Heteronuclear 1D and 2D NMR Resonances Detected by Chemical Exchange Saturation Transfer to Water

A method to detect NMR spectra from heteronuclei through the modulation that they impose on a water resonance is exemplified. The approach exploits chemical exchange saturation transfers, which can magnify the signal of labile protons through their influence on a water peak. To impose a heteronuclear modulation on water, an HMQC‐type sequence was combined with the FLEX approach. 1D ¹⁵N NMR spectra of exchanging sites could thus be detected, with about tenfold amplifications over the ¹⁵N modulations afforded by conventionally detected HMQC NMR spectroscopy. Extensions of this approach enable 2D heteronuclear acquisitions on directly bonded ¹H–¹⁵N spin pairs, also with significant signal amplification. Despite the interesting limits of detection that these signal enhancements could open in NMR spectroscopy, these gains are constrained by the rates of solvent exchange of the targeted heteronuclear pairs, as well as by spectrometer instabilities affecting the intense water resonances detected in these experiments.