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

IntroductionA 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.MethodsThe 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)) H26C13.6N6O0.8S2Cl1.2Au1.2, 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.ConclusionsThese 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.