Design and Characterization of Two Bifunctional Cryptophane A‐Based Host Molecules for Xenon Magnetic Resonance Imaging Applications

Abstract

AbstractCryptophanes have been shown to be a promising tool in xenon magnetic resonance imaging (MRI) applications. The affinity of xenon for molecular host structures such as cryptophane‐A (CrA) and the large xenon chemical shift that can be detected in the presence of such hosts has motivated the synthesis of a number of cryptophane‐based MRI biosensors. Bifunctional biosensors that incorporate both a fluorophore and a cryptophane moiety are flexible tools for evaluating the intracellular localization and quantifying cellular uptake/binding of such xenon hosts in conjunction with testing their MRI capabilities. In this study, we compare the performance of a new compound that bears tetramethylrhodamine (TAMRA), CrA‐PEG‐TAMRA (PEG=polyethylene glycol), with our previously synthesized compound in which fluorescein (FAM) was the optical reporter. We demonstrate that these biosensors are suitable candidates for MRI‐based cell‐tracking studies; specifically, the new addition of a rhodamine derivative will allow for multiplexing experiments and showed slightly improved NMR spectroscopic behavior. Importantly, both biosensors display equally good cell‐labeling efficiency, which facilitates the acquisition of high‐quality xenon magnetic resonance images in two different cell lines. This study describes a simple synthetic approach for the production of biologically compatible bifunctional compounds. These biosensors can be used as they are for cell labeling but can also serve as building blocks for further functionalization and cryptophane‐based xenon biosensor design with MRI and fluorescence multiplexing options.