Cryptophane host molecules provide ultrasensitive contrast agents for ¹²⁹Xe NMR/MRI. To investigate key features of cryptophane–Xe sensing behavior, we designed a novel water-soluble cryptophane with a pendant hydrophobic adamantyl moiety, which has good affinity for a model receptor, beta-cyclodextrin (β-CD). Adamantyl-functionalized cryptophane-A (AFCA) was synthesized and characterized for Xe affinity, ¹²⁹Xe NMR signal, and aggregation state at varying AFCA and β-CD concentrations. The Xe–AFCA association constant was determined by fluorescence quenching, K_A = 114,000 ± 5000 M^–1 at 293 K, which is the highest reported affinity for a cryptophane host in phosphate-buffered saline (pH 7.2). No hyperpolarized (hp) ¹²⁹Xe NMR peak corresponding to AFCA-bound Xe was directly observed at high (100 μM) AFCA concentration, where small cryptophane aggregates were observed, and was only detected at low (15 μM) AFCA concentration, where the sensor remained fully monomeric in solution. Additionally, we observed no change in the chemical shift of AFCA-encapsulated ¹²⁹Xe after β-CD binding to the adamantyl moiety and a concomitant lack of change in the size distribution of the complex, suggesting that a change in the aggregation state is necessary to elicit a ¹²⁹Xe NMR chemical shift in cryptophane-based sensing. These results aid in further elucidating the recently discovered aggregation phenomenon, highlight limitations of cryptophane-based Xe sensing, and offer insights into the design of monomeric, high-affinity Xe sensors.

中文翻译：

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具有创纪录高 Xe 亲和力的单体 Cryptophane 深入了解聚合相关传感

^{Cryptophane 主体分子为129} Xe NMR/MRI提供超灵敏的造影剂。为了研究cryptophane-Xe传感行为的关键特征，我们设计了一种新型水溶性cryptophane，它带有一个疏水性金刚烷基侧基，对模型受体β-环糊精（β-CD）具有良好的亲和力。合成了金刚烷基功能化的cryptophane-A (AFCA)，并在不同的AFCA 和β-CD 浓度下对Xe 亲和力、¹²⁹ Xe NMR 信号和聚集状态进行了表征。Xe-AFCA 缔合常数通过荧光猝灭测定，K _A = 114,000 ± 5000 M ^–1在 293 K，这是报道的对磷酸盐缓冲盐水 (pH 7.2) 中的cryptophane 宿主的最高亲和力。无超极化 (hp)^{与 AFCA 结合的 Xe 对应的129} Xe NMR 峰在高 (100 μM) AFCA 浓度下直接观察到，其中观察到小的cryptophane 聚集体，并且仅在低 (15 μM) AFCA 浓度下检测到，其中传感器在溶液中保持完全单体. 此外，我们观察到在 β-CD 与金刚烷基部分结合后，AFCA 封装的¹²⁹ Xe 的化学位移没有变化，同时复合物的尺寸分布也没有变化，这表明聚集状态的变化是必要的引出¹²⁹基于cryptophane的传感中的Xe NMR化学位移。这些结果有助于进一步阐明最近发现的聚集现象，突出基于加密的 Xe 传感的局限性，并为单体、高亲和力 Xe 传感器的设计提供见解。