Tuning the Redox Sensitivity of MnII/MnIII-Bispidine MRI Probes by the Introduction of a Phenolate Donor

In the objective of exploiting the MnII/III redox couple combined with the bispidine scaffold for the development of redox-responsive magnetic resonance imaging (MRI) probes, we have designed and synthesized H3L1 ligand, featuring a phenol pendant arm. This novel ligand is hypothesized to lower the MnII/III redox potential relative to previously reported derivatives, while retaining the high kinetic inertness and good relaxivity properties characteristic of MnII bispidine complexes. The [MnIIL1(H2O)]- complex exhibits high thermodynamic stability (log KMnIIL1 = 14.2), notable kinetic inertness (dissociation half-life, t1/2 = 20.4 h at pH 6 in the presence of 50 equiv of ZnII), and high relaxivity (r1 = 3.91 mM-1s-1 at 60 MHz, 25 °C, pH 7), highlighting the suitability of the MnII complex as a platform for MRI probe development. Electrochemical studies revealed a significantly lower oxidation potential (E1/2 = 306 mV vs SCE) compared to other Mn-bispidine chelates, enabling successful synthesis of the oxidized [MnIIIL1] form in methanol. Although the aqueous stability of the +III oxidation state remains limited and highly dependent on water content, these results demonstrate that the incorporation of a phenolate donor effectively tunes the MnII/III redox properties of the bispidine scaffold.