Hyperpolarized Xe NMR signal advancement by metal-organic framework entrapment in aqueous solution

Abstract

We report hyperpolarized Xe signal advancement by metal-organic framework (MOF) entrapment (Hyper-SAME) in aqueous solution. The 129Xe NMR signal is drastically promoted by entrapping the Xe into the pores of MOFs. The chemical shift of entrapped 129Xe is clearly distinguishable from that of free 129Xe in water, due to the surface and pore environment of MOFs. The influences from the crystal size of MOFs and their concentration in water are studied. A zinc imidazole MOF, zeolitic imidazole framework-8 (ZIF-8), with particle size of 110 nm at a concentration of 100 mg/mL, was used to give an NMR signal with intensity four times that of free 129Xe in water. Additionally, Hyper-SAME is compatible with hyperpolarized 129Xe chemical exchange saturation transfer. The 129Xe NMR signal can be amplified further by combining the two techniques. More importantly, Hyper-SAME provides a way to make detection of hyperpolarized 129Xe in aqueous solution convenient and broadens the application area of MOFs.

129Xe NMR on Porous Materials: Basic Principles and Recent Applications

“…HP xenon entrapped in ZIF‐8 crystallites in aqueous solution has recently been shown to increase the hyperpolarized signal intensity by a factor of four compared to xenon dissolved in water. [ 117 ] The authors compare this entrapment of xenon in a MOF to xenon in molecular cages such as cryptophane‐A, used in medical imaging for specific binding to certain biomolecules. [ 118,119 ] As the xenon signal intensity in such cages is often very low, HP xenon‐ZIF signals were found to be 200 times higher than those of the xenon‐cryptophane‐A complex.…”

Coloring ultrasensitive MRI with tunable metal–organic frameworks

“… 29 The resulting 129 Xe in cages produces new signals that can be separated from the dissolved free 129 Xe signals in tissues and blood. Some nanostructures, such as porous nanoparticles, 30 nanoemulsions, 31 dendrimers, 32 proteins, 33 and genetically encoded reporters, 34,35 could provide host cavities for xenon binding and exchange. Nevertheless, 129 Xe signals in most of the developed nanocages are broad, due to the complicated exchange processes and the intricate chemical microenvironments.…”

Ultrasensitive molecular building block for biothiol NMR detection at picomolar concentrations

“…Hyperpolarized 129 Xe probes that result in specific molecular imaging have been considered (Spence et al, 2001). The usefulness of 129 Xe signals stems from a potential 100,000-fold enhancement through hyperpolarization (Zeng et al, 2020a), enabling its detection at ultralow concentrations. Also, the extremely high sensitivity of the 129 Xe atom to its local chemical environment (Schro ¨der, 2013) due to its large polarizable electronic cloud confers it the potential to distinguish different molecules or biomarkers (Palaniappan et al, 2014;Taratula and Dmochowski, 2010).…”

“…The other advantage of CEST is that the contrast mechanism can be switched on and off, as a way to minimize false positive outcomes. For Hyper-CEST, the signal is generated from the interaction between Xe and Xe host molecules, such as cryptophane-A (Schro ¨der et al, 2006), cucurbit [6]uril (Kunth et al, 2015), protein (Wang et al, 2016), gas vesicles (Shapiro et al, 2014), pillararene (Adiri et al, 2013), nanoemulsions (Stevens et al, 2013), metal-organic capsules (Roukala et al, 2015;Du et al, 2020), and metal-organic frameworks (Yang et al, 2021;Zeng et al, 2020a). These host molecules bind with Xe transiently and generate a characteristic 129 Xe chemical shift that is used to help localize the signal in the tissue of interest.…”