High Exchange Rate Complexes of ¹²⁹Xe with Water‐Soluble Pillar[5]arenes for Adjustable Magnetization Transfer MRI

Abstract

Macrocyclic host structures for generating transiently bound Xe have been used in various ultra-sensitive NMR and MRI applications for molecular sensing of biochemical analytes. They are based on hyperpolarized nuclei chemical exchange saturation transfer (Hyper-CEST). Here, we tested a set of water-soluble pillar[5]arenes with different counterions in order to compare their potential contrast agent abilities with that of cryptophane-A (CrA), the most widely used host for such purposes. The exchange of Xe with such compounds was found to be sensitive to the type of ions present in solution and can be used for switchable magnetization transfer (MT) contrast that arises from off-resonant pre-saturation. We demonstrate that the adjustable MT magnitude depends on the interplay of saturation parameters and found that the optimum MT contrast surpasses the CrA CEST performance at moderate saturation power. Since modification of such water-soluble pillar[5]arenes is straightforward, these compounds can be considered a promising platform for designing various sensors that may complement the field of Xe HyperCEST-based biosensing MRI.

Molecular Sensing with Host Systems for Hyperpolarized 129Xe

“…In some cases, Xe hosts with a defined cavity have shown an unexpectedly high exchange rate such that the observation of a dedicated signal from bound Xe becomes difficult or even impossible [ 124 , 125 ]. The presence of the host pool is nevertheless detectable in the z-spectrum and manifests as a significant broadening of the saturation response from the bulk pool.…”

“…In a subsequent study, our lab tested Xe binding to several water soluble pillar[5]arenes differing only by the counterions (e.g., Na + , NH 4 + , Br − ) mainly through magnetization transfer (MT) experiments of loosely bound Xe [ 125 ]. This screening led to the conclusion that Xe is displaying fast exchange that is tunable by counterions impacting the exchange kinetics.…”

Supramolecular nanotheranostics based on pillarenes

“…Furthermore, DOX was introduced into the [2]rotaxane by covalent imine bonds, serving as anticancer drugs trigged upon hydrolysis of imine bonds 73. Adjustable magnetization transfer MRI was realized based on the complex of water-soluble pillar[5]arene and 129 Xe, indicating that pillarene derivatives are the promising candidates to design biosensors to expand the diagnosis 74. Evtugyn and coworkers reported the electrochemical sensor prepared by modifying carbon black and pillar[5]arene on glassy carbon electrode, which could be applied for the detection of organic acid and DNA 75.…”

Probing Reversible Guest Binding with Hyperpolarized 129Xe-NMR: Characteristics and Applications for Cucurbit[n]urils

“…Altogether, the in vitro investigation of host systems for reversible binding of Xe and competitive guest can be accelerated significantly to allow for screening of novel supramolecular complexes. Recent examples are the investigation of an entire set of water-soluble pillar [5]arenes [156] and the monitoring of progressive Xe displacement from CB [6] through the enzymatic production of cadaverine [153] (see also Section 5.1).…”