Reaction Kinetics, Mechanisms and Catalysis

, Volume 127, Issue 2, pp 561–581 | Cite as

Quantum chemical evaluation of the role of \({{{\text{HO}}_{2}}^{ \cdot }}\) radicals in the kinetics of the methyl linoleate oxidation in micelles

  • Mikhail Soloviev
  • Ivan MoskalenkoEmail author
  • Eugene Pliss


The process of lipid peroxidation (LPO) plays an extremely important role in the human body due to the fact that its uncontrolled development can lead to oxidative stress and a number of serious diseases. The traditional approach to the analysis of the mechanism and kinetics of LPO is based on the well-known ideas that emerged from the study of radical-chain oxidation of hydrocarbons in a homogeneous medium. However, the distinctive feature of LPO is that this process is heterogeneous and the processes of diffusion of active intermediates between the aqueous and hydrocarbon phases should play a significant role in it. In the present work, an attempt has been made to theoretically estimate the contribution of these processes to the oxidation kinetics of model substances used in practice in the study of LPO. In the course of the calculations, a quantum chemical and kinetic analysis of the role of hydroperoxyl radical in the radical-chain mechanism of oxidation of methyl linoleate in micelles was carried out. The molecular dynamics method shows the important role of changing the dynamic rigidity of a hydrocarbon fragment of a chain during the formation of a peroxyl radical and hydroperoxyl group during the oxidation of a substrate in a heterogeneous medium. Quantum chemical calculations of the thermodynamics of reactions involving \({{{\text{HO}}_{2}}^{ \cdot }}\) radicals and the effects of their solvation made it possible to estimate the kinetic constants of the reaction rates. Using kinetic modeling, their relative contribution to the oxidation kinetics was revealed. In this case, it is possible to explain a number of anomalies associated with the oxidation of polyunsaturated fatty acids and their esters in micelles compared with their oxidation in a homogeneous hydrocarbon medium.


Hydroperoxyl radical Peroxide oxidation Lipids Micelles Kinetic modeling 



This work was supported by Russian Foundation for Basic Research (Grant No. 18-03-00644).

Supplementary material

11144_2019_1613_MOESM1_ESM.pdf (357 kb)
Supplementary material 1 (PDF 356 kb)


  1. 1.
    Porter NA (2013) A perspective on free radical autoxidation: the physical organic chemistry of polyunsaturated fatty acid and sterol peroxidation. J Org Chem 1:1. CrossRefGoogle Scholar
  2. 2.
    Pratt DA, Tallman KA, Porter NA (2011) Free radical oxidation of polyunsaturated lipids: new mechanistic insights and the development of peroxyl radical clocks. Acc Chem Res 44:458–467. CrossRefGoogle Scholar
  3. 3.
    Yin H, Xu L, Porter NA (2011) Free radical lipid peroxidation: mechanisms and analysis. Chem Rev 111:5944–5972. CrossRefGoogle Scholar
  4. 4.
    Jodko-Piórecka K, Litwinienko G (2015) Antioxidant activity of dopamine and L-DOPA in lipid micelles and their cooperation with an analogue of α-tocopherol. Free Radic Biol Med 83:1–11. CrossRefGoogle Scholar
  5. 5.
    Jodko-Piórecka K, Cedrowski J, Litwinienko G (2017) Physico-chemical principles of antioxidant action, including solvent and matrix dependence and interfacial phenomena. B: Meas. Antioxid. Act. Capacit. Wiley, Chichester, pp 225–272Google Scholar
  6. 6.
    Roginskii VA (1996) Kinetics of the chain oxidation of methyl linoleate in aqueous micellar solutions of sodium dodecyl sulfate. Kinet Catal 37:488–494Google Scholar
  7. 7.
    Bielski BHJ, Arudi RL, Sutherland MW (1982) A study of the reactivity of HO2/O2 with unsaturated fatty acids. J Biol Chem 31:175–184Google Scholar
  8. 8.
    Panov A (2018) Perhydroxyl radical (HO2·) as inducer of the isoprostane lipid Peroxidation in mitochondria. Mol Biol 52:295–305. CrossRefGoogle Scholar
  9. 9.
    Roginsky V, Barsukova T (2001) Superoxide dismutase inhibits lipid peroxidation in micelles. Chem Phys Lipids 111:87–91. CrossRefGoogle Scholar
  10. 10.
    Tikhonov IV, Pliss EM, Borodin LI et al (2015) Stable nitroxyl radicals and hydroxylamines as inhibitors of oxidation of methyl linoleate in micelles. Russ Chem Bull 64:2438–2443CrossRefGoogle Scholar
  11. 11.
    Tikhonov IV, Pliss E, Borodin LI, Sen’ VD (2015) Stable Five-membered cyclic nitroxyl radicals as inhibitors of the oxidation of methyl linoleate in micelles. Russ Chem Bull 64:2869–2871CrossRefGoogle Scholar
  12. 12.
    Tikhonov IV, Pliss EM, Borodin LI, Sen’ VD (2016) Effect of superoxide dismutase on the oxidation of methyl linoleate in micelles inhibited by nitroxyl radicals. Russ Chem Bull 65:2985–2987. CrossRefGoogle Scholar
  13. 13.
    Moskalenko IV, Tikhonov IV, Pliss EM et al (2018) Kinetic isotope effect in the oxidation reaction of linoleic acid esters in micelles. Russ J Phys Chem B 12:987–991. CrossRefGoogle Scholar
  14. 14.
    Cedrowski J, Litwinienko G, Baschieri A, Amorati R (2016) Hydroperoxyl radicals (HOO.): vitamin E regeneration and H-Bond effects on the hydrogen atom transfer. Chem A 22:16441–16445. Google Scholar
  15. 15.
    Amorati R, Baschieri A, Valgimigli L (2017) Measuring antioxidant activity in bioorganic samples by the differential oxygen uptake apparatus: recent advances. J Chem 2017:1–12. CrossRefGoogle Scholar
  16. 16.
    Zaikov GE, Howard JA, Ingold KU (1969) Absolute rate constants for hydrocarbon autoxidation. XIII. Aldehydes: photo-oxidation, co-oxidation, and inhibition. Can J Chem 47:3017–3029. CrossRefGoogle Scholar
  17. 17.
    Pliss E, Machtin V, Soloviev M et al (2018) The role of solvation in the kinetics and the mechanism of hydroperoxide radicals addition to π-bonds of 1,2-diphenylethylene and 1,4-diphenylbutadiene-1,3. Int J Chem Kinet 50:397–409. CrossRefGoogle Scholar
  18. 18.
    Pliss EM, Machtin VA, Grobov AM et al (2017) Kinetics and mechanism of radical-chain oxidation of 1,2-substituted ethylene and 1,4-substituted butadiene-1,3. Int J Chem Kinet 49:173–181. CrossRefGoogle Scholar
  19. 19.
    Pliss E, Machtin V, Pliss R et al (2018) The effect of solvation on the reactivity of 1,1-substituted ethylenes in hydroperoxyl radical addition reactions. React Kinet Mech Catal 123:559–571. CrossRefGoogle Scholar
  20. 20.
    Sirick A, Lednev S, Moskalenko I et al (2016) Kinetic features of chain initiation reactions during the oxidation of unsaturated compounds in media of different polarity. React Kinet Mech Catal 117:405–415. CrossRefGoogle Scholar
  21. 21.
    Harrison KA, Haidasz EA, Griesser M, Pratt DA (2018) Inhibition of hydrocarbon autoxidation by nitroxide-catalyzed cross-dismutation of hydroperoxyl and alkylperoxyl radicals. Chem Sci 9:6068–6079. CrossRefGoogle Scholar
  22. 22.
    Pliss RE, Machtin VA, Loshadkin D et al (2014) The mechanism of inhibited oxidation of norbornene series bicycloolefins. Pet Chem 54:382–386. CrossRefGoogle Scholar
  23. 23.
    Foti MC, Sortino S, Ingold KU (2005) New insight into solvent effects on the formal HOO. + HOO. reaction. Chem A 11:1942–1948. Google Scholar
  24. 24.
    Baschieri A, Valgimigli L, Gabbanini S et al (2018) Extremely fast hydrogen atom transfer between nitroxides and HOO · radicals and implication for catalytic coantioxidant systems. J Am Chem Soc 140:10354–10362. CrossRefGoogle Scholar
  25. 25.
    de Grey ADNJ (2002) HO2: the forgotten radical. DNA Cell Biol 21:251–257. CrossRefGoogle Scholar
  26. 26.
    Muñoz-Rugeles L, Galano A, Alvarez-Idaboy JR (2018) The other side of the superoxide radical anion: its ability to chemically repair DNA oxidized sites. Chem Commun. Google Scholar
  27. 27.
    Yazu K, Yamamoto Y, Ukegawa K, Niki E (1996) Mechanism of lower oxidizability of eicosapentaenoate than linoleate in aqueous micelles. Lipids 31:337–340. CrossRefGoogle Scholar
  28. 28.
    Antunes F, Barclay LRC, Vinqvist MR, Pinto RE (1998) Determination of propagation and termination rate constants by using an extension to the rotating-sector method: application to PLPC and DLPC bilayers. Int J Chem Kinet 30:753–767CrossRefGoogle Scholar
  29. 29.
    Barclay LRC (1993) 1992 syntex award lecture. Model biomembranes: quantitative studies of peroxidation, antioxidant action, partitioning, and oxidative stress. Can J Chem 71:1–16CrossRefGoogle Scholar
  30. 30.
    Garrec J, Monari A, Assfeld X et al (2014) Lipid peroxidation in membranes: the peroxyl radical does not « float». J Phys Chem Lett 5:1653–1658. CrossRefGoogle Scholar
  31. 31.
    Moskalenko IV, Petrova SY, Pliss EM et al (2016) Effect of microheterogeneity on the kinetics of oxidation of methyl linoleate in micelles. Russ J Phys Chem B 10:260–262. CrossRefGoogle Scholar
  32. 32.
    Tikhonov IV, Pliss EM, Borodin LI, Sen VD (2017) Superoxide radicals in the kinetics of nitroxide-inhibited oxidation of methyl linoleate in micelles. Russ J Phys Chem B 11:400–402. CrossRefGoogle Scholar
  33. 33.
    Hohenberg P, Kohn W (1964) Inhomogeneous electron gas. Phys Rev 136:B864–B871. CrossRefGoogle Scholar
  34. 34.
    Kohn W, Sham LJ (1965) Self-consistent equations including exchange and correlation effects. Phys Rev 1:1. Google Scholar
  35. 35.
    Becke AD (1993) Density-functional thermochemistry. III. The role of exact exchange. J Chem Phys 98:5648–5652. CrossRefGoogle Scholar
  36. 36.
    Miehlich B, Savin A, Stoll H, Preuss H (1989) Results obtained with the correlation energy density functionals of becke and Lee, Yang and Parr. Chem Phys Lett 157:200–206. CrossRefGoogle Scholar
  37. 37.
    Mueller MP (2007) Fundamentals of quantum chemistry: molecular spectroscopy and modern electronic structure computations. Springer, New YorkGoogle Scholar
  38. 38.
    Valiev M, Bylaska EJ, Govind N et al (2010) NWChem: a comprehensive and scalable open-source solution for large scale molecular simulations. Comput Phys Commun 181:1477–1489. CrossRefGoogle Scholar
  39. 39.
    Marenich AV, Cramer CJ, Truhlar DG (2009) 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 113:6378–6396. CrossRefGoogle Scholar
  40. 40.
    York DM, Karplus M (1999) A smooth solvation potential based on the conductor-like screening model. J Phys Chem A 103:11060–11079. CrossRefGoogle Scholar
  41. 41.
    Jorgensen WL, Briggs JM, Leonor Contreras M (1990) Relative partition coefficients for organic solutes from fluid simulations. J Phys Chem 94:1683–1686. CrossRefGoogle Scholar
  42. 42.
    Bussi G, Donadio D, Parrinello M (2007) Canonical sampling through velocity rescaling. J Chem Phys. doi 10(1063/1):2408420Google Scholar
  43. 43.
    Roschek B, Tallman KA, Rector CL et al (2006) Peroxyl radical clocks. J Org Chem 71:3527–3532. CrossRefGoogle Scholar
  44. 44.
    Yamamoto Y, Haga S, Niki E, Kamiya Y (1984) Oxidation of lipids. V. Oxidation of methyl linoleate in aqueous dispersion. Bull Chem Soc Jpn 57:1260–1264. CrossRefGoogle Scholar

Copyright information

© Akadémiai Kiadó, Budapest, Hungary 2019

Authors and Affiliations

  1. 1.P. G. Demidov Yaroslavl State UniversityYaroslavlRussian Federation

Personalised recommendations