Ratiometric pH Imaging with a CoII2 MRI Probe via CEST Effects of Opposing pH Dependences

We report a Co2-based magnetic resonance (MR) probe that enables the ratiometric quantitation and imaging of pH through chemical exchange saturation transfer (CEST). This approach is illustrated in a series of air- and water-stable CoII2 complexes featuring CEST-active tetra(carboxamide) and/or hydroxyl-substituted bisphosphonate ligands. For the complex bearing both ligands, variable-pH CEST and NMR analyses reveal highly shifted carboxamide and hydroxyl peaks with intensities that increase and decrease with increasing pH, respectively. The ratios of CEST peak intensities at 104 and 64 ppm are correlated with solution pH in the physiological range 6.5–7.6 to construct a linear calibration curve of log(CEST104 ppm/CEST64 ppm) versus pH, which exhibits a remarkably high pH sensitivity of 0.99(7) pH unit–1 at 37 °C. In contrast, the analogous CoII2 complex with a CEST-inactive bisphosphonate ligand exhibits no such pH response, confirming that the pH sensitivity stems from the integration of amide and hydro...