Skip to main content
SpringerLink
Log in

Investigation of oxygen influence to the optical properties of tirapazamine

  • Original Paper
  • Published:
Journal of Molecular Modeling Aims and scope Submit manuscript

Abstract

New data on 3-amino-1,2,4-benzotriazine 1,4-dioxide (tirapazamine) fluorescence has been obtained using the Perkin–Elmer Lambda 950 UV–Vis-NIR spectrophotometer experimental technique in combination with the extensive DFT-theory approach. Based on the results obtained, we revealed that the optical properties of the molecule under study remain significantly unchanged when the number of oxygen substitutions decreases from 2 to 0. Here we also present the results of the study of the influence of acetonitrile and ethyl acetate on the fluorescence of tirapazamine with the different number of oxygen atoms. Results of our investigation indicate the formation of anion in the case of 3-amino-1,2,4-benzotriazine 1,4-dioxide with two oxygen atoms and their transformation to tirapazamine with one oxygen atom.

Graphical abstract

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

Fig. 1
Fig. 2
Fig. 3
Scheme 1
Scheme 2

Similar content being viewed by others

Data availability

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

Code availability

Not applicable.

References

  1. Avendaño C, Menéndez JC (2008) Anticancer drugs acting via radical species, photosensitizers and photodynamic therapy of cancer, in medicinal chemistry of anticancer drugs. Elsevier B.V., ISBN 978–0–444–52824–7

  2. Poole JS, Hadad CM, Platz MS, Fredin ZP, Pickard L, Guerrero EL, Kessler M, Chowdhury G, Kotandeniy D, Gates KS (2002) Photochemical electron transfer reactions of tirapazamine. Photochem Photobiol 75(4):339–345

    Article  CAS  Google Scholar 

  3. Reichardt C (1979) Solvent effects in organic chemistry, pp. 225–262. Verlag Chemie, Weinheim

  4. Shi X, Poole JS, Emenike I, Burdzinski G, Platz MS (2005) Time resolved spectroscopy of the excited singlet states of tirapazamine and desoxytirapazamine. J Phys Chem A 109:1491–1496

    Article  CAS  Google Scholar 

  5. Gauthier J, Duceppe JS (1984) Synthesis of novel imidazo[1,2-a][3,1]benzothiazines, imidazo[1,2-a]-[1,2,4]benzotriazines, and 4H-imidazo[2,3-c]pyrido[2,3-e][1,4]oxazines. J Heterocycl Chem 21:1081–1086

    Article  CAS  Google Scholar 

  6. Pazdera P, Potacek M (1988) 4-Substituted 2-nitrophenylguanidines I. Synthesis and cyclization of 4-substituted 2-nitrophenylguanidines. Chem Papers 42:527–537

    CAS  Google Scholar 

  7. Hay MP, Gamage SA, Kovacs MS, Pruijn FB, Anderson RF, Patterson AV, Wilson WR, Brown JM, Denny WA (2003) Structure−activity relationships of 1, 2, 4-benzotriazine 1, 4-dioxides as hypoxia-selective analogues of tirapazamine. J Med Chem 46(1):169–182

    Article  CAS  Google Scholar 

  8. Gaussian 09, Revision A.02, Frisch MJ, Trucks GW, Schlegel HB, Scuseria GE, Robb MA, Cheeseman JR, Scalmani G, Barone V, Petersson GA, Nakatsuji H, Li X, Caricato M, Marenich A, Bloino J, Janesko BG, Gomperts R, Mennucci B, Hratchian HP, Ortiz JV, Izmaylov AF, Sonnenberg JL, Williams-Young D, Ding F, Lipparini F, Egidi F, Goings J, Peng B, Petrone A, Henderson T, Ranasinghe D, Zakrzewski VG, Gao J, Rega N, Zheng G, Liang W, 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 JA, Jr, Peralta JE, Ogliaro F, Bearpark M, Heyd JJ, Brothers E, Kudin KN, Staroverov VN, Keith T, Kobayashi R, Normand J, Raghavachari K, Rendell A, Burant JC, Iyengar SS, Tomasi J, Cossi M, Millam JM, Klene M, Adamo C, Cammi R, Ochterski JW, Martin RL, Morokuma K, Farkas O, Foresman JB, Fox DJ (2016) Gaussian, Inc., Wallingford CT

  9. Cardia R, Malloci G, Mattoni A, Cappellini G (2014) Effects of TIPS-functionalization and perhalogenation on the electronic, optical, and transport properties of angular and compact dibenzochrysene. J Phys Chem A 2118(28):5170–5177

    Article  Google Scholar 

  10. Cardia R, Malloci G, Rignanese GM, Blasé X, Molteni E, Cappellini G (2016) Electronic and optical properties of hexathiapentacene in the gas and crystal phases. Phys Rev B 93:235132

    Article  Google Scholar 

  11. Dardenne N, Cardia R, Li J, Malloci G, Cappellini G, Blasé X, Charlier JC, Rignanese G (2017) Tuning optical properties of dibenzochrysenes by functionalization: a many-body perturbation theory study. Phys Chem C 121(44):24480–24488

    Article  CAS  Google Scholar 

  12. Antidormi A, Aprile G, Cappellini G, Cara E, Cardia R, Colombo L, Farris R, d’Ischia M, Mehrabanian M, Melis C, Mula G, Pezzella A, Pinna E, Riva ER (2018) Physical and chemical control of interface stability in porous Si–eumelanin hybrids. J Phys Chem C 122(49):28405–28415

    Article  CAS  Google Scholar 

  13. Mocci P, Cardia R, Cappellini G (2018) Inclusions of Si-atoms in graphene nanostructures: a computational study on the ground-state electronic properties of Coronene and Ovalene. J Phys Conf Ser 956(1):012020

    Article  Google Scholar 

  14. Mocci P, Cardia R, Cappellini G (2018) Si-atoms substitutions effects on the electronic and optical properties of coronene and ovalene. New J Phys 20(11):113008

    Article  CAS  Google Scholar 

  15. Kumar A, Cardia R, Cappellini G (2018) Electronic and optical properties of chromophores from bacterial cellulose. Cellulose 25(4):2191–2203

    Article  CAS  Google Scholar 

  16. Szafran M, Koput J (2001) Ab initio and DFT calculations of structure and vibrational spectra of pyridine and its isotopomers. J. Mol. Struct 565±566: 439–448

  17. Begue D, Carbonniere P, Pouchan C (2005) Calculations of vibrational energy levels by using a hybrid ab initio and DFT quartic force field: application to acetonitrile. J Phys Chem A 109(20):4611–4616

    Article  CAS  Google Scholar 

  18. Parac M, Grimme S (2003) A TDDFT study of the lowest excitation energies of polycyclic aromatic hydrocarbon. Chem Phys 292(1):11–21

    Article  CAS  Google Scholar 

  19. Lee C, Yang W, Parr RG (1988) Development of the Colle-Salvetti correlation-energy formula into a functional of the electron density. Phys Rev B 37(2):785–789

    Article  CAS  Google Scholar 

  20. Becke AD (1993) Density functional thermochemistry. III. The role of exact exchange. J Chem Phys 98:5648–5652

    Article  CAS  Google Scholar 

  21. Kendall RA, Dunning TH Jr, Harrison RJ (1992) Electron affinities of the first-row atoms revisited. Systematic basis sets and wave functions. J Chem Phys 96:6796–6806

    Article  CAS  Google Scholar 

  22. Schlegel HB (1982) Optimization of equilibrium geometries and transition structures. J Comp Chem 3:214–218

    Article  CAS  Google Scholar 

  23. Casida ME, Huix-Rotllant M (2012) Progress in time-dependent density-functional theory. Annu Rev Phys Chem 63:287–323

    Article  CAS  Google Scholar 

  24. Caillie C, Amos RD (2000) Geometric derivatives of density functional theory excitation energies using gradient-corrected functionals. Chem Phys Lett 317:159–164

    Article  Google Scholar 

  25. Adamo C, Jacquemin (2013) The calculations of excited-state properties with time-dependent density functional theory. Chem Soc Rev 42: 845-856

  26. Cancès E, Mennucci B (1998) New applications of integral equations methods for solvation continuum models: ionic solutions and liquid crystals. J Math Chem 23:309–326

    Article  Google Scholar 

  27. Cancès E, Mennucci B, Tomasi J (1997) A new integral equation formalism for the polarizable continuum model: theoretical background and applications to isotropic and anisotropic dielectrics. J Chem Phys 107:3032

    Article  Google Scholar 

  28. Mennucci B, Cancès E, Tomasi J (1997) Evaluation of solvent effects in isotropic and anisotropic dielectrics and in ionic solutions with a unified integral equation method: theoretical bases, computational implementation, and numerical applications. J Phys Chem B 101:10506–10517

    Article  CAS  Google Scholar 

  29. Miertus S, Scrocco E, Tomasi J (1981) Electrostatic interaction of a solute with a continuum. A direct utilizaion of AB initio molecular potentials for the prevision of solvent effects. . 117–129

  30. Cammi R, Tomasi J (1995) Remarks on the use of the apparent surface charges (ASC) methods in solvation problems: iterative versus matrix-inversion procedures and the renormalization of the apparent charges. . 1449–1458

  31. Cammi R (2009) Quantum cluster theory for the polarizable continuum model I The CCSD level with analytical first and second derivatives. J Chem Phys 131:164104

    Article  CAS  Google Scholar 

  32. Shen X, Laber CH, Sarkar U, Galazzi F, Johnson KM, Mahieu NG, Hillebrand R, Fuchs-Knotts T, Barnes CL, Baker GA, Gates KS (2018) Exploiting the inherent photophysical properties of the major tirapazamine metabolite in the development of profluorescent substrates for enzymes that catalyze the bioreductive activation of hypoxia-selective anticancer prodrugs. J Org Chem 83:3126–3131

    Article  CAS  Google Scholar 

  33. Poole JS, Hadad CM, Platz MS, Fredin ZP, Pickard L, Guerrero EL, Kessler M, Chowdhury G, Kotandeniya D, Gates KS (2002) Photochemical electron transfer reactions of tirapazamine. Photochem Photobiol 75:339–345

    Article  CAS  Google Scholar 

  34. Boldrini B, Cavalli E, Painelli A, Terenziani F (2002) Polar dyes in solution: a joint experimental and theoretical study of absorption and emission band shapes. J Phys Chem A 106(26):6286–6294

    Article  CAS  Google Scholar 

  35. Shi X, Poole JS, Emenike I, Burdzinski G, Platz MS (2005) Time-resolved spectroscopy of the excited singlet states of tirapazamine and desoxytirapazamine. J Phys Chem A 109:1491–1496

    Article  CAS  Google Scholar 

  36. Šarlauskas J, Nemeikaitė-Čėnienė A, Marozienė A, Misevičienė L, Lesanavičius M, Čėnas N (2018) Enzymatic single-electron reduction and aerobic cytotoxicity of tirapazamine and its 1-oxide and nor-oxide metabolites. Chemija 29:273–280

    Article  Google Scholar 

  37. Nemeikaitė-Čėnienė A, Šarlauskas J, Jonušienė V, Marozienė A, Misevičienė L, Yantsevich AV, Čėnas N (2019) Kinetics of flavoenzyme-catalyzed reduction of tirapazamine derivatives: implications for their prooxidant cytotoxicity. Int J Mol Sci 20: pii: E4602

  38. Romero J, Mathom T, Limso-Vietra P, Probst M (2021) Electronic structure and reactivity of tirapazamine as a radiosensitizer. J Mol Model 27:177

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This work was carried out within the CA18212 – Molecular Dynamics in the GAS program. The authors are grateful for the high-performance computing resources provided by the Information Technology Open Access Centre of Vilnius University. Special thanks to Justina Jovaisaite for the discussion on the spectra measurement.

Author information

Authors and Affiliations

  1. Life Sciences Centre, Institute of Biochemistry, Vilnius University, Sauletekio av. 7, Vilnius, Lithuania

    Jonas Sarlauskas

  2. Vilnius University Institute of Photonics and Nanotechnology, Faculty of Physics, Vilnius University, Sauletekio av. 3, 10257, Vilnius, Lithuania

    Kamile Tulaite

  3. Institute of Theoretical Physics and Astronomy, Vilnius University, Sauletekio av. 3, Vilnius, Lithuania

    Jelena Tamuliene

Authors
  1. Jonas Sarlauskas
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kamile Tulaite
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jelena Tamuliene
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

All authors contributed to the study’s conception and design. Material preparation, data collection, and analysis were performed by J. Sarlauskas, K. Tulaite, and J. Tamuliene. The first draft of the manuscript was written by J. Tamuliene, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Jelena Tamuliene.

Ethics declarations

Conflict of interest

The authors declare no competing interests.

Additional information

Publisher's note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sarlauskas, J., Tulaite, K. & Tamuliene, J. Investigation of oxygen influence to the optical properties of tirapazamine. J Mol Model 28, 96 (2022). https://doi.org/10.1007/s00894-022-05085-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s00894-022-05085-z

Keywords

Search

Navigation