Biological Trace Element Research

, Volume 183, Issue 2, pp 396–401 | Cite as

A Spectroscopic Study of Interaction of Auricyanide with n-Acetylcysteine

  • Syed G. T. Kazimi
  • Mohammad S. IqbalEmail author
  • C. Frank ShawIII


Interaction of auricyanide, an important metabolite of anti-arthritic gold-based drug auranofin, was studied in vitro with a pharmacologically active ligand n-acetylcysteine with a view to understand reactivity of gold in vivo. Formation of reduction product aurocyanide occurred through mono- and di-n-acetylcysteine-substituted intermediates. The product and intermediates were identified and monitored spectrophotometrically and by electrospray ionization mass spectrometry. This study suggests successive substitution with n-acetylcysteine through trans effect. At equimolar concentrations of auricyanide and n-acetylcysteine, only mono-substituted mixed-ligand complex was formed. Substitution of the data obtained to various kinetic models suggested that the reaction orders are 0.6 in terms of n-acetylcysteine, 1.5 in terms of auricyanide, and 2 overall. The intermediates detected in this work may help to synthesize more effective and less toxic gold drugs.


Auricyanide n-acetylcysteine Electrospray ionization mass spectroscopy (ESI-MS) Rheumatoid arthritis UV-vis spectroscopy 



SGTK thanks Higher Education Commission of Pakistan for the award of indigenous PhD scholarship.

Compliance with Ethical Standards

No animals, humans, or their materials were used in this work.

Conflict of Interest

The authors declare that they have no conflict of interest.


  1. 1.
    Sadler PJ (1976) The biological chemistry of gold. Gold Bull 9:110–118CrossRefGoogle Scholar
  2. 2.
    Forestier J (1935) Rheumatoid arthritis and its treatment with gold salts—results of six years experience. J Lab Clin Med 20:827–840Google Scholar
  3. 3.
    Shaw CF III (1999) Gold-based therapeutic agents. Chem Rev 99:2589–2600CrossRefGoogle Scholar
  4. 4.
    Shaw III CF (1999) In: Schmidbaur H (ed) Gold: progress in the chemistry, biochemistry and technology, J. Wiley & Sons, Chichester, p 259–308Google Scholar
  5. 5.
    Mirabelli CK, Hill DT, Faucette LF et al (1987) Antitumor activity of bis(diphenylphosphino)alkanes, their gold(I) coordination complexes, and related compounds. J Med Chem 30:2181–2190CrossRefPubMedGoogle Scholar
  6. 6.
    Simon TM, Kunishima DH, Vibert GJ, Lorber A (1981) Screening trial with the coordinated gold compound auranofin using mouse lymphocytic leukemia P388. Cancer Res 41:94–97PubMedGoogle Scholar
  7. 7.
    Marzano C, Gandin V, Folda A et al (2007) Inhibition of thioredoxin reductase by auranofin induces apoptosis in cisplatin-resistant human ovarian cancer cells. Free Radic Biol Med 42(6):872–881CrossRefPubMedGoogle Scholar
  8. 8.
    Debnath A, Parsonage D, Andrade RM et al (2012) A high-throughput drug screen for Entamoeba histolytica identifies a new lead and target. Nat Med 18:956–960CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Yangyuoru PM, Webb JW, Shaw CF III (2008) Glutathionato-S-Gold(III) complexes formed as intermediates in the reduction of auricyanide by glutathione. J Inorg Biochem 102:584–593CrossRefPubMedGoogle Scholar
  10. 10.
    Shaw CF III (1989) The protein chemistry of antiarthiritic gold(I) thiolates and related complexes. Comments Inorg Chem 8:233–267CrossRefGoogle Scholar
  11. 11.
    Best SL, Sadler PJ (1996) Gold drugs: mechanism of action and toxicity. Gold Bull 29:87–93CrossRefGoogle Scholar
  12. 12.
    Graham GG, Ziegler JB, Champion GD (1993) Medicinal chemistry of gold. Agents Action Suppl 44:209–217Google Scholar
  13. 13.
    Shaw CF III, Cancro MP, Witkiewiez PL, Eldridge J (1980) Gold(III) oxidation of disulfides in aqueous solution. Inorg Chem 19:3198–3201CrossRefGoogle Scholar
  14. 14.
    Witkiewiez PL, Shaw III CF (1981) Oxidative cleavage of peptide and protein disulphide bonds by gold(III): a mechanism for gold toxicity. J Soc Chem Comm 1111–1114Google Scholar
  15. 15.
    Isab AA, Sadler PJ (1977) Reactions of gold(III) ions with ribonuclease a and methionine derivatives in aqueous solution. Biochim Biophys Acta 492:322–330CrossRefPubMedGoogle Scholar
  16. 16.
    Elder RC, Eidsness MK, Heeg MJ, Tepperman KG, Shaw III CF, Schaeffer N (1983) Extended X-ray absorption fine structure (EXAFS) spectroscopy and X-ray absorption near edge spectroscopy (XANES) in Gold-Based Antiarthritic Drugs and Metabolites, ACS Symp Ser 209, Chapter 20:385–400Google Scholar
  17. 17.
    Eidsness MK, Elder RC (1987) Synchrotron X-ray studies of metal-based drugs and metabolites. Chem Rev 87:1027–1046CrossRefGoogle Scholar
  18. 18.
    Verwilghen J, Kingsley GH, Gambling L, Panayi GS (1992) Activation of gold-reactive T lymphocytes in rheumatoid arthritis patients. Arthr Rheum 35:1413–1418CrossRefGoogle Scholar
  19. 19.
    Shaw CF III, Schraa S, Gleichmann E et al (1994) Redox chemistry and [Au(CN)2] in the formation of gold metabolites. Metal-Based Drugs 1:351–362CrossRefGoogle Scholar
  20. 20.
    Canumalla AJ, Al-Zamil N, Philips M, Isab AA, Shaw CF III (2001) Redox and ligand exchange reactions of potential gold(I) and gold(III)-cyanide metabolites under biomimetic conditions. J Inorg Biochem 85:67–76CrossRefPubMedGoogle Scholar
  21. 21.
    Graham GG, Haavisto TM, Jones HM, Champion GD (1984) The effect of cyanide on the uptake of gold by red blood cells. Biochem Pharmacol 33:1257–1262CrossRefPubMedGoogle Scholar
  22. 22.
    Lewis D, Capell HA, McNiel CJ, Iqbal MS, Brown DH, Smith WE (1983) Gold levels produced by treatment with auranofin and sodium aurothiomalate. Ann Rheum Dis 42:566–570CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Lavoie S, Murray MM, Deppen P et al (2008) Glutathione precursor, N-acetyl-cysteine, improves mismatch negativity in schizophrenia patients. Neuropsychopharmacology 33(9):2187–2199CrossRefPubMedGoogle Scholar
  24. 24.
    Lippard SJ (1983) Platinum, gold and other metal chemotherapeutic agents. ACS Symp Ser 209:356Google Scholar
  25. 25.
    Ford-Smith MH, Habeeb JJ, Rawsthorne JH (1972) Kinetics and thermodynamics of the oxidative-addition reaction of iodine with the dicyanoaurate(I) ion in aqueous solution. J Chem Soc Dalton Trans 2116–2120Google Scholar
  26. 26.
    Perumareddi JR, Liehr AD, Adamson AW (1963) Ligand field theory of transition metal cyanide complexes. Part I. The zero, one and two electron or hole configurations. J Amer Chem Soc 85(3): 249–259Google Scholar
  27. 27.
    Noszal B, Visky D, Kraszni M (2000) Population, acid−base, and redox properties of N-acetylcysteine conformers. J Med Chem 43(11):2176–2182CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2017
Corrected publication September/2017

Authors and Affiliations

  • Syed G. T. Kazimi
    • 1
  • Mohammad S. Iqbal
    • 2
    Email author
  • C. Frank ShawIII
    • 3
  1. 1.Department of ChemistryUniversity of SargodhaSargodhaPakistan
  2. 2.Department of ChemistryForman Christian CollegeLahorePakistan
  3. 3.Department of ChemistryIllinois State UniversityNormalUSA

Personalised recommendations