Hydroxypyridinonate Complex Stability of Group (IV) Metals and Tetravalent f‑Block Elements: The Key to the Next Generation of Chelating Agents for Radiopharmaceuticals

The solution thermodynamics of the water-soluble complexes formed between 3,4,3-LI­(1,2-HOPO) and Zr­(IV) or Pu­(IV) were investigated to establish the metal coordination properties of this octadentate chelating agent. Stability constants log β₁₁₀ = 43.1 ± 0.6 and 43.5 ± 0.7 were determined for [Zr­(IV)­(3,4,3-LI­(1,2-HOPO))] and [Pu­(IV)­(3,4,3-LI­(1,2-HOPO))], respectively, by spectrophotometric competition titrations against Ce­(IV). Such high thermodynamic stabilities not only confirm the unparalleled Pu­(IV) affinity of 3,4,3-LI­(1,2-HOPO) as a decorporation agent but also corroborate the great potential of hydroxypyridinonate ligands as new ⁸⁹Zr-chelating platforms for immuno-PET applications. These experimental values are in excellent agreement with previous estimates and are discussed with respect to ionic radius and electronic configuration, in comparison with those of Ce­(IV) and Th­(IV). Furthermore, a liquid chromatography assay combined with mass spectrometric detection was developed to probe the separation of the neutral [M­(IV)­(3,4,3-LI­(1,2-HOPO))] complex species (M = Zr, Ce, Th, and Pu), providing additional insight into the coordination differences between group IV and tetravalent f-block metals and on the role of d and f orbitals in bonding interactions