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The spermine-based hydroxypyridonate octadentate chelator 3,4,3-LI(1,2-HOPO) was investigated for its ability to act as an antenna that sensitizes the emission of Sm(III), Eu(III), and Tb(III) in the Visible range (Φ(tot) = 0.2-7%) and the emission of Pr(III), Nd(III), Sm(III), and Yb(III) in the Near Infra-Red range, with decay times varying from 1.78 μs to 805 μs at room temperature. The particular luminescence spectroscopic properties of these lanthanide complexes formed with 3,4,3-LI(1,2-HOPO) were used to characterize their respective solution thermodynamic stabilities as well as those of the corresponding La(III), Gd(III), Dy(III), Ho(III), Er(III), Tm(III), and Lu(III) complexes. The remarkably high affinity of 3,4,3-LI(1,2-HOPO) for lanthanide metal ions and the resulting high complex stabilities (pM values ranging from 17.2 for La(III) to 23.1 for Yb(III)) constitute a necessary but not sufficient criterion to consider this octadentate ligand an optimal candidate for in vivo metal decorporation. The in vivo lanthanide complex stability and decorporation capacity of the ligand were assessed, using the radioactive isotope (152)Eu as a tracer in a rodent model, which provided a direct comparison with the in vitro thermodynamic results and demonstrated the great potential of 3,4,3-LI(1,2-HOPO) as a therapeutic metal chelating agent.

3,4,3-LI(1,2-HOPO): In vitro formation of highly stable lanthanide complexes translates into efficacious in vivo europium decorporation