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

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(Ill) 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 Au-198 complexes were evaluated in vitro at the tracer level for stability in phosphate-buffered saline at pH 7.4 and 37 degrees C. One of these complexes [Au-198(3,4-HxTSE)] showed high in vitro stability and was further evaluated in vivo in normal mice. Results: [Au(ATSM)]AUCl(4)center dot 2CH(3)OH, (ATSM=diacetyl-bis(N-4-methylthiosemicarbazone)) H14C8N6O2S2Cl4Au2 center dot 2CH(3)OH, crystallized from methanol in the monoclinic space group P21/n with a=14.7293(13) angstrom, b=7.7432(7) angstrom, c=20.4363(18) angstrom, beta=100.140(2)degrees, V=2294.4 (4) angstrom(3), Z=4; [Au(3,4-HxTSE)]Cl center dot CH3CH2OH/AuCl2, (3,4-HxTSE=3,4-hexanedione-bis(N-4-ethylthiosemicarbazone)) H26C13.6N6O0.8S2Cl1.2Au1.2, crystallized from ethanol in the monoclinic space group P21/c with a=10.1990(10) angstrom, b=13.8833(14) angstrom, c=15.1752(15) angstrom, beta=99.353(2)degrees, V=2120.2 (4) angstrom, Z=4. Conclusions: These studies revealed poor stability of the [Au-198][Au(3,4-HxTSE)](+) complex; however, crystal structure data suggest potential alterations to the ligand backbone may increase stability. (C) 2010 Elsevier Inc. All rights reserved.