Rotaxane Probes for the Detection of Hydrogen Peroxide by 129 Xe HyperCEST NMR Spectroscopy

The development of sensitive and chemically selective MRI contrast agents is imperative for the early detection and diagnosis of many diseases. Conventional responsive contrast agents used in H MRI are impaired by the high abundance of protons in the body. Xe hyperCEST NMR/MRI comprises a highly sensitive complement to traditional H MRI because of its ability to report specific chemical environments. To date, the scope of responsive Xe NMR contrast agents lacks breadth in the specific detection of small molecules, which are often important markers of disease. Herein, we report the synthesis and characterization of a rotaxane-based Xe hyperCEST NMR contrast agent that can be turned on in response to H O , which is upregulated in several disease states. Added H O was detected by Xe hyperCEST NMR spectroscopy in the low micromolar range, as well as H O produced by HEK 293T cells activated with tumor necrosis factor.