Molecular Imaging, Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP), 13125 Berlin, Germany.
Molecules. 2020 Oct 11;25(20):4627. doi: 10.3390/molecules25204627.
Hyperpolarized noble gases have been used early on in applications for sensitivity enhanced NMR. Xe has been explored for various applications because it can be used beyond the gas-driven examination of void spaces. Its solubility in aqueous solutions and its affinity for hydrophobic binding pockets allows "functionalization" through combination with host structures that bind one or multiple gas atoms. Moreover, the transient nature of gas binding in such hosts allows the combination with another signal enhancement technique, namely chemical exchange saturation transfer (CEST). Different systems have been investigated for implementing various types of so-called Xe biosensors where the gas binds to a targeted host to address molecular markers or to sense biophysical parameters. This review summarizes developments in biosensor design and synthesis for achieving molecular sensing with NMR at unprecedented sensitivity. Aspects regarding Xe exchange kinetics and chemical engineering of various classes of hosts for an efficient build-up of the CEST effect will also be discussed as well as the cavity design of host molecules to identify a pool of bound Xe. The concept is presented in the broader context of reporter design with insights from other modalities that are helpful for advancing the field of Xe biosensors.
在灵敏度增强 NMR 的应用中，早期就使用了超极化惰性气体。由于氙气不仅可用于检测气体驱动的空腔，还可用于其他各种应用，因此受到了广泛的探索。其在水溶液中的溶解度及其对疏水性结合口袋的亲和力，使其可通过与结合一个或多个气体原子的主体结构进行“功能化”。此外，这种主体结构中气体结合的瞬态特性允许与另一种信号增强技术（即化学交换饱和转移（CEST））结合。已经研究了不同的系统来实现各种类型的所谓 Xe 生物传感器，其中气体与靶向主体结合以检测分子标记物或感知生物物理参数。本综述总结了用于实现具有前所未有的灵敏度的 NMR 分子传感的生物传感器设计和合成方面的进展。还将讨论 Xe 交换动力学和各种主体类别（以有效地建立 CEST 效应）的化学工程方面，以及主体分子腔的设计以确定结合 Xe 的池。该概念是在其他模态的见解的更广泛的报告设计背景下提出的，这些见解有助于推进 Xe 生物传感器领域的发展。
