Complexes of d-block metal ions with N-trifluoroethyl cyclam derivatives with bifunctional phosphinic acid pendant arms as ¹⁹F MRI probes.

Authors

Adam Svítok, Jan Kotek, Andrej Šmelko, Petr Hermann

Published in

Dalton transactions (Cambridge, England : 2003). Aug 03, 2026. Epub Aug 03, 2026.

Abstract

As ¹⁹F nuclei are not naturally present in the body, ¹⁹F MRI requires suitable probes. Nonetheless, ¹⁹F MRI signals are usually weak due to the low achievable concentration of the probes and the long T₁ relaxation times of the ¹⁹F nucleus. To increase the sensitivity of ¹⁹F MRI, shortening the ¹⁹F relaxation times in complexes of paramagnetic metal ions with fluorinated ligands is a common practice. However, complexes of simple ligands remain insufficient. To improve the efficacy of the probes by increasing the number of ¹⁹F nuclei or to obtain responsive/targeted ¹⁹F MRI probes, the complexes should be conjugated to other molecules. Here, we report on the preparation and properties of paramagnetic Ni^II and Co^II complexes of cyclam derivatives suitable for conjugation. All ligands contain two -CH₂CF₃ groups bound to trans macrocyclic amines to provide the ¹⁹F MRI signal and two phosphinic acid pendant arms, easily modifiable for further conjugation. The complexes are kinetically inert and form multiple diastereoisomers due to a combination of nitrogen- and phosphorus-atom-based chirality. The properties relevant to ¹⁹F MRI probes are the same for all diastereoisomers. The ¹⁹F T₁ relaxation times of the Ni^II complexes are almost identical (2-3 ms at 7-14 T) and independent of the phosphorus substituent but are too short for standard ¹⁹F MRI sequences. However, the Co^II complex of the P-aminomethyl derivative exhibits a good T₁ and ratio, ∼16 ms and ∼0.4, respectively, at 7 T. These properties are better than those of Co^II complexes with longer Co⋯F distances suggested in the literature, making the presented complexes optimal for Co^II-based ¹⁹F MRI probes. This work shows that transition metal ion complexes of cyclam derivatives bearing six equivalent fluorine atoms and two phosphinic acid pendant arms are suitable as conjugatable ¹⁹F MRI probes. Moreover, the results show that substitutions on the phosphorus atoms do not alter key relaxation properties, offering opportunities to tune this family of ¹⁹F MRI probes.

PMID:
42544501
Bibliographic data and abstract were imported from PubMed on 03 Aug 2026.

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