Skip to main content
SpringerLink
Log in

Photooxygenation mechanisms in naproxen–amino acid linked systems

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

Abstract

The photooxygenation of model compounds containing the two enantiomers of naproxen (NPX) covalently linked to histidine (His), tryptophan (Trp) and tyrosine (Tyr) has been investigated by steady state irradiation, fluorescence spectroscopy and laser flash photolysis. The NPX–His systems presented the highest oxygen-mediated photoreactivity. Their fluorescence spectra matched that of isolated NPX and showed a clear quenching by oxygen, leading to a diminished production of the NPX triplet excited state (3NPX*–His). Analysis of the NPX–His and NPX–Trp photolysates by UPLC-MS–MS revealed in both cases the formation of two photoproducts, arising from the reaction of singlet oxygen (1O2) with the amino acid moiety. The most remarkable feature of NPX–Trp systems was a fast and stereoselective intramolecular fluorescence quenching, which prevented the efficient formation of3NPX*–Trp, thus explaining their lower reactivity towards photooxygenation. Finally, the NPX–Tyr systems were nearly unreactive and exhibited photophysical properties essentially coincident with those of the parent NPX. Overall, these results point to a type II photooxygenation mechanism, triggered by generation of1O2 from the3NPX* chromophore.

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

Notes and references

  1. L. I. Grossweiner and K. C. Smith, Photochemistry, in The Science of Photobiology, ed. K. C. Smith, Plenum Press, New York, 2nd edn, 1989, pp. 47–78.

    Chapter  Google Scholar 

  2. L. Pretali and A. Albini, in CRC Handbook of Organic Photochemistry and Photobiology, ed. A. Griesbeck, M. Oelgemö ller and F. Ghetti, CRC Press, Boca Raton, FL, 3rd edn, 2012, pp. 369–391.

  3. C. S. Foote, Definition of type I and type II photosensitized oxidation, Photochem. Photobiol. 1991, 54, 659.

    Article  CAS  Google Scholar 

  4. K. Briviba, L. O. Klotz and H. Sies, Toxic and signaling effects of photochemically generated singlet oxygen in biological systems, Biol. Chem. 1997, 378, 1259–1265.

    CAS  PubMed  Google Scholar 

  5. M. J. Davies, Singlet oxygen-mediated damage to proteins and its consequences, Biochem. Biophys. Res. Commun. 2003, 305, 761–770.

    Article  CAS  Google Scholar 

  6. M. J. Davies, Reactive species formed on proteins exposed to singlet oxygen, Photochem. Photobiol. Sci. 2004, 3, 17–25.

    Article  CAS  Google Scholar 

  7. A. W. Girotti, Photosensitized oxidation of membrane lipids: reaction pathways, cytotoxic effects, and cytoprotective mechanisms, J. Photochem. Photobiol., B 2001, 63, 103–113.

    Article  CAS  Google Scholar 

  8. I. Andreu, I. M. Morera, F. Boscá, L. Sánchez, P. Camps and M. A. Miranda, Cholesterol-diaryl ketone stereoisomeric dyads as models for clean type I and type II photooxygenation mechanisms, Org. Biomol. Chem. 2008, 6, 860–867.

    Article  CAS  Google Scholar 

  9. E. R. Stadtman, Oxidation of free amino acids and amino acid residues in proteins by radiolysis and by metal-catalysed reactions, Annu. Rev. Biochem. 1993, 62, 797–821.

    Article  CAS  Google Scholar 

  10. W. M. Garrison, Reaction mechanisms in the radiolysis of peptides, polypeptides and proteins, Chem. Rev. 1987, 87, 381–398.

    Article  CAS  Google Scholar 

  11. P. U. Giacomoni, Sun Protection in Man, Comprehensive Series in Photosciences, Elsevier, Amsterdam, 2001, vol.3,.

  12. R. C. Straight and J. D. Spikes, Photosensitized oxidation of biomolecules. in Polymers and Biopolymers, ed. A. A. Frimer and O. Singlet, CRC Press, Boca Raton, FL, 1985, pp. 91–143.

  13. A. Wright, W. A. Bubb, C. L. Hawkins and M. J. Davies, Singlet oxygen mediated protein oxidation: evidence for the formation of reactive side-chain peroxides on tyrosine residues, Photochem. Photobiol. 2002, 76, 35–46.

    Article  CAS  Google Scholar 

  14. V. V. Agon, W. A. Bubb, A. Wright, C. L. Hawkins and M. J. Davies, Sensitizer-mediated photooxidation of histidine residues: evidence for the formation of reactive side-chain peroxides, Free Radical Biol. Med. 2006, 40, 698–710.

    Article  CAS  Google Scholar 

  15. J. E. Huyett, P. E. Doan, R. Gurbiel, A. L. P. Houseman, M. Sivaraja, D. B. Goodin and B. M. Hoffman, Compound ES of cytochrome c peroxidase contains a Trp π-cation radical: characterization by CW and pulsed Q-band ENDOR spectroscopy, J. Am. Chem. Soc. 1995, 117, 9033–9041.

    Article  CAS  Google Scholar 

  16. R. W. Redmond and J. N. Gamlin, A compilation of singlet oxygen yields from biologically relevant molecules, Photochem. Photobiol. 1999, 70, 391–475.

    Article  CAS  Google Scholar 

  17. A. J. Lewis and D. E. Furst, Nonsteroidal Anti-Inflammatory Drugs: Mechanisms and Clinical Uses, Marcel Dekker, New York, 2nd edn, 1994.

    Google Scholar 

  18. F. Boscá, M. L. Marín and M. A. Miranda, Photoreactivity of the nonsteroidal anti-inflammatory 2-arylpropionic acids with photosensitizing side effects, Photochem. Photobiol. 2001, 74, 637–655.

    Article  Google Scholar 

  19. G. M. J. Beijersbergen van Henegouwen, Phototoxicity of drugs and other xenobiotics, J. Photochem. Photobiol., B 1991, 10, 183–210.

    Article  CAS  Google Scholar 

  20. M. A. Miranda, J. V. Castell, D. Hernández, M. J. Gómez-Lechón, F. Boscá, I. M. Morera and Z. Sarabia, Drug-photosensitized protein modifications: identification of the reactive sites and elucidation of the reaction mechanisms with tiaprofenic acid/albumin as model system, Chem. Res. Toxicol. 1998, 11, 172–177.

    Article  CAS  Google Scholar 

  21. M. C. Jiménez, U. Pischel and M. A. Miranda, Photoinduced processes in naproxen-based chiral dyads, J. Photochem. Photobiol., C 2007, 8, 128–142.

    Article  Google Scholar 

  22. A. Catalfo, G. Bracchitta, G. de Guidi, Role of aromatic amino acid tryptophan UVA-photoproducts in the determination of drug photosensitization mechanism: a comparison between methylene blue and naproxen, Photochem. Photobiol. Sci. 2009, 8, 1467–1475.

    Article  CAS  Google Scholar 

  23. I. Vayá, R. Pérez-Ruiz, V. Lhiaubet-Vallet, M. C. Jiménez and M. A. Miranda, Drug-protein interactions assessed by fluorescence measurements in the real complexes and in model dyads, Chem. Phys. Lett. 2010, 486, 147–153.

    Article  Google Scholar 

  24. I. Vayá, M. C. Jiménez and M. A. Miranda, Excited state interactions in flurbiprofen-tryptophan dyads, J. Phys. Chem. B 2007, 111, 9363–9371.

    Article  Google Scholar 

  25. I. Vayá, P. Bonancía, M. C. Jiménez, D. Markovitsi, T. Gustavsson and M. A. Miranda, Excited state interactions between flurbiprofen and tryptophan in drug-protein complexes and in model dyads. Fluorescence studies from the femtosecond to the nanosecond time domains, Phys. Chem. Chem. Phys. 2013, 15, 4727–4734.

    Article  Google Scholar 

  26. A. G. Griesbeck, J. Neudörfl, A. de Kiff, Photoinduced electron-transfer chemistry of the bielectrophoric N-phthaloyl derivatives of the amino acids tyrosine, histidine and tryptophan, Beilstein J. Org. Chem. 2011, 7, 518–524.

    Article  CAS  Google Scholar 

  27. B. Giese, M. Wang, J. Gao, M. Stoltz, P. Müller and M. Graber, Electron relay race in peptides, J. Org. Chem. 2009, 74, 3621–3625.

    Article  CAS  Google Scholar 

  28. M. Cordes, A. Köttgen, C. Jasper, O. Jacques, H. Boudebous and B. Giese, Influence of amino acid side chains on long-distance electron transfer in peptides: electron hopping via “stepping stones”, Angew. Chem., Int. Ed. 2008, 47, 3461–3463.

    Article  CAS  Google Scholar 

  29. B. Abraham and L. A. Kelly, Photooxidation of amino acids and proteins mediated by novel 1,8-naphthalimide derivatives, J. Phys. Chem. B 2003, 107, 12534–12541.

    Article  CAS  Google Scholar 

  30. E. Cadenas, Biochemistry of oxygen toxicity, Annu. Rev. Biochem. 1989, 58, 79–110.

    Article  CAS  Google Scholar 

  31. D. de la Peña, C. Martí, S. Nonell, L. A. Martínez and M. A. Miranda, Time-resolved near infrared studies on singlet oxygen production by the photosensitizing 2-arylpropionic acids, Photochem. Photobiol. 1997, 65, 828–832.

    Article  Google Scholar 

  32. B. A. Kerwin and R. L. Remmele, Protect from light: photodegradation and protein biologics, J. Pharm. Sci. 2007, 96, 1468–1479.

    Article  CAS  Google Scholar 

  33. P. Kang and C. S. Foote, Synthesis of a C-13, N-15 labeled imidazole and characterization of the 2,5-endoperoxide and its decomposition, Tetrahedron Lett. 2000, 41, 9623–9626.

    Article  CAS  Google Scholar 

  34. I. Saito, T. Matsuura, M. Nakagawa and T. Hino, Peroxidic intermediates in photosensitized oxygenation of tryptophan derivatives, Acc. Chem. Res. 1977, 10, 346–352.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Departamento de Química/Instituto de Tecnología Química UPV-CSIC, Universitat Politècnica de València, Camino de Vera s/n, E-46022, Valencia, Spain

    Ignacio Vayá, M. Consuelo Jiménez & Miguel A. Miranda

  2. Unidad Mixta de Investigación IIS La Fe-UPV, Hospital La Fe, Avda. Campanar 21, 46009, Valencia, Spain

    Inmaculada Andreu

Authors
  1. Ignacio Vayá
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Inmaculada Andreu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. M. Consuelo Jiménez
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Miguel A. Miranda
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to M. Consuelo Jiménez or Miguel A. Miranda.

Additional information

Dedicated to the memory of Prof. Nicholas J. Turro.

Electronic supplementary information (ESI) available: Additional X-ray structures, photodegradation kinetics, UV, fluorescence and transient absorption data (8 pages). CCDC 662964, 662965, 662957, 662958, 662959 and 662960. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c3pp50252j

Rights and permissions

Reprints and permissions

About this article

Cite this article

Vayá, I., Andreu, I., Jiménez, M.C. et al. Photooxygenation mechanisms in naproxen–amino acid linked systems. Photochem Photobiol Sci 13, 224–230 (2014). https://doi.org/10.1039/c3pp50252j

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1039/c3pp50252j

Search

Navigation