Is Indolinonic Hydroxylamine a Promising Artificial Antioxidant? | The

Subscriber access provided by Macquarie University

B: Biophysics; Physical Chemistry of Biological Systems and Biomolecules

Is Indolinonic Hydroxylamine a Promising Artificial Antioxidant? Quan V. Vo, Mai Van Bay, Pham Cam Nam, and Adam Mechler J. Phys. Chem. B, Just Accepted Manuscript • DOI: 10.1021/acs.jpcb.9b05160 • Publication Date (Web): 28 Aug 2019 Downloaded from pubs.acs.org on August 30, 2019

Just Accepted “Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted online prior to technical editing, formatting for publication and author proofing. The American Chemical Society provides “Just Accepted” as a service to the research community to expedite the dissemination of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts appear in full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been fully peer reviewed, but should not be considered the official version of record. They are citable by the Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered to authors. Therefore, the “Just Accepted” Web site may not include all articles that will be published in the journal. After a manuscript is technically edited and formatted, it will be removed from the “Just Accepted” Web site and published as an ASAP article. Note that technical editing may introduce minor changes to the manuscript text and/or graphics which could affect content, and all legal disclaimers and ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors or consequences arising from the use of information contained in these “Just Accepted” manuscripts.

is published by the American Chemical Society. 1155 Sixteenth Street N.W., Washington, DC 20036 Published by American Chemical Society. Copyright © American Chemical Society. However, no copyright claim is made to original U.S. Government works, or works produced by employees of any Commonwealth realm Crown government in the course of their duties.

Page 1 of 29 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

The Journal of Physical Chemistry

Is Indolinonic Hydroxylamine a Promising Artificial Antioxidant? Quan V. Vo1,2*, Mai Van Bay3, Pham Cam Nam4 and Adam Mechler5 1Department

for Management of Science and Technology Development, Ton Duc Thang

University, Ho Chi Minh City 700000, Vietnam 2Faculty

of Applied Sciences, Ton Duc Thang University, Ho Chi Minh City 700000, Vietnam

3Department

of Chemistry, The University of Da Nang - University of Science and

Education, Da Nang 550000, Vietnam. 4Department

of Chemical Engineering, The University of Da Nang - University of Science

and Technology, Da Nang 550000, Vietnam 5Department

of Chemistry and Physics, La Trobe University, Victoria 3086, Australia

*Corresponding author: [email protected] Abstract: Indolinonic hydroxylamine (IH) is a new-generation artificial antioxidant that, due to its ability to fraction into apolar environments, is considered for prevention against lipid peroxidation. For this reason, it is important to understand, and compare, its activity in polar and non-polar environments. In this study, the antioxidant activity of IH has been evaluated against HO and HOO radicals in water and, for a lipid-mimetic environment, pentyl ethanoate solvent, using kinetic calculations. It was found that the overall reaction rate constant of the HO radical scavenging is more than seven times higher in aqueous (8.98×109 M1 s1) than in apolar media (1.22×109 M1 s1). However, HOO scavenging was 35 times faster in apolar media (1.00×105 M1 s1 vs 2.80×103 M1 s1). In lipid environment the HAT mechanism was favored for the antioxidant activity for both radical species, whereas in aqueous solution the SET mechanism defined the HO, whereas HAT the HOO

1 ACS Paragon Plus Environment

The Journal of Physical Chemistry 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 2 of 29

scavenging. IH was shown to be one of the most active antioxidants in lipid environment, an essential characteristic for the protection of biological systems. 1. Introduction Indolinonic hydroxylamine (IH, Figure 1) and related aminoxyls are described as new-generation antioxidants1, garnering substantial attention due to their excellent free radical scavenging activity in lipidic environments2-9. Computational studies suggest that the O-H bond dissociation energies (BDE-OH) of the hydroxylamine moieties of IH and its derivatives are much lower than that of vitamin E, indicating that the IH analogues may have stronger antioxidant activity than the natural vitamin E10. Studies also showed that radicals formed by the N-O-H bonds i.e. phthalimide N-oxyl radicals are efficient oxidation catalysts of hydrocarbons or other substrates11,12. IH analogs and derivatives have been proposed for incorporation into medicinal compounds6,13,14. Thus far all computational studies evaluated the antioxidant activity of IHs by the hydrogen atom transfer (HAT) mechanism, characterizing activity based on the calculated BDE(OH)s1,10. The antioxidant activity however may follow instead the single electron transfer followed by-proton transfer (SET-PT) or sequential proton loss electron transfer (SPLET) mechanisms15-19. The dominance of HAT has not been demonstrated, therefore the antioxidant activity of IH should be investigated comparing these three main mechanisms rather than limiting calculations to HAT alone. Furthermore, it should be noted that in aqueous solutions IH is involved in acid-base equilibria. The anionic species have been implicated before in radical scavenging activity, and they may have higher activities than the neutral species20. Therefore, calculations that only consider the thermodynamic properties of neutral IH may underestimate its activity. Thus, a study of antioxidant 2 ACS Paragon Plus Environment

Page 3 of 29 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


properties of IH should consider the three main potential mechanistic pathways by both thermochemical and kinetic calculations to better understand the antioxidant properties of IH20-22. Given that IH is implicated in protecting lipids from oxidative damage, calculations should be performed in lipidic environments as well. Therefore, this study aims to (1) investigate the antioxidant activity of IH considering the three main antioxidant mechanisms in aqueous as well as lipid media, using thermodynamic calculations; (2) evaluate the scavenging of typical radicals HO and HOO by kinetic study; and (3) reveal the favored antioxidant mechanism of IH specific to each reactive oxygen species and chemical environments.

Figure 1. The structure of indolinonic hydroxylamine. 2. Computational methods M05-2X/6-311++G(d,p) method with the solvation model density (SMD) were used for kinetic calculations in both water and pentyl ethanoate solvents for their demonstrated high accuracy in predicting kinetic properties18,20,23,24. The rate constant (k) was calculated by using the conventional transition state theory (TST) and 1M standard state as:25-30 𝑘 = 𝜎𝜅

𝑘𝐵𝑇 ℎ

𝑒 ―(Δ𝐺

≠

)/𝑅𝑇

Where kB and h are the Boltzmann and Planck constants, respectively, ∆G≠ is Gibbs free energy of activation of the studied reaction,  is the reaction symmetry number that 3 ACS Paragon Plus Environment


Page 4 of 29

represents reaction path degeneracy (which was calculated following the literature31,32), the number of possible different but equivalent reaction pathways, and  accounts for tunneling corrections which were calculated using Eckart barrier33. The Marcus Theory was used to estimate the reaction barriers of SET reactions34-37. To avoid over-penalizing entropy losses in solution, in this study the solvent cage effects were included following the corrections proposed by Okuno38, adjusted with the free volume theory according to the Benson correction20,39. These corrections have been successfully used to study the radical scavenging activity of antioxidants in solution20,40-42 and are in good agreement with activity data independently obtained by Ardura et al43. For rate constants that were close to the diffusion limit a correction was applied to yield realistic results20. The apparent rate constants (kapp) were calculated following the Collins–Kimball theory in the solvents at 298.15K44; the steady-state Smoluchowski rate constant (kD) for an irreversible bimolecular diffusioncontrolled reaction was calculated following the literature20,45. For the species that have multiple conformers, all of these were investigated and the conformer with the lowest electronic energy was included in the analysis. The hindered internal rotation treatment was also applied to the single bonds to ensure that the obtained conformer has the lowest electronic energy46,47. All transition states were characterized by the existence of only one single imaginary frequency. Intrinsic coordinate calculations (IRCs) were performed to ensure that each transition state is corrected. All calculations were performed with the Gaussian 09 suite of programs48. In this study, the Eyringpy program was used as it is highly recommended for calculating rate constants in both gas phase and solvent environments18,23,49,50. Atom-in-molecule (AIM) analysis51 was performed by using the AIM2000 software52. 4 ACS Paragon Plus Environment

Page 5 of 29 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


3. Results and discussions 3.1. Thermodynamic study 3.1.1. Acid–base equilibria As expected, the lowest PA value was calculated at O10H bond (Table S1, SI). Thus this group was used to investigate the acid–base equilibria of IH. It was shown that the model E1 (1) has the mean unsigned errors lower than 1 pKa for most of the test functionals53. Thus the pKa of IH was calculated by using the model E1 and measured by the equation 2., in which the [H2O] value is 55.55 mol.L-153-55. IHOH + OH(3H2O)  IHO(H2O) + 3H2O

(1)

pKa = Gs/RTln(10) + 14 + 3log[10]

(2)

The calculated pKa value in this work was 22.3. Given that there is no data on the pKa of IH in the literature, the validity of this value is assessed as follows. It is generally observed that the pKa values in water are lower than in other polar but aprotic solvents such as DMSO solvent by about 1-2 pK units56. In our calculation, the pKa of IH in water is lower than the pKa of the structurally similar acid PhN(Bz)OH in DMSO (pKa(DMSO)=23.8) by  1.5 pK unit57. Therefore, the calculated pKa of 22.3 of IH is in the expected range. Consistently at physiological pH (7.40) neutral IH is the dominant species, and thus it is used for further studies. 3.1.2. Mechanism valuating The reactivity of IH toward R (R= HO and HOO ) radicals in aqueous and lipid (pentyl ethanoate) environments were assessed by three typical antioxidant mechanisms: hydrogen atom transfer (HAT), sequential electron transfer (SET), and radical adduct formation (RAF). The processes can be described with the following reactions: 5 ACS Paragon Plus Environment


where

Page 6 of 29

IH + R  IH + R

(SET)

(3)

IH + R  IH + RH

(HAT)

(4)

IH + R  IHR

(RAF)

(5)

R = HO, HOO To initial evaluate the antioxidant activity of IH, the BDEs of possible XH (X = C, N,

O) bonds were calculated by using M05-2X/6-311++G(d,p) model of chemistry in both water and pentyl ethanoate solvents and presented in Table S1, SI. It was found that the lowest BDE value was calculated for the O10H bond at 70.7 and 68.2 kcal/mol in water and pentyl ethanoate, respectively. The results are in good agreement with previous reports of calculated values using G3B3 method1 and the accurate calculating method CBSQB3 (70.5 kcal/mol). The BDEs for C2-H and N-H are slightly higher at 80.9 and 92.5 kcal/mol in aqueous, as well as 79.3 and 92.2 kcal/mol in lipidic media, respectively. BDEs for the other CH bonds are significantly higher in the range of 114.5 to 117.9 kcal/mol. This suggests that the C(5-8)H bonds do not play any role in the radical scavenging action of IH and thus they are omitted in the following calculations. The calculated IE values of IH are 102.7 and 129.6 kcal/mol in polar and non-polar solvents, respectively (Table S1, SI), suggesting that radical scavenging following the SET mechanism is more favored in aqueous environment than in lipidic environment. The Gibbs free energies (Go) of the reactions of IH with HO and HOO radicals following the SET, HAT and RAF, respectively, were calculated and shown in Table 1. It was found that the reactions of IH with the HO radical are always spontaneous (Go 1 and the small EHD ( 4.8 kcal/mol). It is important to note that the formation of new H17∙∙∙O21 bond is more stable in pentyl ethanoate (EHD = 32.7 kcal/mol) than in water (EHD = 28.8 kcal/mol), while the bond dissociation energy of H17∙∙∙O10 bond is lower in water (EHD = 184.0 kcal/mol) than in pentyl ethanoate (EHD176.2 kcal/mol) (Table 4). This may explain the higher stability of the IHO10-H-OOH TS in the lipid environment (E = 1.9 kcal/mol) than in water (E = 4.3 kcal/mol) (Table 3) and the highest rate constant of HIO10H + HOO in pentyl ethanoate solvent. 4. Conclusions The antioxidant activity of IH has been evaluated by the scavenging of hydroxyl and hydroperoxyl radicals in water and pentyl ethanoate solvents. It was found that even though the overall reaction rate constant of the HO radical scavenging is more than seven times higher in aqueous (8.98×109 M1 s1) than in lipidic media (1.22×109 M1 s1), the figure is about 35 times higher in lipidic media for the hydroperoxyl radical scavenging. It was shown that the SET mechanism contributes more than 66% in the overall rate constant of the HO radical scavenging in water, but it has no impacts on the rate constant in pentyl ethanoate solvent and in the HOO scavenging, which is governed by the HAT mechanism. The HOO radical scavenging of IH is about 29 and 17 times faster than those of Trolox and ascorbic acid in pentyl ethanoate solvent, respectively. Thus IH holds the potential for use in preventing oxidative degradation in lipid environments.



Page 16 of 29

Conflicts of interest There are no conflicts to declare Acknowledgements The research is funded by Vietnam National Foundation for Science and Technology Development (NAFOSTED) under grant number 104.06-2018.308. Supporting Information The Supporting Information is available free of charge on the ACS Publications website at DOI: The Cartesian coordinates, the frequency and energies of all of the transition states in water and pentyl ethanoate. References (1)

Li, M.-J.; Liu, L.; Fu, Y.; Guo, Q.-X. Accurate Bond Dissociation Enthalpies of Popular Antioxidants Predicted by the Oniom-G3b3 Method. J. Mol. Struct: THEOCHEM 2007, 815, 1-9.

(2)

Damiani, E.; Carloni, P.; Biondi, C.; Greci, L. Increased Oxidative Modification of Albumin when Illuminated in Vitro in the Presence of A Common Sunscreen Ingredient: Protection by Nitroxide Radicals. Free Radic. Biol. Med. 2000, 28, 193201.

(3)

Damiani, E.; Greci, L.; Rizzoli, C. Reaction of Indolinonic Aminoxyls with Nitric Oxide. J. Chem. Soc. Perkin Transactions 2 2001, 1139-1144.

(4)

Damiani, E.; Kalinska, B.; Canapa, A.; Canestrari, S.; Wozniak, M.; Olmo, E.; Greci, L. The Effects of Nitroxide Radicals on Oxidative DNA Damage. Free Radic. Biol. Med. 2000, 28, 1257-1265. 16 ACS Paragon Plus Environment

Page 17 of 29 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

(5)


Damiani, E.; Paganga, G.; Greci, L.; Rice-Evans, C. Inhibition of Copper-Mediated Low Density Lipoprotein Peroxidation by Quinoline and Indolinone Nitroxide Radicals. Biochem. Pharmacol. 1994, 48, 1155-61.

(6)

Wang, P. G.; Xian, M.; Tang, X.; Wu, X.; Wen, Z.; Cai, T.; Janczuk, A. J. Nitric Oxide Donors: Chemical Activities and Biological Applications. Chem. Rev. 2002, 102, 10911134.

(7)

Amorati, R.; Lucarini, M.; Mugnaini, V.; Pedulli, G. F.; Roberti, M.; Pizzirani, D. Antioxidant Activity of Hydroxystilbene Derivatives in Homogeneous Solution. J. Org. Chem. 2004, 69, 7101-7107.

(8)

Goldstein, S.; Samuni, A.; Merenyi, G. Reactions of Nitric Oxide, Peroxynitrite, and Carbonate Radicals with Nitroxides and their Corresponding Oxoammonium Cations. Chem. Res. Toxicol. 2004, 17, 250-257.

(9)

Noguchi, N.; Damiani, E.; Greci, L.; Niki, E. Action of Quinolinic and Indolinonic Aminoxyls as Radical-Scavenging Antioxidants. Chem. Phys. Lipids 1999, 99, 11-19.

(10)

Zhang, H.-Y.; Wang, L.-F. Theoretical Elucidation on Structure-Antioxidant Activity Relationships for Indolinonic Hydroxylamines. Bioorg. Med. Chem. Lett. 2002, 12, 225-227.

(11)

Amorati, R.; Lucarini, M.; Mugnaini, V.; Pedulli, G. F.; Minisci, F.; Recupero, F.; Fontana, F.;

Astolfi, P.; Greci, L. Hydroxylamines as Oxidation Catalysts:

Thermochemical and Kinetic Studies. J. Org. Chem. 2003, 68, 1747-1754. (12)

Sakaguchi, S.; Nishiwaki, Y.; Kitamura, T.; Ishii, Y. Efficient Catalytic Alkane Nitration With NO2 under Air Assisted by N-Hydroxyphthalimide. Angew. Chem. Int. Ed. 2001, 40, 222-224. 17 ACS Paragon Plus Environment


(13)

Page 18 of 29

Sharma, P.; Thummuri, D.; Reddy, T. S.; Senwar, K. R.; Naidu, V.; Srinivasulu, G.; Bharghava, S. K.; Shankaraiah, N. New (E)-1-Alkyl-1H-Benzo [D] Imidazol-2-Yl) Methylene) Indolin-2-ones: Synthesis, in Vitro Cytotoxicity Evaluation And Apoptosis Inducing Studies. Eur. J. Med. Chem. 2016, 122, 584-600.

(14)

Wu, S.-Y.; Ma, X.-P.; Liang, C.; Mo, D.-L. Synthesis of N-Aryl Oxindole Nitrones Through a Metal-Free Selective N-Arylation Process. J. Org. Chem. 2017, 82, 32323238.

(15)

Rimarčík, J.; Lukeš, V.; Klein, E.; Ilčin, M. Study of the Solvent Effect on the Enthalpies of Homolytic and Heterolytic N–H Bond Cleavage in P-Phenylenediamine and Tetracyano-P-Phenylenediamine. J. Mol. Struct: THEOCHEM 2010, 952, 25-30.

(16)

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.

(17)

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.

(18)

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.

(19)

Vo, Q. V.; Nam, P. C.; Thong, N. M.; Trung, N. T.; Phan, C.-T. D.; Mechler, A. Antioxidant Motifs in Flavonoids: O–H versus C–H Bond Dissociation. ACS Omega 2019, 4, 8935-8942.


Page 19 of 29 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

(20)


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.

(21)

Liu, Y.; Yin, C.; Smith, M. C.; Liu, S.; Chen, M.; Zhou, X.; Xiao, C.; Dai, D.; Takahashi, K.; Dong, W. Kinetics of the Reaction of the Simplest Criegee Intermediate with Ammonia: a Combination of Experiment and Theory. Phys. Chem. Chem. Phys. 2018, 20, 29669-29676.

(22)

Liu, Y.; Liu, F.; Liu, S.; Dai, D.; Dong, W.; Yang, X. A Kinetic Study of The CH2OO Criegee Intermediate Reaction with SO2,(H2O)2, CH2I2 and I Atoms using OH Laser Induced Fluorescence. Phys. Chem. Chem. Phys. 2017, 19, 20786-20794.

(23)

Okada, Y.; Tanaka, K.; Sato, E.; Okajima, H. Kinetics and Antioxidative Sites of Capsaicin in Homogeneous Solution. J. Am. Oil Chem. Soc. 2010, 87, 1397-1405.

(24)

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.

(25)

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.

(26)

Eyring, H. The Activated Complex in Chemical Reactions. J. Chem. Phys. 1935, 3, 107115.

(27)

Truhlar, D. G.; Hase, W. L.; Hynes, J. T. Current Status of Transition-State Theory. J. Phys. Chem. 1983, 87, 2664-2682.



(28)

Page 20 of 29

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.

(29)

Furuncuoglu, T.; Ugur, I.; Degirmenci, I.; Aviyente, V. Role of Chain Transfer Agents in Free Radical Polymerization Kinetics. Macromolecules 2010, 43, 1823-1835.

(30)

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, 971977.

(31)

Pollak, E.; Pechukas, P. Symmetry Numbers, not Statistical Factors, Should be used in Absolute Rate Theory and in Broensted Relations. J. Am. Chem. Soc. 1978, 100, 2984-2991.

(32)

Fernández-Ramos, A.; Ellingson, B. A.; Meana-Pañeda, R.; Marques, J. M.; Truhlar, D. G. Symmetry Numbers and Chemical Reaction Rates. Theor. Chem. Acc. 2007, 118, 813-826.

(33)

Eckart, C. The Penetration of a Potential Barrier by Electrons. Phy. Rev. 1930, 35, 1303.

(34)

Marcus, R. A. Chemical and Electrochemical Electron-Transfer Theory. Annu. Rev. Phys. Chem. 1964, 15, 155-196.

(35)

Marcus, R. A. Electron Transfer Reactions in Chemistry. Theory and Experiment. Rev. Mod. Phys. 1993, 65, 599.


Page 21 of 29 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

(36)


Lu, Y.; Wang, A.; Shi, P.; Zhang, H. A Theoretical Study on the Antioxidant Activity of Piceatannol and Isorhapontigenin Scavenging Nitric Oxide and Nitrogen Dioxide Radicals. PloS one 2017, 12, e0169773.

(37)

Lu, Y.; Wang, A.; Shi, P.; Zhang, H.; Li, Z. Quantum Chemical Study on the Antioxidation Mechanism of Piceatannol and Isorhapontigenin toward Hydroxyl and Hydroperoxyl Radicals. PloS one 2015, 10, e0133259.

(38)

Okuno, Y. Theoretical Investigation of the Mechanism of the Baeyer-Villiger Reaction in Nonpolar Solvents. Chem.: Eur. J. 1997, 3, 212-218.

(39)

Benson, S., The foundations of chemical kinetics: . Malabar, Florida, 1982.

(40)

Iuga, C.; Alvarez-Idaboy, J. R.; Vivier-Bunge, A. ROS Initiated Oxidation of Dopamine under Oxidative Stress Conditions in Aqueous and Lipidic Environments. J. Phys. Chem. B 2011, 115, 12234-12246.

(41)

Alvarez-Idaboy, J. R.; Reyes, L.; Mora-Diez, N. The mechanism of the Baeyer–Villiger rearrangement: quantum chemistry and TST study supported by experimental kinetic data. Org. Biomol. Chem. 2007, 5, 3682-3689.

(42)

Alvarez-Idaboy, J. R.; Reyes, L.; Cruz, J. A new specific mechanism for the acid catalysis of the addition step in the Baeyer− Villiger rearrangement. Org. Lett. 2006, 8, 1763-1765.

(43)

Ardura, D.; López, R.; Sordo, T. L. Relative gibbs energies in solution through continuum models: effect of the loss of translational degrees of freedom in bimolecular reactions on gibbs energy barriers. J. Phys. Chem. B 2005, 109, 2361823623.



(44)

Page 22 of 29

Collins, F. C.; Kimball, G. E. Diffusion-Controlled Reaction Rates. J. Colloid Sci. 1949, 4, 425-437.

(45)

Von Smoluchowski, M. Mathematical Theory of the Kinetics of the Coagulation of Colloidal Solutions. Z. Phys. Chem 1917, 92, 129-68.

(46)

Mai, T. V.-T.; Duong, M. v.; Le, X. T.; Huynh, L. K.; Ratkiewicz, A. Direct Ab Initio Dynamics Calculations of Thermal Rate Constants For The CH4+ O2= CH3+ HO2 Reaction. Struct. Chem. 2014, 25, 1495-1503.

(47)

Le, T. H.; Tran, T. T.; Huynh, L. K. Identification of Hindered Internal Rotational Mode for Complex Chemical Species: A Data Mining Approach with Multivariate Logistic Regression Model. Chemom. Intell. Lab. Syst. 2018, 172, 10-16.

(48)

Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.; Cheeseman, J. R.; Scalmani, G.; Barone, V.; B. Mennucci; G. A. Petersson, et al. Gaussian 09, Gaussian, Inc., Wallingford CT, 2009.

(49)

E. Dzib; J. L. Cabellos; F. Ortiz-Chi; S. Pan; A. Galano; G. Merino Eyringpy 1.0.2, Cinvestav, Mérida, Yucatán, 2018.

(50)

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.

(51)

Bader, R. F. A Quantum Theory of Molecular Structure and its Applications. Chem. Rev. 1991, 91, 893-928.

(52)

Biegler-König, F., AIM 2000, University of Applied Sciences, Bielefeld, Germany, 2000.


Page 23 of 29 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

(53)


Rebollar-Zepeda, A. M.;

Campos-Hernández, T.;

Ramírez-Silva, M. T.;

Rojas-

Hernández, A.; Galano, A. Searching for Computational Strategies to Accurately Predict pK as of Large Phenolic Derivatives. J. Chem. Theory Comput. 2011, 7, 25282538. (54)

Pliego Jr, J. R. Thermodynamic Cycles and the Calculation of pKa. Chem. Phys. Lett. 2003, 367, 145-149.

(55)

Bryantsev, V. S.; Diallo, M. S.; Goddard Iii, W. A. Calculation of Solvation Free Energies of Charged Solutes Using Mixed Cluster/Continuum Models. J. Phys. Chem. B 2008, 112, 9709-9719.

(56)

Matthews, W. S.; Bares, J. E.; Bartmess, J. E.; Bordwell, F.; Cornforth, F. J.; Drucker, G. E.; Margolin, Z.; McCallum, R. J.; McCollum, G. J.; Vanier, N. R. Equilibrium Acidities of Carbon Acids. Vi. Establishment of an Absolute Scale of Acidities in Dimethyl Sulfoxide Solution. J. Am. Chem. Soc. 1975, 97, 7006-7014.

(57)

Bordwell, F. G.; Liu, W.-Z. Equilibrium Acidities and Homolytic Bond Dissociation Energies of N−H and/or O−H Bonds in N-Phenylhydroxylamine and its Derivatives. J. Am. Chem. Soc. 1996, 118, 8777-8781.

(58)

León-Carmona, J. R.; Galano, A. Is Caffeine A Good Scavenger of Oxygenated Free Radicals? J. Phys. Chem. B 2011, 115, 4538-4546.

(59)

Galano, A. On the Direct Scavenging Activity of Melatonin Towards Hydroxyl and a Series of Peroxyl Radicals. Phys. Chem. Chem. Phys. 2011, 13, 7178-7188.

(60)

Pérez-González, A.; Galano, A. Oh Radical Scavenging Activity of Edaravone: Mechanism and Kinetics. J. Phys. Chem. B 2010, 115, 1306-1314.



(61)

Page 24 of 29

Galano, A.; Alvarez-Idaboy, J. R.; Francisco-Márquez, M. Physicochemical Insights on the Free Radical Scavenging Activity of Sesamol: Importance of the Acid/Base Equilibrium. J. Phys. Chem. B 2011, 115, 13101-13109.

(62)

León-Carmona, J. R.; Alvarez-Idaboy, J. R.; Galano, A. On the Peroxyl Scavenging Activity of Hydroxycinnamic Acid Derivatives: Mechanisms, Kinetics, And Importance of the Acid–Base Equilibrium. Phys. Chem. Chem. Phys. 2012, 14, 1253412543.

(63)

Galano, A.; Francisco-Márquez, M.; Alvarez-Idaboy, J. R. Mechanism and Kinetics Studies on the Antioxidant Activity of Sinapinic Acid. Phys. Chem. Chem. Phys. 2011, 13, 11199-11205.

(64)

Galano, A.; Alvarez-Idaboy, J. R.; Francisco-Márquez, M.; Medina, M. E. A Quantum Chemical Study on the Free Radical Scavenging Activity of Tyrosol and Hydroxytyrosol. Theor. Chem. Acc. 2012, 131, 1173.

(65)

Galano, A.;

Francisco-Márquez, M.; Alvarez-Idaboy, J. R. Canolol: A Promising

Chemical Agent Against Oxidative Stress. Phys. Chem. Chem. Phys. 2011, 115, 85908596. (66)

Rozas, I.; Alkorta, I.; Elguero, J. Behavior of Ylides Containing N, O, And C Atoms as Hydrogen Bond Acceptors. J. Am. Chem. Soc. 2000, 122, 11154-11161.


Page 25 of 29 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


TOC Graphic



Figure 1 34x38mm (600 x 600 DPI)

ACS Paragon Plus Environment

Page 26 of 29

Page 27 of 29 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


Figure-2 180x177mm (300 x 300 DPI)



Figure-3 167x123mm (300 x 300 DPI)


Page 28 of 29

Page 29 of 29 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


Figure-4 79x66mm (600 x 600 DPI)


Is Indolinonic Hydroxylamine a Promising Artificial Antioxidant? | The

Recommend Documents