Tales of the Unexpected: The Case of Zirconium(IV) Complexes with Desferrioxamine

摘要

The Zr⁴⁺ complexes with desferrioxamine (H3DFO) and its derivatives are the only ⁸⁹Zr-based imaging agents for proton emission tomography (PET) that have been used so far in clinical trials. Nevertheless, a complete speciation of the Zr⁴⁺/H3DFO system in solution has never been performed and the stability constants of the relevant complexes are still unknown. Here we report, for the first time, the speciation of this system in water, performed by potentiometric titrations, and the determination of the stability constants of all complexes formed in the pH range 2.5–11.5. Surprisingly, although desferrioxamine gives rise to very stable 1:1 complexes with Zr⁴⁺ (logK = 36.14 for Zr⁴⁺ + DFO³⁻ = [ZrDFO]⁺), 2:2 and 2:3 ones are also formed in solution. Depending on the conditions, these binuclear complexes can be main species in solution. These results were corroborated by small-angle X-ray scattering (SAXS) and MALDI mass spectrometry analyses of complex solutions. Information on complex structures was obtained by means of density functional theory (DFT) calculations.