Decacationic Pillar[5]arene: A New Scaffold for the Development of 129Xe MRI Imaging Agents.

P U Ashvin I Fernando,Brenton Deboef,Alanna Wade,Joseph D Brown,Paul T Cesana,Vira Grynko,Lauren E Seveney,Mitchell S Albert,Francis T Hane,Yurii Shepelytskyi,Adriana M Mendieta

doi:10.1021/acsomega.0c02565

Abstract

A decacationic water-soluble pillar[5]arene possessing a nonsolvated hydrophobic core has been designed and synthesized. This supramolecular host is capable of binding xenon, as evidenced by hyperCEST depletion experiments. Fluorescence-based studies also demonstrate that xenon binds into the cavity of the pillararene with an association constant of 4.6 × 103 M–1. These data indicate that the water-soluble pillararene is a potential scaffold for building contrast agents that can be detected by xenon-129 magnetic resonance imaging.

Highlights

While the majority of the work in the field of 129Xe magnetic resonance imaging (MRI) has focused on the development of targeted biosensors for molecular imaging applications, we propose that nontargeted 129Xe MRI contrast agents could be a useful alternative to conventional metal-based contrast agents.[1−3] Inhaled 129Xe is nontoxic, readily distributes throughout the body, and can be detected using a conventional MRI instrument with a broadband receiver and coil.[4−7] Localized contrast can be achieved by employing macrocyclic agents that reversibly bind 129Xe in vivo
We describe the development of a water-soluble xenon-binding macrocycle and its detection via hyperCEST in a clinical MRI instrument
We describe how computational studies assisted in the design and synthesis of a new xenon-binding motif, which is the first step toward the development of a new class of potential 129Xe contrast agents based on the pillar[5]arene macrocycle core

Summary

■ INTRODUCTION

While the majority of the work in the field of 129Xe magnetic resonance imaging (MRI) has focused on the development of targeted biosensors for molecular imaging applications, we propose that nontargeted 129Xe MRI contrast agents could be a useful alternative to conventional metal-based contrast agents.[1−3] Inhaled 129Xe is nontoxic, readily distributes throughout the body, and can be detected using a conventional MRI instrument with a broadband receiver and coil.[4−7] Localized contrast can be achieved by employing macrocyclic agents that reversibly bind 129Xe in vivo. We quantify its affinity for the noble gas, and we show that the binding of Xe in the water-soluble pillararene can be detected via hyperCEST using a clinical MRI scanner, validating its potential as a contrast agent for 129Xe MRI, and laying the necessary groundwork for subsequent in vivo imaging studies

■ RESULTS AND DISCUSSION

■ CONCLUSIONS

■ REFERENCES