High Sensitive NMR Detection For Zn²⁺ Ions Using¹²⁹Xe Based Molecular Sensor

Zinc is an essential trace element in the human body and is the second most abundant transition metal in the living organisms. Zn2+ions not only constitute many enzymes and proteins, but also play a key role in various physiological processes. Either a deficiency or excess of Zn2+ions will cause a physiological dysfunction of the organism. It is of great significance to develop a highly sensitive and specific method for the detection of Zn2+ions. NMR molecular sensors could provide a potential tool for detecting the Zn2+ions in the living organisms because of their characteristic non-invasive and non-destructive approaches. Although Zn2+ions are involved in large numbers of physiopathological processes, non-invasive detection of Zn2+ions in opaque biological samples remains a huge challenge be used in the monitoring of Zn2+ions and investigating Zn2+ions related physiopathological processes in biological organisms. The application of MR has been therefore limited for their intrinsic low sensitivity at thermal equilibrium. In contrast, the use of a hyperpolarized129Xe based NMR molecular sensor suggests a possible solution. The nuclear spin of the xenon atom can be hyperpolarized by a spin-exchange optical pumping (SEOP) technique, and the resulted nuclear spin polarization could be enhanced by four orders of magnitude in comparison to the Boltzmann polarization, leading to an amplification of the NMR sensitivity by a factor of10,000. Using the hyperpolarized (HP) xenon NMR molecular sensor, the low concentration special detectiong can be conducted. Here, we have shown the rational design of the HP129Xe-based NMR molecular sensor and the specific determination of Zn2+We develop a novel zinc-responsive hyperpolarized Xe-based NMR molecular sensor. This HP Xe-based NMR molecular sensor is synthesized by attaching2-(diphenylphosphino) benzenamine as ligand for zinc ions to the xenon-binding supramolecular cage. In the design of molecular sensor, we explore the possibility of a-cyclodextrin and its derivatives as the xenon-binding supramolecular cage part. But129Xe NMR experiments show that a-cyclodextrin and its derivatives are not suitable as "cage" molecules. Then we use the cryptophane as the xenon-binding supramolecular cage. We use the new hyperpolarized129Xe-based NMR molecular sensor to detect the zinc ions, the129Xe NMR spectroscopy of such molecular sensor is shifted up to6.4ppm in the presence of Zn2+ions, which is nearly four times larger than that of the reported similar sensor. The application of the sensor would benefit low concentration detection by using indirect NMR/MRI method. The response exhibites high sensitivity and selectivity as discriminated from other six potentially competing metal ions. The strategy is generally applicable in developing sensitive and selective sensors for quantitative determination of zinc ions.