Mixed Tridentate π -Donor and Monodentate π -Acceptor Ligands as Chelating Systems for Rhenium-188 and Technetium-99m Nitrido Radiopharmaceuticals
A new molecular metallic fragment for labeling biologically active molecules with 99mTc and 188Re is described.
This system is composed of a combination of tridentate π-donor and monodentate π-acceptor ligands bound to a
[M Ξ N]2+ group (M = 99mTc, 188Re) in a pseudo square-pyramidal geometry. A simple structural model of the new metallic
fragment was obtained by reacting the ligand 2, 2’-iminodiethanethiol [H2NS2 = NH(CH2CH2SH)2] and monodentate tertiary
phosphines with the [M Ξ N]2+ group (M = 99mTc, 188Re). In the resulting complexes (dubbed3+1complexes), the tridentate
ligand binds the [MΞN]2+ core through the two deprotonated, negatively charged, thiol sulfur atoms and the neutral,
protonated, amine nitrogen atom. The residual fourth position of the five-coordinated arrangement is occupied by a
phosphine ligand. The chemical identity of these model 99mTc and 188Re compounds was established by comparison with
the chromatographic properties of the corresponding complexes obtained at the macroscopic level with the long–lived
99gTc and natural Re isotopes. The investigation was further extended to comprise a series of ligands formed by simple
combinations of two basic amino acids or pseudo-amino acids to yield potential tridentate chelating systems having [S, N,
S] and [N, N, S] as sets of π-donor atoms. Labeling yields and in vitro stability were investigated using different ancillary
ligands. Results showed that SNS-type ligands afforded the highest labeling yields and the most robust 3+1 nitrido complexes
with both 99mTc and 188Re. Thus, the new chelating system can be conveniently employed for labeling peptides and
other biomolecules with the [MΞN]2+ group.
Keywords: Technetium-99m, rhenium-188, nitrido radiopharmaceuticals, 3+1 complexes, peptide chelators.
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