Novel 15-crown-5 ether or β-diketone incorporated gadolinium complexes for the detection of potassium ions or magnesium and calcium ions

Novel gadolinium complexes (KMR-series: KMR-K and KMR-Mg), which have a bis-15-crown-5 ether or a charged β-diketone structure as a recognition site, have been designed, synthesized and applied for the detection of K+ or of Mg2+ and Ca2+ using MRI or NMR techniques. The measurements are based on the modulation of the longitudinal relaxation time (T1) of water protons in proximity of the gadolinium complexes. Relaxivity measurements of KMR-K1 in aqueous solution showed that the initial longitudinal relaxivity value (r1) of 5.05 mM−1 s−1 is monotonously decreasing with increasing K+ concentrations, reaching a final value of 4.78 mM−1 s−1. This decrease is attributed to a change in the second sphere of hydration of the gadolinium (Gd3+) complex (KMR-K), resulting in a K+ concentration-dependent contrast in MR images. From stoichiometric analysis using mass spectrometry and UV/VIS spectrometry, a 1 : 1 complex formation between KMR-K1 and K+ in a sandwich-type manner with a log K of 3.20 was confirmed. In the case of KMR-Mg, the initial r1 value of 4.98 mM−1 s−1 is monotonously decreasing with increasing Mg2+ or Ca2+ concentrations, reaching a final value of 3.95 or 4.16 mM−1 s−1, respectively, resulting in Mg2+ and Ca2+ concentration-dependent contrast in MR images. The formation of a 1 : 1 complex with a log K of 2.33 for Mg2+ and 1.91 for Ca2+ was confirmed. KMR-K1 and KMR-Mg are the first ion-selective or ion-sensitive gadolinium complexes for K+ or Mg2+ and Ca2+, respectively.