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

Imaging extracellular Cu 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 Cu, particularly versus the more abundant Zn ions, is highly challenging. We present here an innovative Cu-responsive MRI contrast agent that contains a bioinspired Cu binding site. This sensor shows a remarkable increase in relaxivity of nearly 400% in the presence of Cu, which could be rationalized in terms of an increase in the hydration number of the Ln ion, as demonstrated by spectroscopic and relaxometric studies and supported by density functional theory calculations. Importantly, the system also shows an unprecedented selectivity for Cu, in particular over Zn. Phantom MRI images were recorded at 9.4 T to highlight the potential of such probes, which lies directly in their bioinspired design.