Amplifying undetectable NMR signals to study host-guest interactions and exchange

The characteristics of host-guest systems, such as molecular recognition, complexation, encapsulation, guest composition, and dynamic exchange, are manifested by changes in the chemical shifts (Δω) in the NMR spectrum. However, in cases where NMR signals cannot be detected, due to low concentrations, poor solubility, or relatively fast exchange, an alternative is needed. Here, we show that by using the magnetization transfer (MT) method, the undetectable NMR signals of host-guest assemblies can be amplified by two orders of magnitude. It is shown that the binding kinetics characteristics of a fluorinated guest and cucurbit[n]uril (CB[n]) hosts in aqueous solutions determine the NMR signal amplification of host-guest assemblies. In addition, by using the MT technique within the ¹⁹F-NMR framework, one can detect μM concentrations of the complex and study the effect of different solutes on the resulting host-guest system. The results expand the “NMR toolbox” available to explore a wider range of dynamic host-guest systems in which NMR signals cannot be detected.