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 Green, Silvia S. Jurisson

Research output: Contribution to journalArticle

14 Citations (Scopus)

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 2010
Externally publishedYes

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Radiochemistry
Gold
X-Rays
Ligands
Thiosemicarbazones
Diacetyl
Imines
X Ray Crystallography
Chelating Agents
Methanol
Mass Spectrometry
Ethanol
Phosphates
In Vitro Techniques

Keywords

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

ASJC Scopus subject areas

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

Cite this

Gold(III) bis-thiosemicarbazonato complexes : synthesis, characterization, radiochemistry and X-ray crystal structure analysis. / Bottenus, Brienne N.; Kan, Para; Jenkins, Tyler; Ballard, Beau; Rold, Tammy L.; Barnes, Charles; Cutler, Cathy; Hoffman, Timothy J.; Green, Mark; Jurisson, Silvia S.

In: Nuclear Medicine and Biology, Vol. 37, No. 1, 01.2010, p. 41-49.

Research output: Contribution to journalArticle

Bottenus, BN, Kan, P, Jenkins, T, Ballard, B, Rold, TL, Barnes, C, Cutler, C, Hoffman, TJ, Green, M & Jurisson, SS 2010, 'Gold(III) bis-thiosemicarbazonato complexes: synthesis, characterization, radiochemistry and X-ray crystal structure analysis', Nuclear Medicine and Biology, vol. 37, no. 1, pp. 41-49. https://doi.org/10.1016/j.nucmedbio.2009.08.003
Bottenus, Brienne N. ; Kan, Para ; Jenkins, Tyler ; Ballard, Beau ; Rold, Tammy L. ; Barnes, Charles ; Cutler, Cathy ; Hoffman, Timothy J. ; Green, Mark ; Jurisson, Silvia S. / Gold(III) bis-thiosemicarbazonato complexes : synthesis, characterization, radiochemistry and X-ray crystal structure analysis. In: Nuclear Medicine and Biology. 2010 ; Vol. 37, No. 1. pp. 41-49.
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title = "Gold(III) bis-thiosemicarbazonato complexes: synthesis, characterization, radiochemistry and X-ray crystal structure analysis",
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) {\AA}, b=7.7432(7) {\AA}, c=20.4363(18) {\AA}, β=100.140(2)°, V=2294.4 (4) {\AA}3, 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) {\AA}, b=13.8833(14) {\AA}, c=15.1752(15) {\AA}, β=99.353(2)°, V=2120.2 (4) {\AA}3, 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.",
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T1 - Gold(III) bis-thiosemicarbazonato complexes

T2 - synthesis, characterization, radiochemistry and X-ray crystal structure analysis

AU - Bottenus, Brienne N.

AU - Kan, Para

AU - Jenkins, Tyler

AU - Ballard, Beau

AU - Rold, Tammy L.

AU - Barnes, Charles

AU - Cutler, Cathy

AU - Hoffman, Timothy J.

AU - Green, Mark

AU - Jurisson, Silvia S.

PY - 2010/1

Y1 - 2010/1

N2 - 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.

AB - 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.

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KW - Gold-199

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