Bis-thiosemicarbazone Ligands as Candidates for Radioantimony(III) Chelation for Use in Theranostic Applications

Thermodynamic stabilization of antimony complexes against hydrolysis in biological environments is critical for the effective delivery of theranostic radionuclides such as ¹¹⁷Sb and ¹¹⁹Sb in nuclear medicine. We report a series of Sb(III) complexes formed with symmetric pentadentate ligands 2,6-diacetylpyridine bis(R-thiosemicarbazone) (R = H, Me, Ph, and 4-OMe/4-Cl derivatives), as well as an asymmetric variant, 2,6-diacetylpyridine-(R₁-thiosemicarbazone)-(R₂-thiosemicarbazone) (R₁ = H, R₂ = Ph). X-ray crystallography reveals planar N₃S₂ pentacoordination around Sb(III), with a labile apical ligand (X = Cl^- or OH^-). DFT calculations confirm the presence of a stereochemically active lone pair trans to the apical ligand, contributing significant steric influence. Solution stability was assessed via UV/vis spectrophotometry in a DMSO solution containing pH 7.4 phosphate-buffered saline over 3 days. Among six complexes, Sb(dapbptsc)X─antimony(III) diacetylpyridine bis(<i>N</i>4-phenyl-3-thiosemicarbazone)─showed the greatest stability, with minimal decoordination. This complex also resists hydrolysis when challenged with excess OH^- and remains intact when challenged with Zn²⁺, Ca²⁺, Mg²⁺ and cysteine, though it is unstable in the presence of Cu²⁺ ions. Overall, these results demonstrate promising stability for Sb(III) complexes, although poor water solubility and the copper-induced degradation underscore a need for further optimization of these ligands.