A gadolinium(III) complex with 8-amidequinoline based ligand as copper(II) ion responsive contrast agent

Abstract

A new Cu²⁺-responsive MRI contrast agent (Gd-QDOTAMA) with a quinoline-based ligand was synthesized and characterized. Relaxivity studies on Gd-QDOTAMA showed that the relaxivity increased from 4.27 mM⁻¹ s⁻¹ to 7.29 mM⁻¹ s⁻¹ in response to equimolar amounts of copper(II) ion, corresponding to ca. 71% relaxivity enhancement. Distinct changes in relaxivity were undetected upon addition of physiologically relevant alkali metal cations (K⁺ or Na⁺), alkaline earth metal cations (Mg²⁺ or Ca²⁺), or d-block metal cations (Zn²⁺, Cu⁺, Fe²⁺, Fe³⁺), indicating a high selectivity for Cu²⁺ over other biologically relevant metal ions. Moreover, the influence of common biological anions at physiological levels on the Cu²⁺-responsive contrast agent was also studied. Luminescence studies on the Eu counterpart Eu-QDOTAMA suggest that the enhancement in relaxivity for Gd-QDOTAMA in response to Cu²⁺ is most likely due to the increased number of inner-sphere water molecules around Gd³⁺ upon Cu²⁺ binding to the 8-amidequinoline moiety. In vitroT₁-weighted phantom images of Gd-QDOTAMA confirmed that signal intensity was markedly increased by the addition of equimolar amounts of Cu²⁺.