Rapid analytical CEST spectroscopy of competitive host–guest interactions using spatial parallelization with a combined approach of variable flip angle, keyhole and averaging (CAVKA)

Abstract

A serious limitation of high resolution ¹²⁹Xe chemical exchange saturation transfer (CEST) NMR spectroscopy for comparing competitive host–guest interactions from different samples is the long acquisition time due to step-wise encoding of the chemical shift dimension. A method of optimized use of ¹²⁹Xe spin magnetization to enable the accelerated and simultaneous acquisition of CEST spectra from multiple samples or regions in a setup is described. The method is applied to investigate the host–guest system of commercially available cucurbit[7]uril (CB7) and xenon with competing guests: cis-1,4-bis(aminomethyl)cyclohexane, cadaverine, and putrescine. Interactions with the different guests prove that the observed CEST signal is from a CB6 impurity and that CB7 itself does not produce a CEST signal. Instead, rapid interactions between xenon and CB7 manifest in the spectrum as a broad saturation response that could be suppressed by cis-1,4-bis(aminomethyl)cyclohexane. This guest prevents interactions at the CB7 portals. The suggested method represents a type of spectroscopic imaging that is capable of capturing the exchange kinetics information of systems that otherwise suffer from shortened T₂ times and yields multiple spectra for comparing exchange conditions with a reduction of >95% in acquisition time. The spectral quality is sufficient to perform quantitative analysis and quantifications relative to a CB6 standard as well as relative to a known blocker concentration (putrescine) that both reveal an unexpectedly high CB6 impurity of ca. 8%.