Gold(III) bis-thiosemicarbazonato complexes: synthesis, characterization, radiochemistry and X-ray crystal structure analysis

Brienne N. Bottenus, Para Kan, Tyler Jenkins, Beau Ballard, Tammy L. Rold, Charles Barnes, Cathy Cutler, Timothy J. Hoffman, Mark A. Green, Silvia S. Jurisson

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14 Scopus citations

Abstract

Introduction: A variety of (bis)thiosemicarbazone-based ligand systems have been investigated as chelating agents for Au(III) complexes with potential radiotherapeutic applications. Ligand systems containing an ethyl, propyl or butyl backbone between the two imine N donors have been synthesized to evaluate chelate ring size effects on the resultant Au(III) complex stability at the macroscopic and radiotracer levels. Methods: The Au(III) complexes were synthesized and characterized by NMR, electrospray ionization mass spectra, elemental analysis and X-ray crystallography. The 198Au complexes were evaluated in vitro at the tracer level for stability in phosphate-buffered saline at pH 7.4 and 37°C. One of these complexes [198Au(3,4-HxTSE)] showed high in vitro stability and was further evaluated in vivo in normal mice. Results: [Au(ATSM)]AuCl4·2CH3OH, (ATSM=diacetyl-bis(N4-methylthiosemicarbazone)) H14C8N6O2S2Cl 4Au2·2CH3OH, crystallized from methanol in the monoclinic space group P21/n with a=14.7293(13) Å, b=7.7432(7) Å, c=20.4363(18) Å, β=100.140(2)°, V=2294.4 (4) Å3, Z=4; [Au(3,4-HxTSE)]Cl·CH3CH2OH/AuCl2 , (3,4-HxTSE=3,4-hexanedione-bis(N4-ethylthiosemicarbazone)) H26C13.6N6O0.8S2C l1.2Au1.2, crystallized from ethanol in the monoclinic space group P21/c with a=10.1990(10) Å, b=13.8833(14) Å, c=15.1752(15) Å, β=99.353(2)°, V=2120.2 (4) Å3, Z=4. Conclusions: These studies revealed poor stability of the [198Au][Au(3,4-HxTSE)]+ complex; however, crystal structure data suggest potential alterations to the ligand backbone may increase stability.

Original languageEnglish (US)
Pages (from-to)41-49
Number of pages9
JournalNuclear Medicine and Biology
Volume37
Issue number1
DOIs
StatePublished - Jan 1 2010

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Keywords

  • Bis-thiosemicarbazones
  • Gold(III)
  • Gold-198
  • Gold-199

ASJC Scopus subject areas

  • Molecular Medicine
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

Cite this

Bottenus, B. N., Kan, P., Jenkins, T., Ballard, B., Rold, T. L., Barnes, C., Cutler, C., Hoffman, T. J., Green, M. A., & Jurisson, S. S. (2010). Gold(III) bis-thiosemicarbazonato complexes: synthesis, characterization, radiochemistry and X-ray crystal structure analysis. Nuclear Medicine and Biology, 37(1), 41-49. https://doi.org/10.1016/j.nucmedbio.2009.08.003