Skip to main content
SpringerLink
Log in

Interactions of pyridinecarboxylic acid chelators with brain metal ions: Cu(II), Zn(II), and Al(III)

  • Chapter
  • First Online:
Metal Ions in Neurological Systems

  • 900 Accesses

Abstract

The interactions of Cu(II), Zn(II), and Al(III) with 1,6-dimethyl-4-hydroxy-3-pyridinecarboxylic acid (DQ716) and 2,6-dimethyl-3-hydroxy-4-pyridinecarboxylic acid (DT726), possible chelating agents in Alzheimer’s disease, were investigated in aqueous solution. The proton dissociation constants of the ligands, the stability constants, and the coordination modes of the metal complexes formed were determined by pH-potentiometric, UV–vis spectrophotometric, and 1H NMR methods. The nitrogen of the pyridine ring changes the proton affinity of the carboxylate and phenolate moieties and these pyridine derivatives form stronger complexes with Cu(II), Zn(II), and Al(III) than salicylic acid. Interactions of the ligands with human serum albumin as their potential transporter in blood were investigated at physiological pH through ultrafiltration by UV-Vis and fluorescence spectroscopy.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Glenner GG, Wong CW (1984) Biochem Biophys Res Commun 120:885

    Article  PubMed  CAS  Google Scholar 

  2. Masters CL, Simms G, Weinman NA, Multhaup G, McDonald BL, Beyreuther K (1985) Proc Natl Acad Sci U S A 82:4245

    Article  CAS  Google Scholar 

  3. Checler F (1995) J Neurochem 65:1431

    Article  PubMed  CAS  Google Scholar 

  4. Atwood CS, Scarpa RC, Huang X, Moir RD, Jones WD, Fairlie DP, Tanzi RE, Bush AI (2000) J Neurochem 75:1219

    Article  PubMed  CAS  Google Scholar 

  5. Lovell MA, Robertson JD, Teesdale WJ, Campbell JL, Markesbery WR (1998) J Neurol Sci 158:47

    Article  PubMed  CAS  Google Scholar 

  6. Bush IA (2003) Trends Neurosci 26:207

    Article  PubMed  CAS  Google Scholar 

  7. Klafki HW, Wiltfang J, Staufenbiel M (1996) Anal Biochem 237:24

    Article  PubMed  CAS  Google Scholar 

  8. Hureau C, Faller P (2009) Biochimie 91:1212

    Article  PubMed  CAS  Google Scholar 

  9. Atwood CS, Perry G, Zeng H, Kato Y, Jones WD, Ling KQ, Huang X, Moir RD, Wang D, Sayre LM (2004) Biochemistry 43:560

    Article  PubMed  CAS  Google Scholar 

  10. Fang CL, Wu WH, Liu Q, Sun X, Ma Y, Zhao YF, Li YM (2010) Regul Pept 163:1

    Article  PubMed  CAS  Google Scholar 

  11. Faller P, Hureau C (2009) Dalton Trans 2009:1080–1094

    Article  Google Scholar 

  12. Atwood CS, Moir RD, Huang X, Bacarra NME, Scarpa RC, Romano DM (1998) J Biol Chem 273:12817

    Article  PubMed  CAS  Google Scholar 

  13. Cuajungco MP, Faget KY, Huang X, Tanzi RE, Bush AI (2000) Ann N Y Acad Sci 920:292

    Article  PubMed  CAS  Google Scholar 

  14. Crichton RR, Ward RJ (2006) Metal-based neurodegeneration: from molecular mechanisms to therapeutic strategies. Wiley, Chichester

    Google Scholar 

  15. Bolognin S, Drago D, Messori L, Zatta P (2009) Med Res Rev 29:547

    Article  PubMed  CAS  Google Scholar 

  16. Bush IA, Tanzi RE (2008) Neurotherapeutics 5:421

    Article  PubMed  CAS  Google Scholar 

  17. Cherny RA, Atwood CS, Xilinas ME, Gray DN, Jones WD, McLean CA, Barnham KJ, Volitakis I, Fraser FW, Kim YS (2001) Neuron 30:665

    Article  PubMed  CAS  Google Scholar 

  18. Adlard PA, Cherny RA, Finkelstein DI, Gautier E, Robb E, Cortes M, Volitakis I, Liu X, Smith JP, Perez K, Laughton K, Li QX, Charman SA, Nicolazzo JA, Wilkins S, Deleva K, Lynch T, Kok G, Ritchie CW, Tanzi RE, Cappai R, Masters CL, Barnham KJ, Bush AI (2008) Neuron 59:43

    Article  PubMed  CAS  Google Scholar 

  19. Hindo SS, Mancino AM, Braymer JJ, Liu Y, Vivekanandan S, Ramamoorthy A, Lim MH (2009) J Am Chem Soc 131:16663

    Article  PubMed  CAS  Google Scholar 

  20. Lakatos A, Zsigó É, Hollender D, Nagy NV, Fülöp L, Simon D, Bozsó Zs, Kiss T (2010) Dalton Trans 39:1302

    Article  PubMed  CAS  Google Scholar 

  21. Green DE, Bowen ML, Scott LE, Storr T, Merkel M, Bohmerle K, Thompson KH, Patrick BO, Schugar HJ, Orvig C (2010) Dalton Trans 39:1604

    Article  PubMed  CAS  Google Scholar 

  22. Sudlow G, Birkett DJ, Wade DN (1975) Clin Exper Pharmacol Physiol 2:129

    Article  CAS  Google Scholar 

  23. Muller N, Lapicque F, Drelon E, Netter P (1994) J Pharm Pharmacol 46:300

    Article  PubMed  CAS  Google Scholar 

  24. Dean A, Ferlin MG, Brun P, Castagliuolo I, Yokel RA, Badocco D, Pastore P, Venzo A, Bombi GG, Di Marco VB (2009) Dalton Trans 2009:1815–1824

    Article  Google Scholar 

  25. Dean A, Di Marco VB (in preparation)

    Google Scholar 

  26. Di Marco VB, Yokel RA, Ferlin MG, Tapparo A, Bombi GG (2002) Eur J Inorg Chem 2002:2648–2655

    Article  Google Scholar 

  27. Sudlow G, Birkett DJ, Wade DN (1975) Mol Pharmacol 11:824

    PubMed  CAS  Google Scholar 

  28. Sudlow G, Birkett DJ, Wade DN (1976) Mol Pharmacol 12:1052

    PubMed  CAS  Google Scholar 

  29. Seedher N, Bhatia S (2006) Pharmacol Res 54:77

    Article  PubMed  CAS  Google Scholar 

  30. Bi S, Song D, Tian Y, Zhou X, Liu Z, Zhang H (2005) Spectrochim Acta A 61:629

    Article  Google Scholar 

  31. Chengnong Y, Jinqiang T, Dan X, Yi L, Zuting P (2006) Chin J Anal Chem 34:796

    Article  Google Scholar 

  32. Ahmad B, Parveen S, Khan RH (2006) Biomacromolecules 7:1350

    Article  PubMed  CAS  Google Scholar 

  33. Scarrow RC, Riley PE, Abu-Dari K, White DL, Raymond KN (1985) Inorg Chem 24:954

    Article  CAS  Google Scholar 

  34. Di Marco VB, Dean A, Ferlin MG, Yokel RA, Li H, Venzo A, Bombi GG (2006) Eur J Inorg Chem 2006:1284–1293

    Article  Google Scholar 

  35. Irving HM, Miles MG, Pettit LD (1967) Anal Chim Acta 38:475

    Article  CAS  Google Scholar 

  36. Di Marco VB, Tapparo A, Bertani R, Bombi GG (1999) Ann Chim (Rome) 89:535

    CAS  Google Scholar 

  37. Covington AK, Paabo M, Robinson RA, Bates RG (1968) Anal Chem 40:700

    Article  CAS  Google Scholar 

  38. Whalley CV, Rankin SM, Hoult JRS, Jessup W, Leake DS (1990) Biochem Pharmacol 39:1743

    Article  PubMed  Google Scholar 

  39. Epps DE, Raub TJ, Caiolfa V, Chiari A, Zamai M (1999) J Pharm Pharmacol 51:41

    Article  PubMed  CAS  Google Scholar 

  40. ZÕkány L, Nagypál I, Peintler G (1991) Technical software distribution, Baltimore

    Google Scholar 

  41. Enyedi ÉA, Farkas E, Dömötör O, Santos MA (2011) J Inorg Biochem 105:326

    Google Scholar 

  42. Kurz H (1986) In: Reidenberg MM, Erill S (eds) Drug protein binding. Praeger, New York, p 70

    Google Scholar 

  43. Martell AE, Smith RM (1982) Critical stability constants, vol 5. Plenum, New York

    Google Scholar 

  44. Kiss T, Atkári K, Jezowska-Bojczuk M, Decock P (1993) J Coord Chem 29:81

    Google Scholar 

Download references

Acknowledgments

The work was made in the frame of the CNR-HAS Bilateral Research Program, and was also supported by the Hungarian Research Funds (TêMOP 4.2.1/B. and OTKA K77833). This paper was also supported by the János Bolyai Research Scholarship of the Hungarian Academy of Sciences (TJ). The project named "TêMOP-4.2.1/B-09/1/KONV-2010-0005 – Creating the Center of Excellence at the University of Szeged" is supported by the European Union and co-financed by the European Regional Fund.

Author information

Authors and Affiliations

  1. Department of Inorganic and Analytical Chemistry, University of Szeged, Szeged, Hungary

    Éva Sija & Tamás Jakusch

  2. Department of Chemical Sciences, University of Padova, Padua, Italy

    Annalisa Dean

  3. Department of Chemical Sciences, University of Padova, via Marzolo 1, 35131, Padua, Italy

    Valerio B. Di Marco

  4. Institute of Science and Molecular Technologies, CNR, Padua, Italy

    Alfonso Venzo

  5. Department of Inorganic and Analytical Chemistry, University of Szeged, 440, Szeged, 6701, Hungary

    Tamás Kiss

Authors
  1. Éva Sija
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Annalisa Dean
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Tamás Jakusch
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Valerio B. Di Marco
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Alfonso Venzo
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Tamás Kiss
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Valerio B. Di Marco or Tamás Kiss .

Editor information

Editors and Affiliations

  1. , Institute of Applied Synthetic Chemistry, Vienna University of Technology, Getreidemarkt 9, Vienna, 1060, Austria

    Wolfgang Linert

  2. Faculty of Chemistry, University of Wroclaw, ul. Fryderyka Joliot Curie 14, Wroclaw, 50-383, Poland

    Henryk Kozlowski

Rights and permissions

Reprints and permissions

Copyright information

© 2012 Springer-Verlag Wien

About this chapter

Cite this chapter

Sija, É., Dean, A., Jakusch, T., Di Marco, V.B., Venzo, A., Kiss, T. (2012). Interactions of pyridinecarboxylic acid chelators with brain metal ions: Cu(II), Zn(II), and Al(III). In: Linert, W., Kozlowski, H. (eds) Metal Ions in Neurological Systems. Springer, Vienna. https://doi.org/10.1007/978-3-7091-1001-0_17

Download citation

Publish with us

Policies and ethics

Search

Navigation