NMR Signal Amplification through Host:Guest Binding Kinetics

CEST (chemical exchange saturation transfer) is an NMR methodology by which the NMR signal of low concentration moieties is amplified through a saturation transfer mechanism. This methodology has been widely used in MRI-based applications for molecular imaging^[1]. Although the CEST methodology have been proposed for ¹H-NMR, the ability to use it with other NMR-observable nuclei^[2],[3] is an advantage for several fields in science, from host:guest chemistry to molecular MR imaging.

Here we employ the CEST technique in the ¹⁹F-NMR framework to amplify signals from extremely low and sometimes “undetectable” ¹⁹F-guests in cucurbit[n]uril (CB[n]) hosts. The proposed approach, which is termed guest exchange saturation transfer (GEST), is performed to study the binding kinetics in host:guest systems. Specifically, ¹⁹F-GEST effect of CB[7] as the host and several ¹⁹F-anesthetics as potential guests is shown. A significant GEST effect arising from CB[7]:fluoroxene host:guest system was observed, with the ability to amplify the ¹⁹F-NMR signal of extremely low concentrations of complexed guest (<µM) by a factor of x1000. Moreover, the effect of the salt content and the temperature on the obtained GEST outcome is discussed. Finally, the potential of ‘GEST’ to be used in molecular ¹⁹F-MRI applications is demonstrated. To summarize, the feasibility of applying the CEST methodology in ¹⁹F-NMR and MRI frameworks through host:guest molecular systems was demonstrated, along with the clear potential of the ¹⁹F-GEST methodology to study host:guest interaction^[4].

[1] A. Bar-Shir et al., ACS Chemical Biology 2015, 10, 1160-1170.

[2] A. Bar-Shir et al., Journal of the American Chemical Society 2015, 137, 78-81.

[3] M. Schnurr et al., Angew Chem Int Ed Engl 2015, 54, 13444-13447.

[4] L. Avram et al., Chemical Science 2016.