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. 2021 May 13;6(20):13391–13397. doi: 10.1021/acsomega.1c01448

Radical Scavenging Activity of Natural Anthraquinones: a Theoretical Insight

Nguyen Quang Trung †,‡, Nguyen Minh Thong §, Dao Hung Cuong †, Tran Duc Manh †, Loc Phuoc Hoang ∥, Nguyen Khoa Hien ⊥, Pham Cam Nam #, Duong Tuan Quang , Adam Mechler ∇, Quan V Vo ○,*
PMCID: PMC8158809  PMID: 34056486

Abstract

graphic file with name ao1c01448_0004.jpg

Anthraquinones (ANQs) isolated from Paederia plants are known to have antidiarrheal, antitussive, anthelmintic, analgesic, anti-inflammatory, antihyperlipidemic, antihyperglycaemic, and antimicrobial activities. The antioxidant properties were also noted but not confirmed thus far. In this study, the superoxide and hydroperoxide radical scavenging activities of six ANQs were evaluated using a computational approach. The results suggest that the ANQs exhibit low HOO• antiradical activity in all environments, including the gas phase (k < 102 M–1 s–1). In contrast, the ANQs might exert excellent O2•– radical scavenging activity, particularly in aqueous solution. The rate constants of the superoxide anion scavenging in water (at pH = 7.4) range from 3.42 × 106 to 3.70 × 108 M–1 s–1. Compared with typical antioxidants such as ascorbic acid and quercetin, the superoxide anion scavenging activity of ANQs is significantly higher. Thus, the ANQs are promising O2•– radical scavengers in polar media.

1. Introduction

Reactive oxygen species (ROS) play an important role in the normal metabolism of humans. They participate in the bacterial ingestion of phagocytes as well as the regulation of signaling pathways, and thus cellular processes related to, for example, metabolism and proliferation.1 However, excess ROS production is harmful to the native biochemistry of the human body, indicted as a common pathway to some incurable conditions including cardiovascular disease, cancer, and diabetes.2−6 The adverse effects of ROS are kept in check by dietary antioxidant intake; several recent studies showed that the antioxidant constituents from natural plants are vital factors in disease prevention.7,8

Species of Polygonaceae, Leguminosae, Rubiaceae, and some 30 other families contain an abundance of natural antioxidants, including but are not limited to phenolic compounds.9,10 Anthraquinones (ANQs) belong to this group but mostly have been used as colorants in food, drugs, and cosmetics.11,12 ANQ derivatives with acidic or polar, hydrophilic substitution such as aloe-emodin, emodin, rhein, chrysophanol, and physcion were described with antiangiogenic activities.13,14 Experimental antioxidant activity data of ANQs that were collected by the 2,2-diphenyl-1-picrylhydrazyl, total reducing power ability, oxygen radical absorbance capacity ,and low-density lipoprotein methods showed that ANQs could exhibit good antioxidant activity.11,15−17

Paederia plants i.e.,P. foetida and P. scandens are distributed widely in temperate and tropical East Asia and tropical South-East Asia.18 These plants are well known not only as traditional food ingredients in daily meals but also as traditional medicinal plants to treat toothache, tumors, rheumatoid arthritis, inflammation, diarrhea, and hemorrhoids.19,20Paederia extracts showed antidiarrheal, antitussive, anthelmintic, analgesic, anti-inflammatory, antihyperlipidemic, antihyperglycaemic, antimicrobial, and antioxidant activity.21−29 From these extracts, a number of ANQs were isolated and characterized including 1,3-dihydroxy-2,4-dimethoxy-9,10-anthraquinone (1), 2-hydroxy-1,4-dimethoxy-9,10-anthraquinone (2), 1-methoxy-2-methoxymethyl-3-hydroxy-9,10-anthraquinone (3), 1-hydroxy-2 hydroxymethyl-9,10-anthraquinone (4), 1-methyl-2,4-dimethoxy-3-hydroxyanthraquinone (5), and 1-methoxy-3-hydroxy-2-ethoxymethylanthraquinone (6) (Figure 1).30,31 ANQ derivatives were also described as photosensitizers to create singlet oxygen and superoxide anions in UV environments,32−34 whereas some studies indicated that these compounds could exhibit the O2•– scavenging activity, particularly in polar environments.35,36 Hence, it is desirable to gather further insights into the radical scavenging activity of ANQs.

Figure 1.

Figure 1

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Structures of the six ANQs in this study.

Previous studies confirmed that the quantum chemical calculation offers a useful and reliable pathway to evaluate the radical scavenging as well as the antioxidant activity of natural products.8,37−42 Thus, in this study, the antioxidant activity of six ANQs (Figure 1) was investigated by using thermodynamic and kinetic calculations. The antioxidant properties of the ANQs were investigated in the HOO• and O2•– radical scavenging reactions in the gas phase as well as physiological environments.

2. Results and Discussion

2.1. Thermodynamic Study

Previous studies indicated that conformation plays an important role in the antioxidant activity of molecules that have multiple stable conformers.8,37 Thus, the studied ANQs were first screened to find the conformers with low electronic energy.43 The five lowest electronic energy conformers were then analyzed to find the most stable conformers, and these forms were used in further computations. For example, for compounds 3 and 6 that contain both methoxy and ethoxy groups, the five lowest electronic energy conformers were analyzed by the M06-2X/6-311++G(d,p) method (Figure S1, Supporting Information) and the most stable forms (3 and 6, >99%) were achieved by using the Maxwell–Boltzmann distribution to estimate the relative populations of conformers.44,45

In the initial step of the study, the thermodynamic parameters, including bond dissociation energies (BDEs), ionization energies (IEs), and proton affinities (PAs) were evaluated for all the studied compounds following the method reported previously.38,40 To save computing time, the BDE and PA values of all possible bonds were first calculated at the M06-2X/3-21G level of theory and the lowest values were then re-computed with a more accurate method (M06-2X/6-311++G(d,p) level of theory). The results are presented in Table 1.

Table 1. Calculated BDEs, PAs, and IEs of Studied Compounds and ΔGo (kcal/mol) for the ANQs + HOO• Reaction Following the FHT, SP, and SET Mechanisms in the Gas Phase.

  FHT
 SP
 SET
comp. positions BDE ΔG positions PA ΔG IE ΔG
1 O3 88.7 1.6 O3 335.1 257.0 180.9 234.2
2 O2 90.6 2.1 O2 334.1 255.7 183.3 237.1
3 C2 83.8 –4.0 O3 334.4 255.8 191.7 244.9
4 C2 79.6 –7.1 O1 347.2 268.3 192.7 245.7
5 O2 88.2 1.1 O2 335.7 258.1 185.9 239.9
6 C2 82.7 –4.4 O3 338.6 260.3 189.1 242.8
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As shown in Table 1, the lowest BDEs (X–H, X = O, C) of the ANQs range from 79.6 to 90.6 kcal/mol. The lowest calculated PAs are observed at (O–H) bonds with PA = 334.1–347.2 kcal/mol, which are significantly higher than the IE values of the ANQs (IE = 180.9–192.7 kcal/mol). Notably, the thermochemical parameters are generally higher than those of natural hydroanthraquinone derivatives (BDE = 76.2–88.6 kcal/mol; PA = 313.8–331.8 kcal/mol; and IE = 172.7–180.3 kcal/mol).46 This result suggests that reducing the carbonyl group (C=O) of the ANQ system to the alcohol group (hydroanthraquinones) may decline the BDE, PA, and IE values and that the antioxidant activity of ANQs may be lower than the activities of the hydroanthraquinones.

The lowest BDE is calculated for the 4–C2–H bond (BDE = 79.6 kcal/mol), while the lowest for PA and IE are observed at compound 2 with PA = 334.1 kcal/mol and 1 with IE = 180.9 kcal/mol. The BDEs of ANQs are higher than those of typical natural antioxidants, such as Trolox, ascorbic acid (BDE < 78 kcal/mol);8,47 thus, the radical scavenging activity of these ANQs following the FHT mechanism is expected to be weaker than the reference antioxidants.

As an initial assessment of the HOO• radical scavenging ability of the ANQs, Gibbs energies (ΔGo) of the reactions between HOO• radicals and the ANQs were calculated for each of the three typical radical scavenging mechanisms: formal hydrogen transfer (FHT),48 sequential proton [SP, first step of SP loss electron transfer mechanism (SPLET)],49−52 and single electron transfer [SET, first step of SET followed by the proton transfer mechanism (SETPT)];7,53 the results are summarized in Table 1. The results showed that the HOO• radical scavenging was only spontaneous (ΔGo < 0) for the FHT mechanism and not for the other two mechanisms (SP and SET) in the gas phase. Thus, these mechanisms can be disregarded in the following kinetic modeling.

2.2. Kinetic Study

2.2.1. HOO• Radical Scavenging of ANQs in the Gas Phase

As shown in the thermodynamic section, the FHT pathway is the favored mechanism for the HOO• radical scavenging of ANQs. Thus, in this section, the kinetic calculations were performed for the H-abstraction of the X–H (X = C, O) bonds with the lowest BDEs (Table 1). The results are shown in Table 2 and Figure 2.

Table 2. Calculated ΔG⧧ (kcal/mol), κ, and kEck (M–1 s–1) for the HOO• Scavenging of the ANQs in the Gas Phase.
reaction ΔH ΔG⧧ κ kEck
1–O3–H + HOO• 7.7 18.0 39.5 1.63 × 101
2–O2–H + HOO• 9.1 19.1 48.5 3.13
3–C2–H + HOO• 8.8 18.2 84.8 2.23 × 101
4–C2–H + HOO• 8.4 17.9 50.6 2.47 × 101
5–O2–H + HOO• 7.0 17.4 61.3 6.63 × 101
6–C2–H + HOO• 7.2 17.1 30.8 5.24 × 101
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Figure 2.

Figure 2

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Optimized geometries of TSs between the studied compounds and HOO• radical in the gas phase following the FHT mechanism.

It is clear from Table 2 that the HOO• radical scavenging of ANQs is slow with kEck = 3.13–66.3 M–1 s–1 and ΔG⧧ = 17.1–19.1 kcal/mol. This is in logical agreement with the high BDE values obtained from the thermodynamic calculations. Previous studies showed that the HOO• antiradical activity of most model lipid media (i.e., in pentyl ethanoate solvent) mainly occurred following the FHT pathway, and the rate constant was usually lower than in the gas phase.39,40,54 Thus, this suggests that the AQNs are not good antioxidants in the lipid media.

2.2.2. HOO• and O2•– Scavenging of ANQs in Aqueous Solution

2.2.2.1. Acid–Base Equilibria

As a requirement of antioxidant activity evaluation in aqueous solution,8,37,48 the molar fractions (f) of the deprotonated state of ANQs were calculated at physiological pH. The alcohol moiety has a dissociation equilibrium as per reaction 1, and the pKa values are calculated according to eq 2 (Table 3).37,40,55

Table 3. Calculated pKa and f at pH = 7.4.
      f
comp. positions pKa HA A–
1 O3–H 6.94 0.253 0.747
  O1–H 10.76a    
2 O2–H 7.00 0.285 0.715
3 O3–H 7.72 0.676 0.324
4 O1–H 8.66 0.948 0.052
5 O2–H 7.53 0.574 0.426
6 O3–H 7.75 0.691 0.309
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a

pKa2.

The calculated pKa values (Table 3) range from 6.94 to 10.76; hence, at pH 7.4, the neutral species are present in 25.3–94.8% and the dissociated state makes up the remaining 5.2–74.7%. Among the studied compounds, 1 could also form a dianion with pKa2 = 10.76. However, at pH 7.4, this state only populates 0.033% of the total concentration of 1; thus, the dianion species can be omitted in the kinetic calculations.

2.2.2.1. 1
2.2.2.1. 2
2.2.2.1. 3

where ΔGBAo was obtained from reaction 2 following eq 4 and m and C0 are fitted parameters directly obtained from ref (55).55

2.2.2.2. Kinetic Study

The study on the HOO• radical scavenging of ANQs in the gas phase showed that the rate constants for this process according to the FHT pathway were low. Thus, the study on radical scavenging in the polar environment only focused on the SPLET mechanism (the second step as the SET mechanism) against typical radicals, that is, HOO• and O2•–. It was already established that the SET mechanism is the main pathway for superoxide anion scavenging in polar media to form stable diradical 3O2.56−58 Therefore, the HOO• and O2•– scavenging of ANQs in aqueous solution could occur via reactions 4–7, and the overall rate constants (koverall) were calculated according to eqs 8 and 9. The results are presented in Table 4.

2.2.2.2. 4
2.2.2.2. 5
2.2.2.2. 6
2.2.2.2. 7
2.2.2.2. 8
2.2.2.2. 9
Table 4. Calculated ΔG⧧ (in kcal/mol), Nuclear Reorganization Energy (λ), and Rate Constants (kapp, kf, M–1 s–1) of the HOO• and O2•– Scavenging of the ANQs in Aqueous Solution Following the SPLET Mechanism.
    HOO•
 O2•–
comp.   ΔG⧧ λ kapp kfa koverall ΔG⧧ λ kapp kfa koverall
1 HA 40.8 22.7 7.90 × 10–18 2.00 × 10–18 1.57 × 101 6.0 20.6 2.60 × 108 6.68 × 107 6.59 × 107
  A– 15.6 19.5 2.10 × 101 1.57 × 101   10.5 20.2 1.30 × 105 9.71 × 104  
2 HA 33.2 30.3 2.90 × 10–12 8.27 × 10–13 2.50 × 10–1 7.8 20.2 1.20 × 107 3.42 × 106 3.42 × 106
  A– 18.1 15.5 3.50 × 10–1 2.50 × 10–1   13.4 19.8 8.60 × 102 6.15 × 102  
3 HA 56.1 18.9 4.70 × 10–29 3.18 × 10–29 7.78 × 10–3 7.1 20.0 4.20 × 107 2.84 × 107 2.84 × 107
  A– 19.7 14.9 2.40 × 10–2 7.78 × 10–3   11.7 19.0 1.70 × 104 5.51 × 103  
4 HA 53.4 17.9 4.50 × 10–27 4.27 × 10–27 4.63 × 10–1 5.7 20.5 3.90 × 108 3.70 × 108 3.70 × 108
  A– 16.2 15.4 8.90 4.63 × 10–1   13 18.7 1.90 × 103 9.88 × 101  
5 HA 42.5 22.7 4.00 × 10–19 2.30 × 10–19 8.95 × 101 8.3 21.1 5.10 × 106 2.93 × 106 2.93 × 106
  A– 14.3 16.4 2.10 × 102 8.95 × 101   13.6 20.4 6.50 × 102 2.77 × 102  
6 HA 49.3 20.9 4.30 × 10–24 2.97 × 10–24 5.56 × 10–3 7.1 20.7 3.70 × 107 2.56 × 107 2.56 × 107
  A– 19.8 14.6 1.80 × 10–2 5.56 × 10–3   11.5 19.3 2.30 × 104 7.11 × 103  
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a

kf = f·kapp.

As shown in Table 4, the neutral states (HA) have virtually no contribution in the HOO• radical scavenging of ANQs in aqueous solution (ΔG⧧ = 33.2–56.1 kcal/mol and kapp = 4.70 × 10–29 to 2.90 × 10–12 M–1 s–1). The HOO• scavenging activity of the anions (A–) is somewhat higher; however, kapp and kf values range from 1.80 × 10–2 to 2.10 × 102 and 5.56 × 10–3 to 8.95 × 101 M–1 s–1, respectively. The highest overall rate constant for the HOO• antiradical activity is koverall = 89.1 M–1 s–1 that is much lower than that of typical natural antioxidants, that is, Trolox8 and ascorbic acid.37 As anticipated based on the energetic analysis above, ANQs exhibit significantly lower (∼105 to 106 times) HOO• radical scavenging activity than natural hydroanthraquinone derivatives,46 particularly in the polar media, emphasizing the importance of the alcohol moieties. Consistently, the studied ANQs are poor HOO• radical scavengers in physiological environments.

However, ANQ compounds exhibit excellent O2•– radical scavenging activity, particularly in polar environments. The anion states have moderate O2•– antiradical activity with kapp = 6.50 × 102 to 1.30 × 105 M–1 s–1, whereas the activities of the HA states fall range from 5.10 × 106 to 3.90 × 108 M–1 s–1. As a result, the koverall range from 3.42 × 106 to 3.70 × 108 M–1 s–1. That is in good agreement with the previous findings in carotenoids.59 Compound 4 exhibits the highest O2•– radical scavenging activity with koverall = 3.70 × 108 M–1 s–1. This is about 100 times higher than that of compound 5 (the lowest O2•– radical scavenger). Compared with typical antioxidants such as ascorbic acid and quercetin (k = 0.1 × 103 to 3.0 × 103 M–1 s–1),60 the superoxide anion scavenging of ANQs is much higher. Thus, ANQs are promising O2•– radical scavengers in polar environments.

3. Conclusions

In this study, the superoxide and HOO• radical scavenging activity of six ANQs was evaluated. It was found that the ANQs have very low HOO• antiradical activity in both gas phase and physiological environments. The rate constants of the HOO• radical scavenging of ANQs are less than 102 M–1 s–1, implying that they are not useful HOO• radical scavengers. However, ANQs were found to be excellent O2•– radical scavengers, particularly in aqueous solution. The rate constants of the superoxide anion scavenging of ANQs range from 3.42 × 106 to 3.70 × 108 M–1 s–1, which is much higher than that of typical antioxidants, such as ascorbic acid and quercetin. Thus, the ANQs are promising O2•– radical scavengers in polar environments.

4. Computational Methods

Thermochemical properties (BDEs, IEs, and PAs) as well as kinetic parameters, activation energies ΔG⧧ (kcal/mol), tunneling corrections (κ), and rate constants (k) in the studied environments (the gas phase and in physiological environments) were computed using the M06-2X functional.48,61−64 M06-2X/6-311++G(d,p) has been well established as a suitable method to compute both thermochemical and kinetic parameters due to its good accuracy compared with the more complex functionals [i.e., G3(MP2)-RAD] and experimental data.8,48,61,64 The quantum mechanic-based test for the overall free radical scavenging activity protocol8,37,61,65−67 was used to perform the kinetic calculations. The rate constant (k) was calculated by using the conventional transition-state theory and 1M standard state at 298.15 K.40,54,62,67−72 The details of the method are shown in Table S3, Supporting Information.54 All DFT calculations in this work were carried out using Gaussian 16 package.73

Acknowledgments

This research is funded by the Vietnam National Foundation for Science and Technology Development (NAFOSTED).

Supporting Information Available

The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acsomega.1c01448.

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

The authors declare no competing financial interest.

Supplementary Material

ao1c01448_si_001.pdf (3.3MB, pdf)

References

  1. Ray P. D.; Huang B.-W.; Tsuji Y. Reactive oxygen species (ROS) homeostasis and redox regulation in cellular signaling. Cell Signal. 2012, 24, 981–990. 10.1016/j.cellsig.2012.01.008. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Mokini Z.; Marcovecchio M. L.; Chiarelli F. Molecular pathology of oxidative stress in diabetic angiopathy: role of mitochondrial and cellular pathways. Diabetes Res. Clin. Pract. 2010, 87, 313–321. 10.1016/j.diabres.2009.11.018. [DOI] [PubMed] [Google Scholar]
  3. Singh U.; Jialal I. Oxidative stress and atherosclerosis. Pathophysiology 2006, 13, 129–142. 10.1016/j.pathophys.2006.05.002. [DOI] [PubMed] [Google Scholar]
  4. Valko M.; Rhodes C. J.; Moncol J.; Izakovic M.; Mazur M. Free radicals, metals and antioxidants in oxidative stress-induced cancer. Chem. Biol. Interact. 2006, 160, 1–40. 10.1016/j.cbi.2005.12.009. [DOI] [PubMed] [Google Scholar]
  5. de las Rivas M.; Lira-Navarrete E.; Daniel E. J. P.; Compañón I.; Coelho H.; Diniz A.; Jiménez-Barbero J.; Peregrina J. M.; Clausen H.; Corzana F. The interdomain flexible linker of the polypeptide GalNAc transferases dictates their long-range glycosylation preferences. Nat. Commun. 2017, 8, 1959. 10.1038/s41467-017-02006-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. 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]
  7. Ingold K. U.; Pratt D. A. Advances in radical-trapping antioxidant chemistry in the 21st century: a kinetics and mechanisms perspective. Chem. Rev. 2014, 114, 9022–9046. 10.1021/cr500226n. [DOI] [PubMed] [Google Scholar]
  8. 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]
  9. Chen A.; Sun L.; Yuan H.; Wu A.; Lu J.; Ma S. Simultaneous qualitative and quantitative analysis of 11 active compounds in rhubarb using two reference substances by UHPLC. J. Sep. Sci. 2018, 41, 3686–3696. 10.1002/jssc.201800479. [DOI] [PubMed] [Google Scholar]
  10. Suzuki H.; Matsumoto T.. Anthraquinone: production by plant cell culture. Medicinal and Aromatic Plants I; Springer, 1988; pp 237–250. [Google Scholar]
  11. Zengin G.; Locatelli M.; Ceylan R.; Aktumsek A. Anthraquinone profile, antioxidant and enzyme inhibitory effect of root extracts of eight Asphodeline taxa from Turkey: can Asphodeline roots be considered as a new source of natural compounds?. J. Enzyme Inhib. Med. Chem. 2016, 31, 754–759. 10.3109/14756366.2015.1063623. [DOI] [PubMed] [Google Scholar]
  12. Zastrow L.; Schwind K.-H.; Schwägele F.; Speer K. Influence of Smoking and Barbecuing on the Contents of Anthraquinone (ATQ) and Polycyclic Aromatic Hydrocarbons (PAHs) in Frankfurter-Type Sausages. J. Agric. Food Chem. 2019, 67, 13998–14004. 10.1021/acs.jafc.9b03316. [DOI] [PubMed] [Google Scholar]
  13. He Z.-H.; He M.-F.; Ma S.-C.; But P. P.-H. Anti-angiogenic effects of rhubarb and its anthraquinone derivatives. J. Ethnopharmacol. 2009, 121, 313–317. 10.1016/j.jep.2008.11.008. [DOI] [PubMed] [Google Scholar]
  14. Yuan X.-L.; Wang X.-F.; Xu K.; Li W.; Chen D.; Zhang P. Characterization of a New Insecticidal Anthraquinone Derivative from an Endophyte of Acremonium vitellinum against Helicoverpa armigera. J. Agric. Food Chem. 2020, 68, 11480–11487. 10.1021/acs.jafc.0c05680. [DOI] [PubMed] [Google Scholar]
  15. Mellado M.; Madrid A.; Peña-cortés H.; López R.; Jara C.; Espinoza L. Antioxidant activity of anthraquinones isolated from leaves of muehlenbeckia hastulata (je sm.) johnst. (polygonaceae). J. Chil. Chem. Soc. 2013, 58, 1767–1770. 10.4067/s0717-97072013000200028. [DOI] [Google Scholar]
  16. Ben Ammar R.; Miyamoto T.; Chekir-Ghedira L.; Ghedira K.; Lacaille-Dubois M.-A. Isolation and identification of new anthraquinones from Rhamnus alaternus L and evaluation of their free radical scavenging activity. Nat. Prod. Res. 2019, 33, 280–286. 10.1080/14786419.2018.1446135. [DOI] [PubMed] [Google Scholar]
  17. Sun Y. N.; Li W.; Lee S. H.; Jang H. D.; Ma J. Y.; Kim Y. H. Antioxidant and anti-osteoporotic effects of anthraquinones and related constituents from the aqueous dissolved Aloe exudates. Nat. Prod. Res. 2017, 31, 2810–2813. 10.1080/14786419.2017.1295238. [DOI] [PubMed] [Google Scholar]
  18. DeFilipps R. A.; Krupnick G. A. The medicinal plants of Myanmar. PhytoKeys 2018, 102, 1–341. 10.3897/phytokeys.102.24380. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Wong K. C.; Tan G. L. Steam volatile constituents of the aerial parts of Paederia foetida L. Flavour Fragrance J. 1994, 9, 25–28. 10.1002/ffj.2730090106. [DOI] [Google Scholar]
  20. Duke J. A.Handbook of Medicinal Herbs; CRC Press, 2002. [Google Scholar]
  21. Afroz S.; Alamgir M.; Khan M.; Jabbar S.; Nahar N.; Choudhuri M. Antidiarrhoeal activity of the ethanol extract of Paederia foetida Linn. (Rubiaceae). J. Ethnopharmacol. 2006, 105, 125–130. 10.1016/j.jep.2005.10.004. [DOI] [PubMed] [Google Scholar]
  22. Osman H.; Rahim A.; Isa N.; Bakhir N. Antioxidant activity and phenolic content of Paederia foetida and Syzygium aqueum. Molecules 2009, 14, 970–978. 10.3390/molecules14030970. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Nosáĺová G.; Mokrý J.; Ather A.; Khan M. Antitussive activity of the ethanolic extract of Paederia foetida (Rubiaceae family) in non-anaesthetized cats. Acta Vet. Brno 2007, 76, 27–33. 10.2754/avb200776010027. [DOI] [Google Scholar]
  24. Dey Y. N.; Pal M. K. Evaluation of anthelmintic activity of leaves of Paederia foetida. Int. J. Pharma Bio Sci. 2011, 2, 227–231. [Google Scholar]
  25. Karmakar U. K.; Akter S.; Sultana S. Investigation of Antioxidant, Analgesic, Antimicrobial, and Anthelmintic Activity of the Aerial parts of Paederia foetida (Family: Rubiaceaea). Jordan J. Pharm. Sci. 2020, 13, 131. [Google Scholar]
  26. De S.; Ravishankar B.; Bhavsar G. C. Investigation of the anti-inflammatory effects of Paederia foetida. J. Ethnopharmacol. 1994, 43, 31–38. 10.1016/0378-8741(94)90113-9. [DOI] [PubMed] [Google Scholar]
  27. Kumar V.; Anwar F.; Ahmed D.; Verma A.; Ahmed A.; Damanhouri Z. A.; Mishra V.; Ramteke P. W.; Bhatt P. C.; Mujeeb M. Paederia foetida Linn. leaf extract: an antihyperlipidemic, antihyperglycaemic and antioxidant activity. BMC Complementary Altern. Med. 2014, 14, 76. 10.1186/1472-6882-14-76. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Borgohain M. P.; Chowdhury L.; Ahmed S.; Bolshette N.; Devasani K.; Das T. J.; Mohapatra A.; Lahkar M. Renoprotective and antioxidative effects of methanolic Paederia foetida leaf extract on experimental diabetic nephropathy in rats. J. Ethnopharmacol. 2017, 198, 451–459. 10.1016/j.jep.2017.01.035. [DOI] [PubMed] [Google Scholar]
  29. Upadhyaya S. Screening of phytochemicals, nutritional status, antioxidant and antimicrobial activity of Paederia foetida Linn. from different localities of Assam, India. J. Pharm. Res. 2013, 7, 139–141. 10.1016/j.jopr.2013.01.015. [DOI] [Google Scholar]
  30. Quang D̵. N. Anthraquinones from the roots of Paederia scandens. Vietnam J. Chem. 2009, 47, 95. [Google Scholar]
  31. Zhang X.; Zhou H.-F.; Li M.-Y.; Yue X.-Y.; Wu T. Three new anthraquinones from aerial parts of Paederia scandens. Chem. Nat. Compd. 2018, 54, 245–248. 10.1007/s10600-018-2314-2. [DOI] [Google Scholar]
  32. Comini L. R.; Núñez Montoya S. C.; Páez P. L.; Argüello G. A.; Albesa I.; Cabrera J. L. Antibacterial activity of anthraquinone derivatives from Heterophyllaea pustulata (Rubiaceae). J. Photochem. Photobiol., B 2011, 102, 108–114. 10.1016/j.jphotobiol.2010.09.009. [DOI] [PubMed] [Google Scholar]
  33. Montoya S. C. N.; Comini L. R.; Sarmiento M.; Becerra C.; Albesa I.; Argüello G. A.; Cabrera J. L. Natural anthraquinones probed as Type I and Type II photosensitizers: singlet oxygen and superoxide anion production. J. Photochem. Photobiol., B 2005, 78, 77–83. 10.1016/j.jphotobiol.2004.09.009. [DOI] [PubMed] [Google Scholar]
  34. Chinami m.; okamoto k.; kato t.; ogura r. Superoxide Anion Radical (O2-) Generation by Adriamycin and Anthraquinone Analogues. Kurume Med. J. 1981, 28, 9–13. 10.2739/kurumemedj.28.9. [DOI] [PubMed] [Google Scholar]
  35. Yen G.; Duh P.-D.; Chuang D.-Y. Antioxidant activity of anthraquinones and anthrone. Food Chem. 2000, 70, 437–441. 10.1016/s0308-8146(00)00108-4. [DOI] [Google Scholar]
  36. Ossowski T.; Pipka P.; Liwo A.; Jeziorek D. Electrochemical and UV-spectrophotometric study of oxygen and superoxide anion radical interaction with anthraquinone derivatives and their radical anions. Electrochim. Acta 2000, 45, 3581–3587. 10.1016/s0013-4686(00)00479-5. [DOI] [Google Scholar]
  37. 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]
  38. Vo Q. V.; Nam P. C.; Bay M. V.; Thong N. M.; Cuong N. D.; Mechler A. Density functional theory study of the role of benzylic hydrogen atoms in the antioxidant properties of lignans. Sci. Rep. 2018, 8, 12361–123610. 10.1038/s41598-018-30860-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Vo Q. V.; Cam Nam P.; Bay M. V.; Minh Thong N.; Hieu L. T.; Mechler A. A theoretical study of the radical scavenging activity of natural stilbenes. RSC Adv. 2019, 9, 42020–42028. 10.1039/c9ra08381b. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. 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]
  41. Leopoldini M.; Russo N.; Toscano M. The molecular basis of working mechanism of natural polyphenolic antioxidants. Food Chem. 2011, 125, 288–306. 10.1016/j.foodchem.2010.08.012. [DOI] [Google Scholar]
  42. 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]
  43. Hehre W.; Yu J.; Klunzinger P.; Lou L.. Spartan Software; Wavefunction Inc.: Irvine, 2000.
  44. Galano A.; Alvarez-Idaboy J. R. Glutathione: mechanism and kinetics of its non-enzymatic defense action against free radicals. RSC Adv. 2011, 1, 1763–1771. 10.1039/c1ra00474c. [DOI] [Google Scholar]
  45. Vo Q. V.; Tam N. M.; Bay M. V.; Mechler A. The radical scavenging activity of natural ramalin: A mechanistic and kinetic study. Chem. Phys. Lett. 2020, 739, 137004. 10.1016/j.cplett.2019.137004. [DOI] [Google Scholar]
  46. 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]
  47. Boulebd H. Comparative study of the radical scavenging behavior of ascorbic acid, BHT, BHA and Trolox: experimental and theoretical study. J. Mol. Struct. 2020, 1201, 127210. 10.1016/j.molstruc.2019.127210. [DOI] [Google Scholar]
  48. 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]
  49. Ames B. N.; Shigenaga M. K.; Hagen T. M. Oxidants, antioxidants, and the degenerative diseases of aging. Proc. Natl. Acad. Sci. U.S.A. 1993, 90, 7915–7922. 10.1073/pnas.90.17.7915. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Wang G.; Xue Y.; An L.; Zheng Y.; Dou Y.; Zhang L.; Liu Y. Theoretical study on the structural and antioxidant properties of some recently synthesised 2,4,5-trimethoxy chalcones. Food Chem. 2015, 171, 89–97. 10.1016/j.foodchem.2014.08.106. [DOI] [PubMed] [Google Scholar]
  51. Estévez L.; Otero N.; Mosquera R. A. A Computational Study on the Acidity Dependence of Radical-Scavenging Mechanisms of Anthocyanidins. J. Phys. Chem. B 2010, 114, 9706–9712. 10.1021/jp1041266. [DOI] [PubMed] [Google Scholar]
  52. Zheng Y.-Z.; Deng G.; Guo R.; Fu Z.-M.; Chen D.-F. Theoretical insight into the antioxidative activity of isoflavonoid: The effect of the C2=C3 double bond. Phytochemistry 2019, 166, 112075. 10.1016/j.phytochem.2019.112075. [DOI] [PubMed] [Google Scholar]
  53. 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]
  54. Boulebd H.; Mechler A.; Hoa N. T.; Vo Q. V. Thermodynamic and Kinetic Studies of the Antiradical Activity of 5-Hydroxymethylfurfural: Computational Insights. New J. Chem. 2020, 44, 9863–9869. 10.1039/d0nj01567a. [DOI] [Google Scholar]
  55. 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]
  56. Karadag A.; Ozcelik B.; Saner S. Review of methods to determine antioxidant capacities. Food Anal. Method. 2009, 2, 41–60. 10.1007/s12161-008-9067-7. [DOI] [Google Scholar]
  57. Nimse S. B.; Pal D. Free radicals, natural antioxidants, and their reaction mechanisms. RSC Adv. 2015, 5, 27986–28006. 10.1039/c4ra13315c. [DOI] [Google Scholar]
  58. Cordova-Gomez M.; Galano A.; Alvarez-Idaboy J. R. Piceatannol, a better peroxyl radical scavenger than resveratrol. RSC Adv. 2013, 3, 20209–20218. 10.1039/c3ra42923g. [DOI] [Google Scholar]
  59. Galano A.; Vargas R.; Martínez A. Carotenoids can act as antioxidants by oxidizing the superoxide radical anion. Phys. Chem. Chem. Phys. 2010, 12, 193–200. 10.1039/b917636e. [DOI] [PubMed] [Google Scholar]
  60. Muhammad H.; Hanif M.; Tahiri I. A.; Versiani M. A.; Shah F.; Khaliq O.; Ali S. T.; Ahmed S. Electrochemical behavior of superoxide anion radical towards quinones: a mechanistic approach. Res. Chem. Intermed. 2018, 44, 6387–6400. 10.1007/s11164-018-3496-8. [DOI] [Google Scholar]
  61. Carreon-Gonzalez M.; Vivier-Bunge A.; Alvarez-Idaboy J. R. Thiophenols, Promising Scavengers of Peroxyl Radicals: Mechanisms and kinetics. J. Comput. Chem. 2019, 40, 2103–2110. 10.1002/jcc.25862. [DOI] [PubMed] [Google Scholar]
  62. 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. Quant. Chem. 2019, 119, e25686 10.1002/qua.25686. [DOI] [Google Scholar]
  63. Zhao Y.; Schultz N. E.; Truhlar D. G. Design of Density Functionals by Combining the Method of Constraint Satisfaction with Parametrization for Thermochemistry, Thermochemical Kinetics, and Noncovalent Interactions. J. Chem. Theory Comput. 2006, 2, 364–382. 10.1021/ct0502763. [DOI] [PubMed] [Google Scholar]
  64. 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]
  65. Alvarez-Idaboy J. R.; 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]
  66. Vo Q. V.; Van Bay M.; 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]
  67. Dzib E.; Cabellos J. L.; Ortiz-Chi F.; Pan S.; Galano A.; Merino G.. Eyringpy 1.0.2; Cinvestav: Mérida, Yucatán, 2018.
  68. 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]
  69. Eyring H. The activated complex in chemical reactions. J. Chem. Phys. 1935, 3, 107–115. 10.1063/1.1749604. [DOI] [Google Scholar]
  70. Truhlar D. G.; Hase W. L.; Hynes J. T. Current status of transition-state theory. J. Phys. Chem. 1983, 87, 2664–2682. 10.1021/j100238a003. [DOI] [Google Scholar]
  71. Furuncuoğlu T.; Ugur I.; Degirmenci I.; Aviyente V. Role of chain transfer agents in free radical polymerization kinetics. Macromolecules 2010, 43, 1823–1835. 10.1021/ma902803p. [DOI] [Google Scholar]
  72. 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]
  73. Frisch M. J., Trucks G. W.; Schlegel H. B.; Scuseria G. E.; Robb M. A.; Cheeseman J. R.; Scalmani G.; Barone V.; 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.; Throssell K.; Montgomery J. A. Jr.; Peralta J. E.; Ogliaro F.; Bearpark M.; Heyd J. J.; Brothers E.; Kudin K. N.; Staroverov V. N.; Kobayashi R.; Normand J.; Raghavachari K.; Rendell A.; Burant J. C.; Iyengar S. S.; Tomasi J.; Cossi M.; Rega N.; Millam J. M.; Klene M.; Knox J. E.; Cross J. B.; Baken 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 Ö.; Foresman J. B.; Ortiz J. V.; Cioslowski J.; Fox D. J.. Gaussian 16, Revision B.01; Gaussian Inc.: Wallingford, CT, 2016.

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