Biological Trace Element Research

, Volume 164, Issue 2, pp 198–204 | Cite as

A New Oxidovanadium(IV) Complex of Oxodiacetic Acid and dppz: Spectroscopic and DFT Study. Antitumor Action on MG-63 Human Osteosarcoma Cell Line

  • Ignacio E. León
  • Beatriz S. Parajón-Costa
  • Carlos A. Franca
  • Susana B. Etcheverry
  • Enrique J. BaranEmail author


The oxidovanadium(IV) complex of oxodiacetic acid (H2ODA) and dppz (dipyrido[3,2-a:2′,3′-c] phenazine) of stoichiometry [VO(ODA)(dppz)]⋅3H2O could be synthesized for the first time by reaction between [VO(ODA)(H2O)2] and dppz. It was characterized by infrared and electronic spectroscopies. Its optimized molecular structure was obtained by DFT calculations, as it was impossible to grow single crystals adequate for crystallographic studies. The antitumor action of the complex on MG-63 human osteosarcoma cell line was also investigated. It was found that it caused a concentration-related inhibitory effect in the concentration range between 5 and 25 μM and diminished the cell viability ca. 45 % in the range from 25 to 100 μM, without dose/response effects in this range. These biological effects are, in general, similar to those previously reported for the related [VO(ODA)(ophen)]⋅1.5H2O complex.


Oxidovanadium(IV) Oxodiacetic acid dppz DFT calculations FTIR spectrum Electronic spectrum Human osteosarcoma cell line 



This research was supported by the Universidad Nacional de La Plata, the Agencia Nacional de Promoción Científica y Tecnológica-ANPCyT (PICT 2218), and the Consejo Nacional de Investigaciones Científicas y Técnicas-CONICET (PIP 1125 and PIP 5078). The authors are indebted to Dr. J. Zinczuk, Instituto de Química de Rosario (IQUIR/CONICET,UNR), Rosario, Argentina, for the synthesis of dppz. IEL is a fellow from CONICET and BSPC, and SBE are members of the Research Career from CONICET. CAF acknowledges the Universidad Nacional de Catamarca for computing time.


  1. 1.
    León IE, Butenko N, Di Virgilio AL, Muglia CI, Baran EJ, Cavaco I, Etcheverry SB (2014) Vanadium and cancer treatment: antitumoral mechanisms of three oxidovanadium(IV) complexes on a human osteosarcoma line. J Inorg Biochem 134:106–117CrossRefPubMedGoogle Scholar
  2. 2.
    Rivadeneira J, Barrio DA, Etcheverry SB, Baran EJ (2007) Spectroscopic characterization of a VO2+ complex of oxodiacetic acid and its bioactivity on osteoblast-like cells in culture. Biol Trace Elem Res 118:159–166CrossRefPubMedGoogle Scholar
  3. 3.
    Leon IE, Etcheverry SB, Parajón-Costa BS, Baran EJ (2012) Spectroscopic characterization of an oxovanadium(IV) complex of oxodiacetic acid and o-phenanthroline. Bioactivity on osteoblast-like cells in culture. Biol Trace Elem Res 147:403–407CrossRefPubMedGoogle Scholar
  4. 4.
    Leon IE, Etcheverry SB, Parajón-Costa BS, Baran EJ (2013) Spectroscopic characterization of an oxovanadium(IV) complex of oxodiacetic acid and 2,2′-bipyridine. Bioactivity on osteoblast-like cells in culture. J Mex Chem Soc 57:175–179Google Scholar
  5. 5.
    Grirrane A, Pastor A, Ienco A, Mealli C, Galindo A (2002) Synthesis and molecular structure of oxydiacetate complexes of nickel(II) and cobalt(II). Theoretical analysis of the planar and non-planar conformation of oxydiacetate ligand and oxydiacetic acid. Dalton Transact 2002:3771–3777CrossRefGoogle Scholar
  6. 6.
    del Rio D, Galindo A, Tejedo J, Bedoya FJ, Ienco A, Mealli C (2000) Synthesis, molecular structure and properties of oxovanadium(IV) complexes containing the oxydiacetate ligand. Inorg Chem Comm 3:32–34CrossRefGoogle Scholar
  7. 7.
    Álvarez L, Grirrane A, Moyano R, Álvarez E, Pastor A, Galindo A (2010) Comparison of the coordination capabilities of thiodiacetate and oxydiacetate ligands through the X-ray characterization and DFT studies of [VO(dta)(phen)]⋅4H2O and [VO(oda)(phen)]⋅1.5H2O. Polyhedron 29:3028–3035CrossRefGoogle Scholar
  8. 8.
    del Rio D, Galindo A, Vicente R, Mealli C, Ienco A, Mais D (2003) Synthesis, molecular structure and properties of oxo-vanadium(IV) complexes containing the oxydiacetate ligand. Dalton Transact 2003:1813–1820Google Scholar
  9. 9.
    Erkkila KE, Odom DT, Barton JK (1999) Recognition and reaction of metallointercalators with DNA. Chem Rev 99:2777–2795CrossRefPubMedGoogle Scholar
  10. 10.
    Liu HK, Sadler PJ (2011) Metal complexes as DNA intercalators. Acc Chem Res 44:349–359CrossRefPubMedGoogle Scholar
  11. 11.
    Chen W, Turro C, Friedman LA, Barton JK, Turro NJ (1997) Resonance Raman investigation of Ru(phen)2(dppz)2+ and related complexes in water and in the presence of DNA. J Phys Chem B 101:6995–7000CrossRefGoogle Scholar
  12. 12.
    Navarro M, Hernández C, Colmenares I, Hernández P, Fernández M, Sierraalta A, Marchán E (2007) Synthesis and characterization of [Au(dppz)2]Cl3. DNA interaction studies and biological activity against Leishmania (L) mexicana. J Inorg Biochem 101:111–116CrossRefPubMedGoogle Scholar
  13. 13.
    Benítez J, Guggeri L, Tomaz I, Arrambide G, Navarro M, Costa Pessoa J, Garat B, Gambino D (2009) Design of vanadium mixed-ligand complexes as potential anti-protozoa agents. J Inorg Biochem 103:609–616CrossRefPubMedGoogle Scholar
  14. 14.
    Benítez J, Guggeri L, Tomaz I, Costa Pessoa J, Moreno V, Lorenzo J, Avilés FX, Garat B, Gambino D (2009) A novel vanadyl complex with a polypyridyl DNA intercalator as ligand: a potential anti-protozoa and anti-tumor agent. J Inorg Biochem 103:1386–1394CrossRefPubMedGoogle Scholar
  15. 15.
    Sánchez-Delgado RA, Anzellotti A, Suárez L (2004) Metal complexes as chemotherapeutic agents against tropical diseases: malaria, trypanosomiasis and leishmaniasis. In: Sigel A, Sigel H (eds) Metal ions in biological systems, vol. 41: Metal ions and their complexes in medication. Marcel Dekker, New York, pp 379–419Google Scholar
  16. 16.
    Navarro M, Gabbiani C, Messori L, Gambino D (2010) Metal-based drugs for malaria, trypanosomiasis and leishmaniasis: recent achievements and perspectives. Drug Disc Today 15:1070–1078CrossRefGoogle Scholar
  17. 17.
    Klein A, Scheiring T, Kaim W (1999) Molecular and crystal structure of an organoplatinum(II) complex with dipyrido[3,2-:2′,3′-c]phenazine (dppz). Z Anorg Allg Chem 625:1177–1180CrossRefGoogle Scholar
  18. 18.
    Smith GF, Cagle FW (1947) The improved synthesis of 5-nitro-1,10-phenanthroline. J Org Chem 12:781–784CrossRefPubMedGoogle Scholar
  19. 19.
    Koft E, Case FH (1962) Substituted 1,10-phenanthrolines. XII. Benzo and pyrido derivatives. J Org Chem 27:865–868CrossRefGoogle Scholar
  20. 20.
    Dickeson JE, Summers LA (1970) Derivatives of 1,10-phenanthroline-5-6-quinone. Aust J Chem 23:1023–1027CrossRefGoogle Scholar
  21. 21.
    Mosmann T (1983) Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 65:55–63CrossRefPubMedGoogle Scholar
  22. 22.
    Zhao Y, Truhlar DG (2008) The M06 suite of density functionals for main group thermochemistry, thermochemical kinetics, noncovalent interactions, excited states, and transition elements: two new functionals and systematic testing of four M06-class functionals and 12 other functionals. Theor Chem Acc 120:215–241CrossRefGoogle Scholar
  23. 23.
    Frisch MJ, Trucks GW, Schlegel HB, Scuseria GE, Robb MA, Cheeseman JR, Scalmani G, Barone V, Mennucci B, Petersson GA, Nakatsuji H, Caricato M, Li X, Hratchian HP, Izmaylov AF, Bloino J, Zheng G, Sonnenberg JL, Hada M, Ehara M, Toyota K, Fukuda R, Hasegawa J, Ishida M, Nakajima T, Honda Y, Kitao O, Nakai H, Vreven T, Montgomery JJA, 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, Rega N, Millam JM, Klene M, Knox JE, Cross JB, Bakken V, Adamo C, Jaramillo J, Gomperts R, Stratmann RE, Yazyev O, Austin AJ, Cammi R, Pomelli C, Ochterski JW, Martin RL, Morokuma K, Zakrzewski VG, Voth GA, Salvador P, Dannenberg JJ, Dapprich S, Daniels AD, Farkas O, Foresman JB, Ortiz JV, Cioslowski J, Fox DJ (2010) Gaussian-09. Gaussian Inc., WallingfordGoogle Scholar
  24. 24.
    Weigend F, Ahlrichs R (2005) Balanced basis sets of split valence, triple zeta valence and quadruple zeta valence qualify for H to Rn: design and assessment of accuracy. Phys Chem Chem Phys 7:3297–3305CrossRefPubMedGoogle Scholar
  25. 25.
    Rappoport D, Furche F (2010) Property-optimized Gaussian basis sets for molecular response calculation. J Chem Phys 133:134105CrossRefPubMedGoogle Scholar
  26. 26.
    Dunning TH Jr, Hay PJ (1976) In: Schaefer HF III (ed) Modern theoretical chemistry, vol 3. Plenum, New York, pp 1–28Google Scholar
  27. 27.
    Hay PJ, Wadt WR (1985) Ab initio effective core potentials for molecular calculations. Potentials for the transition metal atoms Sc to Hg. J Chem Phys 82:270CrossRefGoogle Scholar
  28. 28.
    Barone V, Cossi M (1998) Quantum calculation of molecular energies and energy gradients in solution by a conductor solvent model. J Phys Chem A 102:1995–2001CrossRefGoogle Scholar
  29. 29.
    Matthewson BJ, Flood A, Polson MIJ, Armstrong C, Phillips DL, Gordon KC (2002) Vibrational spectra of dipyrido[3,2-a:2′,3′-c]phenazine and its radical anion analyzed by ab initio calculations and deuteration studies. Bull Chem Soc Jpn 75:933–942CrossRefGoogle Scholar
  30. 30.
    Lin-Vien D, Colthup NB, Fateley WG, Grasselli JG (1991) The handbook of infrared and Raman characteristic frequencies of organic molecules. Academic, BostonGoogle Scholar
  31. 31.
    Smith B (1999) Infrared spectral interpretation. CRC, Boca RatonGoogle Scholar
  32. 32.
    Siebert H (1966) Anwendungen der Schwingungsspektroskopie in der Anorganischen Chemie. Springer, BerlinCrossRefGoogle Scholar
  33. 33.
    Libowitzky E (1999) Correlation of O-H stretching frequencies and O-HO hydrogen bond lengths in minerals. Monatsh Chem 130:1047–1059CrossRefGoogle Scholar
  34. 34.
    Nakamoto K (1997) Infrared and Raman spectra of inorganic and coordination compounds, 5th edn. Wiley, New YorkGoogle Scholar
  35. 35.
    Baran EJ (2001) Review: spectroscopic studies of oxovanadium coordination compounds. J Coord Chem 54:215–238CrossRefGoogle Scholar
  36. 36.
    Bishayee A, Wagharay A, Patel MA, Chatterjee M (2010) Vanadium in the detection, prevention and treatment of cancer: the in vivo evidence. Cancer Lett 294:1–12CrossRefPubMedGoogle Scholar
  37. 37.
    Rehder D (2008) Bioinorganic vanadium chemistry. Wiley, ChichesterCrossRefGoogle Scholar
  38. 38.
    Baran EJ (2008) Vanadium detoxification: chemical and biochemical aspects. Chem Biodivers 5:1475–1484CrossRefPubMedGoogle Scholar
  39. 39.
    Rehder D (2012) The potentiality of vanadium in medicinal applications. Future Med Chem 4:1823–1837CrossRefPubMedGoogle Scholar
  40. 40.
    Mohsen AB, Machado I, Cai Y, Schaefer KL, Serra M, Hogendoorn PC, Llombart-Bosch A, Cleton-Jansen AM (2011) Functional characterization of osteosarcoma cell lines provides representative models to study the human disease. Lab Investig 91:1195–1205CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Ignacio E. León
    • 1
    • 2
  • Beatriz S. Parajón-Costa
    • 2
  • Carlos A. Franca
    • 2
  • Susana B. Etcheverry
    • 1
    • 2
  • Enrique J. Baran
    • 2
    Email author
  1. 1.Cátedra de Bioquímica Patológica, Facultad de Ciencias ExactasUniversidad Nacional de La PlataLa PlataArgentina
  2. 2.Centro de Química Inorgánica (CEQUINOR/CONICET, UNLP), Facultad de Ciencias ExactasUniversidad Nacional de La PlataLa PlataArgentina

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