Lanthanide complexes (Gd$^{III}$ and Eu$^{III}$) based on a DOTA-TEMPO platform for redox monitoring via relaxivity

International audience; Three lanthanide complexes (Ln=Gd, Eu) based on a DO3 A ([Ln(L$_1$)]) or DO2 A ([Ln(L$_{2-3}$)]$^+$) platform appended by a redox active TEMPO-based arm were prepared. Complex [Ln(L$_2$)]$^+$) shows an alkyne arm, offering the possibility of postfunctionalization by click reaction to yield [Ln(L$_3$)]$^+$). The complexes demonstrate a redox response whereby the hydroxylamine, nitroxide and oxoammonium forms of the arm can be obtained in turn. Luminescence measurements on the europium complexes support an octadentate (L$_1$, L$_3$) or heptadentate (L$_2$) chelation by the ligand, with one water molecule in the inner coordination sphere. The relaxivity was determined from 20 kHz to 30 MHz by fast-field cycling NMR. The three Gd-III complexes under their hydroxylamine form [Gd(L$_1$)] and [Gd(L$_{2-3}$)]$^+$) show $r_1$ values of 7.0, 5.1 and 5.0 mM$^{-1}$ s$^{-1}$ (30 KHz), which increase to 8.8, 5.5 and 6.1 mM$^{-1}$ s$^{-1}$ in the nitroxide form. The radical complexes are not toxic against M21 cell lines, at least up to 40 $\mu$M. By using EPR spectroscopy we establish that they do not penetrate the cells with the exception of [Eu(L$_2$)]$^+$.