Lanthanide complexes of DOTA-nitroxide conjugates for redox imaging: spectroelectrochemistry, CEST, relaxivity, and cytotoxicity.

The lanthanide(iii) complexes (Gd, Eu, Dy, and Yb) of DOTA tris(amide) and bis(amide) derivatives (L1 and L2) featuring one redox active TEMPO arm were prepared. Ligand L2 harbours an alkyne fragment for further functionalization. The X-ray crystal structure of ligand L2 in complexation with Na+ was solved. The complexes showed in their CV one oxidation wave (0.26-0. 34 V vs. Fc+/Fc) due to an oxoammonium/nitroxide redox couple and a broad reduction corresponding to the nitroxide/hydroxylamine system. The Eu complexes demonstrated the presence of one water molecule in their coordination sphere. The nitroxide complexes were characterized by EPR spectroscopy, showing the typical 3-line pattern in the high temperature regime, which is quenched upon the addition of ascorbate (reduction into hydroxylamine). In their nitroxide form, the complexes show essentially no CEST peak. Conversely, the reduced complexes demonstrate a 12% CEST peak at 51 ppm, corresponding to the metal bound water molecule. Fast exchange precluded the CEST activity for the amide protons. All the complexes proved to be essentially non-toxic for M21 cells at concentrations up to 50 µM.

Structural and spectroscopic investigations of nine-coordinate redox active lanthanide complexes with a pincer O,N,O ligand.

The lanthanide complexes EuL3, GdL3, YbL3 and LuL3 of the N,N'-bis(2-hydroxy-di-3,5-tert-butylphenyl)amine were prepared. The X-Ray crystal structures of GdL3 and LuL3 demonstrated a nine-coordinate sphere with three ligand molecules under their anionic diamagnetic form (Cat-N-BQ)-. The complexes showed three oxidation events (Eox11/2 = 0.15-0.16 V, E1/22 = 0.51-55 V, and E1/23 = 0.75-0.78 V vs. Fc+/Fc) via cyclic voltammetry, corresponding to the successive oxidation of the aminophenolate moeities to iminosemiquinone species. The complexes GdL3 and YbL3 were characterized by EPR spectroscopy, allowing for the determination of the zero field splitting (ZFS) parameters in the first case. The monocations (LnL3)+ and monoanions (LnL3)- were electrochemically generated (Ln = Eu, Gd, Yb, Lu), as well as the dications YbL32+ and LuL32+. The spins are antiferromagnetically exchange coupled in the diradical species LuL32+ (|D| = 260 MHz, E = 0). All the complexes (incl. neutral) possess a strong absorption band in the NIR region (730-840 nm, ε > 19 mM-1 cm-1) corresponding to ligand-based transitions.

A redox active switch for lanthanide luminescence in phenolate complexes.

The reversible oxidation of coordinated phenolates into phenoxyl radicals results in a dramatic quenching (>95%) of the luminescence of the f metal ion.