Hyper-CEST NMR of metal organic polyhedral cages reveals hidden diastereomers with diverse guest exchange kinetics

Abstract

Guest capture and release are important properties of self-assembling nanostructures. Over time, a significant fraction of guests might engage in short-lived states with different symmetry and stereoselectivity and transit frequently between multiple environments, thereby escaping common spectroscopy techniques. Here, we investigate the cavity of an iron-based metal organic polyhedron (Fe-MOP) using spin-hyperpolarized 129Xe Chemical Exchange Saturation Transfer (hyper-CEST) NMR. We report strong signals unknown from previous studies that persist under different perturbations. On-the-fly delivery of hyperpolarized gas yields CEST signatures that reflect different Xe exchange kinetics from multiple environments. Dilute pools with ~ 104-fold lower spin numbers than reported for directly detected hyperpolarized nuclei are readily detected due to efficient guest turnover. The system is further probed by instantaneous and medium timescale perturbations. Computational modeling indicates that these signals originate likely from Xe bound to three Fe-MOP diastereomers (T, C3, S4). The symmetry thus induces steric effects with aperture size changes that tunes selective spin manipulation as it is employed in CEST MRI agents and, potentially, impacts other processes occurring on the millisecond time scale.

Xenon Induces Its Own Preferred Heterochiral Host from Exclusive Homochiral Assembly

“…However, a tedious synthesis is usually required. , In contrast, assembled hosts are barely explored. Only a few hydrogen-bonding assemblies , and metal-assembled M 4 L 6 cages − have been investigated, and a highest binding affinity of 16 M –1 was reported among them …”

Structural and functional imaging of brains

“…In addition, the 129 Xe signal can be enhanced more than 10,000-fold than that of thermal polarization by SEOP techniques, thereby enabling 129 Xe MRI/MRS in brain [76,77,357]. In order to improve the specificity, researchers have designed a series of probes targeting different substances (e.g., biothiol) based on cage-like probe molecules such as cryptophane, cucurbit [6]uril, pillar [5]arene, gas vesicle, and metal-organic frameworks [358][359][360][361][362][363][364]. And the further application of 129 Xe in brain needs to improve the specificity and water solubility of probe.…”

Radiofrequency labeling strategies in chemical exchange saturation transfer MRI

“…These sections are followed by a discussion of strategies and techniques for improving the sensitivity and specificity of CEST MRI studies using saturation and excitation‐based RF labeling approaches. We focus on protons, but the concepts discussed can be generalized to heteronuclear CEST experiments 36–41 . Additionally, the RF labeling methods can be combined with novel acquisition approaches 42–46 to achieve specific and rapid CEST imaging.…”

“…We focus on protons, but the concepts discussed can be generalized to heteronuclear CEST experiments. [36][37][38][39][40][41] Additionally, the RF labeling methods can be combined with novel acquisition approaches [42][43][44][45][46] to achieve specific and rapid CEST imaging.…”