Symmetric CEST-active lanthanide complexes for redox monitoring

Abstract

Two symmetric ligands harbouring two TEMPO radicals and two functionalized acetamide arms (R = OMe (L₁), CF₃ (L₂)) were prepared and chelated to lanthanide ions (Eu^III, Yb^III for both L₁ and L₂, Dy^III for L₁). Luminescence measurements on the europium complexes support the coordination of a single water molecule. The TEMPO arms are magnetically interacting in L₁ (and its complexes) but not in L₂. The TEMPO moieties can be reversibly oxidized into an oxoammonium (0.33–0.36 V vs. Fc⁺/Fc) or reduced into a hydroxylamine (ill-defined redox wave, reduction by ascorbate), which are both diamagnetic. The europium complexes [Eu(L₁)]³⁺ and [Eu(L₂)]³⁺ in their hydroxylamine form exhibit a temperature dependent CEST effect, which is maximal at 25 °C (30%) and 37 °C (12%), respectively. The CEST activity is dramatically reduced in the corresponding nitroxide forms due to the paramagnetism of the ligand. The europium complexes show no cytotoxicity against M21 cell lines over long incubation times (72 h) at high concentration (40 μM).