How Do You Detect the Undetectable?

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 relative 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 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 obtained host-guest system. The results expand the “NMR toolbox” to explore a wider range of dynamic host-guest systems in which NMR signals cannot be detected.

CB[8]:halothane host-guest system in D2O. a) DFT minimized energy structures of CB[8], halothane and halothane@CB[8]. (b) 19F-NMR spectrum of 2 mM halothane and 0.2 mM CB[8] in D2O. (c) Relative 19F-NMR signal of halothane as function of the frequency of the applied saturation pulse (i.e., z-spectrum). (d) MT effect for CB[8]:halothane solutions with various molar ratios.

[1] Liat Avram, Mark A. Iron and Amnon Bar-Shir, Chemical Science 2016, 7, 6905-6909. (DOI: 10.1039/C6SC04083G)