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

Abstract

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.