Cite this paper: Vietnam J Chem., 2021, 59(2), 211-220 Article DOI: 10.1002/vjch.202000168 Chrysin flavonoid adsorbed on B12N12 nanocage - A novel antioxidant nanomaterial Atefeh Khalili1, Mohammad T Baei2*, Seyed Hossein Hosseini Ghaboos1 Department of Food Science and Technology, Azadshahr Branch, Islamic Azad University, Azadshahr, Golestan, Iran, postal code: 49617-89985 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 B12N12 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 (5OH), 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 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 [7] incarnate, 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 211 Wiley Online Library © 2021 Vietnam Academy of Science and Technology, Hanoi & Wiley-VCH GmbH Vietnam Journal of Chemistry Mohammad T Baei et al 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 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: COMPUTATIONAL METHODS 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: 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 M06-2XD3 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 (Ead) of chrysin on the B12N12 surface is obtained using the following equation: Ead = ECYS - B12N12 - (ECYS + E B12N12) + EBSSE (1) where ECYS - B12N12 is the energy of CYS/B12N12 system E B12N12 and ECYS 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) BDE = ΔH (ArOº) + ΔH (Hº) – ΔH (ArOH) (3) 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] RESULTS AND DISCUSSION 3.1 Adsorption behavior of Chrysin on B12N12 nanocage Figures and 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 Th symmetry which is composed of six 4-membered rings (4-MR) and eight 6membered 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 FMO analysis represents that the © 2021 Vietnam Academy of Science and Technology, Hanoi & Wiley-VCH GmbH www.vjc.wiley-vch.de 212 Vietnam Journal of Chemistry HOMO and LUMO distributions are mostly localized on the boron and nitrogen atoms of the B12N12 nanocage as shown in figure MEP plot of Chrysin flavonoid adsorbed on B12N12 nanocage… 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 B3PW91D3 method are similar to the M06-2X-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 © 2021 Vietnam Academy of Science and Technology, Hanoi & Wiley-VCH GmbH www.vjc.wiley-vch.de 213 Vietnam Journal of Chemistry 1.29 Å in the CYS/B12N12 system by the B3PW91D3 and M06-2X-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 M062X-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 Mohammad T Baei et al 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 B12N12 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 © 2021 Vietnam Academy of Science and Technology, Hanoi & Wiley-VCH GmbH www.vjc.wiley-vch.de 214 Chrysin flavonoid adsorbed on B12N12 nanocage… Vietnam Journal of Chemistry at the M06-2X-D3 level as listed in table 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, 7OH 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 (5OH) 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 BDE Solvent Vacuum Benzene Ethanol Water 5O-H 100.44 98.65 94.61 94.82 CYS 7O-H 89.42 89.60 91.92 92.91 B12N12-CYS system 5O-H 7O-H 98.42 92.90 95.59 93.06 92.45 93.78 92.80 95.55 ΔBDE 5O-H -2.02 -3.06 -2.16 -2.02 7O-H 3.48 3.46 1.86 2.64 © 2021 Vietnam Academy of Science and Technology, Hanoi & Wiley-VCH GmbH www.vjc.wiley-vch.de 215 Vietnam Journal of Chemistry Mohammad T Baei et al 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 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 CYS B12N12-CYS system IP IP Vacuum 182.71 185.87 3.16 Benzene 159.57 174.44 14.87 Ethanol 141.09 148.41 7.32 Water 140.59 146.29 5.70 Solvent ΔIP 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 © 2021 Vietnam Academy of Science and Technology, Hanoi & Wiley-VCH GmbH www.vjc.wiley-vch.de 216 Chrysin flavonoid adsorbed on B12N12 nanocage… Vietnam Journal of Chemistry 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 PDE Solvent Vacuum Benzene Ethanol Water CYS 5O-H 230.54 37.77 16.10 21.11 B12N12-CYS system 5O-H 7O-H 225.36 219.21 19.83 17.30 6.62 7.97 13.38 16.14 7O-H 219.51 28.70 13.41 19.20 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 and 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 ΔPDE 5O-H -5.18 -17.94 -9.48 -7.73 7O-H -0.30 -11.40 -5.44 -3.06 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 (PACYS/B12N12 –PACYS) in environments were 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 PA Solvent Vacuum Benzene Ethanol Water CYS 5O-H 7O-H 351.84 334.40 113.89 98.62 49.29 41.75 50.24 43.96 B12N12-CYS system 5O-H 7O-H 321.19 309.41 91.09 82.93 38.86 35.68 41.35 38.94 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 ΔPA 5O-H -30.65 -22.80 -10.43 -8.89 7O-H -24.99 -15.69 -6.07 -5.02 whereas these parameters are generally implemented in defining the thermodynamically preferred reaction pathway in the free radical scavenging reactions Tables 1, 2, and 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 © 2021 Vietnam Academy of Science and Technology, Hanoi & Wiley-VCH GmbH www.vjc.wiley-vch.de 217 Vietnam Journal of Chemistry Mohammad T Baei et al 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 B12N12 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 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 ETE Solvent Vacuum Benzene Ethanol Water CYS 5O-H 61.41 83.45 107.90 111.46 7O-H 67.82 89.65 112.75 115.83 B12N12-CYS system 5O-H 7O-H 90.04 84.51 103.18 108.81 116.17 120.70 118.33 121.08 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/631G* and M06-2X-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 Egap 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, SETPT 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 Δ ETE 5O-H 28.63 19.73 8.27 6.87 7O-H 16.69 19.16 7.95 5.25 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 REFERENCES J B Harborne The Flavonoids: Advances in Research since 1986, Chapman and Hall, London, 1994 Y Fu, J Chen, Y-J Li, Y-F Zheng, P Li © 2021 Vietnam Academy of Science and Technology, Hanoi & Wiley-VCH GmbH www.vjc.wiley-vch.de 218 Vietnam Journal of Chemistry 10 11 12 13 Antioxidant and anti-inflammatory activities of six flavonoids separated from licorice, Food Chem., 2013, 141, 1063-1071 R Anandhi, T Annadurai, T S Anitha, A R Muralidharan, K Najmunnisha, V Nachiappan, P A Thomas, P Geraldine Antihypercholesterolemic and antioxidative effects of an extract of the oyster mushroom, Pleurotus ostreatus, and its major constituent, chrysin, in Triton WR-1339-induced hypercholesterolemic rats, J Physiol Biochem., 2013, 69(2), 313-323 M Debiaggi, F Tateo, L Pagani, M Luini, E Romero Effects of propolis flavonoids on virus infectivity and replication, Microbiologica, 1990, 13(3), 207-213 I Martos, F Ferreres, F A Tomas-Barberan Identification of flavonoid markers for the botanical origin of Eucalyptus honey, Journal of Agricultural and Food Chemistry, 2000, 48(5), 1498-1502 C Wolfman, H Viola, A Paladini, F Dajas, J H Medina Possible anxiolytic effects of chrysin, a central benzodiazepine receptor ligand isolated from Passiflora coerulea, Pharmacology, Biochemistry and Behavior, 1994, 47(1), 1-4 E Brown, N S Hurd, S McCall, T E Ceremuga Evaluation of the anxiolytic effects of chrysin, a Passiflora incarnate extract, in the laboratory rat, AANA Journal, 2007, 75(5), 333-337 Harminder, V Singh, A K Chaudhary A review on the taxonomy, ethnobotany, chemistry and pharmacology of Oroxylum indicum vent, Indian Journal of Pharmaceutical Sciences, 2011, 73(5) 483-490 S Feng, H Zhang, C Zhi, X.-D Gao, H Nakanishi pH-responsive charge-reversal polymerfunctionalized boron nitride nanospheres for intracellular doxorubicin delivery, Int J Nanomed., 2018, 13, 641-652 X Li, C Zhi, N Hanagata, M Yamaguchi, Y Bando, D Golberg Boron nitride nanotubes functionalized with mesoporous silica for intracellular delivery of chemotherapy drugs, Chem Commun., 2013, 49, 7337-7339 D Golberg, Y Bando, Y Huang, T Terao, M Mitome, C Tang, C Zhi Boron nitride nanotubes and nanosheets, ACS Nano, 2010, 4, 2979-2993 O Ste´phan, Y Bando, A Loiseau, F Willaime, N Shramchenko, T Tamiya, T Sato Formation of small single-layer and nested BN cages under electron irradiation of nanotubes and bulk material, Appl Phys A, 1998, 67, 107-111 G Ciofani, S Danti, D D’Alessandro, S Moscato, A Menciassi Assessing cytotoxicity of boron nitride nanotubes: Interference with the MTT assay, Biochem Biophys Res Commun., 2010, 394, 405411 14 A Merlo, V R S S Mokkapati, S Pandit, I Chrysin flavonoid adsorbed on B12N12 nanocage… Mijakovic Boron nitride nanomaterials: biocompatibility and bio-applications, Biomater Sci., 2018, 6, 2298-2311 15 G Sathishkumar, R Bharti, P K Jha, M Selvakumar, G Dey, R Jha, M Jeyaraj, M Mandal, S Sivaramakrishnan Dietary flavone chrysin (5,7dihydroxyflavone ChR) functionalized highly-stable metal nanoformulations for improved anticancer applications, RSC Adv., 2015, 5, 89869-89878 16 M Bezi Javan, A Soltani, E Tazikeh Lemeski, A Ahmadi, S Moazen Rad Interaction of B12N12 nanocage with cysteine through various functionalities: a DFT study, Superlattice Microstruct., 2016, 100, 2437 17 A Soltani, A Sousaraei, M Bezi Javan, M Eskandari, H Balakheyli Electronic and optical properties of 5-AVA functionalized BN nanocages: a DFT study, New J Chem., 2016, 40, 7018-7026 18 E Andrade-Jorge, A K Garcia-Avila, A L Ocampo-Nestor, J G Trujillo-Ferrara, M A Soriano-Ursua Advances of bioinformatics applied to development and evaluation of boron-containing compounds, Curr Org Chem., 2018, 22, 298-306 19 R Pino-Rios, E Chigo-Anota, E Shakerzadeh, G Cárdenas-Jirón B12N12 cluster as a collector of noble gases: A quantum chemical study, Phys E (Amsterdam, Neth.), 2020, 115, 113697 20 Y Zhao, D G Truhlar Hybrid Meta Density Functional Theory Methods for Thermochemistry, Thermochemical Kinetics, and Noncovalent Interactions: The MPW1B95 and MPWB1K Models and Comparative Assessments for Hydrogen Bonding and van der Waals Interaction, J Phys Chem A, 2004, 108, 6908 21 Y Zhao, D G Truhlar The M06 suite of density functionals for main group thermochemistry, thermochemical kinetics, noncovalent interactions, excited states, and transition elements: two new functionals and systematic testing of four M06-class functionals and 12 other functionals, Theor Chem Acc., 2008, 120, 215 22 R C Binning Jr, L A Curtiss Compact contracted basis sets for third-row atoms: Ga-Kr, J Comput Chem., 1990, 11, 1206-1216 23 J P Blaudeau, M P McGrath, L A Curtiss, L Radom Extension of Gaussian-2 (G2) theory to molecules containing third-row atoms K and Ca, J Chem Phys., 1997, 107, 5016-5021 24 M J Frisch, G W Trucks, H B Schlegel, G E Scuseria, M A Robb, J R Cheeseman, et al., Gaussian, Inc., Wallingford CT, 2009 25 A V Marenich, C J Cramer, D G Truhlar Universal Solvation Model Based on Solute Electron Density and on a Continuum Model of the Solvent Defined by the Bulk Dielectric Constant and Atomic Surface Tensions, J Phys Chem B, 2009, 113, 63786396 © 2021 Vietnam Academy of Science and Technology, Hanoi & Wiley-VCH GmbH www.vjc.wiley-vch.de 219 Vietnam Journal of Chemistry 26 Z Marković, D Milenković, J Đorović, J M D Marković, V Stepanić, B Lučić, D Amić PM6 and DFT study of free radical scavenging activity of morin, Food Chem., 2012, 134, 1754-1760 27 K Jomova, M Lawson, L Drostinova, P Lauro, P Poprac, V Brezova et al Protective role of quercetin against copper(II)-induced oxidative stress: a spectroscopic, theoretical and DNA damage study Food Chem Toxicol., 2017, 110, 340-350 28 Y Zheng, G Deng, D -F Chen, R Guo, R C Lai The influence of C2 double bond C3 double bond on the antiradical activity of flavonoid: Different mechanisms analysis, Phytochemistry, 2019, 157, 17 Mohammad T Baei et al Selvakumar, G Dey, R Jha, M Jeyaraj, M Mandal, S Sivaramakrishnan Dietary flavone chrysin (5,7dihydroxyflavone ChR) functionalized highly-stable metal nanoformulations for improved anticancer applications, RSC Adv., 2015, 5, 89869-89878 32 J Cano Ordaz, E Chigo Anota, M Salazar Villanueva, M Castro Possibility of a magnetic [BN fullerene: B6 cluster]-nanocomposite as a vehicle for the delivery of dapsone, New J Chem., 2017, 41, 8045-8052 33 N Gerayeli, M Tafazzoli, M Ghiasi Theoretical Study on Glycosyl Group Effect on Antioxidant Ability of Chrysin Bioflavonoid, Phys Chem Res., 2016, 4, 643-654 29 J Rimarclk, V Lukes, E Klein, M Ilcin Study of the solvent effect on the enthalpies of homolytic and heterolytic N–H bond cleavage in pphenylenediamine and tetracyano-pphenylenediamine, J Mol Struc, THEOCHEM, 2010, 952, 25-30 34 E Klein, V Lukes DFT/B3LYP Study of the Substituent Effect on the Reaction Enthalpies of the Individual Steps of Single Electron Transfer-Proton Transfer and Sequential Proton Loss Electron Transfer Mechanisms of Phenols Antioxidant Action, J Phys Chem A, 2006, 110, 12312-12320 30 V D Parker Homolytic bond (H-A) dissociation free energies in solution Applications of the standard potential of the (H+/H.bul.) couple, J Am Chem Soc., 1992, 114, 7458-7462 35 E Klein, J Rimarcik, V Lukes DFT/B3LYP Study of the O–H Bond Dissociation Enthalpies and Proton Affinities of para- and meta-Substituted Phenols in Water and Benzene, Acta Chim Slov., 2009, 2, 3751 31 G Sathishkumar, R Bharti, P K Jha, M Corresponding author: Mohammad T Baei Department of Chemistry Azadshahr Branch, Islamic Azad University, Azadshahr, Golestan, Iran E-mail: Baei52@yahoo.com © 2021 Vietnam Academy of Science and Technology, Hanoi & Wiley-VCH GmbH www.vjc.wiley-vch.de 220 ... 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... 701 8-7 026 18 E Andrade-Jorge, A K Garcia-Avila, A L Ocampo-Nestor, J G Trujillo-Ferrara, M A Soriano-Ursua Advances of bioinformatics applied to development and evaluation of boron-containing compounds,... et al Selvakumar, G Dey, R Jha, M Jeyaraj, M Mandal, S Sivaramakrishnan Dietary flavone chrysin (5,7dihydroxyflavone ChR) functionalized highly-stable metal nanoformulations for improved anticancer