A Bioinspired Cu²⁺-Responsive Magnetic Resonance Imaging Contrast Agent with Unprecedented Turn-On Response and Selectivity

Imaging extracellular Cu²⁺ in vivo is of paramount interest due to its biological importance in both physiological and pathological states. Magnetic resonance imaging (MRI) is a powerful technique to do so. However, the development of efficient MRI contrast agents selective for Cu²⁺, particularly versus the more abundant Zn²⁺ ions, is highly challenging. We present here an innovative Cu²⁺-responsive MRI contrast agent that contains a bioinspired Cu²⁺ binding site. This sensor shows a remarkable increase in relaxivity of nearly 400% in the presence of Cu²⁺, which could be rationalized in terms of an increase in the hydration number of the Ln³⁺ ion, as demonstrated by spectroscopic and relaxometric studies and supported by density functional theory calculations. Importantly, the system also shows an unprecedented selectivity for Cu²⁺, in particular over Zn²⁺. Phantom MRI images were recorded at 9.4 T to highlight the potential of such probes, which lies directly in their bioinspired design.