Advertisement

Ligand Exchange/Scrambling Study of Gold(I)-Phosphine Complexes in the Solid Phase by DESI-MS Analysis

  • Syed G. T. Kazimi
  • Mohammad S. IqbalEmail author
  • Christopher C. Mulligan
  • C. Frank ShawIII
  • Fozia Iram
  • Ashley R. Stelmack
  • Ian S. Campbell
Research Article

Abstract

Only a few analytical techniques are available for the characterization of mechanochemical synthetic reaction products. We demonstrate here that DESI-MS is a powerful technique for this purpose, combining the selectivity of MS-based assays with the simplicity and in situ analysis capability of ambient ionization methods. In this work, we report that auranofin, a gold-based drug, and its precursor triethylphosphine gold(I) chloride undergo a complex array of ligand exchange/scrambling reactions with thiol-containing amino acids in the solid state. The products were readily characterized by DESI-MS analysis from the solid-phase reaction, clearly exhibiting ligand exchange and scrambling, with independent confirmation by solid state 13C-NMR. The thioglucose and triethylphosphine moieties exchanged with cysteine and its derivatives, whereas the glutathione replaced 2,3,4,6-tetra-o-acetyl-β-1-d-glucopyranose only. It was concluded that ligand exchange and scrambling reactions can be carried out in the solid state, and some of the unique products reported in this study can be conveniently prepared through mechanochemical synthesis in good yields (> 98%), as demonstrated by synthesis of (l-cysteinato-S)-triethylphosphine gold(I) from triethylphosphine gold(I) chloride and l-cysteine.

Keywords

Gold complexes Auranofin Ligand exchange Ligand scrambling DESI-MS Ambient mass spectrometry 

Notes

Acknowledgements

The authors would like to dedicate this work to the late C. Frank Shaw III and his research in metal-based therapeutics. SGTK acknowledges HEC Pakistan for a PhD scholarship award.

Supplementary material

13361_2019_2319_MOESM1_ESM.docx (353 kb)
ESM 1 (DOCX 353 kb)

References

  1. 1.
    Shaw III, C.F.: Gold-based therapeutic agents. Chem. Rev. 99, 2589–2600 (1999)CrossRefGoogle Scholar
  2. 2.
    Sutton, B.M., McGusty, E., Walz, D.T., Di Martino, M.J.: Oral gold. Antiarthritic properties of alkylphosphinegold coordination complexes. J. Med. Chem. 15, 1095–1098 (1972)CrossRefGoogle Scholar
  3. 3.
    Debnath, A., Parsonage, D., Andrade, R.M., He, C., Cobo, E.R., Hirata, K., Chen, S., Garcìa-Rivera, G., Orozco, E., Martinez, M.B., Gunatilleke, S.S., Barrios, A.M., Arkin, M.R., Poole, L.B., McKerrow, J.H., Reed, S.L.: A high-throughput drug screen for Entamoeba histolytica identifies a new lead and target. Nat. Med. 18, 956–960 (2012)CrossRefGoogle Scholar
  4. 4.
    Messori, L., Marcon, G.: Metal ions and their complexes in medication. In: Sigel, A., Sigel, H. (eds.) Metal ions in biological systems, vol. 41, pp. 385–425. Marcel Dekker, Inc., New York (2004)Google Scholar
  5. 5.
    Tiekink, E.R.T.: Gold derivatives for the treatment of cancer. Crit. Rev. Oncol. Hematol. 42, 225–248 (2002)CrossRefGoogle Scholar
  6. 6.
    Balema, V.P., Wiench, J.W., Pruski, M., Pecharsky, V.K.: Solvent-free mechanochemical synthesis of two Pt complexes: Cis-(Ph3P)2PtCl2 and Cis-(Ph3P)2PtCO3. Chem. Comm. 1606–1607 (2002)Google Scholar
  7. 7.
    Garay, A.L., Pichon, A., James, S.L.: Solvent-free synthesis of metal complex. Chem. Soc. Rev. 36, 846–855 (2007)CrossRefGoogle Scholar
  8. 8.
    Orita, A., Jiang, L., Nakano, T., Ma, N., Otera, J.: Solventless reaction dramatically accelerates supramolecular self-assembly. Chem. Comm. 1362–1363 (2002)Google Scholar
  9. 9.
    Yangyuoru, P.M., Webb, J.W., Shaw, C.F.: Glutathionato-S-gold(III) complexes formed as intermediates in the reduction of auricyanide by glutathione. J. Inorg. Biochem. 102, 584–593 (2008)CrossRefGoogle Scholar
  10. 10.
    Yangyuoru, P.M., Webb, J.W., Shaw, C.F.: Proton-linked bi-and tri-metallic gold cyanide complexes observed by ESI-MS spectrometry. J. Inorg. Biochem. 102, 576–583 (2008)CrossRefGoogle Scholar
  11. 11.
    Di Marco, V.B., Bombi, G.G.: Electrospray mass spectrometry (ESI-MS) in the study of metal-ligand solution equilibria. Mass. Spec. Rev. 25, 347–379 (2005)CrossRefGoogle Scholar
  12. 12.
    Talib, J., Beck, J.L., Ralph, S.F.: A mass spectrometric investigation of the binding of gold antiarthritic agents and the metabolite [Au(CN)2] to human serum albumin. J. Biol. Inorg. Chem. 11, 559–570 (2006)CrossRefGoogle Scholar
  13. 13.
    Hill, D.T., Isab, A.A., Griswold, D.E., DiMartino, M.J., Matz, E.D., Figueroa, A.L., Wawro, J.E., DeBrosse, C., Reiff, W.M., Elder, R.C., Jones, B., Webb, J.W., Shaw, C.F.: Seleno-Auranofin (Et3PAuSe-tagl): synthesis, spectroscopic (EXAFS 197Au Mössbauer, 31P, 1H, 13C, and 77Se NMR, ESI-MS) characterization, biological activity, and rapid serum albumin-induced Triethylphosphine oxide generation. Inorg. Chem. 49, 7663–7675 (2010)CrossRefGoogle Scholar
  14. 14.
    Shoeib, T., Atkinson, D.W., Sharp, B.L.: Structural analysis of the anti-arthritic drug Auranofin: its complex with cysteine, selenocysteine and their fragmentation products. Inorg. Chim. Acta. 363, 184–192 (2010)CrossRefGoogle Scholar
  15. 15.
    Monge, M.E., Harris, G.A., Dwivedi, P., Fernàndez, F.M.: Mass spectrometry: recent advances in direct open air surface sampling/ionization. Chem. Rev. 113, 2269–2308 (2013)CrossRefGoogle Scholar
  16. 16.
    Venter, A.R., Douglass, K.A., Shelley, J.T., Hasman, G., Honarvar, E.: Mechanisms of real-time, proximal sample processing during ambient ionization mass spectrometry. Anal. Chem. 86, 233–249 (2014)CrossRefGoogle Scholar
  17. 17.
    Feider, C.L., Krieger, A., DeHoog, R.J., Eberlin, L.S.: Ambient ionization mass spectrometry: recent developments and applications. Anal. Chem. 91, 4266–4290 (2019)CrossRefGoogle Scholar
  18. 18.
    Vircks, K.E., Mulligan, C.C.: Rapid screening of synthetic cathinones as trace residues and in authentic seizures using a portable mass spectrometer equipped with desorption electrospray ionization. Rapid Commun. Mass Spectrom. 26, 2665–2672 (2012)CrossRefGoogle Scholar
  19. 19.
    O’Leary, A.E., Hall, S.E., Vircks, K.E., Mulligan, C.C.: Monitoring the clandestine synthesis of methamphetamine in real-time with ambient sampling portable mass spectrometry. Anal. Methods. 7, 7156–7163 (2015)CrossRefGoogle Scholar
  20. 20.
    Lawton, Z.E., Traub, A., Fatigante, W.L., Mancias, J., O’Leary, A.E., Hall, S.E., Wieland, J.R., Oberacher, J., Gizzi, M.C., Mulligan, C.C.: Analytical validation of a portable mass spectrometer featuring interchangeable, Ambient ionization sources for high throughput forensic evidence screening. J. Am. Soc. Mass Spectrom. 6, 1048–1059 (2017)CrossRefGoogle Scholar
  21. 21.
    Fedick, P.W., Fatigante, W.L., Lawton, Z.E., O’Leary, A.E., Hall, S.E., Bain, R.M., Aryton, S.T., Ludwig, J.A., Mulligan, C.C.: A low-cost, simplified platform of interchangeable, ambient ionization sources for rapid, forensic evidence screening on portable mass spectrometric instrumentation. Instruments. 2, (2018).  https://doi.org/10.3390/instruments2020005
  22. 22.
    Lostun, D., Perez, C.J., Licence, P., Barrett, D.A.: Reactive DESI-MS imaging of biological tissues with dicationic ion-pairing compounds. Anal. Chem. 87, 3286–3293 (2015)CrossRefGoogle Scholar
  23. 23.
    Ma, X., Zhang, S., Zhang, X.: An instrumental perspective on reaction monitoring by ambient mass spectrometry. TrAC. Trend. Anal. Chem. 35, 50–66 (2012)CrossRefGoogle Scholar
  24. 24.
    Badu-Tawiah, A.K., Eberlin, L.S., Ouyang, Z., Cooks, R.G.: Chemical aspects of the extractive methods of ambient ionization mass spectrometry. Ann. Rev. Phys. Chem. 64, 481–505 (2013)CrossRefGoogle Scholar
  25. 25.
    Liu, P., Lanekoff, I.T., Laskin, J., Dewald, H.D., Chen, H.: Study of electrochemical reactions using nanospray desorption electrospray ionization mass spectrometry. Anal. Chem. 84, 5737–5743 (2012)CrossRefGoogle Scholar
  26. 26.
    Brown, T.A., Chen, H., Zare, R.N.: Detection of the short-lived radical cation intermediate in the electrooxidation of N, N-dimethylaniline by mass spectrometry. Angew. Chem. Int. Ed. 54(38), 11183–11185 (2015)CrossRefGoogle Scholar
  27. 27.
    Xie, Y., He, L.F., Lin, S.C., Su, H.F., Xie, S.Y., Huang, R.B., Zheng, L.S.: Desorption electrospray ionization mass spectrometry for monitoring the kinetics of Baeyer-Villiger solid-state organic reactions. J. Am. Soc. Mass Spectrom. 20, 2087–2092 (2009)CrossRefGoogle Scholar
  28. 28.
    Takàts, Z., Wiseman, J.M., Gologan, B., Cooks, R.G.: Mass spectrometry sampling under ambient conditions with desorption electrospray ionization. Science. 306, 471–473 (2004)CrossRefGoogle Scholar
  29. 29.
    Hill, D.T., Sutton, B.M.: (2,3,4,6-Tetra-O-acetyl-l-thio-β-d-glucopyranosato-S)(triethylphosphine)Gold, C20H34AuO9P5. Cryst. Struct. Commun. 9, 679–686 (1980)Google Scholar
  30. 30.
    Badu-Tawiah, A., Bland, C., Campbell, D.I., Cooks, R.G.: Non-aqueous spray solvent and solubility effects in desorption electrospray ionization. J. Am. Soc. Mass Spectrom. 21, 572–579 (2010)CrossRefGoogle Scholar
  31. 31.
    Bristow, T.W., Ray, A.D., O’Kearney-McMullan, A., Lim, L., McCullough, B., Zammataro, A.: On-line monitoring of continuous flow chemical synthesis using a portable small footprint mass spectrometer. J. Am. Soc. Mass Spectrom. 25, 1794–1802 (2014)CrossRefGoogle Scholar
  32. 32.
    McBride, E.M., Verbeck, G.F.: A mass spectrometer in every fume hood. J. Am. Soc. Mass Spectrom. 29, 1555–1566 (2018)CrossRefGoogle Scholar

Copyright information

© American Society for Mass Spectrometry 2019

Authors and Affiliations

  1. 1.Department of ChemistryUniversity of SargodhaSargodhaPakistan
  2. 2.Department of Chemistry, Forman Christian CollegeLahorePakistan
  3. 3.Department of ChemistryIllinois State UniversityNormalUSA
  4. 4.Department of ChemistryLCW UniversityLahorePakistan
  5. 5.Department of Chemistry and PhysicsFlorida Gulf Coast UniversityFort MyersUSA

Personalised recommendations