Skip to main content
NCBI home page
ACS Omega logoLink to ACS Omega
. 2021 Oct 4;6(41):27546–27551. doi: 10.1021/acsomega.1c04569

Antioxidant Activity of Natural Samwirin A: Theoretical and Experimental Insights

Thuc Dinh Ngoc †,*, Mai Vu Thi Ha †, Thanh Nguyen Le ‡, Thi Van Anh Nguyen §, Adam Mechler ∥, Nguyen Thi Hoa ⊥, Quan V Vo ⊥,*
PMCID: PMC8529648  PMID: 34693175

Abstract

graphic file with name ao1c04569_0005.jpg

Samwirin A (SW), a natural compound isolated from Sambucus williamsii or Rourea harmandiana, is known to exhibit potent antiosteoporosis activity and promote cell proliferation in rat osteoblast-like UMR 106 cells. Antiosteoporosis activity suggests that the compound must also exhibit antioxidant activity but this has not been studied thus far. In the present study, the antioxidant activity of SW was examined by experimental and computational studies. It was found that SW exhibits good hydroperoxyl scavenging activity, particularly in water at physiological pH (koverall = 1.01 × 107 M–1 s–1). The single-electron transfer mechanism defines the HOO• + SW reaction in water, while the activity in the lipid medium is moderate and it follows the formal hydrogen transfer mechanism. The rate constant of the HOO• scavenging reaction in the aqueous solution is about 78 times higher than the reference compound Trolox. The computational results are in line with experimental data underscoring that SW is a promising radical scavenger in aqueous media at physiological pH.

1. Introduction

Samwirin A (SW, Figure 1) is a rare neolignan compound isolated from the stems and branches of Sambucus williamsii(1) and Cichorium glandulosum roots, respectively.2SW showed antiosteoporosis activity, significantly promoting cell proliferation on rat osteoblast-like UMR 106 cells.1 Recently, we have identified SW in stems of Rourea harmandiana (Table S2, Supporting Information), a plant that was used as a traditional drug to treat bone fractures.3

Figure 1.

Figure 1

Open in a new tab

Chemical structure of samwirin A (SW).

Oxidative stress is one of the primary factors contributing to the pathogenesis of osteoporosis.4 Clinical studies demonstrated that increased oxidative stress shows a significant correlation with decreased bone mineral density. In osteoporotic women, the blood level of antioxidants was low, and supplementing antioxidants led to a measurable increase in bone mineral density.5,6 In vitro studies also showed that the presence of reactive oxygen species (ROS) increases osteoclast activity and reduces osteoblast metabolisms. The oxidative stress-induced inhibition of osteoblast metabolisms can be prevented by treatment with antioxidants.6 Several natural compounds show antiosteoporosis activity attributed to their antioxidant capacities.7,8 As mentioned above, SW has demonstrated an antiosteoporosis effect; furthermore, SW contains two phenolic groups in its structure (Figure 1), which is a good indicator of antioxidant activity, yet the antioxidant properties of SW have not been studied thus far.

Previous studies have shown that quantum chemistry offers a convenient avenue for studying the structure–activity relationship in bioactive molecules, informing drug development efforts with potential activity motifs.9−17 Consistently, the combination of theoretical and experimental studies can evaluate the antioxidant activity of natural products effectively and accurately.18−20 Thus, in this work, the antioxidant activity of SW from R. harmandiana was investigated by both computational and experimental methods.

2. Results and Discussion

2.1. ABTS Antioxidant Assay

To initial evaluate the antioxidant activity of SW, the ABTS assay was performed following the literature,21 using Trolox as a reference antioxidant. It was found that SW is only capable of substantially lower ABTS•+ scavenging activity (IC50 = 74.27 ± 5.94 μM) than Trolox (IC50 = 25.16 ± 1.64 μM) under the studied conditions. To correctly interpret this result, one has to consider that ABTS assay is performed in an organic solvent, and thus the result indicates that the radical scavenging activity of SW in organic solvents is lower than that of Trolox. However, this activity in water, particularly at physiological pH, might be improved due to the deprotonation of phenolic groups17,22 (O5–H and O4′–H), and this needs further investigation by quantum chemical calculations.

2.2. HOO• Radical Scavenging Activity of SW

2.2.1. Gas-Phase Evaluation

In the absence of any double bonds in the chemical structure, the antioxidant activity of a phenolic compound can occur according to either of the three typical mechanisms: sequential proton-loss electron transfer (SPLET), formal hydrogen transfer (FHT), and single-electron transfer proton transfer (SETPT).23,24 Thus, in the first step, key thermodynamic parameters of SW were calculated: proton affinity (PA), bond dissociation enthalpy (BDE), and ionization energy (IE), which characterize the propensity of the compound to react via the SPLET, FHT, and SETPT pathways, respectively. Thus, these parameters were first calculated in the gas phase at the M06-2X/6-311++G(d,p) level of theory (Table 1).22,25

Table 1. Computed Thermodynamic Parameters and ΔG° (kcal mol–1) of the First Step of SW + HOO• Reactions Following either FHT, SPLET, or SETPT Mechanism.
  FHT
 SP
 SET
Positions BDE ΔG° PA ΔG° IE ΔG°
C2–H 83.4 –2.1     165.1 142.6
C3–H 85.8 –1.0    
O5–H 82.5 –3.7 342.4 190.5
O4′–H 87.2 1.2 341.7 189.3
Open in a new tab

The lowest BDE value was predicted for O5–H at 82.5 kcal mol–1. This value is still higher than the lowest BDEs of resveratrol (83.9 kcal mol–1),26 piceatannol (73.127 or 75.128 kcal mol–1), Trolox (73.0 kcal mol–1),29 or ascorbic acid (73.9 kcal mol–1).29 The BDE values of the C2(3)–H bonds are 83.4 and 85.8 kcal mol–1, respectively, while that of the O5–H is lower than the O4′–H bond by about 4.7 kcal mol–1. The PA values for O5(4′)–H bonds (PA = 342.4 and 341.7 kcal mol–1, respectively) are significantly higher than the related BDEs. At the same time, the ionization of SW is more difficult than the bond dissociation, as shown by the higher IE value (IE = 165.1 kcal mol–1). The data (Table S3, Supporting Information) show that the lowest BDE was obtained at the O5–H bond (BDE(O5–H) = 80.6–82.1 kcal mol–1) in all of the studied solvents and it is lower than the IE values by about 19.3–42.6 kcal mol–1. Consistently, the antioxidant activity of SW in the gas phase and organic solvents is expected to favor the FHT pathway.

To confirm the preferred antioxidant pathway, the Gibbs free-energy changes of the first steps of the SW + HOO• reactions were also calculated following each of the pathways (Table 1). The HOO• + SW reactions are only spontaneous for FHT (ΔG° = −3.7 to 1.2 kcal mol–1), whereas the other reactions are not spontaneous with high positive Gibbs free-energy change values (ΔG°(SP) = 189.3–190.5 kcal mol–1 and ΔG°(SET) = 142.6 kcal mol–1). Thus, the calculated data suggest that the SW + HOO• reaction in the gas phase can only follow the FHT reaction, and this pathway should be investigated in the kinetic study.

The kinetics of the SW + HOO• reaction was computed following the FHT pathway using the quantum mechanics-based test for the overall free-radical scavenging activity (QM-ORSA) protocol (Table 2 and Figure 2).30,31 The study showed that the HOO• quenching of SW was defined by the hydrogen transfer of the O5–H bond with ΔG≠ = 12.0 kcal mol–1, kEck = 6.63 × 105 M–1 s–1, Γ = 98.1%, while the radical trapping of the other reactions makes only minor contributions with Γ = 0.2 – 1.1%. The tunneling corrections (calculated using the Eckart barrier32) closely correlated with the rate constants of the HOO• scavenging activity. Tunneling corrections are introduced to account for the ability of the hydrogen atoms to tunnel through the potential barrier in reactions involving hydrogen abstraction, hence the correlation is expected33 but not always observed; here, it confirms the suitability of the FHT model. The overall rate constant of the SW + HOO• reaction is koverall = 6.75 × 105 M–1 s–1, which is around 27.7 times lower than that of Trolox (k = 1.87 × 107 M–1 s–1).22

Table 2. Computed ΔH, ΔG≠ in kcal mol–1, Tunneling Corrections (κ), kEck (M–1 s–1), and Branching Ratios (Γ, %) for the HOO• + SW Reactions.
positions ΔH ΔG≠ κ kEck Γ
C2–H 5.8 16.5 710.1 3.85 × 103 0.6
C3–H 6.2 16.3 221.4 1.57 × 103 0.2
O5–H 2.3 12.0 62.1 6.63 × 105 98.1
O4′–H 7.3 16.6 1625.9 7.23 × 103 1.1
koverall       6.75 × 105  
Open in a new tab
Figure 2.

Figure 2

Open in a new tab

Optimized structures of transition states (TS) along the FHT mechanism of the SW + HOO• reaction in different media (W: water; G: gas phase; D: dimethyl sulfoxide (DMSO); and P: pentyl ethanoate).

2.2.2. Antiradical Activity of SW in Solvents

Previous studies confirmed that the protonation state could strongly influence the HOO• radical scavenging activity of phenolic compounds.25,31,34 Thus, in this section, the proton dissociation equilibria of SW were first considered. As it was found in the thermodynamic study, the lowest PA value in the gas phase was of the O4′–H bond. The calculations for a water medium (Table S3, Supporting Information) showed that the deprotonation can occur in two steps: at O4′–H (PA = 45.4 kcal mol–1) and O5–H (PA = 46.6 kcal mol–1) bonds, respectively. Therefore, the pKa values were calculated for these bonds following previous studies (Figure 3).25,35 The calculated pKa1 and pKa2 were 9.71 and 10.22, respectively. Based on the calculated pKa values, in the aqueous solution at pH = 7.40, SW exists predominantly in two states: neutral (HA, 99.5%) and anionic (A–, 0.5%), whereas the neutral state (HA) is the main form of SW in the lipid medium. Thus, the kinetics of the SW + HOO• reaction in the physiological environments were computed following the QM-ORSA protocol,14,36 using the solvation model based on the quantum mechanical charge density of a solute molecule interacting with a continuum (SMD)37 to account for the role of the solvent. This approach to model the role of media on radical reactions has been verified in previous works.14,34,36 Since in previous works, pentyl ethanoate and water were used to model the physiological environments to account for the conditions of the ABTS assay, here, DMSO was also modeled for comparison. The overall rate constants koverall were determined following reactions 1 and 2, and the results are presented in Table 3.

Figure 3.

Figure 3

Open in a new tab

Acid dissociation equilibria of SW at pH = 7.40.

Table 3. Computed ΔG≠ (kcal mol–1), κ, kapp, kf, koverall (M–1 s–1), Molar Fractions (f), and Γ at 298.15 K for the SW + HOO• Reaction in the Studied Mediac.
solvents mechanisms ΔG≠ κ kapp f kf Γ kTrolox
pentyl ethanoate FHT 14.6 389.7 5.20 × 104     100.0 1.00 × 105b
DMSO FHT 16.1 688.5 6.70 × 103     100.0 1.20 × 104
water SET 4.6 16.6a 2.00 × 109 0.005 1.00 × 107 98.8  
FHT 15.7 6108.9 1.20 × 105 0.995 1.19 × 105 1.2  
koverall   1.01 × 107   1.30 × 105b
Open in a new tab
a

Nuclear reorganization energy (λ, kcal mol–1).

b

Ref (22).

c

f = %A–/100; kf = f ·kapp; Γ = kf × 100/koverall.

In water at physiological pH

2.2.2. 1

In aprotic media

2.2.2. 2

As shown in Table 3, the rate constant of the HOO• + SW reaction in pentyl ethanoate and DMSO are moderate with the overall rate constants koverall = 5.20 × 104 and 6.70 × 103 M–1 s–1, respectively. Thus, as shown in the gas-phase results, SW exhibits lower HOO• radical scavenging activity than Trolox (koverall(pentyl ethanoate) = 1.00 × 105 M–1 s–1,22koverall(DMSO) = 1.20 × 104 M–1 s–1) in organic solvents. This is in line with the experimental data from the ABTS assay and confirms that the antiradical activity of SW is lower than that of Trolox in DMSO. The rate constant of the HOO• + SW-O5–H reaction also makes a small contribution with a rate constant of kf = 1.19 × 105 M–1 s–1; however, this reaction only contributes ∼1.2% of the overall antiradical activity. In contrast, the SW shows good HOO• scavenging activity in water at physiological pH with koverall = 1.01 × 107 M–1 s–1, which is about 78 times faster than that of Trolox (k = 1.30 × 105 M–1 s–1).22 Comparison with some natural products indicated that the HOO• radical trapping activity of SW in water at physiological pH is fairly similar to ascorbic acid (k = 9.97 × 107 M–1 s–1),36 resveratrol (k = 5.62 × 107 M–1 s–1),38 higenamine (k = 1.23 × 108 M–1 s–1),39 or daphnetin (k = 1.51 × 107 M–1 s–1).40 Thus, SW is a promising antioxidant in water at physiological pH.

3. Conclusions

The antioxidant activity of phenolic compound samwirin A (SW) from R. harmandiana was successfully investigated. Calculations suggest that SW can exhibit moderate antiradical activity in nonpolar media (k = 6.75 × 105 M–1 s–1, 5.20 × 104 M–1 s–1 and 6.70 × 103 M–1 s–1 in the gas phase, pentyl ethanoate, and DMSO, respectively), while it can exert good activity with koverall = 1.01 × 107 M–1 s–1 in water at physiological pH. The H-abstraction at the O5–H bond following the FHT pathway decides the HOO• radical trapping of SW in the lipid media, while SET dominates in polar environments, as expected for a weak acidic compound. Compared with Trolox, the rate constant of the HOO• + SW reaction in the lipid medium is slightly lower, whereas in an aqueous solution, it is about 78 times higher. The results of the calculations are in line with experimental results and suggest that SW is a promising natural free radical scavenger in an aqueous physiological environment.

4. Experimental and Computational Methods

4.1. ABTS•+ Radical Scavenging Activity

The ability of compounds to scavenge the ABTS•+ radical is performed according to the method described previously.21 The ABTS•+ radical cation is generated by mixing an aqueous solution of potassium persulfate (2.45 mM) and ABTS (7 mM) in the dark at room temperature for 12–16 h before use. The solutions of ABTS•+ were diluted in ethanol to give the working solution with an absorbance of 0.70 ± 0.02 at 734 nm. SW, which was isolated from R. harmandiana (Table S2, Supporting Information), was dissolved in DMSO 100% and diluted into concentrations from 0.006 to 1.0 mg/ml. Then, 190 μL of the working solution of ABTS•+ was mixed with 10 μL of samples at different concentrations, and the absorbance was measured at a wavelength of 734 nm. Trolox at 0.625, 1.25, 2.5, 5.0, and 10 μg/mL was used as a positive control. The percentage of radical inhibition was calculated using the following formula

4.1.

where Ac is the absorbance of the negative control (containing all reagents except the tested compound) and As is the absorbance of the tested sample. The IC50, which is the concentration of the sample at which the sample would inhibit the free radical by 50%, was calculated.

4.2. Computational Methods

All density functional theory (DFT) calculations were carried out with the Gaussian 09 suite of programs.41 The M06-2X functional42 and the 6-311++G(d,p) basis set were used for all calculations. The M06-2X functional offers one of the most reliable methods to study thermodynamics and kinetics of radical reactions.17,30,31,34,36,42,43 The kinetic calculations were performed following the QM-ORSA protocol,14,36 following the literature,17,31,44−49 and are shown in Table S1, Supporting Information.

Acknowledgments

This research was funded by the Vietnam National Foundation for Science and Technology Development (NAFOSTED) under grant no. 104.01-2018.08.

Supporting Information Available

The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acsomega.1c04569.

  • Thermodynamic parameters, Cartesian coordinates, and frequency and energies of all of the transition states in the studied environments (PDF)

The authors declare no competing financial interest.

Supplementary Material

ao1c04569_si_001.pdf (862.4KB, pdf)

References

  1. Xiao H.-H.; Dai Y.; Wong M.-S.; Yao X.-S. Two new phenylpropanoids and one new sesquiterpenoid from the bioactive fraction of S. williamsii. J. Asian Nat. Prod. Res. 2015, 17, 625–632. 10.1080/10286020.2015.1046448. [DOI] [PubMed] [Google Scholar]
  2. Wang R.; Zheng G.; Dang T.; Jin P.; Yao J.; Su L.; Yao G.; Qin D. Chemical constituents from the roots of C. glandulosum Boiss. et Huet (Asteraceae). Biochem. Syst. Ecol. 2021, 96, 104261 10.1016/j.bse.2021.104261. [DOI] [Google Scholar]
  3. Osman C. P.; Zahari Z.; Adenan M. I.; Zohdi R. M. A review on traditional uses, phytochemistry, and pharmacology of the genus Rourea. J. Appl. Pharm. Sci. 2019, 9, 125–131. 10.7324/JAPS.2019.90918. [DOI] [Google Scholar]
  4. Arai M.; Shibata Y.; Pugdee K.; Abiko Y.; Ogata Y. Effects of reactive oxygen species (ROS) on antioxidant system and osteoblastic differentiation in MC3T3-E1 cells. IUBMB Life 2007, 59, 27–33. 10.1080/15216540601156188. [DOI] [PubMed] [Google Scholar]
  5. Maggio D.; Barabani M.; Pierandrei M.; Polidori M. C.; Catani M.; Mecocci P.; Senin U.; Pacifici R.; Cherubini A. Marked decrease in plasma antioxidants in aged osteoporotic women: results of a cross-sectional study. J. Clin. Endocrinol. Metab. 2003, 88, 1523–1527. 10.1210/jc.2002-021496. [DOI] [PubMed] [Google Scholar]
  6. Morton D. J.; Barrett-Connor E. L.; Schneider D. L. Vitamin C supplement use and bone mineral density in postmenopausal women. J. Bone Miner. Res. 2001, 16, 135–140. 10.1359/jbmr.2001.16.1.135. [DOI] [PubMed] [Google Scholar]
  7. Lee S.-H.; Ding Y.; Yan X. T.; Kim Y.-H.; Jang H.-D. Scopoletin and scopolin isolated from Artemisia iwayomogi suppress differentiation of osteoclastic macrophage RAW 264.7 cells by scavenging reactive oxygen species. J. Nat. Prod. 2013, 76, 615–620. 10.1021/np300824h. [DOI] [PubMed] [Google Scholar]
  8. Suh K. S.; Lee Y. S.; Kim Y. S.; Choi E. M. Sciadopitysin protects osteoblast function via its antioxidant activity in MC3T3-E1 cells. Food Chem. Toxicol. 2013, 58, 220–227. 10.1016/j.fct.2013.04.028. [DOI] [PubMed] [Google Scholar]
  9. Wright J. S.; Johnson E. R.; DiLabio G. A. Predicting the Activity of Phenolic Antioxidants: Theoretical Method, Analysis of Substituent Effects, and Application to Major Families of Antioxidants. J. Am. Chem. Soc. 2001, 123, 1173–1183. 10.1021/ja002455u. [DOI] [PubMed] [Google Scholar]
  10. Abdel-Rahman M. A.; Al-Hashimi N.; Shibl M. F.; Yoshizawa K.; El-Nahas A. M. Thermochemistry and Kinetics of the Thermal Degradation of 2-Methoxyethanol as Possible Biofuel Additives. Sci. Rep. 2019, 9, 4535 10.1038/s41598-019-40890-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Mahyuddin M. H.; Shiota Y.; Yoshizawa K. Methane selective oxidation to methanol by metal-exchanged zeolites: a review of active sites and their reactivity. Catal. Sci. Technol. 2019, 9, 1744–1768. 10.1039/C8CY02414F. [DOI] [Google Scholar]
  12. Ramos M.; Dias D.; Justino L.; Verissimo L.; Valente A.; Esteso M.; Ribeiro A.; Leaist D.; Pina J.; Cabral A.; Rodrigo M. Interactions between glycyl-L-phenylalanine and β-cyclodextrin from diffusion, spectroscopic and computational studies. J. Mol. Liq. 2020, 315, 113704 10.1016/j.molliq.2020.113704. [DOI] [Google Scholar]
  13. Aguado R.; Murtinho D.; Valente A. J. Association of antioxidant monophenolic compounds with β-cyclodextrin-functionalized cellulose and starch substrates. Carbohydr. Polym. 2021, 267, 118189 10.1016/j.carbpol.2021.118189. [DOI] [PubMed] [Google Scholar]
  14. Galano A.; Raúl Alvarez-Idaboy J. Computational strategies for predicting free radical scavengers’ protection against oxidative stress: Where are we and what might follow?. Int. J. Quantum Chem. 2019, 119, e25665 10.1002/qua.25665. [DOI] [Google Scholar]
  15. Carro J.; Ferreira P.; Rodríguez L.; Prieto A.; Serrano A.; Balcells B.; Ardá A.; Jiménez-Barbero J.; Gutiérrez A.; Ullrich R.; Hofrichter M.; Martínez A. T. 5-hydroxymethylfurfural conversion by fungal aryl-alcohol oxidase and unspecific peroxygenase. FEBS J. 2015, 282, 3218–3229. 10.1111/febs.13177. [DOI] [PubMed] [Google Scholar]
  16. Cuétara-Guadarrama F.; Hernández-Huerta E.; Rojo-Portillo T.; Reyes-López E.; Jiménez-Barbero J.; Cuevas G. Experimental and theoretical study of the role of CH/π interactions in the aminolysis reaction of acetyl galactoside. Carbohydr. Res. 2019, 486, 107821 10.1016/j.carres.2019.107821. [DOI] [PubMed] [Google Scholar]
  17. Vo Q. V.; Bay M. V.; Nam P. C.; Quang D. T.; Flavel M.; Hoa N. T.; Mechler A. Theoretical and Experimental Studies of the Antioxidant and Antinitrosant Activity of Syringic Acid. J. Org. Chem. 2020, 85, 15514–15520. 10.1021/acs.joc.0c02258. [DOI] [PubMed] [Google Scholar]
  18. Boulebd H.; Khodja I. A.; Bay M. V.; Hoa N. T.; Mechler A.; Vo Q. V. Thermodynamic and kinetic studies of the radical scavenging behavior of hydralazine and dihydralazine: theoretical insights. J. Phys. Chem. B 2020, 124, 4123–4131. 10.1021/acs.jpcb.0c02439. [DOI] [PubMed] [Google Scholar]
  19. Galano A.; Mazzone G.; Alvarez-Diduk R.; Marino T.; Alvarez-Idaboy J. R.; Russo N. Food antioxidants: chemical insights at the molecular level. Annu. Rev. Food Sci. Technol. 2016, 7, 335–352. 10.1146/annurev-food-041715-033206. [DOI] [PubMed] [Google Scholar]
  20. Zhang H.-Y. Theoretical methods used in elucidating activity differences of phenolic antioxidants. J. Am. Oil Chem. Soc. 1999, 76, 745–748. 10.1007/s11746-999-0170-8. [DOI] [Google Scholar]
  21. Re R.; Pellegrini N.; Proteggente A.; Pannala A.; Yang M.; Rice-Evans C. Antioxidant activity applying an improved ABTS radical cation decolorization assay. Free Radical Biol. Med. 1999, 26, 1231–1237. 10.1016/S0891-5849(98)00315-3. [DOI] [PubMed] [Google Scholar]
  22. Vo Q. V.; Thong N. M.; Le Huyen T.; Nam P. C.; Tam N. M.; Hoa N. T.; Mechler A. A thermodynamic and kinetic study of the antioxidant activity of natural hydroanthraquinones. RSC Adv. 2020, 10, 20089–20097. 10.1039/D0RA04013D. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Galano A. Free radicals induced oxidative stress at a molecular level: the current status, challenges and perspectives of computational chemistry based protocols. J. Mex. Chem. Soc. 2015, 59, 231–262. 10.29356/jmcs.v59i4.81. [DOI] [Google Scholar]
  24. Zheng Y.-Z.; Deng G.; Liang Q.; Chen D.-F.; Guo R.; Lai R.-C. Antioxidant activity of quercetin and its glucosides from propolis: A theoretical study. Sci. Rep. 2017, 7, 7543 10.1038/s41598-017-08024-8. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Vo Q. V.; Hoa N. T.; Nam P. C.; Quang D. T.; Mechler A. In Silico Evaluation of the Radical Scavenging Mechanism of Mactanamide. ACS Omega 2020, 5, 24106–24110. 10.1021/acsomega.0c03646. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Shang Y.; Zhou H.; Li X.; Zhou J.; Chen K. Theoretical studies on the antioxidant activity of viniferifuran. New J. Chem. 2019, 43, 15736–15742. 10.1039/C9NJ02735A. [DOI] [Google Scholar]
  27. Vo Q. V.; Bay M. V.; Nam P. C.; Mechler A. Is Indolinonic Hydroxylamine a Promising Artificial Antioxidant?. J. Phys. Chem. B 2019, 123, 7777–7784. 10.1021/acs.jpcb.9b05160. [DOI] [PubMed] [Google Scholar]
  28. Zheng Y.-Z.; Chen D.-F.; Deng G.; Guo R.; Fu Z.-M. The antioxidative activity of piceatannol and its different derivatives: Antioxidative mechanism analysis. Phytochemistry 2018, 156, 184–192. 10.1016/j.phytochem.2018.10.004. [DOI] [PubMed] [Google Scholar]
  29. Xue Y.; Zheng Y.; An L.; Dou Y.; Liu Y. Density functional theory study of the structure–antioxidant activity of polyphenolic deoxybenzoins. Food Chem. 2014, 151, 198–206. 10.1016/j.foodchem.2013.11.064. [DOI] [PubMed] [Google Scholar]
  30. Alberto M. E.; Russo N.; Grand A.; Galano A. A physicochemical examination of the free radical scavenging activity of Trolox: mechanism, kinetics and influence of the environment. Phys. Chem. Chem. Phys. 2013, 15, 4642–4650. 10.1039/c3cp43319f. [DOI] [PubMed] [Google Scholar]
  31. Dzib E.; Cabellos J. L.; Ortíz-Chi F.; Pan S.; Galano A.; Merino G. Eyringpy: A Program for Computing Rate Constants in the Gas Phase and in Solution. Int. J. Quantum Chem. 2019, 119, e25686 10.1002/qua.25686. [DOI] [Google Scholar]
  32. Eckart C. The penetration of a potential barrier by electrons. Phys. Rev. 1930, 35, 1303. 10.1103/PhysRev.35.1303. [DOI] [Google Scholar]
  33. Khristov S.; Georgiev Z. Tunneling corrections in chemical kinetics. J. Phys. Chem. A 1971, 75, 1748–1756. 10.1021/j100906a019. [DOI] [Google Scholar]
  34. Galano A.; Alvarez-Idaboy J. R. Kinetics of radical-molecule reactions in aqueous solution: A benchmark study of the performance of density functional methods. J. Comput. Chem. 2014, 35, 2019–2026. 10.1002/jcc.23715. [DOI] [PubMed] [Google Scholar]
  35. Galano A.; Pérez-González A.; Castañeda-Arriaga R.; Muñoz-Rugeles L.; Mendoza-Sarmiento G.; Romero-Silva A.; Ibarra-Escutia A.; Rebollar-Zepeda A. M.; León-Carmona J. R.; Hernández-Olivares M. A.; Alvarez-Idaboy J. R. Empirically Fitted Parameters for Calculating p K a Values with Small Deviations from Experiments Using a Simple Computational Strategy. J. Chem. Inf. Model. 2016, 56, 1714–1724. 10.1021/acs.jcim.6b00310. [DOI] [PubMed] [Google Scholar]
  36. Galano A.; Alvarez-Idaboy J. R. A computational methodology for accurate predictions of rate constants in solution: Application to the assessment of primary antioxidant activity. J. Comput. Chem. 2013, 34, 2430–2445. 10.1002/jcc.23409. [DOI] [PubMed] [Google Scholar]
  37. Marenich A. V.; Cramer C. J.; Truhlar D. G. 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, 6378–6396. 10.1021/jp810292n. [DOI] [PubMed] [Google Scholar]
  38. Iuga C.; Alvarez-Idaboy J. R. l.; Russo N. Antioxidant activity of trans-resveratrol toward hydroxyl and hydroperoxyl radicals: a quantum chemical and computational kinetics study. J. Org. Chem. 2012, 77, 3868–3877. 10.1021/jo3002134. [DOI] [PubMed] [Google Scholar]
  39. Romeo I.; Parise A.; Galano A.; Russo N.; Alvarez-Idaboy J. R.; Marino T. The antioxidant capability of higenamine: Insights from theory. Antioxidants 2020, 9, 358. 10.3390/antiox9050358. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Boulebd H.; Khodja I. A. A detailed DFT-based study of the free radical scavenging activity and mechanism of daphnetin in physiological environments. Phytochemistry 2021, 189, 112831 10.1016/j.phytochem.2021.112831. [DOI] [PubMed] [Google Scholar]
  41. Frisch M. J.; Trucks G. W.; Schlegel H. B.; Scuseria G. E.; Robb M. A.; Cheeseman J. R.; Scalmani G.; Barone V.; Mennucci B.; Petersson G. A.; Nakatsuji H.; Caricato M.; Li X.; Hratchian H. P.; Izmaylov A. F.; Bloino J.; Zheng G.; Sonnenberg J. L.; Hada M.; Ehara M.; Toyota K.; Fukuda R.; Hasegawa J.; Ishida M.; Nakajima T.; Honda Y.; Kitao O.; Nakai H.; Vreven T.; Montgomery J. A. Jr.; Peralta J. E.; Ogliaro F.; Bearpark M. J.; Heyd J.; Brothers E. N.; Kudin K. N.; Staroverov V. N.; Kobayashi R.; Normand J.; Raghavachari K.; Rendell A. P.; Burant J. C.; Iyengar S. S.; Tomasi J.; Cossi M.; Rega N.; Millam N. J.; Klene M.; Knox J. E.; Cross J. B.; Bakken V.; Adamo C.; Jaramillo J.; Gomperts R.; Stratmann R. E.; Yazyev O.; Austin A. J.; Cammi R.; Pomelli C.; Ochterski J. W.; Martin R. L.; Morokuma K.; Zakrzewski V. G.; Voth G. A.; Salvador P.; Dannenberg J. J.; Dapprich S.; Daniels A. D.; Farkas O.; Foresman J. B.; Ortiz J. V.; Cioslowski J.; Fox D. J.. Gaussian 09; Gaussian, Inc.: Wallingford CT, 2009.
  42. Zhao Y.; Truhlar D. G. How Well Can New-Generation Density Functionals Describe the Energetics of Bond-Dissociation Reactions Producing Radicals?. J. Phys. Chem. A 2008, 112, 1095–1099. 10.1021/jp7109127. [DOI] [PubMed] [Google Scholar]
  43. Alvarez-Idaboy J. R. l.; Galano A. On the Chemical Repair of DNA Radicals by Glutathione: Hydrogen Vs Electron Transfer. J. Phys. Chem. B 2012, 116, 9316–9325. 10.1021/jp303116n. [DOI] [PubMed] [Google Scholar]
  44. Evans M. G.; Polanyi M. Some applications of the transition state method to the calculation of reaction velocities, especially in solution. Trans. Faraday Soc. 1935, 31, 875–894. 10.1039/tf9353100875. [DOI] [Google Scholar]
  45. Eyring H. The Activated Complex in Chemical Reactions. J. Chem. Phys. 1935, 3, 107–115. 10.1063/1.1749604. [DOI] [Google Scholar]
  46. Truhlar D. G.; Hase W. L.; Hynes J. T. Current Status of Transition-State Theory. J. Phys. Chem. B 1983, 87, 2664–2682. 10.1021/j100238a003. [DOI] [Google Scholar]
  47. Furuncuoğlu T.; Uğur I.; Değirmenci I.; Aviyente V. Role of chain transfer agents in free radical polymerization kinetics. Macromolecules 2010, 43, 1823–1835. 10.1021/ma902803p. [DOI] [Google Scholar]
  48. Vélez E.; Quijano J.; Notario R.; Pabón E.; Murillo J.; Leal J.; Zapata E.; Alarcón G. A computational study of stereospecifity in the thermal elimination reaction of menthyl benzoate in the gas phase. J. Phys. Org. Chem. 2009, 22, 971–977. 10.1002/poc.1547. [DOI] [Google Scholar]
  49. Dzib E.; Cabellos J. L.; Ortiz-Chi F.; Pan S.; Galano A.; Merino G.. Eyringpy 1.0.2; Cinvestav: Mérida, Yucatán, 2018.

Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

ao1c04569_si_001.pdf (862.4KB, pdf)

Articles from ACS Omega are provided here courtesy of American Chemical Society

RESOURCES