thus create this nanocage more reactive

Besides, the adsorption of CYS on the B12N12

surface plays a significant role in the antioxidative

activity of CYS Therefore, in this research, M062X

method was used to study the influence of the CYS

adsorption on the B12N12 nanocage on the

antioxidative activity of CYS based on HAT,

SET-PT and SPLET methods For this objective, values

of the BDE, IP, PDE, PA, and ETE were evaluated

in vacuum, ethanol, benzene, and water

environments to better comprehend the antiradical

progress of the studied systems In the vacuum and

benzene environments, except for compound

CYS/B12N12 in benzene phase, BDEs values are

smaller than the IP and PA Therefore, in the phases,

the antioxidative progress of the CYS and

CYS/B12N12 complex undergoes the HAT

mechanism with most possibility In ethanol and water environments, sequences for BDE, IP and PA can be arranged in the following order: PA < BDE <

IP Therefore, in the environments, SPLET is the most remarkable method in the antioxidative progress of the CYS and CYS/B12N12 systems In the vacuum and the solvent environments, the values of ETE and IP for the CYS are smaller than those of CYS/B12N12 system In vacuum, benzene, ethanol, and water environments, the BDE (5O-H), PDE, PA values of CYS/B12N12 are smaller than that of CYS system As a result, the adsorption of CYS on B12N12

nanocage would improve the antioxidative activity

of the CYS The outcome of this work indicates that the CYS adsorption on the B12N12 surface improves the antiradical activity of CYS and this fact may be effective in the progress of new antiradicals and also

on the studies of the other structural characters on the antioxidative activity of flavonoids in future

Acknowledgments This work was financially

supported by Islamic Azad University, Azadshahr Branch

Conflict of interest The authors declare that they

have no conflict of interest

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Corresponding author: Mohammad T Baei

Department of Chemistry Azadshahr Branch, Islamic Azad University, Azadshahr, Golestan, Iran

E-mail: Baei52@yahoo.com