A smart copper(ii)-responsive binuclear gadolinium(iii) complex-based magnetic resonance imaging contrast agent

Abstract

A novel Gd-DO3A-type bismacrocyclic complex, [Gd₂(DO3A)₂BMPNA], with a Cu²⁺-selective binding unit was synthesized as a potential “smart” copper(II)-responsive magnetic resonance imaging (MRI) contrast agent. The relaxivity of the complex was modulated by the presence or absence of Cu²⁺; in the absence of Cu²⁺, the complex exhibited a relatively low relaxivity value (6.40 mM⁻¹ s⁻¹), while the addition of Cu²⁺ triggered an approximately 76% enhancement in relaxivity (11.28 mM⁻¹ s⁻¹). Moreover, this Cu²⁺-responsive contrast agent was highly selective in its response to Cu²⁺ over other biologically-relevant metal ions. The influence of some common biological anions on the Cu²⁺-responsive contrast agent and the luminescence lifetime of the complex were also studied. The results of the luminescence lifetime measurements indicated that the enhancement in relaxivity was mainly ascribed to the increased number of inner-sphere water molecules binding to the paramagnetic Gd³⁺ core upon the addition of Cu²⁺. In addition, the visual change associated with the significantly enhanced relaxivity due to the addition of Cu²⁺ was observed from T₁-weighted phantom images.