Rotaxane probes for the detection of hydrogen peroxide by 129Xe hyperCEST NMR

• Published in: Angewandte Chemie International Edition 2019-06, Vol.58 (29), p.9948-9953
• Main Authors: Klass, Sarah H., Truxal, Ashley E., Fiala, Tahoe A., Kelly, Joseph, Nguyen, Dang, Finbloom, Joel, Wemmer, David E., Pines, Alexander, Francis, Matthew B.
• Format: Article
• Language: English
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.201903045

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 1 H MRI are impaired by the high abundance of protons in the body. 129 Xe hyperCEST NMR/MRI comprises a highly sensitive complement to traditional 1 H MRI due to its ability to report specific chemical environments. To date, the scope of responsive 129 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 129 Xe hyperCEST NMR contrast agent that can be turned on in response to H 2 O 2 , which is upregulated as a result several disease states. Added H 2 O 2 was detected by 129 Xe hyperCEST NMR in the low μM range, as well as H 2 O 2 produced by HEK 293T cells activated with tumor necrosis factor. The CB6 molecule can host single 129 Xe atoms in its interior cavity, creating a distinct chemical environment that can be observed by 129 Xe hyperCEST NMR. To create a “turn on” probe, CB6 can be threaded onto a molecular axle and capped by two stoppers to prevent the entry of 129 Xe into the CB6 interior. Selective cleavage of one stopper group by H 2 O 2 releases CB6, producing a hyperCEST response.