Rational design of hyperpolarized xenon NMR molecular sensor for the selective and sensitive determination of zinc ions

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. Here, we developed a novel zinc-responsive hyperpolarized (HP) 129Xe-based NMR molecular sensor. This HP 129Xe-based NMR molecular sensor was synthesized by attaching 2-(diphenylphosphino) benzenamine as ligand for zinc ions to the xenon-binding supramolecular cage, cryptophane. The 129Xe NMR spectroscopy of such molecular sensor was shifted up to 6.4 ppm in the presence of Zn2+ ions, which was 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 exhibited high sensitivity and selectivity as discriminated from other six potentially competing metal ions. The application of this sensor in the analysis of zinc ions in the rat serum samples was also evaluated. The strategy is generally applicable in developing sensitive and selective sensors for quantitative determination of zinc ions.