Skip to main content
SpringerLink
Log in

Reaction of the m-THPC triplet state with the antioxidant Trolox and the anesthetic Propofol: Modulation of photosensitization mechanisms relevant to photodynamic therapy?

  • Paper
  • Published:
Photochemical & Photobiological Sciences Aims and scope Submit manuscript

Abstract

Antioxidants may affect the outcome of photodynamic therapy (PDT) through the inactivation of reactive oxygen species. Their direct interaction with photosensitizers excited at the triplet state is also worthy of interest. This process is investigated by laser flash photolysis of m-THPC (meso-tetra(3-hydroxyphenyl)chlorin, Foscan) hydroalcoholic solutions added with Trolox (TrOH), a standard antioxidant or Propofol (PfOH, Diprivan®), a common anesthetic agent also characterized for its antioxidant properties. Transient UV-visible absorption spectra, kinetics at selected wavelengths and final spectra after extensive laser irradiation show that both compounds react with the m-THPC triplet state,3m-THPC, to ultimately restore the photosensitizer in its ground state. For PfOH, this process mainly appears as a single step obeying pseudo-first order kinetics. The bimolecular rate constant for the quenching of3m-THPC by PfOH is around 2 × 106 M-1 s-1, a value increased to some extent by the water content of the solution. A bimolecular reaction between3m-THPC and TrOH is observed with a rate constant of similar magnitude and dependence upon water. However, the reaction leads, at least partly, to intermediate species assigned to the TrO? radical and the m-THPC anion radical. Within a few ms, these species back react to yield m-THPC in its ground state. A general mechanism involving an intermediate activated complex with some charge transfer character is proposed. Depending on the redox potentials for the oxidation of the antioxidant, this complex evolves predominantly either toward the formation of radicals (TrOH) or back to the photosensitizer ground state (PfOH). Notably, the kinetics data suggest that Propofol may quench3m-THPC at concentrations relevant of clinical situation in PDT involving anesthesia.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. J. D. Spikes, Photodynamic reactions in photomedicine, in The Science of Photomedicine, ed. J. D. Regan and J. A. Parrish, Plenum Press, New York, 1982, pp. 113–144.

    Chapter  Google Scholar 

  2. J. P. Celli, B. Q. Spring, I. Rizvi, C. L. Evans, K. S. Samkoe, S. Verma, B. W. Pogue, T. Hasan, Imaging and photodynamic therapy: mechanisms, monitoring, and optimization, Chem. Rev., 2010, 110, 2795–2838.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. T. J. Dougherty, C. J. Gomer, B. W. Henderson, G. Jori, D. Kessel, M. Korbelik, J. Moan, Q. Peng, Photodynamic therapy, J. Natl. Cancer Inst., 1998, 90, 889–905.

    Article  CAS  PubMed  Google Scholar 

  4. K. Plaetzer, B. Krammer, J. Berlanda, F. Berr, T. Kiesslich, Photophysics and photochemistry of photodynamic therapy: fundamental aspects, Lasers Med. Sci., 2009, 24, 259–268.

    Article  CAS  PubMed  Google Scholar 

  5. S. B. Brown, E. A. Brown, I. Walker, The present and future role of photodynamic therapy in cancer treatment, Lancet Oncol., 2004, 5, 497–508.

    Article  CAS  PubMed  Google Scholar 

  6. H. Van den Bergh, On the evolution of some endoscopic light delivery systems for photodynamic therapy, Endoscopy, 1998, 30, 392–407.

    Article  PubMed  Google Scholar 

  7. H. Van den Bergh, Photodynamic therapy of age-related macular degeneration: History and principles, Semin. Ophthalmol., 2001, 16, 181–200.

    Article  PubMed  Google Scholar 

  8. B. Halliwell and J. M. C. Gutteridge, in Free radicals in biology and medicine, Oxford University Press, Oxford, third edn, 1999.

    Google Scholar 

  9. M. C. Foti, Antioxidant properties of phenols, J. Pharm. Pharmacol., 2007, 59, 1673–1685.

    Article  CAS  PubMed  Google Scholar 

  10. J. E. Packer, T. F. Slater, R. L. Willson, Direct observation of a free radical interaction between vitamin E and vitamin C, Nature, 1979, 278, 737–738.

    Article  CAS  PubMed  Google Scholar 

  11. K. Mukai, K. Daifuku, K. Okabe, T. Teiichi, K. Inoue, Structure–Activity Relationship in the Quenching Reaction of Singlet Oxygen by Tocopherol (Vitamin E) Derivatives and Related Phenols. Finding of Linear Correlation between the Rates of Quenching of Singlet Oxygen and Scavenging of Peroxyl and Phenoxyl Radicals in Solution, J. Org. Chem., 1991, 56, 4188–4192.

    Article  CAS  Google Scholar 

  12. V. W. Bowry, R. Stocker, Tocopherol-mediated peroxidation. The prooxidant effect of vitamin E on the radical-initiated oxidation of human low-density lipoprotein, J. Am. Chem. Soc., 1993, 115, 6029–6044.

    Article  CAS  Google Scholar 

  13. O. Dangles, C. Dufour, G. Fargeix, Inhibition of lipid peroxidation by quercetin and quercetin derivatives: antioxidant and prooxidant effects, J. Chem. Soc., Perkin Trans. 2, 2000, 1215–1222.

    Google Scholar 

  14. P. Filipe, J. Haigle, J. N. Silva, J. Freitas, A. Fernandes, J. C. Maziere, C. Maziere, R. Santus, P. Morliere, Anti- and pro-oxidant effects of quercetin in copper-induced low density lipoprotein oxidation. Quercetin as an effective antioxidant against pro-oxidant effects of urate, Eur. J. Biochem., 2004, 271, 1991–1999.

    Article  CAS  PubMed  Google Scholar 

  15. F. Bohm, R. Edge, S. Foley, L. Lange, T. G. Truscott, Antioxidant inhibition of porphyrin-induced cellular phototoxicity, J. Photochem. Photobiol., B, 2001, 65, 177–183.

    Article  CAS  Google Scholar 

  16. E. Ben-Hur, S. Rywkin, I. Rosenthal, N. E. Geacintov, B. Horowitz, Virus inactivation in red cell concentrates by photosensitization with phthalocyanines: protection of red cells but not of vesicular stomatitis virus with a water-soluble analogue of vitamin E, Transfusion, 1995, 35, 401–406.

    Article  CAS  PubMed  Google Scholar 

  17. I. Rosenthal, E. Ben-Hur, Ascorbate-assisted, phthalocyanine-sensitized photohaemolysis of human erythrocytes, Int. J. Radiat. Biol.., 1992, 62, 481–486.

    Article  CAS  PubMed  Google Scholar 

  18. A. W. Girotti, J. P. Thomas, J. E. Jordan, Prooxidant and antioxidant effects of ascorbate on photosensitized peroxidation of lipids in erythrocyte membranes, Photochem. Photobiol., 1985, 41, 267–276.

    Article  CAS  PubMed  Google Scholar 

  19. G. J. Bachowski, K. M. Morehouse, A. W. Girotti, Porphyrin-sensitized photoreactions in the presence of ascorbate: oxidation of cell membrane lipids and hydroxyl radical traps, Photochem. Photobiol., 1988, 47, 635–645.

    Article  CAS  PubMed  Google Scholar 

  20. I. Shevchuk, V. Chekulayev, L. Chekulayeva, Enhancement of the efficiency of photodynamic therapy of tumours by t-butyl-4-hydroxyanisole, J. Photochem. Photobiol., B, 1998, 45, 136–143.

    Article  CAS  Google Scholar 

  21. V. Melnikova, L. Bezdetnaya, I. Belitchenko, A. Potapenko, J. L. Merlin, F. Guillemin, Meta-tetra(hydroxyphenyl)chlorin-sensitized photodynamic damage of cultured tumor and normal cells in the presence of high concentrations of alpha-tocopherol, Cancer Lett., 1999, 139, 89–95.

    Article  CAS  PubMed  Google Scholar 

  22. L. Aarts, R. von der Hee, I. Dekker, J. de Jong, H. Langemeijer, A. Bast, The widely used anesthetic agent propofol can replace alpha-tocopherol as an antioxidant, FEBS Lett., 1995, 357, 83–85.

    Article  CAS  PubMed  Google Scholar 

  23. O. Eriksson, P. Pollesello, N. E. Saris, Inhibition of lipid peroxidation in isolated rat liver mitochondria by the general anaesthetic propofol, Biochem. Pharmacol., 1992, 44, 391–393.

    Article  CAS  PubMed  Google Scholar 

  24. A. Mouithys-Mickalad, P. Hans, G. Deby-Dupont, M. Hoebeke, C. Deby, M. Lamy, Propofol reacts with peroxynitrite to form a phenoxyl radical: demonstration by electron spin resonance, Biochem. Biophys. Res. Commun., 1998, 249, 833–837.

    Article  CAS  PubMed  Google Scholar 

  25. O. Friaa, V. Chaleix, M. Lecouvey, D. Brault, Reaction between the anesthetic agent propofol and the free radical DPPH in semiaqueous media: kinetics and characterization of the products, Free Radical Biol. Med., 2008, 45, 1011–1018.

    Article  CAS  Google Scholar 

  26. H. M. Bryson, B. R. Fulton, D. Faulds, Propofol. An update of its use in anaesthesia and conscious sedation, Drugs, 1995, 50, 513–559.

    Article  CAS  PubMed  Google Scholar 

  27. V. O. Melnikova, L. N. Bezdetnaya, D. Brault, A. Y. Potapenko, F. Guillemin, Enhancement of meta-tetrahydroxyphenylchlorin-sensitized photodynamic treatment on human tumor xenografts using a water-soluble vitamin E analogue, Trolox, Int. J. Cancer, 2000, 88, 798–803.

    Article  CAS  PubMed  Google Scholar 

  28. R. Bonnett, R. D. White, U. J. Winfield, M. C. Berenbaum, Hydroporphyrins of the meso-tetra(hydroxyphenyl)porphyrin series as tumour photosensitizers, Biochem. J., 1989, 261, 277–280.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. H. Mojzisova, S. Bonneau, P. Maillard, K. Berg, D. Brault, Photosensitizing properties of chlorins in solution and in membrane-mimicking systems, Photochem. Photobiol. Sci., 2009, 8, 778–787.

    Article  CAS  PubMed  Google Scholar 

  30. O. Friaa, D. Brault, Kinetics of the reaction between the antioxidant Trolox and the free radical DPPH in semi-aqueous solution, Org. Biomol. Chem., 2006, 4, 2417–2423.

    Article  CAS  PubMed  Google Scholar 

  31. R. Bonnett, P. Charlesworth, B. D. Djelal, S. Foley, D. J. McGarvey, T. G. Truscott, Photophysical properties of 5,10,15,20-tetrakis(m-hydroxyphenyl)porphyrin-(m-THPP), 5,10,15,20-tetrakis(m-hydroxyphenyl)chlorin (m-THPC) and 5,10,15,20-tetrakis(m-hydroxyphenyl)bacteriochlorin (m-THPBC): a comparative study, J. Chem. Soc., Perkin Trans. 2, 1999, 325–328.

    Google Scholar 

  32. D. Brault, C. Vever-Bizet, M. Rougée, R. Bensasson, Photophysical properties of a chlorin, a potent sensitizer for photochemotherapy, Photochem. Photobiol., 1988, 47, 151–154.

    Article  CAS  Google Scholar 

  33. C. Capellos and B. H. J. Bielski, in Kinetic systems, Wiley-Interscience, New York, 1972.

    Google Scholar 

  34. S. Sasnouski, V. Zorin, I. Khludeyev, M. A. D’Hallewin, F. Guillemin, L. Bezdetnaya, Investigation of Foscan interactions with plasma proteins, Biochim. Biophys. Acta, Gen. Subj., 2005, 1725, 394–402.

    Article  CAS  Google Scholar 

  35. M. J. Davies, L. G. Forni, R. L. Willson, Vitamin E analogue Trolox C. E.s.r. and pulse-radiolysis studies of free-radical reactions, Biochem. J., 1988, 255, 513–522.

    CAS  PubMed  PubMed Central  Google Scholar 

  36. R. H. Bisby, C. G. Morgan, I. Hamblett, A. A. Gorman, Quenching of singlet oxygen by Trolox C, ascorbate, and amino acids: Effects of pH and temperature, J. Phys. Chem. A, 1999, 103, 7454–7459.

    Article  CAS  Google Scholar 

  37. P. Neta, R. E. Huie, P. Maruthamuthu, S. Steenken, Solvent effects in the reactions of peroxyl radicals with organic reductants. Evidence for proton-transfer-mediated electron transfer, J. Phys. Chem., 1989, 93, 7654–7659.

    Article  CAS  Google Scholar 

  38. S. Nonell, L. Moncayo, F. Trull, F. Amatguerri, E. A. Lissi, A. T. Soltermann, S. Criado, N. A. Garcia, Solvent Influence on the Kinetics of the Photodynamic Degradation of Trolox, a Water-Soluble Model-Compound for Vitamin-E, J. Photochem. Photobiol., B, 1995, 29, 157–162.

    Article  CAS  Google Scholar 

  39. B. Heyne, D. Brault, M. P. Fontaine-Aupart, S. Kohnen, F. Tfibel, A. Mouithys-Mickalad, G. Deby-Dupont, P. Hans, M. Hoebeke, Reactivity towards singlet oxygen of propofol inside liposomes and neuronal cells, Biochim. Biophys. Acta, Gen. Subj., 2005, 1724, 100–107.

    Article  CAS  Google Scholar 

  40. B. Heyne, S. Kohnen, D. Brault, A. Mouithys-Mickalad, F. Tfibel, P. Hans, M. P. Fontaine-Aupart, M. Hoebeke, Investigation of singlet oxygen reactivity towards propofol, Photochem. Photobiol. Sci., 2003, 2, 939–945.

    Article  CAS  PubMed  Google Scholar 

  41. G. Cauzzo, G. Gennari, G. Jori, J. D. Spikes, The effect of chemical structure on the photosensitizing efficiencies of porphyrins, Photochem. Photobiol., 1977, 25, 389–395.

    Article  CAS  PubMed  Google Scholar 

  42. G. J. Kavarnos, N. J. Turro, Photosensitization by reversible electron transfer: Theories, experimental evidence, and examples, Chem. Rev., 1986, 86, 401–449.

    Article  CAS  Google Scholar 

  43. T. W. Dixon, D. Murphy, Determination of the acidity constants of some phenol radical cations by means of electron spin resonance, J. Chem. Soc., Faraday Trans. 2, 1976, 72, 1221–1230.

    Article  CAS  Google Scholar 

  44. M. J. Thomas, B. H. J. Bielski, Oxidation and reaction of Trolox c, a tocopherol analogue, in aqueous solution. A pulse-radiolysis study, J. Am. Chem. Soc., 1989, 111, 3315–3319.

    Article  CAS  Google Scholar 

  45. G. Peychal-Heiling, G. S. Wilson, Electrochemical Studies of Tetraphenylporphin, Tetraphenylchlorin, and Tetraphenylbacteriochlorin, Anal. Chem., 1971, 43, 550–556.

    Article  Google Scholar 

  46. M. A. J. Rodgers, Reflections on type I photodynamic damages, J. Photochem. Photobiol., B, 1993, 18, 296–298.

    Article  CAS  Google Scholar 

  47. L. Shen, Theoretical investigation on the triplet excited state properties of the porphyrin-related photosensitizers and the implications in illustrating their photosensitization mechanisms, J. Mol. Struct.: THEOCHEM., 2008, 862, 130–132.

    Article  CAS  Google Scholar 

  48. S. Steenken, P. Neta, One-electron redox potentials of phenols. Hydroxy- and aminophenols and related compounds of biological interest, J. Phys. Chem., 1982, 86, 3661–3667.

    Article  CAS  Google Scholar 

  49. D. E. Pissinis, J. M. Marioli, Electrochemical detection of 2,6-diisopropylphenol (propofol) in reversed phase HPLC at high pH, J. Liq. Chromatogr. Relat. Technol., 2007, 30, 1787–1795.

    Article  CAS  Google Scholar 

  50. J. Stradins, B. Hasanli, Anodic voltammetry of phenol and benzenethiol derivatives.: Part 1. Influence of pH on electro-oxidation potentials of substituted phenols and evaluation of p Ka from anodic voltammetry data, J. Electroanal. Chem., 1993, 353, 57–69.

    Article  CAS  Google Scholar 

  51. E. J. Lien, S. Ren, H. H. Bui, R. Wang, Quantitative structure–activity relationship analysis of phenolic antioxidants, Free Radical Biol. Med., 1999, 26, 285–294.

    Article  CAS  Google Scholar 

  52. R. Bonnett, C. Lambert, E. J. Land, P. A. Scourides, R. S. Sinclair, T. G. Truscott, The triplet and radical species of hematoporphyrin and some of its derivatives, Photochem. Photobiol., 1983, 38, 1–8.

    Article  CAS  PubMed  Google Scholar 

  53. P. Neta, A. Scherz, H. Levanon, Electron transfer reactions involving porphyrins and chlorophyll a, J. Am. Chem. Soc., 1979, 101, 3624–3629.

    Article  CAS  Google Scholar 

  54. R. H. Bisby, S. Ahmed, R. B. Cundall, Repair of amino acid radicals by a vitamin E analogue, Biochem. Biophys. Res. Commun., 1984, 119, 245–251.

    Article  CAS  PubMed  Google Scholar 

  55. S. Steenken and P. Neta, Transient Phenoxyl Radicals: Formation and Properties in Aqueous Solutions, in Phenols, ed. Z. Rappoport, John Wiley & Sons, Ltd, Chichester, UK, 2003, pp. 1107–1152.

    Chapter  Google Scholar 

  56. B. Heyne, F. Tfibel, M. Hoebeke, P. Hans, V. Maurel, M. P. Fontaine-Aupart, Photochemistry of 2,6-diisopropylphenol (propofol), Photochem. Photobiol. Sci., 2006, 5, 1059–1067.

    Article  CAS  PubMed  Google Scholar 

  57. J. Jakus, O. Farkas, Photosensitizers and antioxidants: a way to new drugs?, Photochem. Photobiol. Sci., 2005, 4, 694–698.

    Article  CAS  PubMed  Google Scholar 

  58. A. Ernst, G. A. Silvestri, D. Johnstone, Interventional pulmonary procedures: Guidelines from the American College of Chest Physicians, Chest, 2003, 123, 1693–1717.

    Article  PubMed  Google Scholar 

  59. C. N. Foroulis, J. A. Thorpe, Photodynamic therapy (PDT) in Barrett’s esophagus with dysplasia or early cancer, Eur. J. Cardiothorac. Surg., 2006, 29, 30–34.

    Article  PubMed  Google Scholar 

  60. S. E. Eggener, J. A. Coleman, Focal treatment of prostate cancer with vascular-targeted photodynamic therapy, TheScientificWorldJOURNAL, 2008, 8, 963–973.

    Article  PubMed  PubMed Central  Google Scholar 

  61. H. Lepor, Vascular targeted photodynamic therapy for localized prostate cancer, Rev. Urol., 2008, 10, 254–261.

    PubMed  PubMed Central  Google Scholar 

  62. J. S. Friedberg, Photodynamic therapy as an innovative treatment for malignant pleural mesothelioma, Semin. Thorac. Cardiovasc. Surg., 2009, 21, 177–187.

    Article  PubMed  Google Scholar 

  63. A. R. Oseroff, S. Shieh, N. P. Frawley, R. Cheney, L. E. Blumenson, E. K. Pivnick, D. A. Bellnier, Treatment of diffuse basal cell carcinomas and basaloid follicular hamartomas in nevoid basal cell carcinoma syndrome by wide-area 5-aminolevulinic acid photodynamic therapy, Arch. Dermatol., 2005, 141, 60–67.

    Article  PubMed  Google Scholar 

  64. A. Maier, F. Tomaselli, V. Matzi, P. Rehak, H. Pinter, F. M. Smolle-Juttner, Does new photosensitizer improve photodynamic therapy in advanced esophageal carcinoma?, Lasers Surg. Med., 2001, 29, 323–327.

    Article  CAS  PubMed  Google Scholar 

  65. N. P. Franks, W. R. Lieb, Molecular and cellular mechanisms of general anaesthesia, Nature, 1994, 367, 607–614.

    Article  CAS  PubMed  Google Scholar 

  66. S. D. Krämer, Liposome/water partitioning: Theory, techniques, and applications, in Pharmacokinetic optimization in drug research, ed. B. Testa, H. Van de Waterbeemd, G. Folkers and R. Guy, Verlag Helvetica Chimica Acta, Zürich, 2001, pp. 401–428.

    Chapter  Google Scholar 

  67. B. W. Pogue, K. D. Paulsen, J. A. O’Hara, C. M. Wilmot, H. M. Swartz, Estimation of oxygen distribution in RIF-1 tumors by diffusion model-based interpretation of pimonidazole hypoxia and eppendorf measurements, Radiat. Res., 2001, 155, 15–25.

    Article  CAS  PubMed  Google Scholar 

  68. T. H. Foster, R. S. Murant, R. G. Bryant, R. S. Knox, S. L. Gibson, R. Hilf, Oxygen consumption and diffusion effects in photodynamic therapy, Radiat. Res., 1991, 126, 296–303.

    Article  CAS  PubMed  Google Scholar 

  69. T. M. Sitnik, J. A. Hampton, B. W. Henderson, Reduction of tumour oxygenation during and after photodynamic therapy in vivo: effects of fluence rate, Br. J. Cancer, 1998, 77, 1386–1394.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Author notes

  1. O. Friaa

    Present address: Department of Physics & Astronomy, McMaster University, Hamilton, Ontario, Canada

Authors and Affiliations

  1. Laboratoire Acides Nucléiques et BioPhotonique (ANBioΦ) Université Pierre & Marie Curie, Tour 32-33, 4ème étage, 4 place Jussieu, F-75252, Paris Cedex05, France

    O. Friaa & D. Brault

  2. CNRS FRE, Université Pierre & Marie Curie, F-75252, Paris Cedex05, France

    O. Friaa & D. Brault

  3. Univ. Paris-Sud, Bât 110, F-91405, Orsay, France

    P. Maillard

  4. Institut Curie, Section de Recherches, Centre Universitaire, Univ. Paris-Sud, F-91405, Orsay, France

    P. Maillard

  5. CNRS GDR, 3049, Photomed, France

    P. Maillard & D. Brault

Authors
  1. O. Friaa
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. P. Maillard
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. D. Brault
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to D. Brault.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Friaa, O., Maillard, P. & Brault, D. Reaction of the m-THPC triplet state with the antioxidant Trolox and the anesthetic Propofol: Modulation of photosensitization mechanisms relevant to photodynamic therapy?. Photochem Photobiol Sci 11, 703–714 (2012). https://doi.org/10.1039/c2pp05354c

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1039/c2pp05354c

Search

Navigation