A Cu(II)2 Paramagnetic Chemical Exchange Saturation Transfer Contrast Agent Enabled by Magnetic Exchange Coupling

The ability of magnetic exchange coupling to enable observation of paramagnetic chemical exchange saturation transfer (PARACEST) in transition metal ions with long electronic relaxation times (τs) is demonstrated. Metalation of the dinucleating, tetra(carboxamide) ligand HL with Cu(2+) in the presence of pyrophosphate (P2O7)(4-) affords the complex [LCu(II)2(P2O7)](-). Solution-phase variable-temperature magnetic susceptibility data reveal weak ferromagnetic superexchange coupling between the two S = 1/2 Cu(II) centers, with a coupling constant of J = +2.69(5) cm(-1), to give an S = 1 ground state. This coupling results in a sharpened NMR line width relative to a GaCu analogue, indicative of a shortening of τs. Presaturation of the amide protons in the Cu2 complex at 37 °C leads to a 14% intensity decrease in the bulk water (1)H NMR signal through the CEST effect. Conversely, no CEST effect is observed in the GaCu complex. These results provide the first example of a Cu-based PARACEST magnetic resonance contrast agent and demonstrate the potential to expand the metal ion toolbox for PARACEST agents through introduction of magnetic exchange coupling.