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 A.; Jurisson, Silvia S.

doi:10.1016/j.nucmedbio.2009.08.003

« Previous Next »Nuclear Medicine and Biology
Volume 37, Issue 1 , Pages 41-49, January 2010

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

Brienne N. Bottenus
- Department of Chemistry, University of Missouri, Columbia, MO 65211, USA
- Harry S Truman Memorial VA Hospital, Columbia, MO 65201, USA
Para Kan
- Department of Chemistry, University of Missouri, Columbia, MO 65211, USA
- University of Missouri Research Reactor (MURR), University of Missouri, Columbia, MO 65211, USA
Tyler Jenkins
- Department of Chemistry, University of Missouri, Columbia, MO 65211, USA
Beau Ballard
- Department of Chemistry, University of Missouri, Columbia, MO 65211, USA
Tammy L. Rold
- Department of Internal Medicine, University of Missouri, Columbia, MO 65211, USA
- Harry S Truman Memorial VA Hospital, Columbia, MO 65201, USA
Charles Barnes
- Department of Chemistry, University of Missouri, Columbia, MO 65211, USA
Cathy Cutler
- University of Missouri Research Reactor (MURR), University of Missouri, Columbia, MO 65211, USA
Timothy J. Hoffman
- Department of Chemistry, University of Missouri, Columbia, MO 65211, USA
- Department of Internal Medicine, University of Missouri, Columbia, MO 65211, USA
- Harry S Truman Memorial VA Hospital, Columbia, MO 65201, USA
Mark A. Green
- School of Pharmacy, Purdue University, West Lafayette, IN 47907, USA
Silvia S. Jurisson
- Department of Chemistry, University of Missouri, Columbia, MO 65211, USA
- University of Missouri Research Reactor (MURR), University of Missouri, Columbia, MO 65211, USA
- Harry S Truman Memorial VA Hospital, Columbia, MO 65201, USA
- Corresponding author. Department of Chemistry, University of Missouri, Columbia, MO 65211, USA. Tel.: +1 573 882 2107; fax: +1 573 882 2754.

Received 4 June 2009; received in revised form 4 August 2009; accepted 8 August 2009. published online 05 October 2009.

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)) H₁₄C₈N₆O₂S₂Cl₄Au₂·2CH₃OH, 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)) H₂₆C_13.6N₆O_0.8S₂Cl_1.2Au_1.2, 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.

Keywords: Gold(III), Gold-198, Gold-199, Bis-thiosemicarbazones