Zinc Sensing with a Pyridine-Based Lanthanide Contrast Agent: Structural Analysis in Aqueous Solution.

Zinc is an important physiological cation, and its misregulation is implicated in various diseases. It is therefore important to be able to image zinc by non-invasive methods such as Magnetic Resonance Imaging (MRI). In this work, we have successfully synthesized a novel Gd-based complex specifically for Zn sensing by MRI. Using a combination of NMR, luminescence, potentiometric, and relaxivity experiments, completed with DFT calculations, we demonstrate that incorporating a short linker between the Zn sensing unit and the Gd complex leads to unique behavior of the system in the absence of Zn. A significant increase in efficacy of the system is observed upon Zn binding, and importantly, the complex is highly selective for Zn relative to other physiological cations. A comprehensive structural study reliably determines the microscopic parameters at the origin of the Zn response, primarily an increase in the number of water molecules directly coordinated to Gd upon Zn binding. Crucially, the system maintains a strong response to Zn binding in the presence of Human Serum Albumin, highlighting its potential for biological applications.