Selective Binding and Quantitation of Calcium with a Cobalt-Based Magnetic Resonance Probe.

We report a cobalt-based paramagnetic chemical exchange saturation transfer (PARACEST) magnetic resonance (MR) probe that is able to selectively bind and quantitate the concentration of Ca ions under physiological conditions. The parent LCo complex features CEST-active carboxamide groups and an uncoordinated crown ether moiety in close proximity to a high-spin pseudo-octahedral Co center. Addition of Na, Mg, K, and Ca leads to binding of these metal ions within the crown ether. Single-crystal X-ray diffraction and solid-state magnetic measurements reveal the presence of a cation-specific coordination environment and magnetic anisotropy of Co, with axial zero-field splitting parameters for the Na- and Ca-bound complexes differing by over 90%. Owing to these differences, solution-based measurements under physiological conditions indicate reversible binding of Na and Ca to give well-separated CEST peaks at 69 and 80 ppm for [LCoNa] and [LCoCa], respectively. Dissociation constants for different cation-bound complexes of LCo, as determined by H NMR spectroscopy, demonstrate high selectivity toward Ca. This finding, in conjunction with the large excess of Na in physiological environments, minimizes interference from related cations, such as Mg and K. Finally, variable-[Ca] CEST spectra establish the ratio between the CEST peak intensities for the Ca- and Na-bound probes (CEST/CEST) as a measure of [Ca], providing the first example of a ratiometric quantitation of Ca concentration using PARACEST. Taken together, these results demonstrate the ability of transition metal PARACEST probes to afford a concentration-independent measure of [Ca] and provide a new approach for designing MR probes for cation sensing.