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 Gd3+-based complex specifically for Zn2+ 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 Zn2+ sensing unit and the Gd3+ complex leads to unique behavior of the system in the absence of Zn2+. A significant increase in efficacy of the system is observed upon Zn2+ binding, and importantly, the complex is highly selective for Zn2+ relative to other physiological cations. A comprehensive structural study reliably determines the microscopic parameters at the origin of the Zn2+ response, primarily an increase in the number of water molecules directly coordinated to Gd3+ upon Zn2+ binding. Crucially, the system maintains a strong response to Zn2+ binding in the presence of Human Serum Albumin, highlighting its potential for biological applications.
Keywords: Molecular Imaging * Zinc * Gadolinium * responsive probe * Magnetic Resonance Imaging.
© 2024 Wiley‐VCH GmbH.